Clinical Review

Recent advances in the understanding and detection of cervical cancer have resulted in a recommendation to increase the screening interval with a Pap smear from annually to every 2 or 3 years for low-risk patients. We know that cervical cancer requires the persistence of high-risk human papillomavirus (HPV) types to develop, and this knowledge has provided high-level evidence that annual cervical cancer screening is not beneficial for most women.

Where does this shift in the surveillance strategy for cervical cancer leave us? Implementing new screening intervals gives us a wonderful opportunity to reevaluate the annual exam, and to educate ourselves and patients about interventions that make an impact on health.

Eliminate the annual exam?

Do we still need routine encounters with our patients? In this article, I address 2 topics that can help answer the question: I review the evidence that supports annual “well-woman” visits and outline the interventions that have proven benefit.

Time to retire a time-honored tradition

The utility of an annual health visit—ie, a comprehensive head-to-toe physical exam coupled with a battery of tests for early identification of disease and intervention—came into question with the rise of evidence-based medicine in the mid-1970s and, eventually, became unsupportable. In 1979, the Canadian Task Force on the Periodic Health Examination concluded that the value of only a few preventive interventions was supported by data. In 1989, Oboler and colleagues concluded that “comprehensive annual exams in asymptomatic adults have little screening value…”¹

The American College of Physicians, American Medical Association, US Preventive Services Task Force (USPSTF), and US Public Health Service all concur: The routine, annual, comprehensive physical exam is unnecessary. Instead, physicians should institute a selective approach to identifying and preventing health problems in all patients—one based on gender, age, health history, and risk factors.

Some interventions have helped

The incidence of, and mortality from, cervical cancer dropped strikingly in the United States with the advent of annual screening with the Pap smear. Mammography has recently been proved to increase the early detection rate of breast cancer and to reduce the rate of death from breast cancer. The challenge we face, therefore, is to determine which screening tests and interventions are valuable and will translate into improved health outcomes. The USPSTF has set out broad recommendations on 10 areas of screening for women:

• monitor blood pressure
  
• screen for cervical and colorectal cancers, depression, diabetes, and osteoporosis
  
• test for chlamydial infection
  
• measure the cholesterol level
  
• perform mammography.
  

New tool helps you develop an exam

Available for you is an excellent online resource developed by the Agency for Healthcare Research and Quality (AHRQ) for adopting the USPSTF screening recommendations. AHRQ has created the “electronic preventive services select” (or ePSS) Web site (http://epss.ahrq.gov), which is searchable by patient sex, age, and behavioral risk factors. The evidence for various preventive services is graded, guiding you on both interventions that are strongly recommended and those that should not be offered routinely because they lack data to support utility.

Make the transition with a systematic approach

We can capitalize on the habit that patients have established and have them come in annually for appropriate, evidence-based services. How do we make the change from the typical ObGyn visit—one that includes a breast and pelvic examination, cervical cancer screening, and mammography—to an evidence-based, annual well-woman visit that can be rapidly implemented and easily documented, using a paper or an electronic medical record?

I recommend creating templates for the annual well-woman visit that are age-specific and include check boxes for the age-appropriate history, physical exam, testing, and counseling that you’ll provide. You can create a distinct form for each of the various age and risk groups or, more simply, devise a single form that includes all guidelines for screening, from which you choose the appropriate areas based, again, on age and risk status.

Build a screening form

What should you include on the template that you create? Here are possible items, based on what I use in my practice:

History. Document the patient’s age, allergies, medications, contraceptive method, and risk factors (eg, smoking, a history of infection with high-risk HPV types, and a significant family history of colon, breast, and ovarian cancer and of heart disease and diabetes). Develop a problem list of concerns that the patient, and you, have. Note: I ask the patient to complete a checklist review of systems at every annual visit; doing so helps identify specific health concerns she may want to discuss.

 

Physical exam. Measure height, weight, body mass index, and blood pressure. Check off items included in the examination of breast, abdominal, and pelvic structures, and elaborate on abnormal findings in a space provided. Include an area on the form for noting “other” concerns, such as findings of skin, musculoskeletal, upper respiratory, and cardiac assessments—any of which is performed as indicated.

Lab testing. Document routine testing with 1) a check box to indicate which tests have been ordered and 2) a line on which to note the tests that were identified as appropriate but were not performed or were deemed inappropriate—and why. Such documentation is helpful when coding pay-for-performance measures.

Counseling. Develop a list that includes smoking cessation, weight loss, exercise, contraception, and prevention of osteoporosis and sexually transmitted infection. The list helps you recall, and discuss, essential areas (TABLE 1).

The goal in developing and using a template? It provides a single, easy-to-use form that is flexible and applicable to all women, and that encourages consistent adherence to guidelines for screening and prevention.

TABLE 1

Remember to provide lifestyle counseling!

Don’t smoke
Drink alcohol in moderation
Eat healthy—ie, high-fiber, low-fat foods, including fruits and vegetables
Exercise often—ie, aerobic, weight-bearing, and balance activities
Maintain healthy weight*
Use a condom during sexual intercourse
Use a contraceptive
*Be prepared to provide strategies for effective, sustainable weight loss to your patients

With a format in place, screen in 7 areas

What do guidelines recommend that we embrace as interventions to make a difference in patients’ long-term health? Research and consensus have established that the annual well-woman visit be organized around clinical areas of concern, comprising 7 primary intervention areas and 3 optional areas of general health (TABLE 2). In addition, ObGyns are well-positioned to add several areas of counseling, support, and intervention:

• lifelong contraception management and planning
  
• pre-pregnancy counseling
  
• prevention of sexually transmitted infection
  
• identification of sexual concerns
  
• management of menopause.
  

Prevention of cervical Ca. With approval last year of the vaccine against several HPV types, we are in an unprecedented position to recommend vaccination against HPV—and other diseases.

Chlamydial infection. “Grade-A” evidence supports annual screening for Chlamydia trachomatis for 1) all sexually active women 25 years and younger and 2) older women who engage in high-risk behavior (eg, more than one sex partner).

Pap smear and HPV typing. ACOG and the American Cancer Society recommend annual Pap smear testing beginning 3 years after the onset of sexual activity and continuing until 30 years of age. Routine testing for high-risk HPV subtypes may be undertaken with the Pap smear for women older than 30 years.

For most women who test negative for HPV and who have negative Pap smear cytology, Pap smear testing should be repeated no more often than every 3 years. Women who are positive for a high-risk HPV type despite a negative Pap smear should continue to be screened annually with cytology and HPV testing.

Breast health. Many groups recommend training women to perform monthly breast self-examination (BSE), although the USPSTF states that there is “insufficient evidence to recommend for or against” BSE. All groups do, however, advise an annual breast examination by a clinician, along with annual or biennial mammography beginning at 40 years of age and annual mammography beginning at 50 years.

Although many women do detect a breast lump when performing a BSE, it is unclear whether BSE improves survival from breast cancer. That’s because many lumps that women discover are benign.

Generally, therefore, I tell patients to pay attention to their breasts as they would other body parts: Don’t ignore an obvious change but don’t feel it is necessary to perform a standardized examination of the breasts monthly; evidence just does not support such a need.

Cardiovascular health. Assess blood pressure in every patient at every visit. Persistently high readings (>130/80 mm Hg) should prompt action—whether lifestyle modification or medication. Many physicians are slow to treat young women with so-called labile or borderline hypertension because the onset of cardiovascular disease is generally at an older age in women, but evidence shows that women suffer from proportionately more strokes at a young age than men do. Aggressive management of persistent hypertension may improve outcome.

• Aspirin therapy is recommended for prevention of stroke in women 45 to 65 years who are at risk. Do not recommend aspirin routinely, however, for women younger than 65 years as a means of preventing myocardial infarction.
  
• Perform a baseline lipid profile on all women older than 45 years. A woman who has a risk factor for cardiovascular disease—smoking, hypertension, obesity or overweight, a family history of early-onset cardiovascular disease—should be screened at any age.
  
• Screening may be performed as a random lipid profile to eliminate the barrier of returning after an 8-hour fast. Only women who have a significant abnormality need to return for repeat testing after an overnight fast.
  
• I usually intervene with lifestyle modification recommendations first—more exercise, weight loss, more monounsaturated fats and omega-3 fats in the diet—and have the patient return for a fasting lipid profile after 3 to 6 months.
  

 

Although quality evidence is lacking on the benefit of counseling about weight reduction and exercise, my experience is that providing a message to patients consistently about a healthy lifestyle is more effective than almost any other medical intervention. To have an impact on cardiovascular health, however, it is imperative that we have basic knowledge about nutrition and exercise physiology—which were not taught in medical school.

It is, clearly, not useful to simply tell a patient to lose weight. Evidence does support sustained weight loss when a person participates in an organized program, such as Weight Watchers. Even moderate weight loss is associated with a reduction in the risk of hypertension, an improvement in lipid levels, and a substantial reduction in the risk of breast cancer.

I find that this last statistic—namely, that lifetime physical activity and maintenance of normal body weight is associated with a 20% to 40% reduction in the risk of breast cancer compared with the risk in women who do not exercise or who gain 10 kg or more above their high school weight—is a huge motivator. Why? It’s well-known that women are more concerned about breast cancer than about cardiovascular disease—even though statistics demonstrate that heart disease is the leading cause of death among women.

Diabetes. Women who have a history of gestational diabetes also have a markedly increased risk of type II diabetes within 5 years of the pregnancy. Clearly, these women, as well as those who are obese, have a strong family history of diabetes, or have abnormal lipid levels, should be screened with a random glucose measurement. Women who suffer chronic monilial infection should also be assessed for diabetes.

Colorectal cancer. The second leading cause of cancer death and the fourth most common cancer in the United States carries the same risk for women as it does for men. Polyps and cancers are more likely to present on the right (ascending) side of the colon in women, however, making screening with flexible sigmoidoscopy potentially less useful.

Sixty-five percent of the US population has not been adequately screened for colorectal cancer. This is regrettable, because good-quality data support an association between screening and a reduction in mortality—even simple screening with annual fecal occult blood testing. Ideally, colon cancer testing in people of average risk should begin at 50 years with either

• colonoscopy every 10 years
  
• flexible sigmoidoscopy every 5 years with or without annual fecal occult blood testing
  
• dual-contrast barium enema every 5 years
  
• fecal occult blood testing annually or
  
• perhaps, virtual colonoscopy or stool-based DNA testing for patients who decline traditional evaluation.
  

Data demonstrate a significant reduction in risk of death from colorectal cancer with annual fecal occult blood testing. Although a single test is only 30% to 50% sensitive (like a Pap smear), a program of repeated annual testing detects colorectal cancer in 92% of cases. Offered annually, fecal occult blood testing reduces deaths from colorectal cancer by 33% at 13 years.

Osteoporosis. For most women, screening for osteoporosis should begin at 65 years with a test of bone mineral density. Younger women who have a significant risk factor (weight, less than 127 pounds; hyperthyroidism; steroid use; a strong family history) might benefit from screening at an earlier age. All women who take more than 7.5 mg of prednisone daily or who have sustained a nontraumatic fracture should be treated to prevent osteoporosis regardless of findings on a dual energy x-ray absortiometry (DEXA) scan.

(Note: It is vital for you to provide osteoporosis screening to Medicare patients because this is 1 of only 2 office-based performance measures in the voluntary Medicare pay-for-performance list for 2007 that are applicable to gynecology practice; the other is screening for incontinence.)

Depression. We know that depression is more common, and tends to present with more physical complaints, in women than in men. Any patient who has vague somatic symptoms, chronic pain, fatigue, decreased libido, and sleep disturbances, or such “hormonal” complaints as premenstrual syndrome and hot flashes, should be screened for depression.

I have found that the Beck Depression Inventory is easy and quick to administer if indicated. This screening instrument can be downloaded from several Web sites (search the terms Beck/Depression/Inventory). For patients who screen positive, provide a resource sheet that includes a listing of specialist referrals and local depression hotline numbers.

TABLE 2

The pillars of an annual primary screening program

ESSENTIAL
Sexually transmitted infection (Chlamydia trachomatis) and cervical cancer (HPV) Breast health Cardiovascular health	Diabetes Colorectal cancer Osteoporosis Depression
OPTIONAL
Bladder health (incontinence) Thyroid disease	Domestic violence

Plus 3 at your discretion

The USPSTF has listed 3 optional areas for annual assessment: thyroid disease, bladder health, and domestic violence.

 

Thyroid. Because thyroid abnormalities are more common in women and because they may have an impact on the regularity of the menstrual cycle and on weight and hair loss, it seems sensible and appropriate to screen on a selected basis with a test of thyroid-stimulating hormone.

Incontinence. You should definitely include this problem in the review-of-systems questionnaire. Doing so will not only help the patient identify an embarrassing problem that she may be reluctant to bring up, but will also help drive additional services in your practice—such as urodynamic evaluation and surgery.

Build a relationship

The annual visit should reinforce the physician–patient relationship by educating women about the appropriate screening tests and supporting them as active participants in their health care. Take a consistent, balanced approach that complies with guidelines but that also addresses the patient’s concerns by incorporating education and appropriate interventions.

Recent advances in the understanding and detection of cervical cancer have resulted in a recommendation to increase the screening interval with a Pap smear from annually to every 2 or 3 years for low-risk patients. We know that cervical cancer requires the persistence of high-risk human papillomavirus (HPV) types to develop, and this knowledge has provided high-level evidence that annual cervical cancer screening is not beneficial for most women.

Where does this shift in the surveillance strategy for cervical cancer leave us? Implementing new screening intervals gives us a wonderful opportunity to reevaluate the annual exam, and to educate ourselves and patients about interventions that make an impact on health.

Eliminate the annual exam?

Do we still need routine encounters with our patients? In this article, I address 2 topics that can help answer the question: I review the evidence that supports annual “well-woman” visits and outline the interventions that have proven benefit.

Time to retire a time-honored tradition

The utility of an annual health visit—ie, a comprehensive head-to-toe physical exam coupled with a battery of tests for early identification of disease and intervention—came into question with the rise of evidence-based medicine in the mid-1970s and, eventually, became unsupportable. In 1979, the Canadian Task Force on the Periodic Health Examination concluded that the value of only a few preventive interventions was supported by data. In 1989, Oboler and colleagues concluded that “comprehensive annual exams in asymptomatic adults have little screening value…”¹

The American College of Physicians, American Medical Association, US Preventive Services Task Force (USPSTF), and US Public Health Service all concur: The routine, annual, comprehensive physical exam is unnecessary. Instead, physicians should institute a selective approach to identifying and preventing health problems in all patients—one based on gender, age, health history, and risk factors.

Some interventions have helped

The incidence of, and mortality from, cervical cancer dropped strikingly in the United States with the advent of annual screening with the Pap smear. Mammography has recently been proved to increase the early detection rate of breast cancer and to reduce the rate of death from breast cancer. The challenge we face, therefore, is to determine which screening tests and interventions are valuable and will translate into improved health outcomes. The USPSTF has set out broad recommendations on 10 areas of screening for women:

• monitor blood pressure
  
• screen for cervical and colorectal cancers, depression, diabetes, and osteoporosis
  
• test for chlamydial infection
  
• measure the cholesterol level
  
• perform mammography.
  

New tool helps you develop an exam

Available for you is an excellent online resource developed by the Agency for Healthcare Research and Quality (AHRQ) for adopting the USPSTF screening recommendations. AHRQ has created the “electronic preventive services select” (or ePSS) Web site (http://epss.ahrq.gov), which is searchable by patient sex, age, and behavioral risk factors. The evidence for various preventive services is graded, guiding you on both interventions that are strongly recommended and those that should not be offered routinely because they lack data to support utility.

Make the transition with a systematic approach

We can capitalize on the habit that patients have established and have them come in annually for appropriate, evidence-based services. How do we make the change from the typical ObGyn visit—one that includes a breast and pelvic examination, cervical cancer screening, and mammography—to an evidence-based, annual well-woman visit that can be rapidly implemented and easily documented, using a paper or an electronic medical record?

I recommend creating templates for the annual well-woman visit that are age-specific and include check boxes for the age-appropriate history, physical exam, testing, and counseling that you’ll provide. You can create a distinct form for each of the various age and risk groups or, more simply, devise a single form that includes all guidelines for screening, from which you choose the appropriate areas based, again, on age and risk status.

Build a screening form

What should you include on the template that you create? Here are possible items, based on what I use in my practice:

History. Document the patient’s age, allergies, medications, contraceptive method, and risk factors (eg, smoking, a history of infection with high-risk HPV types, and a significant family history of colon, breast, and ovarian cancer and of heart disease and diabetes). Develop a problem list of concerns that the patient, and you, have. Note: I ask the patient to complete a checklist review of systems at every annual visit; doing so helps identify specific health concerns she may want to discuss.

 

Physical exam. Measure height, weight, body mass index, and blood pressure. Check off items included in the examination of breast, abdominal, and pelvic structures, and elaborate on abnormal findings in a space provided. Include an area on the form for noting “other” concerns, such as findings of skin, musculoskeletal, upper respiratory, and cardiac assessments—any of which is performed as indicated.

Lab testing. Document routine testing with 1) a check box to indicate which tests have been ordered and 2) a line on which to note the tests that were identified as appropriate but were not performed or were deemed inappropriate—and why. Such documentation is helpful when coding pay-for-performance measures.

Counseling. Develop a list that includes smoking cessation, weight loss, exercise, contraception, and prevention of osteoporosis and sexually transmitted infection. The list helps you recall, and discuss, essential areas (TABLE 1).

The goal in developing and using a template? It provides a single, easy-to-use form that is flexible and applicable to all women, and that encourages consistent adherence to guidelines for screening and prevention.

TABLE 1

Remember to provide lifestyle counseling!

Don’t smoke
Drink alcohol in moderation
Eat healthy—ie, high-fiber, low-fat foods, including fruits and vegetables
Exercise often—ie, aerobic, weight-bearing, and balance activities
Maintain healthy weight*
Use a condom during sexual intercourse
Use a contraceptive
*Be prepared to provide strategies for effective, sustainable weight loss to your patients

With a format in place, screen in 7 areas

What do guidelines recommend that we embrace as interventions to make a difference in patients’ long-term health? Research and consensus have established that the annual well-woman visit be organized around clinical areas of concern, comprising 7 primary intervention areas and 3 optional areas of general health (TABLE 2). In addition, ObGyns are well-positioned to add several areas of counseling, support, and intervention:

• lifelong contraception management and planning
  
• pre-pregnancy counseling
  
• prevention of sexually transmitted infection
  
• identification of sexual concerns
  
• management of menopause.
  

Prevention of cervical Ca. With approval last year of the vaccine against several HPV types, we are in an unprecedented position to recommend vaccination against HPV—and other diseases.

Chlamydial infection. “Grade-A” evidence supports annual screening for Chlamydia trachomatis for 1) all sexually active women 25 years and younger and 2) older women who engage in high-risk behavior (eg, more than one sex partner).

Pap smear and HPV typing. ACOG and the American Cancer Society recommend annual Pap smear testing beginning 3 years after the onset of sexual activity and continuing until 30 years of age. Routine testing for high-risk HPV subtypes may be undertaken with the Pap smear for women older than 30 years.

For most women who test negative for HPV and who have negative Pap smear cytology, Pap smear testing should be repeated no more often than every 3 years. Women who are positive for a high-risk HPV type despite a negative Pap smear should continue to be screened annually with cytology and HPV testing.

Breast health. Many groups recommend training women to perform monthly breast self-examination (BSE), although the USPSTF states that there is “insufficient evidence to recommend for or against” BSE. All groups do, however, advise an annual breast examination by a clinician, along with annual or biennial mammography beginning at 40 years of age and annual mammography beginning at 50 years.

Although many women do detect a breast lump when performing a BSE, it is unclear whether BSE improves survival from breast cancer. That’s because many lumps that women discover are benign.

Generally, therefore, I tell patients to pay attention to their breasts as they would other body parts: Don’t ignore an obvious change but don’t feel it is necessary to perform a standardized examination of the breasts monthly; evidence just does not support such a need.

Cardiovascular health. Assess blood pressure in every patient at every visit. Persistently high readings (>130/80 mm Hg) should prompt action—whether lifestyle modification or medication. Many physicians are slow to treat young women with so-called labile or borderline hypertension because the onset of cardiovascular disease is generally at an older age in women, but evidence shows that women suffer from proportionately more strokes at a young age than men do. Aggressive management of persistent hypertension may improve outcome.

• Aspirin therapy is recommended for prevention of stroke in women 45 to 65 years who are at risk. Do not recommend aspirin routinely, however, for women younger than 65 years as a means of preventing myocardial infarction.
  
• Perform a baseline lipid profile on all women older than 45 years. A woman who has a risk factor for cardiovascular disease—smoking, hypertension, obesity or overweight, a family history of early-onset cardiovascular disease—should be screened at any age.
  
• Screening may be performed as a random lipid profile to eliminate the barrier of returning after an 8-hour fast. Only women who have a significant abnormality need to return for repeat testing after an overnight fast.
  
• I usually intervene with lifestyle modification recommendations first—more exercise, weight loss, more monounsaturated fats and omega-3 fats in the diet—and have the patient return for a fasting lipid profile after 3 to 6 months.
  

 

Although quality evidence is lacking on the benefit of counseling about weight reduction and exercise, my experience is that providing a message to patients consistently about a healthy lifestyle is more effective than almost any other medical intervention. To have an impact on cardiovascular health, however, it is imperative that we have basic knowledge about nutrition and exercise physiology—which were not taught in medical school.

It is, clearly, not useful to simply tell a patient to lose weight. Evidence does support sustained weight loss when a person participates in an organized program, such as Weight Watchers. Even moderate weight loss is associated with a reduction in the risk of hypertension, an improvement in lipid levels, and a substantial reduction in the risk of breast cancer.

I find that this last statistic—namely, that lifetime physical activity and maintenance of normal body weight is associated with a 20% to 40% reduction in the risk of breast cancer compared with the risk in women who do not exercise or who gain 10 kg or more above their high school weight—is a huge motivator. Why? It’s well-known that women are more concerned about breast cancer than about cardiovascular disease—even though statistics demonstrate that heart disease is the leading cause of death among women.

Diabetes. Women who have a history of gestational diabetes also have a markedly increased risk of type II diabetes within 5 years of the pregnancy. Clearly, these women, as well as those who are obese, have a strong family history of diabetes, or have abnormal lipid levels, should be screened with a random glucose measurement. Women who suffer chronic monilial infection should also be assessed for diabetes.

Colorectal cancer. The second leading cause of cancer death and the fourth most common cancer in the United States carries the same risk for women as it does for men. Polyps and cancers are more likely to present on the right (ascending) side of the colon in women, however, making screening with flexible sigmoidoscopy potentially less useful.

Sixty-five percent of the US population has not been adequately screened for colorectal cancer. This is regrettable, because good-quality data support an association between screening and a reduction in mortality—even simple screening with annual fecal occult blood testing. Ideally, colon cancer testing in people of average risk should begin at 50 years with either

• colonoscopy every 10 years
  
• flexible sigmoidoscopy every 5 years with or without annual fecal occult blood testing
  
• dual-contrast barium enema every 5 years
  
• fecal occult blood testing annually or
  
• perhaps, virtual colonoscopy or stool-based DNA testing for patients who decline traditional evaluation.
  

Data demonstrate a significant reduction in risk of death from colorectal cancer with annual fecal occult blood testing. Although a single test is only 30% to 50% sensitive (like a Pap smear), a program of repeated annual testing detects colorectal cancer in 92% of cases. Offered annually, fecal occult blood testing reduces deaths from colorectal cancer by 33% at 13 years.

Osteoporosis. For most women, screening for osteoporosis should begin at 65 years with a test of bone mineral density. Younger women who have a significant risk factor (weight, less than 127 pounds; hyperthyroidism; steroid use; a strong family history) might benefit from screening at an earlier age. All women who take more than 7.5 mg of prednisone daily or who have sustained a nontraumatic fracture should be treated to prevent osteoporosis regardless of findings on a dual energy x-ray absortiometry (DEXA) scan.

(Note: It is vital for you to provide osteoporosis screening to Medicare patients because this is 1 of only 2 office-based performance measures in the voluntary Medicare pay-for-performance list for 2007 that are applicable to gynecology practice; the other is screening for incontinence.)

Depression. We know that depression is more common, and tends to present with more physical complaints, in women than in men. Any patient who has vague somatic symptoms, chronic pain, fatigue, decreased libido, and sleep disturbances, or such “hormonal” complaints as premenstrual syndrome and hot flashes, should be screened for depression.

I have found that the Beck Depression Inventory is easy and quick to administer if indicated. This screening instrument can be downloaded from several Web sites (search the terms Beck/Depression/Inventory). For patients who screen positive, provide a resource sheet that includes a listing of specialist referrals and local depression hotline numbers.

TABLE 2

The pillars of an annual primary screening program

ESSENTIAL
Sexually transmitted infection (Chlamydia trachomatis) and cervical cancer (HPV) Breast health Cardiovascular health	Diabetes Colorectal cancer Osteoporosis Depression
OPTIONAL
Bladder health (incontinence) Thyroid disease	Domestic violence

Plus 3 at your discretion

The USPSTF has listed 3 optional areas for annual assessment: thyroid disease, bladder health, and domestic violence.

 

Thyroid. Because thyroid abnormalities are more common in women and because they may have an impact on the regularity of the menstrual cycle and on weight and hair loss, it seems sensible and appropriate to screen on a selected basis with a test of thyroid-stimulating hormone.

Incontinence. You should definitely include this problem in the review-of-systems questionnaire. Doing so will not only help the patient identify an embarrassing problem that she may be reluctant to bring up, but will also help drive additional services in your practice—such as urodynamic evaluation and surgery.

Build a relationship

The annual visit should reinforce the physician–patient relationship by educating women about the appropriate screening tests and supporting them as active participants in their health care. Take a consistent, balanced approach that complies with guidelines but that also addresses the patient’s concerns by incorporating education and appropriate interventions.

Recent advances in the understanding and detection of cervical cancer have resulted in a recommendation to increase the screening interval with a Pap smear from annually to every 2 or 3 years for low-risk patients. We know that cervical cancer requires the persistence of high-risk human papillomavirus (HPV) types to develop, and this knowledge has provided high-level evidence that annual cervical cancer screening is not beneficial for most women.

Where does this shift in the surveillance strategy for cervical cancer leave us? Implementing new screening intervals gives us a wonderful opportunity to reevaluate the annual exam, and to educate ourselves and patients about interventions that make an impact on health.

Eliminate the annual exam?

Do we still need routine encounters with our patients? In this article, I address 2 topics that can help answer the question: I review the evidence that supports annual “well-woman” visits and outline the interventions that have proven benefit.

Time to retire a time-honored tradition

The utility of an annual health visit—ie, a comprehensive head-to-toe physical exam coupled with a battery of tests for early identification of disease and intervention—came into question with the rise of evidence-based medicine in the mid-1970s and, eventually, became unsupportable. In 1979, the Canadian Task Force on the Periodic Health Examination concluded that the value of only a few preventive interventions was supported by data. In 1989, Oboler and colleagues concluded that “comprehensive annual exams in asymptomatic adults have little screening value…”¹

The American College of Physicians, American Medical Association, US Preventive Services Task Force (USPSTF), and US Public Health Service all concur: The routine, annual, comprehensive physical exam is unnecessary. Instead, physicians should institute a selective approach to identifying and preventing health problems in all patients—one based on gender, age, health history, and risk factors.

Some interventions have helped

The incidence of, and mortality from, cervical cancer dropped strikingly in the United States with the advent of annual screening with the Pap smear. Mammography has recently been proved to increase the early detection rate of breast cancer and to reduce the rate of death from breast cancer. The challenge we face, therefore, is to determine which screening tests and interventions are valuable and will translate into improved health outcomes. The USPSTF has set out broad recommendations on 10 areas of screening for women:

• monitor blood pressure
  
• screen for cervical and colorectal cancers, depression, diabetes, and osteoporosis
  
• test for chlamydial infection
  
• measure the cholesterol level
  
• perform mammography.
  

New tool helps you develop an exam

Available for you is an excellent online resource developed by the Agency for Healthcare Research and Quality (AHRQ) for adopting the USPSTF screening recommendations. AHRQ has created the “electronic preventive services select” (or ePSS) Web site (http://epss.ahrq.gov), which is searchable by patient sex, age, and behavioral risk factors. The evidence for various preventive services is graded, guiding you on both interventions that are strongly recommended and those that should not be offered routinely because they lack data to support utility.

Make the transition with a systematic approach

We can capitalize on the habit that patients have established and have them come in annually for appropriate, evidence-based services. How do we make the change from the typical ObGyn visit—one that includes a breast and pelvic examination, cervical cancer screening, and mammography—to an evidence-based, annual well-woman visit that can be rapidly implemented and easily documented, using a paper or an electronic medical record?

I recommend creating templates for the annual well-woman visit that are age-specific and include check boxes for the age-appropriate history, physical exam, testing, and counseling that you’ll provide. You can create a distinct form for each of the various age and risk groups or, more simply, devise a single form that includes all guidelines for screening, from which you choose the appropriate areas based, again, on age and risk status.

Build a screening form

What should you include on the template that you create? Here are possible items, based on what I use in my practice:

History. Document the patient’s age, allergies, medications, contraceptive method, and risk factors (eg, smoking, a history of infection with high-risk HPV types, and a significant family history of colon, breast, and ovarian cancer and of heart disease and diabetes). Develop a problem list of concerns that the patient, and you, have. Note: I ask the patient to complete a checklist review of systems at every annual visit; doing so helps identify specific health concerns she may want to discuss.

 

Physical exam. Measure height, weight, body mass index, and blood pressure. Check off items included in the examination of breast, abdominal, and pelvic structures, and elaborate on abnormal findings in a space provided. Include an area on the form for noting “other” concerns, such as findings of skin, musculoskeletal, upper respiratory, and cardiac assessments—any of which is performed as indicated.

Lab testing. Document routine testing with 1) a check box to indicate which tests have been ordered and 2) a line on which to note the tests that were identified as appropriate but were not performed or were deemed inappropriate—and why. Such documentation is helpful when coding pay-for-performance measures.

Counseling. Develop a list that includes smoking cessation, weight loss, exercise, contraception, and prevention of osteoporosis and sexually transmitted infection. The list helps you recall, and discuss, essential areas (TABLE 1).

The goal in developing and using a template? It provides a single, easy-to-use form that is flexible and applicable to all women, and that encourages consistent adherence to guidelines for screening and prevention.

TABLE 1

Remember to provide lifestyle counseling!

Don’t smoke
Drink alcohol in moderation
Eat healthy—ie, high-fiber, low-fat foods, including fruits and vegetables
Exercise often—ie, aerobic, weight-bearing, and balance activities
Maintain healthy weight*
Use a condom during sexual intercourse
Use a contraceptive
*Be prepared to provide strategies for effective, sustainable weight loss to your patients

With a format in place, screen in 7 areas

What do guidelines recommend that we embrace as interventions to make a difference in patients’ long-term health? Research and consensus have established that the annual well-woman visit be organized around clinical areas of concern, comprising 7 primary intervention areas and 3 optional areas of general health (TABLE 2). In addition, ObGyns are well-positioned to add several areas of counseling, support, and intervention:

• lifelong contraception management and planning
  
• pre-pregnancy counseling
  
• prevention of sexually transmitted infection
  
• identification of sexual concerns
  
• management of menopause.
  

Prevention of cervical Ca. With approval last year of the vaccine against several HPV types, we are in an unprecedented position to recommend vaccination against HPV—and other diseases.

Chlamydial infection. “Grade-A” evidence supports annual screening for Chlamydia trachomatis for 1) all sexually active women 25 years and younger and 2) older women who engage in high-risk behavior (eg, more than one sex partner).

Pap smear and HPV typing. ACOG and the American Cancer Society recommend annual Pap smear testing beginning 3 years after the onset of sexual activity and continuing until 30 years of age. Routine testing for high-risk HPV subtypes may be undertaken with the Pap smear for women older than 30 years.

For most women who test negative for HPV and who have negative Pap smear cytology, Pap smear testing should be repeated no more often than every 3 years. Women who are positive for a high-risk HPV type despite a negative Pap smear should continue to be screened annually with cytology and HPV testing.

Breast health. Many groups recommend training women to perform monthly breast self-examination (BSE), although the USPSTF states that there is “insufficient evidence to recommend for or against” BSE. All groups do, however, advise an annual breast examination by a clinician, along with annual or biennial mammography beginning at 40 years of age and annual mammography beginning at 50 years.

Although many women do detect a breast lump when performing a BSE, it is unclear whether BSE improves survival from breast cancer. That’s because many lumps that women discover are benign.

Generally, therefore, I tell patients to pay attention to their breasts as they would other body parts: Don’t ignore an obvious change but don’t feel it is necessary to perform a standardized examination of the breasts monthly; evidence just does not support such a need.

Cardiovascular health. Assess blood pressure in every patient at every visit. Persistently high readings (>130/80 mm Hg) should prompt action—whether lifestyle modification or medication. Many physicians are slow to treat young women with so-called labile or borderline hypertension because the onset of cardiovascular disease is generally at an older age in women, but evidence shows that women suffer from proportionately more strokes at a young age than men do. Aggressive management of persistent hypertension may improve outcome.

• Aspirin therapy is recommended for prevention of stroke in women 45 to 65 years who are at risk. Do not recommend aspirin routinely, however, for women younger than 65 years as a means of preventing myocardial infarction.
  
• Perform a baseline lipid profile on all women older than 45 years. A woman who has a risk factor for cardiovascular disease—smoking, hypertension, obesity or overweight, a family history of early-onset cardiovascular disease—should be screened at any age.
  
• Screening may be performed as a random lipid profile to eliminate the barrier of returning after an 8-hour fast. Only women who have a significant abnormality need to return for repeat testing after an overnight fast.
  
• I usually intervene with lifestyle modification recommendations first—more exercise, weight loss, more monounsaturated fats and omega-3 fats in the diet—and have the patient return for a fasting lipid profile after 3 to 6 months.
  

 

Although quality evidence is lacking on the benefit of counseling about weight reduction and exercise, my experience is that providing a message to patients consistently about a healthy lifestyle is more effective than almost any other medical intervention. To have an impact on cardiovascular health, however, it is imperative that we have basic knowledge about nutrition and exercise physiology—which were not taught in medical school.

It is, clearly, not useful to simply tell a patient to lose weight. Evidence does support sustained weight loss when a person participates in an organized program, such as Weight Watchers. Even moderate weight loss is associated with a reduction in the risk of hypertension, an improvement in lipid levels, and a substantial reduction in the risk of breast cancer.

I find that this last statistic—namely, that lifetime physical activity and maintenance of normal body weight is associated with a 20% to 40% reduction in the risk of breast cancer compared with the risk in women who do not exercise or who gain 10 kg or more above their high school weight—is a huge motivator. Why? It’s well-known that women are more concerned about breast cancer than about cardiovascular disease—even though statistics demonstrate that heart disease is the leading cause of death among women.

Diabetes. Women who have a history of gestational diabetes also have a markedly increased risk of type II diabetes within 5 years of the pregnancy. Clearly, these women, as well as those who are obese, have a strong family history of diabetes, or have abnormal lipid levels, should be screened with a random glucose measurement. Women who suffer chronic monilial infection should also be assessed for diabetes.

Colorectal cancer. The second leading cause of cancer death and the fourth most common cancer in the United States carries the same risk for women as it does for men. Polyps and cancers are more likely to present on the right (ascending) side of the colon in women, however, making screening with flexible sigmoidoscopy potentially less useful.

Sixty-five percent of the US population has not been adequately screened for colorectal cancer. This is regrettable, because good-quality data support an association between screening and a reduction in mortality—even simple screening with annual fecal occult blood testing. Ideally, colon cancer testing in people of average risk should begin at 50 years with either

• colonoscopy every 10 years
  
• flexible sigmoidoscopy every 5 years with or without annual fecal occult blood testing
  
• dual-contrast barium enema every 5 years
  
• fecal occult blood testing annually or
  
• perhaps, virtual colonoscopy or stool-based DNA testing for patients who decline traditional evaluation.
  

Data demonstrate a significant reduction in risk of death from colorectal cancer with annual fecal occult blood testing. Although a single test is only 30% to 50% sensitive (like a Pap smear), a program of repeated annual testing detects colorectal cancer in 92% of cases. Offered annually, fecal occult blood testing reduces deaths from colorectal cancer by 33% at 13 years.

Osteoporosis. For most women, screening for osteoporosis should begin at 65 years with a test of bone mineral density. Younger women who have a significant risk factor (weight, less than 127 pounds; hyperthyroidism; steroid use; a strong family history) might benefit from screening at an earlier age. All women who take more than 7.5 mg of prednisone daily or who have sustained a nontraumatic fracture should be treated to prevent osteoporosis regardless of findings on a dual energy x-ray absortiometry (DEXA) scan.

(Note: It is vital for you to provide osteoporosis screening to Medicare patients because this is 1 of only 2 office-based performance measures in the voluntary Medicare pay-for-performance list for 2007 that are applicable to gynecology practice; the other is screening for incontinence.)

Depression. We know that depression is more common, and tends to present with more physical complaints, in women than in men. Any patient who has vague somatic symptoms, chronic pain, fatigue, decreased libido, and sleep disturbances, or such “hormonal” complaints as premenstrual syndrome and hot flashes, should be screened for depression.

I have found that the Beck Depression Inventory is easy and quick to administer if indicated. This screening instrument can be downloaded from several Web sites (search the terms Beck/Depression/Inventory). For patients who screen positive, provide a resource sheet that includes a listing of specialist referrals and local depression hotline numbers.

TABLE 2

The pillars of an annual primary screening program

ESSENTIAL
Sexually transmitted infection (Chlamydia trachomatis) and cervical cancer (HPV) Breast health Cardiovascular health	Diabetes Colorectal cancer Osteoporosis Depression
OPTIONAL
Bladder health (incontinence) Thyroid disease	Domestic violence

Plus 3 at your discretion

The USPSTF has listed 3 optional areas for annual assessment: thyroid disease, bladder health, and domestic violence.

 

Thyroid. Because thyroid abnormalities are more common in women and because they may have an impact on the regularity of the menstrual cycle and on weight and hair loss, it seems sensible and appropriate to screen on a selected basis with a test of thyroid-stimulating hormone.

Incontinence. You should definitely include this problem in the review-of-systems questionnaire. Doing so will not only help the patient identify an embarrassing problem that she may be reluctant to bring up, but will also help drive additional services in your practice—such as urodynamic evaluation and surgery.

Build a relationship

The annual visit should reinforce the physician–patient relationship by educating women about the appropriate screening tests and supporting them as active participants in their health care. Take a consistent, balanced approach that complies with guidelines but that also addresses the patient’s concerns by incorporating education and appropriate interventions.

Four studies caught my eye this past year. The first describes the use of systematic methodology to confirm the diagnosis of primary cytomegalovirus (CMV) infection in pregnancy and lower the rate of unnecessary pregnancy termination. Investigators were able to reclassify approximately 70% of women who had been diagnosed with CMV infection and reduce the number of pregnancy terminations by 73%.

Two other studies help define the emerging problem of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection, when to look for it, and how to treat it. In the first, researchers isolated S. aureus from the wounds of 320 patients with community-acquired infection and tested the samples for methicillin resistance, finding a prevalence of 59%. In the second study, investigators analyzed culture specimens from pregnant women for the presence of group B streptococci and S. aureus colonization. They found colonization with group B streptococci to be significantly associated with S. aureus colonization, with a prevalence odds ratio of 2.1.

The fourth study concerns the human papillomavirus (HPV) vaccine. Women given an HPV-16 L1 virus-like particle vaccine and followed for 4 years remained 100% free of cervical intraepithelial neoplasia (CIN) grades 2 and 3, unlike women who received placebo.

I believe these 4 studies represent the most significant developments of the past year in the field of infectious disease.

Don’t rush a diagnosis of CMV infection in pregnancy

Guerra B, Simonazzi G, Banfi A, et al. Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. Am J Obstet Gynecol. 2007;196:221.e1–6.

CMV infection is a common and important perinatal pathogen. Each year in the United States, approximately 1% of gravidas acquire primary infection. Of these, about 40% transmit infection to the fetus. The rate of transmission is highest when maternal infection occurs in the third trimester, but the risk of serious fetal injury is greatest when maternal infection occurs in the first trimester. Ten percent to 20% of congenitally infected infants are acutely symptomatic at birth. Approximately 20% of these newborns die; most survivors have serious long-term complications. In contrast, CMV infection that recurs during pregnancy poses only minimal risk to the baby.¹

Many women choose to have their pregnancy terminated when they learn they have a primary CMV infection.

Details of the study

This retrospective study was designed to determine whether a systematic diagnostic algorithm reduces the rate of unnecessary abortion in women who have apparent acute CMV infection during pregnancy. Guerra and colleagues evaluated 1,857 consecutive patients in practices in Italy who had a positive anti-CMV immunoglobulin M (IgM) antibody assay in the first or second trimester and were referred to a tertiary care facility for further diagnostic testing. Universal screening for CMV is now common among practitioners in Italy, and virtually all of these patients were completely asymptomatic.

At the tertiary facility, investigators tested again for CMV-specific IgM, as well as IgG, by enzyme immunoassay. They also tested for IgM by immunoblot and determined the avidity of anti-CMV IgG. Women who had IgG of low or moderate avidity with confirmed IgM, and those who clearly seroconverted to IgG were assumed to have a primary infection.

Women who were positive for IgM with high-avidity IgG were assumed to have nonprimary infection. Women who were seronegative for both antibodies were classified as uninfected. Those who were IgM-negative with high-avidity IgG were classified as previously infected. Women with an acute infection were then counseled by a specialist and offered amniocentesis and targeted ultrasonography.

Only 11.9% of women with primary infection chose abortion

Of the 1,857 women in this study, 445 were classified as having primary infection (group 1); 53 (11.9%) women elected to terminate their pregnancy. At autopsy, 38 of the 53 fetuses were found to be infected. In the other 15 cases, the pregnancy was terminated in the first trimester, and postmortem examination was not performed.

In the 1,205 women found to have nonprimary infection or previous infection (group 2), only 5 (0.4%) had the pregnancy terminated in the first trimester, and no postmortem examinations were performed. The difference in the observed rates of abortion between groups 1 and 2 was highly significant (P<.001).

 

Given their observations in group 1, the authors estimated that, on the basis of the initial screening tests at the referring institutions, approximately 196 (11.9%) of all patients in groups 1 and 2 would have elected abortion. By using confirmatory tests combined with counseling by a specialist, the authors were able to reduce the number of abortions from 196 to 53, a 73% decrease.

Always confirm an initial diagnosis

Given the ominous prognosis for congenital CMV infection and the major psychological implications and sobering finality of abortion, it is imperative that clinicians confirm the diagnosis of primary CMV infection. Because most cases of CMV infection in immunocompetent adults are asymptomatic, the diagnosis is typically confirmed by serology. Unfortunately, the serologic tests for CMV are not as straight-forward and reliable as tests for other viral infections such as rubella. Commercially available tests for anti-CMV IgM often have false-positive and false-negative results. In addition, IgM antibody may be detected as long as 9 months after a primary infection and may subsequently re-appear during reactivation of a latent infection or reinfection.^2,3

Be selective, on the basis of risk factors and clinical manifestations, when screening pregnant women for cytomegalovirus infection.

Routine screening is not necessary

The authors’ findings vividly illustrate the potential errors that can occur when a large number of asymptomatic patients are routinely screened for CMV. Because of these pitfalls, I do not recommend routine screening. Rather, screening should be selective, directed at women who:

• have clinical manifestations of CMV infection
• are immunosuppressed
• have small children in daycare or work in daycare themselves or
• have documented exposure to someone with CMV infection.

If the initial immunoassay for CMV IgM is positive, a confirmatory immunoblot test for IgM should be performed, as well as avidity testing for IgG.

If primary infection is confirmed, the patient should undergo targeted ultrasonography and amniocentesis to assess for manifestations of congenital infection and to detect CMV in amniotic fluid by culture or polymerase chain reaction (PCR) testing. If the sonogram shows signs of fetal injury, or the PCR test is positive, the woman should be counseled about the options, which include experimental immunotherapy with hyperimmune anti-CMV globulin⁴ and pregnancy termination.

The study by Guerra and colleagues is a welcome addition to the obstetric literature. By using a systematic diagnostic algorithm that included an enzyme-linked immunosorbent assay and an immunoblot assay for IgM antibody and avidity testing for IgG antibody, the authors were able to reclassify approximately 70% of patients as either uninfected or previously infected. As a result, they reduced the number of pregnancy terminations by 73%, an objective end-point that clearly has great social, economic, and medical impact.

Most community S. aureus infections are methicillin-resistant

Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666–674.

Moran and colleagues reviewed the records of 422 adults with acute purulent and soft-tissue infections who were evaluated in 11 university-affiliated emergency departments in August 2004. Wounds were routinely cultured. When S. aureus was isolated, the organisms were tested for antimicrobial susceptibility to identify those that were methicillin-resistant. The PCR test was used to identify genes for staphylococcal enterotoxins A through E and H, toxic shock syndrome toxin, and Panton–Valentin leukocidin. The same methodology was used to identify the gene complex staphylococcal cassette chromosome mec (SCCmec). This complex contains the mecA gene that confers methicillin resistance.

Of the 422 patients, 320 (76%) had S. aureus isolated from their wound. The prevalence of methicillin resistance was 59%. Ninety-seven percent of MRSA isolates were pulsed-field type USA 300. SCCmec type IV and the Panton–Valentin leukocidin gene were detected in 98% of MRSA isolates. Other toxin genes were rare.

Only 2 drugs were 100% effective

Among MRSA isolates, 100% were susceptible to rifampin and trimethoprim-sulfamethoxazole (TMP-SMX), 95% were susceptible to clindamycin, and 92% were sensitive to tetracycline. Only 60% were sensitive to fluoroquinolones, and only 6% were sensitive to erythromycin. Only 43% of patients received initial empiric therapy with antibiotics to which their organisms were sensitive.

Reason to worry

S. aureus is an important pathogen in obstetric patients. It is the causative organism of toxic shock syndrome and the dominant pathogen in patients with puerperal mastitis, as well as one of the key causes of postoperative wound infection. When penicillin was developed in 1941, all strains of S. aureus were sensitive to the drug. Within a few short years, however, most hospital-acquired strains became resistant.

Methicillin was introduced in 1961 to treat these resistant staphylococcal species. Unfortunately, by the mid-1960s, methicillin-resistant S. aureus (MRSA) infections began to appear. By the 1990s, MRSA infections were common in hospitalized patients, particularly in intensive care units. Hospital-acquired MRSA isolates are often sensitive to only a few select antibiotics such as vancomycin, linezolid, and quinupristin/dalfopristin.⁵

 

In the late 1990s and early 2000s, MRSA began to appear in community-acquired infections in both adults and children. Most of these isolates have been implicated in skin and soft-tissue infections, but some have been responsible for invasive infection, bacteremia, and even death.⁶ Compared with hospital-acquired MRSA, these community isolates are more likely to be sensitive to commonly used antibiotics.

Always culture an infected wound

Knowledge of these sensitivity patterns is of great importance. Regrettably, as noted by Moran and associates, more than half of the patients (57%) were initially treated with antibiotics to which their infecting organism was resistant.

The clinical implications are clear:

• We must be aware that many community-acquired soft-tissue infections will be caused by drug-resistant staphylococci.
• Because antibiotic resistance is so prevalent, a culture of the infected wound should be obtained routinely so that antimicrobial therapy can be modified if the patient fails to respond to initial treatment.
• Antibiotic therapy alone is rarely sufficient for abscesses in the soft tissue and skin; adequate surgical drainage is essential.
• Fundamental infection-control measures, such as careful handwashing, adequate skin preparation prior to surgery, and local wound care, are of greater importance than ever.

Most cases of community-acquired MRSA have been isolated from skin and soft tissue; surgical drainage is necessary when infection advances to abscess in those sites.

In gravidas with group B strep, look for S. aureus

Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstet Gynecol. 2006;108:482–487.

To assess the prevalence of methicillin-sensitive and community-acquired methicillin-resistant S. aureus colonization in pregnant women, Chen and colleagues evaluated de-identified culture specimens that had originally been submitted to the microbiology laboratory for identification of group B streptococcal infection. As opposed to hospital-associated MRSA isolates, community-associated methicillin-resistant strains were defined as those possessing the type IV or V staphylococcal chromosomal cassette mec element and lacking a multi-drug-resistant phenotype.

Of the 2,963 culture specimens in the prospective surveillance study, 743 (25%) were positive for group B streptococci, and 507 (17%) were positive for S. aureus. Group B streptococcal colonization was significantly associated with S. aureus colonization; the prevalence odds ratio was 2.1. Fourteen of the 507 S. aureus isolates were methicillin-resistant (2.8%; 95% confidence interval [CI] 1.4–4.2%). Thirteen of the 14 strains (93%) were community-acquired.

S. aureus may cause sepsis, wound infection, bacteremia, and other ills

The unique feature of this study is the observation that vaginal colonization with group B streptococci was significantly associated with colonization with S. aureus—one of the possible causative pathogens in chorioamnionitis, endometritis, wound infection, bacteremia, puerperal mastitis, and toxic shock syndrome. The organism also may cause serious neonatal infection, particularly sepsis.

The prevalence of group B streptococcal colonization in this study (25.1%, 95% CI 23.5–26.7%) is comparable to data reported from several other investigators.⁷ Colonized women are at increased risk for chorioamnionitis and puerperal endometritis, and their infants are at increased risk of sepsis, pneumonia, and meningitis. Fortunately, intrapartum antibiotic prophylaxis significantly reduces the risk of both maternal and neonatal group B streptococcal infection.⁸

As I noted earlier in this update, the antimicrobial susceptibility of S. aureus has become increasingly limited, particularly in light of the recent increase in both hospital- and community-acquired methicillin-resistant strains. In this study by Chen and colleagues, 2.8% of S. aureus isolates were methicillin-resistant. Of these, all but one were community-acquired.

Clinical suggestions

These findings certainly do not indicate the need for routine cultures for S. aureus vaginal colonization in all pregnant women. Nor are cultures needed in women who test positive for group B streptococci at 35 to 37 weeks. However, clinicians should be alert for possible staphylococcal infections, such as wound abscess, furuncle, carbuncle, or mastitis, in these women. If such an infection appears, obtain a culture of the purulent collection. Pending the result, treat the patient empirically with a drug that is likely to be effective against community-acquired MRSA. One hundred percent of these strains are sensitive to rifampin and TMP-SMX, and 90% to 95% are sensitive to tetracycline.⁹

Univalent HPV vaccine is 100% effective against CIN grades 2, 3

Mao C, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia. Obstet Gynecol. 2006;107:18–27.

Mao and colleagues set out to assess the long-term protection of a univalent HPV vaccine against CIN grades 2, 3. Their prospective, randomized, double-blind, placebo-controlled trial involved 2,391 women, aged 16 to 23 years, who received either 40 μg of HPV-16 L1 virus-like particle vaccine or placebo intramuscularly at day 1, month 2, and month 6. Genital samples for HPV-16 DNA and cervical cytology specimens were collected at day 1, month 7, and then every 6 months for 48 months. A radioimmunoassay was used to assess antibody titers to HPV-16.

 

Vaccinated women avoided CIN

Of the 750 women who received placebo, 6 developed HPV-16–related CIN 2, and 6 developed CIN 3. Among the 755 vaccinated women, no cases of CIN occurred. Thus, the vaccine was 100% effective in this trial (95% CI 65–100%).

Among women who received placebo, 111 cases of persistent HPV-16 infection occurred, compared with 7 cases in vaccinated women (vaccine efficacy 94%; 95% CI 88–98%).

Following immunization, antibody to HPV-16 peaked at month 7, declined through month 18, and remained stable between months 30 and 48.

Any effective vaccine is important

Because 3,500 to 4,000 women still die from cervical cancer each year in the United States, and almost 274,000 die worldwide, the development of any HPV vaccine that provides lasting protection against CIN is important.

The vaccine evaluated by Mao and colleagues targeted a single strain of HPV, genotype 16. The recently approved quadrivalent vaccine, Gardasil, targets types 6, 11, 16, and 18. Of the more than 100 genotypes of HPV that have been discovered, approximately 30 are present in the mucosa of the genital tract, and 15 of these 30 are associated with cervical cancer. However, 2 HPV strains—types 16 and 18—are responsible for about two thirds of all cases of cervical cancer; 90% of genital warts cases result from infection with types 6 and 11.¹⁰

Emphasize to patients that preexisting cytologic abnormalities and genital warts don’t respond to vaccination against human papillomavirus.The Advisory Committee on Immunization Practices recommends that the quadrivalent vaccine be given to girls at age 11 or 12 years, prior to the onset of sexual activity, to be maximally effective against all 4 genotypes included in the vaccine.¹⁰

If a woman is infected with HPV prior to vaccination, she may develop abnormal cervical cytology related to the genotypes in the vaccine, as well as genotypes not included. Nevertheless, ACOG recommends that the vaccine be considered in all females ages 9 to 26.¹¹ HPV genotyping is not recommended before giving the vaccine because any type of routine screening reduces the cost-effectiveness of the vaccination program.¹⁰

Fundamentals of vaccination

The quadrivalent vaccine must be administered intramuscularly (0.5 mL) in 3 doses on day 1 and at 2 and 6 months. The principal adverse effect is a local reaction such as pain, swelling, or pruritus at the injection site. Low-grade fever occurs in approximately 10% of patients.

Although the vaccine is classified by the FDA as pregnancy category B, the manufacturer recommends against its use during pregnancy. It may be administered to lactating women, however. The approximate cost of the 3-dose series, including administration fees, is $400 to $500.

It’s a vaccine, not a treatment

Patients need to understand that vaccination is not a treatment for preexisting cytologic abnormalities or genital warts. Nor can it be expected to be perfectly protective over a person’s lifetime against infection caused by genotypes 6, 11, 16, and 18. Women must continue to have regular cytologic screening. No reliable scientific data suggest that vaccination of young girls will increase sexual promiscuity in the adolescent population.¹⁰

The author reports no financial relationships relevant to this article.

Four studies caught my eye this past year. The first describes the use of systematic methodology to confirm the diagnosis of primary cytomegalovirus (CMV) infection in pregnancy and lower the rate of unnecessary pregnancy termination. Investigators were able to reclassify approximately 70% of women who had been diagnosed with CMV infection and reduce the number of pregnancy terminations by 73%.

Two other studies help define the emerging problem of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection, when to look for it, and how to treat it. In the first, researchers isolated S. aureus from the wounds of 320 patients with community-acquired infection and tested the samples for methicillin resistance, finding a prevalence of 59%. In the second study, investigators analyzed culture specimens from pregnant women for the presence of group B streptococci and S. aureus colonization. They found colonization with group B streptococci to be significantly associated with S. aureus colonization, with a prevalence odds ratio of 2.1.

The fourth study concerns the human papillomavirus (HPV) vaccine. Women given an HPV-16 L1 virus-like particle vaccine and followed for 4 years remained 100% free of cervical intraepithelial neoplasia (CIN) grades 2 and 3, unlike women who received placebo.

I believe these 4 studies represent the most significant developments of the past year in the field of infectious disease.

Don’t rush a diagnosis of CMV infection in pregnancy

Guerra B, Simonazzi G, Banfi A, et al. Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. Am J Obstet Gynecol. 2007;196:221.e1–6.

CMV infection is a common and important perinatal pathogen. Each year in the United States, approximately 1% of gravidas acquire primary infection. Of these, about 40% transmit infection to the fetus. The rate of transmission is highest when maternal infection occurs in the third trimester, but the risk of serious fetal injury is greatest when maternal infection occurs in the first trimester. Ten percent to 20% of congenitally infected infants are acutely symptomatic at birth. Approximately 20% of these newborns die; most survivors have serious long-term complications. In contrast, CMV infection that recurs during pregnancy poses only minimal risk to the baby.¹

Many women choose to have their pregnancy terminated when they learn they have a primary CMV infection.

Details of the study

This retrospective study was designed to determine whether a systematic diagnostic algorithm reduces the rate of unnecessary abortion in women who have apparent acute CMV infection during pregnancy. Guerra and colleagues evaluated 1,857 consecutive patients in practices in Italy who had a positive anti-CMV immunoglobulin M (IgM) antibody assay in the first or second trimester and were referred to a tertiary care facility for further diagnostic testing. Universal screening for CMV is now common among practitioners in Italy, and virtually all of these patients were completely asymptomatic.

At the tertiary facility, investigators tested again for CMV-specific IgM, as well as IgG, by enzyme immunoassay. They also tested for IgM by immunoblot and determined the avidity of anti-CMV IgG. Women who had IgG of low or moderate avidity with confirmed IgM, and those who clearly seroconverted to IgG were assumed to have a primary infection.

Women who were positive for IgM with high-avidity IgG were assumed to have nonprimary infection. Women who were seronegative for both antibodies were classified as uninfected. Those who were IgM-negative with high-avidity IgG were classified as previously infected. Women with an acute infection were then counseled by a specialist and offered amniocentesis and targeted ultrasonography.

Only 11.9% of women with primary infection chose abortion

Of the 1,857 women in this study, 445 were classified as having primary infection (group 1); 53 (11.9%) women elected to terminate their pregnancy. At autopsy, 38 of the 53 fetuses were found to be infected. In the other 15 cases, the pregnancy was terminated in the first trimester, and postmortem examination was not performed.

In the 1,205 women found to have nonprimary infection or previous infection (group 2), only 5 (0.4%) had the pregnancy terminated in the first trimester, and no postmortem examinations were performed. The difference in the observed rates of abortion between groups 1 and 2 was highly significant (P<.001).

 

Given their observations in group 1, the authors estimated that, on the basis of the initial screening tests at the referring institutions, approximately 196 (11.9%) of all patients in groups 1 and 2 would have elected abortion. By using confirmatory tests combined with counseling by a specialist, the authors were able to reduce the number of abortions from 196 to 53, a 73% decrease.

Always confirm an initial diagnosis

Given the ominous prognosis for congenital CMV infection and the major psychological implications and sobering finality of abortion, it is imperative that clinicians confirm the diagnosis of primary CMV infection. Because most cases of CMV infection in immunocompetent adults are asymptomatic, the diagnosis is typically confirmed by serology. Unfortunately, the serologic tests for CMV are not as straight-forward and reliable as tests for other viral infections such as rubella. Commercially available tests for anti-CMV IgM often have false-positive and false-negative results. In addition, IgM antibody may be detected as long as 9 months after a primary infection and may subsequently re-appear during reactivation of a latent infection or reinfection.^2,3

Be selective, on the basis of risk factors and clinical manifestations, when screening pregnant women for cytomegalovirus infection.

Routine screening is not necessary

The authors’ findings vividly illustrate the potential errors that can occur when a large number of asymptomatic patients are routinely screened for CMV. Because of these pitfalls, I do not recommend routine screening. Rather, screening should be selective, directed at women who:

• have clinical manifestations of CMV infection
• are immunosuppressed
• have small children in daycare or work in daycare themselves or
• have documented exposure to someone with CMV infection.

If the initial immunoassay for CMV IgM is positive, a confirmatory immunoblot test for IgM should be performed, as well as avidity testing for IgG.

If primary infection is confirmed, the patient should undergo targeted ultrasonography and amniocentesis to assess for manifestations of congenital infection and to detect CMV in amniotic fluid by culture or polymerase chain reaction (PCR) testing. If the sonogram shows signs of fetal injury, or the PCR test is positive, the woman should be counseled about the options, which include experimental immunotherapy with hyperimmune anti-CMV globulin⁴ and pregnancy termination.

The study by Guerra and colleagues is a welcome addition to the obstetric literature. By using a systematic diagnostic algorithm that included an enzyme-linked immunosorbent assay and an immunoblot assay for IgM antibody and avidity testing for IgG antibody, the authors were able to reclassify approximately 70% of patients as either uninfected or previously infected. As a result, they reduced the number of pregnancy terminations by 73%, an objective end-point that clearly has great social, economic, and medical impact.

Most community S. aureus infections are methicillin-resistant

Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666–674.

Moran and colleagues reviewed the records of 422 adults with acute purulent and soft-tissue infections who were evaluated in 11 university-affiliated emergency departments in August 2004. Wounds were routinely cultured. When S. aureus was isolated, the organisms were tested for antimicrobial susceptibility to identify those that were methicillin-resistant. The PCR test was used to identify genes for staphylococcal enterotoxins A through E and H, toxic shock syndrome toxin, and Panton–Valentin leukocidin. The same methodology was used to identify the gene complex staphylococcal cassette chromosome mec (SCCmec). This complex contains the mecA gene that confers methicillin resistance.

Of the 422 patients, 320 (76%) had S. aureus isolated from their wound. The prevalence of methicillin resistance was 59%. Ninety-seven percent of MRSA isolates were pulsed-field type USA 300. SCCmec type IV and the Panton–Valentin leukocidin gene were detected in 98% of MRSA isolates. Other toxin genes were rare.

Only 2 drugs were 100% effective

Among MRSA isolates, 100% were susceptible to rifampin and trimethoprim-sulfamethoxazole (TMP-SMX), 95% were susceptible to clindamycin, and 92% were sensitive to tetracycline. Only 60% were sensitive to fluoroquinolones, and only 6% were sensitive to erythromycin. Only 43% of patients received initial empiric therapy with antibiotics to which their organisms were sensitive.

Reason to worry

S. aureus is an important pathogen in obstetric patients. It is the causative organism of toxic shock syndrome and the dominant pathogen in patients with puerperal mastitis, as well as one of the key causes of postoperative wound infection. When penicillin was developed in 1941, all strains of S. aureus were sensitive to the drug. Within a few short years, however, most hospital-acquired strains became resistant.

Methicillin was introduced in 1961 to treat these resistant staphylococcal species. Unfortunately, by the mid-1960s, methicillin-resistant S. aureus (MRSA) infections began to appear. By the 1990s, MRSA infections were common in hospitalized patients, particularly in intensive care units. Hospital-acquired MRSA isolates are often sensitive to only a few select antibiotics such as vancomycin, linezolid, and quinupristin/dalfopristin.⁵

 

In the late 1990s and early 2000s, MRSA began to appear in community-acquired infections in both adults and children. Most of these isolates have been implicated in skin and soft-tissue infections, but some have been responsible for invasive infection, bacteremia, and even death.⁶ Compared with hospital-acquired MRSA, these community isolates are more likely to be sensitive to commonly used antibiotics.

Always culture an infected wound

Knowledge of these sensitivity patterns is of great importance. Regrettably, as noted by Moran and associates, more than half of the patients (57%) were initially treated with antibiotics to which their infecting organism was resistant.

The clinical implications are clear:

• We must be aware that many community-acquired soft-tissue infections will be caused by drug-resistant staphylococci.
• Because antibiotic resistance is so prevalent, a culture of the infected wound should be obtained routinely so that antimicrobial therapy can be modified if the patient fails to respond to initial treatment.
• Antibiotic therapy alone is rarely sufficient for abscesses in the soft tissue and skin; adequate surgical drainage is essential.
• Fundamental infection-control measures, such as careful handwashing, adequate skin preparation prior to surgery, and local wound care, are of greater importance than ever.

Most cases of community-acquired MRSA have been isolated from skin and soft tissue; surgical drainage is necessary when infection advances to abscess in those sites.

In gravidas with group B strep, look for S. aureus

Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstet Gynecol. 2006;108:482–487.

To assess the prevalence of methicillin-sensitive and community-acquired methicillin-resistant S. aureus colonization in pregnant women, Chen and colleagues evaluated de-identified culture specimens that had originally been submitted to the microbiology laboratory for identification of group B streptococcal infection. As opposed to hospital-associated MRSA isolates, community-associated methicillin-resistant strains were defined as those possessing the type IV or V staphylococcal chromosomal cassette mec element and lacking a multi-drug-resistant phenotype.

Of the 2,963 culture specimens in the prospective surveillance study, 743 (25%) were positive for group B streptococci, and 507 (17%) were positive for S. aureus. Group B streptococcal colonization was significantly associated with S. aureus colonization; the prevalence odds ratio was 2.1. Fourteen of the 507 S. aureus isolates were methicillin-resistant (2.8%; 95% confidence interval [CI] 1.4–4.2%). Thirteen of the 14 strains (93%) were community-acquired.

S. aureus may cause sepsis, wound infection, bacteremia, and other ills

The unique feature of this study is the observation that vaginal colonization with group B streptococci was significantly associated with colonization with S. aureus—one of the possible causative pathogens in chorioamnionitis, endometritis, wound infection, bacteremia, puerperal mastitis, and toxic shock syndrome. The organism also may cause serious neonatal infection, particularly sepsis.

The prevalence of group B streptococcal colonization in this study (25.1%, 95% CI 23.5–26.7%) is comparable to data reported from several other investigators.⁷ Colonized women are at increased risk for chorioamnionitis and puerperal endometritis, and their infants are at increased risk of sepsis, pneumonia, and meningitis. Fortunately, intrapartum antibiotic prophylaxis significantly reduces the risk of both maternal and neonatal group B streptococcal infection.⁸

As I noted earlier in this update, the antimicrobial susceptibility of S. aureus has become increasingly limited, particularly in light of the recent increase in both hospital- and community-acquired methicillin-resistant strains. In this study by Chen and colleagues, 2.8% of S. aureus isolates were methicillin-resistant. Of these, all but one were community-acquired.

Clinical suggestions

These findings certainly do not indicate the need for routine cultures for S. aureus vaginal colonization in all pregnant women. Nor are cultures needed in women who test positive for group B streptococci at 35 to 37 weeks. However, clinicians should be alert for possible staphylococcal infections, such as wound abscess, furuncle, carbuncle, or mastitis, in these women. If such an infection appears, obtain a culture of the purulent collection. Pending the result, treat the patient empirically with a drug that is likely to be effective against community-acquired MRSA. One hundred percent of these strains are sensitive to rifampin and TMP-SMX, and 90% to 95% are sensitive to tetracycline.⁹

Univalent HPV vaccine is 100% effective against CIN grades 2, 3

Mao C, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia. Obstet Gynecol. 2006;107:18–27.

Mao and colleagues set out to assess the long-term protection of a univalent HPV vaccine against CIN grades 2, 3. Their prospective, randomized, double-blind, placebo-controlled trial involved 2,391 women, aged 16 to 23 years, who received either 40 μg of HPV-16 L1 virus-like particle vaccine or placebo intramuscularly at day 1, month 2, and month 6. Genital samples for HPV-16 DNA and cervical cytology specimens were collected at day 1, month 7, and then every 6 months for 48 months. A radioimmunoassay was used to assess antibody titers to HPV-16.

 

Vaccinated women avoided CIN

Of the 750 women who received placebo, 6 developed HPV-16–related CIN 2, and 6 developed CIN 3. Among the 755 vaccinated women, no cases of CIN occurred. Thus, the vaccine was 100% effective in this trial (95% CI 65–100%).

Among women who received placebo, 111 cases of persistent HPV-16 infection occurred, compared with 7 cases in vaccinated women (vaccine efficacy 94%; 95% CI 88–98%).

Following immunization, antibody to HPV-16 peaked at month 7, declined through month 18, and remained stable between months 30 and 48.

Any effective vaccine is important

Because 3,500 to 4,000 women still die from cervical cancer each year in the United States, and almost 274,000 die worldwide, the development of any HPV vaccine that provides lasting protection against CIN is important.

The vaccine evaluated by Mao and colleagues targeted a single strain of HPV, genotype 16. The recently approved quadrivalent vaccine, Gardasil, targets types 6, 11, 16, and 18. Of the more than 100 genotypes of HPV that have been discovered, approximately 30 are present in the mucosa of the genital tract, and 15 of these 30 are associated with cervical cancer. However, 2 HPV strains—types 16 and 18—are responsible for about two thirds of all cases of cervical cancer; 90% of genital warts cases result from infection with types 6 and 11.¹⁰

Emphasize to patients that preexisting cytologic abnormalities and genital warts don’t respond to vaccination against human papillomavirus.The Advisory Committee on Immunization Practices recommends that the quadrivalent vaccine be given to girls at age 11 or 12 years, prior to the onset of sexual activity, to be maximally effective against all 4 genotypes included in the vaccine.¹⁰

If a woman is infected with HPV prior to vaccination, she may develop abnormal cervical cytology related to the genotypes in the vaccine, as well as genotypes not included. Nevertheless, ACOG recommends that the vaccine be considered in all females ages 9 to 26.¹¹ HPV genotyping is not recommended before giving the vaccine because any type of routine screening reduces the cost-effectiveness of the vaccination program.¹⁰

Fundamentals of vaccination

The quadrivalent vaccine must be administered intramuscularly (0.5 mL) in 3 doses on day 1 and at 2 and 6 months. The principal adverse effect is a local reaction such as pain, swelling, or pruritus at the injection site. Low-grade fever occurs in approximately 10% of patients.

Although the vaccine is classified by the FDA as pregnancy category B, the manufacturer recommends against its use during pregnancy. It may be administered to lactating women, however. The approximate cost of the 3-dose series, including administration fees, is $400 to $500.

It’s a vaccine, not a treatment

Patients need to understand that vaccination is not a treatment for preexisting cytologic abnormalities or genital warts. Nor can it be expected to be perfectly protective over a person’s lifetime against infection caused by genotypes 6, 11, 16, and 18. Women must continue to have regular cytologic screening. No reliable scientific data suggest that vaccination of young girls will increase sexual promiscuity in the adolescent population.¹⁰

The author reports no financial relationships relevant to this article.

Four studies caught my eye this past year. The first describes the use of systematic methodology to confirm the diagnosis of primary cytomegalovirus (CMV) infection in pregnancy and lower the rate of unnecessary pregnancy termination. Investigators were able to reclassify approximately 70% of women who had been diagnosed with CMV infection and reduce the number of pregnancy terminations by 73%.

Two other studies help define the emerging problem of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection, when to look for it, and how to treat it. In the first, researchers isolated S. aureus from the wounds of 320 patients with community-acquired infection and tested the samples for methicillin resistance, finding a prevalence of 59%. In the second study, investigators analyzed culture specimens from pregnant women for the presence of group B streptococci and S. aureus colonization. They found colonization with group B streptococci to be significantly associated with S. aureus colonization, with a prevalence odds ratio of 2.1.

The fourth study concerns the human papillomavirus (HPV) vaccine. Women given an HPV-16 L1 virus-like particle vaccine and followed for 4 years remained 100% free of cervical intraepithelial neoplasia (CIN) grades 2 and 3, unlike women who received placebo.

I believe these 4 studies represent the most significant developments of the past year in the field of infectious disease.

Don’t rush a diagnosis of CMV infection in pregnancy

Guerra B, Simonazzi G, Banfi A, et al. Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. Am J Obstet Gynecol. 2007;196:221.e1–6.

CMV infection is a common and important perinatal pathogen. Each year in the United States, approximately 1% of gravidas acquire primary infection. Of these, about 40% transmit infection to the fetus. The rate of transmission is highest when maternal infection occurs in the third trimester, but the risk of serious fetal injury is greatest when maternal infection occurs in the first trimester. Ten percent to 20% of congenitally infected infants are acutely symptomatic at birth. Approximately 20% of these newborns die; most survivors have serious long-term complications. In contrast, CMV infection that recurs during pregnancy poses only minimal risk to the baby.¹

Many women choose to have their pregnancy terminated when they learn they have a primary CMV infection.

Details of the study

This retrospective study was designed to determine whether a systematic diagnostic algorithm reduces the rate of unnecessary abortion in women who have apparent acute CMV infection during pregnancy. Guerra and colleagues evaluated 1,857 consecutive patients in practices in Italy who had a positive anti-CMV immunoglobulin M (IgM) antibody assay in the first or second trimester and were referred to a tertiary care facility for further diagnostic testing. Universal screening for CMV is now common among practitioners in Italy, and virtually all of these patients were completely asymptomatic.

At the tertiary facility, investigators tested again for CMV-specific IgM, as well as IgG, by enzyme immunoassay. They also tested for IgM by immunoblot and determined the avidity of anti-CMV IgG. Women who had IgG of low or moderate avidity with confirmed IgM, and those who clearly seroconverted to IgG were assumed to have a primary infection.

Women who were positive for IgM with high-avidity IgG were assumed to have nonprimary infection. Women who were seronegative for both antibodies were classified as uninfected. Those who were IgM-negative with high-avidity IgG were classified as previously infected. Women with an acute infection were then counseled by a specialist and offered amniocentesis and targeted ultrasonography.

Only 11.9% of women with primary infection chose abortion

Of the 1,857 women in this study, 445 were classified as having primary infection (group 1); 53 (11.9%) women elected to terminate their pregnancy. At autopsy, 38 of the 53 fetuses were found to be infected. In the other 15 cases, the pregnancy was terminated in the first trimester, and postmortem examination was not performed.

In the 1,205 women found to have nonprimary infection or previous infection (group 2), only 5 (0.4%) had the pregnancy terminated in the first trimester, and no postmortem examinations were performed. The difference in the observed rates of abortion between groups 1 and 2 was highly significant (P<.001).

 

Given their observations in group 1, the authors estimated that, on the basis of the initial screening tests at the referring institutions, approximately 196 (11.9%) of all patients in groups 1 and 2 would have elected abortion. By using confirmatory tests combined with counseling by a specialist, the authors were able to reduce the number of abortions from 196 to 53, a 73% decrease.

Always confirm an initial diagnosis

Given the ominous prognosis for congenital CMV infection and the major psychological implications and sobering finality of abortion, it is imperative that clinicians confirm the diagnosis of primary CMV infection. Because most cases of CMV infection in immunocompetent adults are asymptomatic, the diagnosis is typically confirmed by serology. Unfortunately, the serologic tests for CMV are not as straight-forward and reliable as tests for other viral infections such as rubella. Commercially available tests for anti-CMV IgM often have false-positive and false-negative results. In addition, IgM antibody may be detected as long as 9 months after a primary infection and may subsequently re-appear during reactivation of a latent infection or reinfection.^2,3

Be selective, on the basis of risk factors and clinical manifestations, when screening pregnant women for cytomegalovirus infection.

Routine screening is not necessary

The authors’ findings vividly illustrate the potential errors that can occur when a large number of asymptomatic patients are routinely screened for CMV. Because of these pitfalls, I do not recommend routine screening. Rather, screening should be selective, directed at women who:

• have clinical manifestations of CMV infection
• are immunosuppressed
• have small children in daycare or work in daycare themselves or
• have documented exposure to someone with CMV infection.

If the initial immunoassay for CMV IgM is positive, a confirmatory immunoblot test for IgM should be performed, as well as avidity testing for IgG.

If primary infection is confirmed, the patient should undergo targeted ultrasonography and amniocentesis to assess for manifestations of congenital infection and to detect CMV in amniotic fluid by culture or polymerase chain reaction (PCR) testing. If the sonogram shows signs of fetal injury, or the PCR test is positive, the woman should be counseled about the options, which include experimental immunotherapy with hyperimmune anti-CMV globulin⁴ and pregnancy termination.

The study by Guerra and colleagues is a welcome addition to the obstetric literature. By using a systematic diagnostic algorithm that included an enzyme-linked immunosorbent assay and an immunoblot assay for IgM antibody and avidity testing for IgG antibody, the authors were able to reclassify approximately 70% of patients as either uninfected or previously infected. As a result, they reduced the number of pregnancy terminations by 73%, an objective end-point that clearly has great social, economic, and medical impact.

Most community S. aureus infections are methicillin-resistant

Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666–674.

Moran and colleagues reviewed the records of 422 adults with acute purulent and soft-tissue infections who were evaluated in 11 university-affiliated emergency departments in August 2004. Wounds were routinely cultured. When S. aureus was isolated, the organisms were tested for antimicrobial susceptibility to identify those that were methicillin-resistant. The PCR test was used to identify genes for staphylococcal enterotoxins A through E and H, toxic shock syndrome toxin, and Panton–Valentin leukocidin. The same methodology was used to identify the gene complex staphylococcal cassette chromosome mec (SCCmec). This complex contains the mecA gene that confers methicillin resistance.

Of the 422 patients, 320 (76%) had S. aureus isolated from their wound. The prevalence of methicillin resistance was 59%. Ninety-seven percent of MRSA isolates were pulsed-field type USA 300. SCCmec type IV and the Panton–Valentin leukocidin gene were detected in 98% of MRSA isolates. Other toxin genes were rare.

Only 2 drugs were 100% effective

Among MRSA isolates, 100% were susceptible to rifampin and trimethoprim-sulfamethoxazole (TMP-SMX), 95% were susceptible to clindamycin, and 92% were sensitive to tetracycline. Only 60% were sensitive to fluoroquinolones, and only 6% were sensitive to erythromycin. Only 43% of patients received initial empiric therapy with antibiotics to which their organisms were sensitive.

Reason to worry

S. aureus is an important pathogen in obstetric patients. It is the causative organism of toxic shock syndrome and the dominant pathogen in patients with puerperal mastitis, as well as one of the key causes of postoperative wound infection. When penicillin was developed in 1941, all strains of S. aureus were sensitive to the drug. Within a few short years, however, most hospital-acquired strains became resistant.

Methicillin was introduced in 1961 to treat these resistant staphylococcal species. Unfortunately, by the mid-1960s, methicillin-resistant S. aureus (MRSA) infections began to appear. By the 1990s, MRSA infections were common in hospitalized patients, particularly in intensive care units. Hospital-acquired MRSA isolates are often sensitive to only a few select antibiotics such as vancomycin, linezolid, and quinupristin/dalfopristin.⁵

 

In the late 1990s and early 2000s, MRSA began to appear in community-acquired infections in both adults and children. Most of these isolates have been implicated in skin and soft-tissue infections, but some have been responsible for invasive infection, bacteremia, and even death.⁶ Compared with hospital-acquired MRSA, these community isolates are more likely to be sensitive to commonly used antibiotics.

Always culture an infected wound

Knowledge of these sensitivity patterns is of great importance. Regrettably, as noted by Moran and associates, more than half of the patients (57%) were initially treated with antibiotics to which their infecting organism was resistant.

The clinical implications are clear:

• We must be aware that many community-acquired soft-tissue infections will be caused by drug-resistant staphylococci.
• Because antibiotic resistance is so prevalent, a culture of the infected wound should be obtained routinely so that antimicrobial therapy can be modified if the patient fails to respond to initial treatment.
• Antibiotic therapy alone is rarely sufficient for abscesses in the soft tissue and skin; adequate surgical drainage is essential.
• Fundamental infection-control measures, such as careful handwashing, adequate skin preparation prior to surgery, and local wound care, are of greater importance than ever.

Most cases of community-acquired MRSA have been isolated from skin and soft tissue; surgical drainage is necessary when infection advances to abscess in those sites.

In gravidas with group B strep, look for S. aureus

Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstet Gynecol. 2006;108:482–487.

To assess the prevalence of methicillin-sensitive and community-acquired methicillin-resistant S. aureus colonization in pregnant women, Chen and colleagues evaluated de-identified culture specimens that had originally been submitted to the microbiology laboratory for identification of group B streptococcal infection. As opposed to hospital-associated MRSA isolates, community-associated methicillin-resistant strains were defined as those possessing the type IV or V staphylococcal chromosomal cassette mec element and lacking a multi-drug-resistant phenotype.

Of the 2,963 culture specimens in the prospective surveillance study, 743 (25%) were positive for group B streptococci, and 507 (17%) were positive for S. aureus. Group B streptococcal colonization was significantly associated with S. aureus colonization; the prevalence odds ratio was 2.1. Fourteen of the 507 S. aureus isolates were methicillin-resistant (2.8%; 95% confidence interval [CI] 1.4–4.2%). Thirteen of the 14 strains (93%) were community-acquired.

S. aureus may cause sepsis, wound infection, bacteremia, and other ills

The unique feature of this study is the observation that vaginal colonization with group B streptococci was significantly associated with colonization with S. aureus—one of the possible causative pathogens in chorioamnionitis, endometritis, wound infection, bacteremia, puerperal mastitis, and toxic shock syndrome. The organism also may cause serious neonatal infection, particularly sepsis.

The prevalence of group B streptococcal colonization in this study (25.1%, 95% CI 23.5–26.7%) is comparable to data reported from several other investigators.⁷ Colonized women are at increased risk for chorioamnionitis and puerperal endometritis, and their infants are at increased risk of sepsis, pneumonia, and meningitis. Fortunately, intrapartum antibiotic prophylaxis significantly reduces the risk of both maternal and neonatal group B streptococcal infection.⁸

As I noted earlier in this update, the antimicrobial susceptibility of S. aureus has become increasingly limited, particularly in light of the recent increase in both hospital- and community-acquired methicillin-resistant strains. In this study by Chen and colleagues, 2.8% of S. aureus isolates were methicillin-resistant. Of these, all but one were community-acquired.

Clinical suggestions

These findings certainly do not indicate the need for routine cultures for S. aureus vaginal colonization in all pregnant women. Nor are cultures needed in women who test positive for group B streptococci at 35 to 37 weeks. However, clinicians should be alert for possible staphylococcal infections, such as wound abscess, furuncle, carbuncle, or mastitis, in these women. If such an infection appears, obtain a culture of the purulent collection. Pending the result, treat the patient empirically with a drug that is likely to be effective against community-acquired MRSA. One hundred percent of these strains are sensitive to rifampin and TMP-SMX, and 90% to 95% are sensitive to tetracycline.⁹

Univalent HPV vaccine is 100% effective against CIN grades 2, 3

Mao C, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia. Obstet Gynecol. 2006;107:18–27.

Mao and colleagues set out to assess the long-term protection of a univalent HPV vaccine against CIN grades 2, 3. Their prospective, randomized, double-blind, placebo-controlled trial involved 2,391 women, aged 16 to 23 years, who received either 40 μg of HPV-16 L1 virus-like particle vaccine or placebo intramuscularly at day 1, month 2, and month 6. Genital samples for HPV-16 DNA and cervical cytology specimens were collected at day 1, month 7, and then every 6 months for 48 months. A radioimmunoassay was used to assess antibody titers to HPV-16.

 

Vaccinated women avoided CIN

Of the 750 women who received placebo, 6 developed HPV-16–related CIN 2, and 6 developed CIN 3. Among the 755 vaccinated women, no cases of CIN occurred. Thus, the vaccine was 100% effective in this trial (95% CI 65–100%).

Among women who received placebo, 111 cases of persistent HPV-16 infection occurred, compared with 7 cases in vaccinated women (vaccine efficacy 94%; 95% CI 88–98%).

Following immunization, antibody to HPV-16 peaked at month 7, declined through month 18, and remained stable between months 30 and 48.

Any effective vaccine is important

Because 3,500 to 4,000 women still die from cervical cancer each year in the United States, and almost 274,000 die worldwide, the development of any HPV vaccine that provides lasting protection against CIN is important.

The vaccine evaluated by Mao and colleagues targeted a single strain of HPV, genotype 16. The recently approved quadrivalent vaccine, Gardasil, targets types 6, 11, 16, and 18. Of the more than 100 genotypes of HPV that have been discovered, approximately 30 are present in the mucosa of the genital tract, and 15 of these 30 are associated with cervical cancer. However, 2 HPV strains—types 16 and 18—are responsible for about two thirds of all cases of cervical cancer; 90% of genital warts cases result from infection with types 6 and 11.¹⁰

Emphasize to patients that preexisting cytologic abnormalities and genital warts don’t respond to vaccination against human papillomavirus.The Advisory Committee on Immunization Practices recommends that the quadrivalent vaccine be given to girls at age 11 or 12 years, prior to the onset of sexual activity, to be maximally effective against all 4 genotypes included in the vaccine.¹⁰

If a woman is infected with HPV prior to vaccination, she may develop abnormal cervical cytology related to the genotypes in the vaccine, as well as genotypes not included. Nevertheless, ACOG recommends that the vaccine be considered in all females ages 9 to 26.¹¹ HPV genotyping is not recommended before giving the vaccine because any type of routine screening reduces the cost-effectiveness of the vaccination program.¹⁰

Fundamentals of vaccination

The quadrivalent vaccine must be administered intramuscularly (0.5 mL) in 3 doses on day 1 and at 2 and 6 months. The principal adverse effect is a local reaction such as pain, swelling, or pruritus at the injection site. Low-grade fever occurs in approximately 10% of patients.

Although the vaccine is classified by the FDA as pregnancy category B, the manufacturer recommends against its use during pregnancy. It may be administered to lactating women, however. The approximate cost of the 3-dose series, including administration fees, is $400 to $500.

It’s a vaccine, not a treatment

Patients need to understand that vaccination is not a treatment for preexisting cytologic abnormalities or genital warts. Nor can it be expected to be perfectly protective over a person’s lifetime against infection caused by genotypes 6, 11, 16, and 18. Women must continue to have regular cytologic screening. No reliable scientific data suggest that vaccination of young girls will increase sexual promiscuity in the adolescent population.¹⁰

The author reports no financial relationships relevant to this article.

Human beings are master adapters. Thrust into a hostile environment, or subjected to other overwhelming forces, we quickly adapt to new demands, however harsh they may be. Then we maintain our new skill set with impressive devotion.

And that is the problem: We embrace our skills long after their usefulness has passed.

Gynecologic surgeons are guilty of the same failing. Although we know the vaginal route to be safer, quicker, cheaper, and easier on the patient, 65% to 70% of us still perform hysterectomy using the abdominal approach.^1,2

The reason? That was the way we were taught, back in the sometimes hostile years of residency, and no compelling force since has caused us to update our behavior.

Let us not cling to abdominal hysterectomy when a less invasive alternative would be better for the patient. Like the vaginal approach, the laparoscopic route has much to offer. Although some surgical teachers have successfully integrated laparoscopic surgery into their residency training programs, many more opportunities are needed. Applications for laparoscopic fellowships continue to increase in number, largely because young physicians feel their training is deficient in this area.

The time has come to refocus our attention on the alternatives to abdominal hysterectomy, and to learn and perform the least invasive surgical approach whenever possible. This article explores in brief the indications, goals, and basic technique for laparoscopic hysterectomy, and the technological developments that have made it timely and safe.

Indications

As always, a thorough pelvic–rectal examination and evaluation of uterine mobility and vaginal accessibility remain the standard of care for deciding the route of hysterectomy. We believe—as many surgeons do—that the size of the uterus is usually irrelevant when determining the surgical approach.

Laparoscopic-assisted vaginal hysterectomy is indicated when the surgeon needs to remove the uterus and cervix vaginally at the time of other laparoscopic procedures, such as excision of endometriosis, appendectomy, or salpingo-oophorectomy.

Total laparoscopic hysterectomy is warranted when vaginal exposure is inadequate, a large uterus would make the vaginal approach too difficult, the patient has undergone multiple surgeries, or an adnexal mass is suspicious for malignancy.

Supracervical laparoscopic hysterectomy is appropriate when there is normal pelvic support without dyspareunia or cervical abnormalities.

Goals of laparoscopic hysterectomy

For both total and supracervical hysterectomy, the first goal is to secure the uterine vessels (FIGURE 1). This goal can be achieved using a number of tools:

• Electrosurgery with bipolar cautery
• Harmonic energy
• Vascular clips
• Ligating suture

Our preference is to clamp and coagulate the uterine vascular bundle using curved ultrasonic shears (Harmonic Ace).³

Secure the uterine vessels at the ascending branches rather than where they enter the lower uterus, as the latter area is in close proximity to the ureter (FIGURE 2). To ensure hemostasis when using the ultrasonic shears, relax tissue tension and activate the device using minimum power.

FIGURE 1 Secure the uterine vessels

The left ascending uterine vessels are secured using the curved, ultrasonic shears.

FIGURE 2 Proximity of key structures

Because the ureter (no. 1) and uterine vessels (no. 2) are in close proximity, it is advisable to secure the vessels at the ascending branches (no. 3).

Secondary goal: Identify tissue structures

To identify the 3 levels of tissue structures in the lower pelvis, it is necessary to manipulate the uterus. We recommend learning to use a laparoscopic uterine tissue manipulator instead of a cervical–vaginal manipulator. The former makes it possible to maintain visualization throughout the procedure, obtain adequate exposure, and control tissue tension.

The 3 levels of tissue to be identified are (FIGURE 3):

• Level 1—ascending uterine vascular bundle
• Level 2—junction of the uterosacral–cardinal ligaments
• Level 3—junction of the cervix and vagina

If the uterus is large enough to interfere with visualization of the uterosacral–cardinal ligaments or the cervical–vaginal junction, or both, in situ tissue morcellation is warranted. This debulking should eventually allow visualization of the lower tissue structures.

FIGURE 3 Three levels of tissue

Level 1 corresponds to the ascending uterine vessels, level 2 to the uterosacral–cardinal ligament junction, and level 3 to the cervical–vaginal junction.

How tissue levels come into play

Total hysterectomy. Level 3 is the end-point. Once the uterine vessels are secured and the levels are identified, perform anterior and posterior colpotomy (FIGURE 4). Using traction and counter-traction, coagulate and divide the broad ligament, starting at level 1 and ending at level 3. Perform this step bilaterally.

 

Remove the cervix, uterus, and adnexa (if planned) via the vagina. Close the vaginal cuff using laparoscopic suturing for appropriate cuff support.⁴

Supracervical hysterectomy. Level 2 is the endpoint. Begin at level 1 using reverse cone drilling (FIGURE 5). This will enable you to reach level 2. Then extract the uterus using the tissue morcellator.

Laparoscopic-assisted vaginal hysterectomy. Clamp, cut, and ligate the uterine vessels vaginally.

FIGURE 4 Anterior and posterior colpotomy

After the uterine vessels are secured and the 3 tissue levels have been identified, perform anterior (A) and posterior (B) colpotomy.

FIGURE 5 Supracervical hysterectomy

Begin the procedure at tissue level 1 using reverse cone drilling to reach the level 2 endpoint.

Always locate the ureter

Regardless of the type of hysterectomy being performed, it is critical to observe the ureter and ensure that it is out of harm’s way before securing the uterine vessels and identifying the tissue levels.

At the end of the procedure, always reduce intra-abdominal pelvic pressure to 5 mm Hg and check all tissue sites for hemostasis.

It isn’t the same old OR

Not so long ago in the mid-1980s, we had fewer trocar options, laparoscopic suturing was limited, unipolar cautery was popular, endocutters could not guarantee hemostasis across staple lines, laparoscopes were large, images were unpredictable, monitors and cameras were nonexistent, and gas insufflators were bulky and slow. Despite these shortcomings, many surgeons and nurses believed minimally invasive surgery conferred advantages worth pursuing.

Then Semm pelviscopy (Kiel, Germany) reached the United States and intrigued American surgeons, both general and gynecologic.⁵ The ability to suture laparoscopically was crucial to the success of advanced operative laparoscopy.⁶ Laparoscopic cholecystectomy emerged, hastening further improvements in equipment and instrumentation.

Beginning in the late 1990s, laparoscopic surgeons witnessed even bigger changes in operating room technologies. The Internet increased the patient’s understanding of her options, and this new awareness motivated hospitals, industry, and physicians to upgrade women’s surgery. One result was specialized gynecologic OR nurse directors with telesurgery/telemedicine integrated into the suites. Digital platform cameras; smaller, clearer laparoscopes; and voice-activated lighting soon followed, as did better insufflators, image capturing, and other advances.

Today we rely on safer electrosurgery units (bipolar and tripolar) and “harmonic” energy.⁷ Tissue extractors enable us to remove large volumes of tissue quickly and safely. And all these developments have led to proven, enhanced outcomes for the patient.³

A promising future

The future for advanced operative laparoscopy is bright. As patients continue to press for minimally invasive procedures, the range of surgical options available to them will expand. To keep up, we will have little choice but to acquire expertise in minimally invasive applications.

Dr. Steven D. McCarus is a consultant to Ethicon Endo-Surgery and Gynecare.

Dr. Tamberly F. McCarus has no financial relationships relevant to this article.

Human beings are master adapters. Thrust into a hostile environment, or subjected to other overwhelming forces, we quickly adapt to new demands, however harsh they may be. Then we maintain our new skill set with impressive devotion.

And that is the problem: We embrace our skills long after their usefulness has passed.

Gynecologic surgeons are guilty of the same failing. Although we know the vaginal route to be safer, quicker, cheaper, and easier on the patient, 65% to 70% of us still perform hysterectomy using the abdominal approach.^1,2

The reason? That was the way we were taught, back in the sometimes hostile years of residency, and no compelling force since has caused us to update our behavior.

Let us not cling to abdominal hysterectomy when a less invasive alternative would be better for the patient. Like the vaginal approach, the laparoscopic route has much to offer. Although some surgical teachers have successfully integrated laparoscopic surgery into their residency training programs, many more opportunities are needed. Applications for laparoscopic fellowships continue to increase in number, largely because young physicians feel their training is deficient in this area.

The time has come to refocus our attention on the alternatives to abdominal hysterectomy, and to learn and perform the least invasive surgical approach whenever possible. This article explores in brief the indications, goals, and basic technique for laparoscopic hysterectomy, and the technological developments that have made it timely and safe.

Indications

As always, a thorough pelvic–rectal examination and evaluation of uterine mobility and vaginal accessibility remain the standard of care for deciding the route of hysterectomy. We believe—as many surgeons do—that the size of the uterus is usually irrelevant when determining the surgical approach.

Laparoscopic-assisted vaginal hysterectomy is indicated when the surgeon needs to remove the uterus and cervix vaginally at the time of other laparoscopic procedures, such as excision of endometriosis, appendectomy, or salpingo-oophorectomy.

Total laparoscopic hysterectomy is warranted when vaginal exposure is inadequate, a large uterus would make the vaginal approach too difficult, the patient has undergone multiple surgeries, or an adnexal mass is suspicious for malignancy.

Supracervical laparoscopic hysterectomy is appropriate when there is normal pelvic support without dyspareunia or cervical abnormalities.

Goals of laparoscopic hysterectomy

For both total and supracervical hysterectomy, the first goal is to secure the uterine vessels (FIGURE 1). This goal can be achieved using a number of tools:

• Electrosurgery with bipolar cautery
• Harmonic energy
• Vascular clips
• Ligating suture

Our preference is to clamp and coagulate the uterine vascular bundle using curved ultrasonic shears (Harmonic Ace).³

Secure the uterine vessels at the ascending branches rather than where they enter the lower uterus, as the latter area is in close proximity to the ureter (FIGURE 2). To ensure hemostasis when using the ultrasonic shears, relax tissue tension and activate the device using minimum power.

FIGURE 1 Secure the uterine vessels

The left ascending uterine vessels are secured using the curved, ultrasonic shears.

FIGURE 2 Proximity of key structures

Because the ureter (no. 1) and uterine vessels (no. 2) are in close proximity, it is advisable to secure the vessels at the ascending branches (no. 3).

Secondary goal: Identify tissue structures

To identify the 3 levels of tissue structures in the lower pelvis, it is necessary to manipulate the uterus. We recommend learning to use a laparoscopic uterine tissue manipulator instead of a cervical–vaginal manipulator. The former makes it possible to maintain visualization throughout the procedure, obtain adequate exposure, and control tissue tension.

The 3 levels of tissue to be identified are (FIGURE 3):

• Level 1—ascending uterine vascular bundle
• Level 2—junction of the uterosacral–cardinal ligaments
• Level 3—junction of the cervix and vagina

If the uterus is large enough to interfere with visualization of the uterosacral–cardinal ligaments or the cervical–vaginal junction, or both, in situ tissue morcellation is warranted. This debulking should eventually allow visualization of the lower tissue structures.

FIGURE 3 Three levels of tissue

Level 1 corresponds to the ascending uterine vessels, level 2 to the uterosacral–cardinal ligament junction, and level 3 to the cervical–vaginal junction.

How tissue levels come into play

Total hysterectomy. Level 3 is the end-point. Once the uterine vessels are secured and the levels are identified, perform anterior and posterior colpotomy (FIGURE 4). Using traction and counter-traction, coagulate and divide the broad ligament, starting at level 1 and ending at level 3. Perform this step bilaterally.

 

Remove the cervix, uterus, and adnexa (if planned) via the vagina. Close the vaginal cuff using laparoscopic suturing for appropriate cuff support.⁴

Supracervical hysterectomy. Level 2 is the endpoint. Begin at level 1 using reverse cone drilling (FIGURE 5). This will enable you to reach level 2. Then extract the uterus using the tissue morcellator.

Laparoscopic-assisted vaginal hysterectomy. Clamp, cut, and ligate the uterine vessels vaginally.

FIGURE 4 Anterior and posterior colpotomy

After the uterine vessels are secured and the 3 tissue levels have been identified, perform anterior (A) and posterior (B) colpotomy.

FIGURE 5 Supracervical hysterectomy

Begin the procedure at tissue level 1 using reverse cone drilling to reach the level 2 endpoint.

Always locate the ureter

Regardless of the type of hysterectomy being performed, it is critical to observe the ureter and ensure that it is out of harm’s way before securing the uterine vessels and identifying the tissue levels.

At the end of the procedure, always reduce intra-abdominal pelvic pressure to 5 mm Hg and check all tissue sites for hemostasis.

It isn’t the same old OR

Not so long ago in the mid-1980s, we had fewer trocar options, laparoscopic suturing was limited, unipolar cautery was popular, endocutters could not guarantee hemostasis across staple lines, laparoscopes were large, images were unpredictable, monitors and cameras were nonexistent, and gas insufflators were bulky and slow. Despite these shortcomings, many surgeons and nurses believed minimally invasive surgery conferred advantages worth pursuing.

Then Semm pelviscopy (Kiel, Germany) reached the United States and intrigued American surgeons, both general and gynecologic.⁵ The ability to suture laparoscopically was crucial to the success of advanced operative laparoscopy.⁶ Laparoscopic cholecystectomy emerged, hastening further improvements in equipment and instrumentation.

Beginning in the late 1990s, laparoscopic surgeons witnessed even bigger changes in operating room technologies. The Internet increased the patient’s understanding of her options, and this new awareness motivated hospitals, industry, and physicians to upgrade women’s surgery. One result was specialized gynecologic OR nurse directors with telesurgery/telemedicine integrated into the suites. Digital platform cameras; smaller, clearer laparoscopes; and voice-activated lighting soon followed, as did better insufflators, image capturing, and other advances.

Today we rely on safer electrosurgery units (bipolar and tripolar) and “harmonic” energy.⁷ Tissue extractors enable us to remove large volumes of tissue quickly and safely. And all these developments have led to proven, enhanced outcomes for the patient.³

A promising future

The future for advanced operative laparoscopy is bright. As patients continue to press for minimally invasive procedures, the range of surgical options available to them will expand. To keep up, we will have little choice but to acquire expertise in minimally invasive applications.

Dr. Steven D. McCarus is a consultant to Ethicon Endo-Surgery and Gynecare.

Dr. Tamberly F. McCarus has no financial relationships relevant to this article.

Human beings are master adapters. Thrust into a hostile environment, or subjected to other overwhelming forces, we quickly adapt to new demands, however harsh they may be. Then we maintain our new skill set with impressive devotion.

And that is the problem: We embrace our skills long after their usefulness has passed.

Gynecologic surgeons are guilty of the same failing. Although we know the vaginal route to be safer, quicker, cheaper, and easier on the patient, 65% to 70% of us still perform hysterectomy using the abdominal approach.^1,2

The reason? That was the way we were taught, back in the sometimes hostile years of residency, and no compelling force since has caused us to update our behavior.

Let us not cling to abdominal hysterectomy when a less invasive alternative would be better for the patient. Like the vaginal approach, the laparoscopic route has much to offer. Although some surgical teachers have successfully integrated laparoscopic surgery into their residency training programs, many more opportunities are needed. Applications for laparoscopic fellowships continue to increase in number, largely because young physicians feel their training is deficient in this area.

The time has come to refocus our attention on the alternatives to abdominal hysterectomy, and to learn and perform the least invasive surgical approach whenever possible. This article explores in brief the indications, goals, and basic technique for laparoscopic hysterectomy, and the technological developments that have made it timely and safe.

Indications

As always, a thorough pelvic–rectal examination and evaluation of uterine mobility and vaginal accessibility remain the standard of care for deciding the route of hysterectomy. We believe—as many surgeons do—that the size of the uterus is usually irrelevant when determining the surgical approach.

Laparoscopic-assisted vaginal hysterectomy is indicated when the surgeon needs to remove the uterus and cervix vaginally at the time of other laparoscopic procedures, such as excision of endometriosis, appendectomy, or salpingo-oophorectomy.

Total laparoscopic hysterectomy is warranted when vaginal exposure is inadequate, a large uterus would make the vaginal approach too difficult, the patient has undergone multiple surgeries, or an adnexal mass is suspicious for malignancy.

Supracervical laparoscopic hysterectomy is appropriate when there is normal pelvic support without dyspareunia or cervical abnormalities.

Goals of laparoscopic hysterectomy

For both total and supracervical hysterectomy, the first goal is to secure the uterine vessels (FIGURE 1). This goal can be achieved using a number of tools:

• Electrosurgery with bipolar cautery
• Harmonic energy
• Vascular clips
• Ligating suture

Our preference is to clamp and coagulate the uterine vascular bundle using curved ultrasonic shears (Harmonic Ace).³

Secure the uterine vessels at the ascending branches rather than where they enter the lower uterus, as the latter area is in close proximity to the ureter (FIGURE 2). To ensure hemostasis when using the ultrasonic shears, relax tissue tension and activate the device using minimum power.

FIGURE 1 Secure the uterine vessels

The left ascending uterine vessels are secured using the curved, ultrasonic shears.

FIGURE 2 Proximity of key structures

Because the ureter (no. 1) and uterine vessels (no. 2) are in close proximity, it is advisable to secure the vessels at the ascending branches (no. 3).

Secondary goal: Identify tissue structures

To identify the 3 levels of tissue structures in the lower pelvis, it is necessary to manipulate the uterus. We recommend learning to use a laparoscopic uterine tissue manipulator instead of a cervical–vaginal manipulator. The former makes it possible to maintain visualization throughout the procedure, obtain adequate exposure, and control tissue tension.

The 3 levels of tissue to be identified are (FIGURE 3):

• Level 1—ascending uterine vascular bundle
• Level 2—junction of the uterosacral–cardinal ligaments
• Level 3—junction of the cervix and vagina

If the uterus is large enough to interfere with visualization of the uterosacral–cardinal ligaments or the cervical–vaginal junction, or both, in situ tissue morcellation is warranted. This debulking should eventually allow visualization of the lower tissue structures.

FIGURE 3 Three levels of tissue

Level 1 corresponds to the ascending uterine vessels, level 2 to the uterosacral–cardinal ligament junction, and level 3 to the cervical–vaginal junction.

How tissue levels come into play

Total hysterectomy. Level 3 is the end-point. Once the uterine vessels are secured and the levels are identified, perform anterior and posterior colpotomy (FIGURE 4). Using traction and counter-traction, coagulate and divide the broad ligament, starting at level 1 and ending at level 3. Perform this step bilaterally.

 

Remove the cervix, uterus, and adnexa (if planned) via the vagina. Close the vaginal cuff using laparoscopic suturing for appropriate cuff support.⁴

Supracervical hysterectomy. Level 2 is the endpoint. Begin at level 1 using reverse cone drilling (FIGURE 5). This will enable you to reach level 2. Then extract the uterus using the tissue morcellator.

Laparoscopic-assisted vaginal hysterectomy. Clamp, cut, and ligate the uterine vessels vaginally.

FIGURE 4 Anterior and posterior colpotomy

After the uterine vessels are secured and the 3 tissue levels have been identified, perform anterior (A) and posterior (B) colpotomy.

FIGURE 5 Supracervical hysterectomy

Begin the procedure at tissue level 1 using reverse cone drilling to reach the level 2 endpoint.

Always locate the ureter

Regardless of the type of hysterectomy being performed, it is critical to observe the ureter and ensure that it is out of harm’s way before securing the uterine vessels and identifying the tissue levels.

At the end of the procedure, always reduce intra-abdominal pelvic pressure to 5 mm Hg and check all tissue sites for hemostasis.

It isn’t the same old OR

Not so long ago in the mid-1980s, we had fewer trocar options, laparoscopic suturing was limited, unipolar cautery was popular, endocutters could not guarantee hemostasis across staple lines, laparoscopes were large, images were unpredictable, monitors and cameras were nonexistent, and gas insufflators were bulky and slow. Despite these shortcomings, many surgeons and nurses believed minimally invasive surgery conferred advantages worth pursuing.

Then Semm pelviscopy (Kiel, Germany) reached the United States and intrigued American surgeons, both general and gynecologic.⁵ The ability to suture laparoscopically was crucial to the success of advanced operative laparoscopy.⁶ Laparoscopic cholecystectomy emerged, hastening further improvements in equipment and instrumentation.

Beginning in the late 1990s, laparoscopic surgeons witnessed even bigger changes in operating room technologies. The Internet increased the patient’s understanding of her options, and this new awareness motivated hospitals, industry, and physicians to upgrade women’s surgery. One result was specialized gynecologic OR nurse directors with telesurgery/telemedicine integrated into the suites. Digital platform cameras; smaller, clearer laparoscopes; and voice-activated lighting soon followed, as did better insufflators, image capturing, and other advances.

Today we rely on safer electrosurgery units (bipolar and tripolar) and “harmonic” energy.⁷ Tissue extractors enable us to remove large volumes of tissue quickly and safely. And all these developments have led to proven, enhanced outcomes for the patient.³

A promising future

The future for advanced operative laparoscopy is bright. As patients continue to press for minimally invasive procedures, the range of surgical options available to them will expand. To keep up, we will have little choice but to acquire expertise in minimally invasive applications.

Dr. Steven D. McCarus is a consultant to Ethicon Endo-Surgery and Gynecare.

Dr. Tamberly F. McCarus has no financial relationships relevant to this article.

CASE Three hours of pushing

C.A., age 29 years, is 40 weeks’ pregnant with her first child. After an unremarkable pregnancy, she arrives at the hospital for cervical ripening and induction of labor. Oxytocin is given, and labor progresses uneventfully. When C.A.’s cervix is dilated 8 cm, however, labor stalls. The physician orders placement of a pressure catheter and increases the dosage of oxytocin, and the cervix dilates fully. Although C.A. pushes well, the vertex descends only from +1 to +2 station (of 5 stations) after 3 hours.

How would you manage this delivery?

One option in C.A.’s case is operative vaginal delivery using the vacuum extractor, which has replaced the forceps as the most commonly used approach for operative vaginal delivery. Like the forceps, the vacuum extractor has vociferous detractors as well as supporters. Liberal use of cesarean section and questions regarding the safety of operative vaginal delivery vis-à-vis cesarean section have fueled the debate over its role in obstetric practice.

Among the benefits of vacuum extraction are its cost-effectiveness and shorter hospital stay (TABLE 1). It also obviates the need for cesarean section, including repeat cesarean. Risks include an increased incidence of genital tract trauma and a greater risk of fetal subgaleal hemorrhage.

We review 4 critical spheres of concern in regard to vacuum extraction:

1. Patient selection
2. Informed consent
3. Technique
4. Documentation

Increased understanding of these aspects of vacuum extraction will improve outcomes for the patient and limit medicolegal risk.

In the case of C.A., the physician offered 3 options:

• Continue maternal expulsive efforts to allow descent
• Attempt delivery by vacuum extraction
• Proceed to cesarean section on the basis of protracted descent.

Risks and benefits were reviewed with the patient, who chose to deliver by cesarean section. A 3,780-g infant in occiput posterior position was delivered safely.

TABLE 1

Delicate balance: Risks and benefits of operative vaginal delivery

WHO?	BENEFIT	RISK
Mother	Cost-effective Less blood loss Lower risk of febrile morbidity Maternal preference No need for cesarean section or repeat cesarean Shorter hospitalization and convalescence	Increased incidence of genital tract trauma Possible damage to pelvic floor, with urinary and anal incontinence
Fetus	Fewer respiratory difficulties at birth	Increased risk of subgaleal hemorrhage Association with shoulder dystocia

1. Patient selection: Maternal and fetal indications

Vacuum extraction may be justified for maternal or fetal indications.^1,2 Maternal indications include prolongation or arrest of the second stage of labor, or the need to shorten the second stage, for reasons such as maternal cardiac disease, complex congenital cardiovascular disorders, and maternal exhaustion.

No definitive time limit for the second stage of labor

There is more flexibility today than in the past about what constitutes a “safe” length of the second stage. Recommendations concerning when the mother should begin pushing—and for how long—have evolved from a strict time limit to a focus on progression. If the fetal heart rate (FHR) tracing is reassuring, the second stage no longer needs to be limited to 2 or 3 hours. On the contrary, if the patient is still able and willing to push, changes in positioning and further expectant management remain acceptable in contemporary practice.³ Otherwise, a trial of vacuum extraction may be appropriate.

Vacuum extraction is particularly useful when the mother has difficulty pushing because of exhaustion and the fetal head has descended enough that it distends the labia between contractions, as in outlet deliveries.

Fetal indications

Fetal indications for operative vaginal delivery include distress, jeopardy, or a “nonreassuring” FHR tracing. Such a tracing may include late and prolonged decelerations, baseline bradycardia or tachycardia with or without variable decelerations, or, occasionally, a normal baseline rate with diminished variability.

Use vacuum or forceps?

The choice depends on which device would achieve delivery in the safest manner with the lowest risk of fetal injury. With the vacuum, force is exerted directly on the fetal scalp and only secondarily on the fetal skull. This puts fetal vessels that traverse the subgaleal space at risk for injury (FIGURE). With forceps, force is exerted directly on the fetal skull and mitigated by the petrous bone. Little or no force is exerted on the fetal scalp, lessening the risk of traumatic injury such as potentially fatal subgaleal hemorrhage.

 

Indications and contraindications for vacuum extraction are similar, but not identical, to those for forceps delivery (TABLE 2).^2,3 The most important determinant for either device is the experience of the operator. You must be familiar with the instrument and technique before making any attempt to assist delivery. An inability to accurately assess fetal position or station, fetopelvic proportion, adequacy of labor, engagement of the fetal head, or any degree of malpresentation (including minor degrees of deflexion) is a contraindication to a trial of operative vaginal delivery.

Vacuum extraction should be reserved for fetuses at more than 34 weeks’ gestation because of the increased risk of intracranial hemorrhage associated with prematurity.

All decisions involving vacuum extraction should be made with caution. The adequacy of the pelvis, estimated fetal size, and any suggestions of fetopelvic disproportion are of particular significance.³

FIGURE

Subgaleal hemorrhage, a deadly complication

Blood can accumulate in a large potential space between the galea aponeurotica and the periosteum of the cranial bones after vacuum extraction. An infant with subgaleal hemorrhage will exhibit a boggy scalp, with swelling that crosses the suture lines and expands head circumferenceTABLE 2

Factors that predict success—or failure—of vacuum extraction

When a woman fits overlapping categories, the decision to use vacuum extraction—or not—may be a judgment call*
GOOD CANDIDACY
Multiparous
Term pregnancy
Occiput anterior position, well-flexed
Wide subpubic arch
Compliant
MARGINAL CANDIDACY
Primiparous
Post-term
Occiput posterior position
Average subpubic arch
Gestational diabetes
Arrest disorders in second stage
POOR CANDIDACY
Protraction disorders in second stage
Narrow subpubic arch
Uncertain position of fetal head
Deflexion or asynclitism
Anticipated large-for-gestational-age infant
Poor maternal compliance
* When faced with a good indication in a marginal candidate, we recommend delivery in a “double setup” situation in which preparations are made for both vacuum extraction and cesarean section. If the vacuum can be properly applied, the first application of traction is crucial. We will only proceed if significant descent is achieved. If the fetal head (not the scalp) can be advanced a full station, then we proceed cautiously. If not, ready access to cesarean section allows for completion of the delivery in a timely manner.

2. Informed consent: Elicit the patient’s desires

Thorough discussion with the patient and her family—to explain the reasoning behind the clinical decision to use the vacuum extractor and delineate the alternatives—is paramount. Moreover, the patient should be encouraged to actively participate in this discussion.

Among the alternatives to vacuum extraction are expectant observation and expedited delivery by cesarean section. Because patients increasingly are requesting elective cesarean section in the absence of obvious obstetric indications, this option should receive extra attention.

Most women still consider vaginal delivery an important milestone of female adulthood. When safety concerns arise and the situation makes vaginal delivery unwise, many women experience disappointment and postpartum depression over their “failed” attempt at vaginal delivery. These perceptions need to be addressed in discussions with the patient.

The risk–benefit equation

Vacuum extraction lessens the risk of maternal lacerations, either of the lower genital tract in the case of obstetric forceps, or of the cervix and lower uterine segment in the case of cesarean section. In addition, vacuum extraction can be performed comfortably in the absence of regional anesthesia.

Avoiding cesarean section can produce multiple benefits

Another maternal benefit of vacuum extraction is the decreased need for cesarean section. A reduction in the primary cesarean rate also lowers the need for repeat cesarean section, which can be more technically challenging than primary C-section due to the presence of dense scar tissue and intra-abdominal adhesions. Cesarean section also increases the risk of placenta accreta, increta, or percreta in subsequent pregnancies. These complications increase the likelihood of emergency hysterectomy, massive blood loss, and serious maternal morbidity and mortality.

Even in the absence of placenta accreta, both primary and repeat cesarean sections raise the risk of hemorrhage and febrile morbidity, prolong convalescence, and increase cost, compared with vaginal delivery. For these reasons, avoiding primary cesarean section can obviate the need for multiple surgical procedures and their attendant risks. The degree to which these factors favor vaginal delivery over cesarean section is subject to debate.

Maternal risks include pelvic floor trauma

Both vacuum extraction and forceps delivery increase the risk of anal sphincter injury and can impair fecal continence.⁴ Both methods also appear to increase trauma to the genital tract in comparison with spontaneous delivery and may predispose the woman to pelvic floor dysfunction, including urinary and anal incontinence.^5-10 However, anal sphincter trauma was less frequent after vacuum extraction than after forceps delivery.¹

Other maternal injuries associated with vacuum extraction include perineal lacerations and injuries to the vulva, vagina, and cervix. Vacuum extraction also has been implicated as a significant risk factor for postpartum hemorrhage¹¹ and genital-tract infection.¹

 

Fewer neonatal respiratory problems with vaginal delivery

Compared with cesarean section, vaginal delivery is thought to diminish the risk of intrapartum aspiration and respiratory problems in the newborn. It also may facilitate the transition from fetal to neonatal circulation and reduce the need for immediate resuscitation at birth.

Neonatal risks include soft-tissue injury and potential hemorrhage

Infants delivered by vacuum extraction have a significantly higher rate of intracranial hemorrhage, brachial plexus injuries, convulsions, central nervous system depression, and the need for mechanical ventilation, compared with spontaneously delivered infants (TABLE 3).^12,13

Although vacuum extraction is associated with a wide range of soft tissue injuries, they are often less serious than the fetal scalp injuries associated with obstetric forceps. Cup marks, bruising, and minor lacerations of the scalp and caput succedaneum are common fetal injuries, although the majority resolve without apparent sequelae.¹⁴

Subgaleal hemorrhage is the most serious neonatal complication of vacuum extraction, occurring in 1% to 3.8% of vacuum extractions (FIGURE).¹⁵ It coexists with neonatal coagulopathy in 19% to 29% of newborns¹⁶ and increases the risk of progression to hemorrhagic shock and death. Subgaleal hemorrhage has a mortality rate ranging from 2.7% to 22.8%.^15-17

Cephalhematoma is another complication associated with vacuum extraction. It involves an accumulation of blood beneath the periosteum of a cranial bone (usually the parietal bone), and it almost always resolves spontaneously. The incidence of cephalhematoma varies. It is significantly more common in deliveries involving vacuum extraction (9.8%) than in forceps deliveries (4.1%).¹⁸ Its incidence increases with the length of time the vacuum cup is applied and with paramedian application.¹⁸

Intracranial hemorrhage occurs in 1 of 860 vacuum extractions, 1 of 664 forceps deliveries, 1 of 954 cesarean deliveries, and 1 of 1,900 spontaneous deliveries.¹² Subdural hemorrhage is the most common form of intracranial hemorrhage and is almost invariably the result of birth trauma. However, asymptomatic subdural hematoma occurs in up to 6.1% of uncomplicated vaginal deliveries.¹⁹

Other, less common types of intracranial hemorrhage, such as subarachnoid, intraventricular, and intraparenchymal hemorrhage, have a more complex etiology, which includes birth asphyxia, hemorrhagic diathesis, infection, and vascular abnormalities.²⁰

Retinal hemorrhage also may occur after vacuum extraction, with an incidence of 49% to 77.8%, compared with 30.3% after forceps delivery, 30.4% after normal vaginal delivery, and 8.3% after cesarean delivery.²¹ It generally resolves spontaneously without any permanent damage.²²

TABLE 3

Vacuum extraction can injure the fetus

DIRECT INJURY
Cephalhematoma
Intracranial hemorrhage (parenchymal, subdural, intraventricular, subarachnoid)
Nerve injury
Scalp laceration, abrasion, ecchymoses, necrosis
Skull fracture
Subgaleal hemorrhage
INDIRECT INJURY
Anemia, hyperbilirubinemia
Brachial plexus injury
Scalp infection or abscess
SOURCE: O’Grady et al31

Shoulder dystocia and brachial plexus palsy

Vacuum extraction also is associated with shoulder dystocia and brachial plexus palsy, although the primary risk factor for these complications is thought to be increased fetal size.^23-25 The incidence of shoulder dystocia with vacuum extraction is 3.5%, compared with 1.5% for forceps delivery.²⁵

The risk of brachial plexus palsy also increases with vacuum extraction, especially as the duration of the procedure increases.²⁵

Less common complications associated with vacuum extraction are skull fractures, fetal hemorrhage from bleeding at the site of scalp electrodes, sepsis originating from infected scalp trauma, and corneal injury.

No long-term impairment

Long-term outcome studies of children delivered by vacuum extraction show no differences in physical or cognitive functioning or intelligence scores, compared with other modes of delivery.²⁶

3. Technique: Create conditions that ensure success

Certain prerequisites to vacuum extraction can assure successful application and strict adherence to protocol. These prerequisites include having an appropriate indication, thorough informed consent, proper maternal positioning, adequate anesthesia, and knowledge of fetal position and station (TABLE 4).¹ These objectives can be accomplished in the following steps:

1. After an informed consent discussion, assess maternal positioning and repeat the pelvic exam. Also ascertain the adequacy of anesthesia. Insert a bladder catheter.
2. Perform a “ghost” trial of vacuum extraction to visualize the procedure before the actual attempt.
3. Test the function of the vacuum.
4. Lubricate the vacuum cup with surgical soap or gel, insert it into the vagina, and maneuver it onto the fetal head. Place the vacuum extractor over the sagittal suture about 6 cm distal to the anterior fontanel and 2 cm proximal to the posterior fontanel. (The illustration on page 74 demonstrates positioning.) Apply a small degree of vacuum (approximately 20 mm Hg). Double-check application.
5. Gradually apply full vacuum (550–600 mm Hg, depending on cup size), allowing the scalp to mold to the extractor cup.
6. Apply 2-handed traction in concert with uterine contractions and supplemented by maternal pushing. Assuming there is no loss of vacuum (“pop-off” of the cup), the initial traction effort should produce a gain in station. If a “pop-off” occurs, a single additional attempt at delivery may be warranted.
7. As the head crowns, perform episiotomy as needed and slowly deliver the fetal head. Remove the vacuum cup.
8. After delivery of the placenta, inspect the vagina, cervix, and perineum closely.
9. Dictate a full operative note and annotate the delivery in the chart. See the section on documentation, below.

 

Vacuum extraction may fail for a number of reasons (TABLE 5).

TABLE 4

Perform these predelivery checks before applying traction

Is anesthesia adequate? Is maternal positioning correct?
Is the bladder empty?
Is the fetus in the proper attitude (flexion)?
Is fetal status reassuring?
Is the vacuum properly applied? The handle of the soft-cup extractor is parallel to the sagittal suture No maternal tissue is beneath the cup margin The middle of the cup is positioned over the point of cranial flexion (point F). This point lies in the midline above the sagittal suture. Cup margins should be about 3 cm distal to the posterior edge of the anterior fontanel
Has the patient been instructed on when and how long to push?
Are the proposed maneuvers appropriate?

TABLE 5

Why might vacuum extraction fail?

INSTRUMENT-RELATED
Pump failure
Vacuum leak
TECHNIQUE-RELATED
Failure to encourage maternal valsalva with traction efforts
Inappropriate intensity of traction
Incorrect axis of traction
Maternal tissue trapped beneath vacuum cup
Poor cup position
OBSTETRIC CONDITIONS
Congenital anomaly anencephaly ventriculomegaly
Fetal macrosomia
Incomplete cervical dilation
Position and attitude problems deflexion occiput posterior position asynclitism
Unappreciated cephalopelvic disproportion
SOURCE: Modified from Plauche et al32

Most important variable: Cup placement

The single most critical step in vacuum extraction is placement of the cup. It should be applied at the point of maximum fetal cranial flexion, which is proximal to the leading edge of the posterior fontanel.

Once full vacuum is achieved, encourage the mother to push with the next contraction, and apply steady traction in concert with her efforts.

The initial application of traction should be directed to maintain proper flexion of the fetal head, and should bring about descent of the fetal head. If there is no descent with the first application of traction, and correct technique and cup placement have been applied, abandon operative vaginal delivery (TABLE 6).

Do not make a further attempt to deliver the child using forceps, as the risk of intracranial hemorrhage appears to be highest in infants delivered using a combination of vacuum extraction and forceps.

TABLE 6

Repeat traction efforts reap a diminishing return

NUMBER OF TRACTION EFFORTS	SUCCESS RATE
	VACUUM EXTRACTION (N=433)	FORCEPS (N=555)
1 or 2	68.4%	38.4%
3 or 4	24.9%	48.6%
5 or more	6.7%	12.9%
Adapted from Sjostedt33

4. Documentation: The chart is the most important witness

The value of complete and contemporaneous notation cannot be overstated. The patient’s chart is the permanent repository of the record of delivery. It is without doubt the most important witness to the event and should be treated as such. Include a dictated operative note as well as notation in the chart itself. Notes should be legible and properly dated, with the time of day indicated.

When operative vaginal delivery is performed, record the following:

• indication for the procedure
• course of labor
• anesthesia
• personnel present
• instruments used
• position and station of the fetal head
• force and duration of traction
• complications, including how they were recognized and managed
• immediate condition of the newborn and all steps taken in resuscitation.

Minimizing medicolegal risk

The best way to prevent an accusation of medical malpractice is to develop strong clinical and interpersonal skills. These simple, intuitive suggestions may help:

• Understand the role of operative vaginal delivery in current practice.
• Develop a simple and interactive discussion model for use in labor and delivery with the patient and her family.
• Consider a woman’s preferences for delivery.
• Know the indications and contraindications for vacuum extraction.
• Use the checks and safeguards listed under 3. Technique: Create conditions that ensure success.
• Perform vacuum extraction in the cesarean section room. Stop the procedure at once if any problem arises, and proceed to cesarean delivery.
• Make all chart notations completely legible, and add dictated notes.

 

If you are a new physician or lack significant experience with vacuum extraction, ask for input, supervision, and education from more experienced clinicians. Also make it a point to ask about department guidelines and review the credentialing process. Once you become adept at vacuum extraction, mentor more junior colleagues.

Two critical concerns

When contemplating vacuum-assisted delivery, 2 risks are paramount:

• failure of the vacuum extractor to achieve delivery
• the potential for fetal and maternal injury.

Training must ensure appropriate case selection and technique. Vacuum extraction must be performed with the same precision and care used with forceps. If application of the device is incorrect, or if there is a wrong direction of traction, excessive traction, or traction in the presence of disproportion, the cup will slip or pop off, and vacuum delivery will fail, with the potential for traumatic fetal injury.

All risks must be discussed with the patient to fulfill informed consent, and the risks and benefits of alternative treatments should be part of the discussion. Active participation, in considering how best to approach delivery, is required of all parties concerned.

The vacuum extractor can be a useful adjunct in certain circumstances, and its use has become widespread in American delivery suites. As with the obstetric forceps, which largely antedated its use, the vacuum extractor can lessen the overall risks of childbirth for both mother and infant.

The authors report no financial relationships relevant to this article.

CASE Three hours of pushing

C.A., age 29 years, is 40 weeks’ pregnant with her first child. After an unremarkable pregnancy, she arrives at the hospital for cervical ripening and induction of labor. Oxytocin is given, and labor progresses uneventfully. When C.A.’s cervix is dilated 8 cm, however, labor stalls. The physician orders placement of a pressure catheter and increases the dosage of oxytocin, and the cervix dilates fully. Although C.A. pushes well, the vertex descends only from +1 to +2 station (of 5 stations) after 3 hours.

How would you manage this delivery?

One option in C.A.’s case is operative vaginal delivery using the vacuum extractor, which has replaced the forceps as the most commonly used approach for operative vaginal delivery. Like the forceps, the vacuum extractor has vociferous detractors as well as supporters. Liberal use of cesarean section and questions regarding the safety of operative vaginal delivery vis-à-vis cesarean section have fueled the debate over its role in obstetric practice.

Among the benefits of vacuum extraction are its cost-effectiveness and shorter hospital stay (TABLE 1). It also obviates the need for cesarean section, including repeat cesarean. Risks include an increased incidence of genital tract trauma and a greater risk of fetal subgaleal hemorrhage.

We review 4 critical spheres of concern in regard to vacuum extraction:

1. Patient selection
2. Informed consent
3. Technique
4. Documentation

Increased understanding of these aspects of vacuum extraction will improve outcomes for the patient and limit medicolegal risk.

In the case of C.A., the physician offered 3 options:

• Continue maternal expulsive efforts to allow descent
• Attempt delivery by vacuum extraction
• Proceed to cesarean section on the basis of protracted descent.

Risks and benefits were reviewed with the patient, who chose to deliver by cesarean section. A 3,780-g infant in occiput posterior position was delivered safely.

TABLE 1

Delicate balance: Risks and benefits of operative vaginal delivery

WHO?	BENEFIT	RISK
Mother	Cost-effective Less blood loss Lower risk of febrile morbidity Maternal preference No need for cesarean section or repeat cesarean Shorter hospitalization and convalescence	Increased incidence of genital tract trauma Possible damage to pelvic floor, with urinary and anal incontinence
Fetus	Fewer respiratory difficulties at birth	Increased risk of subgaleal hemorrhage Association with shoulder dystocia

1. Patient selection: Maternal and fetal indications

Vacuum extraction may be justified for maternal or fetal indications.^1,2 Maternal indications include prolongation or arrest of the second stage of labor, or the need to shorten the second stage, for reasons such as maternal cardiac disease, complex congenital cardiovascular disorders, and maternal exhaustion.

No definitive time limit for the second stage of labor

There is more flexibility today than in the past about what constitutes a “safe” length of the second stage. Recommendations concerning when the mother should begin pushing—and for how long—have evolved from a strict time limit to a focus on progression. If the fetal heart rate (FHR) tracing is reassuring, the second stage no longer needs to be limited to 2 or 3 hours. On the contrary, if the patient is still able and willing to push, changes in positioning and further expectant management remain acceptable in contemporary practice.³ Otherwise, a trial of vacuum extraction may be appropriate.

Vacuum extraction is particularly useful when the mother has difficulty pushing because of exhaustion and the fetal head has descended enough that it distends the labia between contractions, as in outlet deliveries.

Fetal indications

Fetal indications for operative vaginal delivery include distress, jeopardy, or a “nonreassuring” FHR tracing. Such a tracing may include late and prolonged decelerations, baseline bradycardia or tachycardia with or without variable decelerations, or, occasionally, a normal baseline rate with diminished variability.

Use vacuum or forceps?

The choice depends on which device would achieve delivery in the safest manner with the lowest risk of fetal injury. With the vacuum, force is exerted directly on the fetal scalp and only secondarily on the fetal skull. This puts fetal vessels that traverse the subgaleal space at risk for injury (FIGURE). With forceps, force is exerted directly on the fetal skull and mitigated by the petrous bone. Little or no force is exerted on the fetal scalp, lessening the risk of traumatic injury such as potentially fatal subgaleal hemorrhage.

 

Indications and contraindications for vacuum extraction are similar, but not identical, to those for forceps delivery (TABLE 2).^2,3 The most important determinant for either device is the experience of the operator. You must be familiar with the instrument and technique before making any attempt to assist delivery. An inability to accurately assess fetal position or station, fetopelvic proportion, adequacy of labor, engagement of the fetal head, or any degree of malpresentation (including minor degrees of deflexion) is a contraindication to a trial of operative vaginal delivery.

Vacuum extraction should be reserved for fetuses at more than 34 weeks’ gestation because of the increased risk of intracranial hemorrhage associated with prematurity.

All decisions involving vacuum extraction should be made with caution. The adequacy of the pelvis, estimated fetal size, and any suggestions of fetopelvic disproportion are of particular significance.³

FIGURE

Subgaleal hemorrhage, a deadly complication

Blood can accumulate in a large potential space between the galea aponeurotica and the periosteum of the cranial bones after vacuum extraction. An infant with subgaleal hemorrhage will exhibit a boggy scalp, with swelling that crosses the suture lines and expands head circumferenceTABLE 2

Factors that predict success—or failure—of vacuum extraction

When a woman fits overlapping categories, the decision to use vacuum extraction—or not—may be a judgment call*
GOOD CANDIDACY
Multiparous
Term pregnancy
Occiput anterior position, well-flexed
Wide subpubic arch
Compliant
MARGINAL CANDIDACY
Primiparous
Post-term
Occiput posterior position
Average subpubic arch
Gestational diabetes
Arrest disorders in second stage
POOR CANDIDACY
Protraction disorders in second stage
Narrow subpubic arch
Uncertain position of fetal head
Deflexion or asynclitism
Anticipated large-for-gestational-age infant
Poor maternal compliance
* When faced with a good indication in a marginal candidate, we recommend delivery in a “double setup” situation in which preparations are made for both vacuum extraction and cesarean section. If the vacuum can be properly applied, the first application of traction is crucial. We will only proceed if significant descent is achieved. If the fetal head (not the scalp) can be advanced a full station, then we proceed cautiously. If not, ready access to cesarean section allows for completion of the delivery in a timely manner.

2. Informed consent: Elicit the patient’s desires

Thorough discussion with the patient and her family—to explain the reasoning behind the clinical decision to use the vacuum extractor and delineate the alternatives—is paramount. Moreover, the patient should be encouraged to actively participate in this discussion.

Among the alternatives to vacuum extraction are expectant observation and expedited delivery by cesarean section. Because patients increasingly are requesting elective cesarean section in the absence of obvious obstetric indications, this option should receive extra attention.

Most women still consider vaginal delivery an important milestone of female adulthood. When safety concerns arise and the situation makes vaginal delivery unwise, many women experience disappointment and postpartum depression over their “failed” attempt at vaginal delivery. These perceptions need to be addressed in discussions with the patient.

The risk–benefit equation

Vacuum extraction lessens the risk of maternal lacerations, either of the lower genital tract in the case of obstetric forceps, or of the cervix and lower uterine segment in the case of cesarean section. In addition, vacuum extraction can be performed comfortably in the absence of regional anesthesia.

Avoiding cesarean section can produce multiple benefits

Another maternal benefit of vacuum extraction is the decreased need for cesarean section. A reduction in the primary cesarean rate also lowers the need for repeat cesarean section, which can be more technically challenging than primary C-section due to the presence of dense scar tissue and intra-abdominal adhesions. Cesarean section also increases the risk of placenta accreta, increta, or percreta in subsequent pregnancies. These complications increase the likelihood of emergency hysterectomy, massive blood loss, and serious maternal morbidity and mortality.

Even in the absence of placenta accreta, both primary and repeat cesarean sections raise the risk of hemorrhage and febrile morbidity, prolong convalescence, and increase cost, compared with vaginal delivery. For these reasons, avoiding primary cesarean section can obviate the need for multiple surgical procedures and their attendant risks. The degree to which these factors favor vaginal delivery over cesarean section is subject to debate.

Maternal risks include pelvic floor trauma

Both vacuum extraction and forceps delivery increase the risk of anal sphincter injury and can impair fecal continence.⁴ Both methods also appear to increase trauma to the genital tract in comparison with spontaneous delivery and may predispose the woman to pelvic floor dysfunction, including urinary and anal incontinence.^5-10 However, anal sphincter trauma was less frequent after vacuum extraction than after forceps delivery.¹

Other maternal injuries associated with vacuum extraction include perineal lacerations and injuries to the vulva, vagina, and cervix. Vacuum extraction also has been implicated as a significant risk factor for postpartum hemorrhage¹¹ and genital-tract infection.¹

 

Fewer neonatal respiratory problems with vaginal delivery

Compared with cesarean section, vaginal delivery is thought to diminish the risk of intrapartum aspiration and respiratory problems in the newborn. It also may facilitate the transition from fetal to neonatal circulation and reduce the need for immediate resuscitation at birth.

Neonatal risks include soft-tissue injury and potential hemorrhage

Infants delivered by vacuum extraction have a significantly higher rate of intracranial hemorrhage, brachial plexus injuries, convulsions, central nervous system depression, and the need for mechanical ventilation, compared with spontaneously delivered infants (TABLE 3).^12,13

Although vacuum extraction is associated with a wide range of soft tissue injuries, they are often less serious than the fetal scalp injuries associated with obstetric forceps. Cup marks, bruising, and minor lacerations of the scalp and caput succedaneum are common fetal injuries, although the majority resolve without apparent sequelae.¹⁴

Subgaleal hemorrhage is the most serious neonatal complication of vacuum extraction, occurring in 1% to 3.8% of vacuum extractions (FIGURE).¹⁵ It coexists with neonatal coagulopathy in 19% to 29% of newborns¹⁶ and increases the risk of progression to hemorrhagic shock and death. Subgaleal hemorrhage has a mortality rate ranging from 2.7% to 22.8%.^15-17

Cephalhematoma is another complication associated with vacuum extraction. It involves an accumulation of blood beneath the periosteum of a cranial bone (usually the parietal bone), and it almost always resolves spontaneously. The incidence of cephalhematoma varies. It is significantly more common in deliveries involving vacuum extraction (9.8%) than in forceps deliveries (4.1%).¹⁸ Its incidence increases with the length of time the vacuum cup is applied and with paramedian application.¹⁸

Intracranial hemorrhage occurs in 1 of 860 vacuum extractions, 1 of 664 forceps deliveries, 1 of 954 cesarean deliveries, and 1 of 1,900 spontaneous deliveries.¹² Subdural hemorrhage is the most common form of intracranial hemorrhage and is almost invariably the result of birth trauma. However, asymptomatic subdural hematoma occurs in up to 6.1% of uncomplicated vaginal deliveries.¹⁹

Other, less common types of intracranial hemorrhage, such as subarachnoid, intraventricular, and intraparenchymal hemorrhage, have a more complex etiology, which includes birth asphyxia, hemorrhagic diathesis, infection, and vascular abnormalities.²⁰

Retinal hemorrhage also may occur after vacuum extraction, with an incidence of 49% to 77.8%, compared with 30.3% after forceps delivery, 30.4% after normal vaginal delivery, and 8.3% after cesarean delivery.²¹ It generally resolves spontaneously without any permanent damage.²²

TABLE 3

Vacuum extraction can injure the fetus

DIRECT INJURY
Cephalhematoma
Intracranial hemorrhage (parenchymal, subdural, intraventricular, subarachnoid)
Nerve injury
Scalp laceration, abrasion, ecchymoses, necrosis
Skull fracture
Subgaleal hemorrhage
INDIRECT INJURY
Anemia, hyperbilirubinemia
Brachial plexus injury
Scalp infection or abscess
SOURCE: O’Grady et al31

Shoulder dystocia and brachial plexus palsy

Vacuum extraction also is associated with shoulder dystocia and brachial plexus palsy, although the primary risk factor for these complications is thought to be increased fetal size.^23-25 The incidence of shoulder dystocia with vacuum extraction is 3.5%, compared with 1.5% for forceps delivery.²⁵

The risk of brachial plexus palsy also increases with vacuum extraction, especially as the duration of the procedure increases.²⁵

Less common complications associated with vacuum extraction are skull fractures, fetal hemorrhage from bleeding at the site of scalp electrodes, sepsis originating from infected scalp trauma, and corneal injury.

No long-term impairment

Long-term outcome studies of children delivered by vacuum extraction show no differences in physical or cognitive functioning or intelligence scores, compared with other modes of delivery.²⁶

3. Technique: Create conditions that ensure success

Certain prerequisites to vacuum extraction can assure successful application and strict adherence to protocol. These prerequisites include having an appropriate indication, thorough informed consent, proper maternal positioning, adequate anesthesia, and knowledge of fetal position and station (TABLE 4).¹ These objectives can be accomplished in the following steps:

1. After an informed consent discussion, assess maternal positioning and repeat the pelvic exam. Also ascertain the adequacy of anesthesia. Insert a bladder catheter.
2. Perform a “ghost” trial of vacuum extraction to visualize the procedure before the actual attempt.
3. Test the function of the vacuum.
4. Lubricate the vacuum cup with surgical soap or gel, insert it into the vagina, and maneuver it onto the fetal head. Place the vacuum extractor over the sagittal suture about 6 cm distal to the anterior fontanel and 2 cm proximal to the posterior fontanel. (The illustration on page 74 demonstrates positioning.) Apply a small degree of vacuum (approximately 20 mm Hg). Double-check application.
5. Gradually apply full vacuum (550–600 mm Hg, depending on cup size), allowing the scalp to mold to the extractor cup.
6. Apply 2-handed traction in concert with uterine contractions and supplemented by maternal pushing. Assuming there is no loss of vacuum (“pop-off” of the cup), the initial traction effort should produce a gain in station. If a “pop-off” occurs, a single additional attempt at delivery may be warranted.
7. As the head crowns, perform episiotomy as needed and slowly deliver the fetal head. Remove the vacuum cup.
8. After delivery of the placenta, inspect the vagina, cervix, and perineum closely.
9. Dictate a full operative note and annotate the delivery in the chart. See the section on documentation, below.

 

Vacuum extraction may fail for a number of reasons (TABLE 5).

TABLE 4

Perform these predelivery checks before applying traction

Is anesthesia adequate? Is maternal positioning correct?
Is the bladder empty?
Is the fetus in the proper attitude (flexion)?
Is fetal status reassuring?
Is the vacuum properly applied? The handle of the soft-cup extractor is parallel to the sagittal suture No maternal tissue is beneath the cup margin The middle of the cup is positioned over the point of cranial flexion (point F). This point lies in the midline above the sagittal suture. Cup margins should be about 3 cm distal to the posterior edge of the anterior fontanel
Has the patient been instructed on when and how long to push?
Are the proposed maneuvers appropriate?

TABLE 5

Why might vacuum extraction fail?

INSTRUMENT-RELATED
Pump failure
Vacuum leak
TECHNIQUE-RELATED
Failure to encourage maternal valsalva with traction efforts
Inappropriate intensity of traction
Incorrect axis of traction
Maternal tissue trapped beneath vacuum cup
Poor cup position
OBSTETRIC CONDITIONS
Congenital anomaly anencephaly ventriculomegaly
Fetal macrosomia
Incomplete cervical dilation
Position and attitude problems deflexion occiput posterior position asynclitism
Unappreciated cephalopelvic disproportion
SOURCE: Modified from Plauche et al32

Most important variable: Cup placement

The single most critical step in vacuum extraction is placement of the cup. It should be applied at the point of maximum fetal cranial flexion, which is proximal to the leading edge of the posterior fontanel.

Once full vacuum is achieved, encourage the mother to push with the next contraction, and apply steady traction in concert with her efforts.

The initial application of traction should be directed to maintain proper flexion of the fetal head, and should bring about descent of the fetal head. If there is no descent with the first application of traction, and correct technique and cup placement have been applied, abandon operative vaginal delivery (TABLE 6).

Do not make a further attempt to deliver the child using forceps, as the risk of intracranial hemorrhage appears to be highest in infants delivered using a combination of vacuum extraction and forceps.

TABLE 6

Repeat traction efforts reap a diminishing return

NUMBER OF TRACTION EFFORTS	SUCCESS RATE
	VACUUM EXTRACTION (N=433)	FORCEPS (N=555)
1 or 2	68.4%	38.4%
3 or 4	24.9%	48.6%
5 or more	6.7%	12.9%
Adapted from Sjostedt33

4. Documentation: The chart is the most important witness

The value of complete and contemporaneous notation cannot be overstated. The patient’s chart is the permanent repository of the record of delivery. It is without doubt the most important witness to the event and should be treated as such. Include a dictated operative note as well as notation in the chart itself. Notes should be legible and properly dated, with the time of day indicated.

When operative vaginal delivery is performed, record the following:

• indication for the procedure
• course of labor
• anesthesia
• personnel present
• instruments used
• position and station of the fetal head
• force and duration of traction
• complications, including how they were recognized and managed
• immediate condition of the newborn and all steps taken in resuscitation.

Minimizing medicolegal risk

The best way to prevent an accusation of medical malpractice is to develop strong clinical and interpersonal skills. These simple, intuitive suggestions may help:

• Understand the role of operative vaginal delivery in current practice.
• Develop a simple and interactive discussion model for use in labor and delivery with the patient and her family.
• Consider a woman’s preferences for delivery.
• Know the indications and contraindications for vacuum extraction.
• Use the checks and safeguards listed under 3. Technique: Create conditions that ensure success.
• Perform vacuum extraction in the cesarean section room. Stop the procedure at once if any problem arises, and proceed to cesarean delivery.
• Make all chart notations completely legible, and add dictated notes.

 

If you are a new physician or lack significant experience with vacuum extraction, ask for input, supervision, and education from more experienced clinicians. Also make it a point to ask about department guidelines and review the credentialing process. Once you become adept at vacuum extraction, mentor more junior colleagues.

Two critical concerns

When contemplating vacuum-assisted delivery, 2 risks are paramount:

• failure of the vacuum extractor to achieve delivery
• the potential for fetal and maternal injury.

Training must ensure appropriate case selection and technique. Vacuum extraction must be performed with the same precision and care used with forceps. If application of the device is incorrect, or if there is a wrong direction of traction, excessive traction, or traction in the presence of disproportion, the cup will slip or pop off, and vacuum delivery will fail, with the potential for traumatic fetal injury.

All risks must be discussed with the patient to fulfill informed consent, and the risks and benefits of alternative treatments should be part of the discussion. Active participation, in considering how best to approach delivery, is required of all parties concerned.

The vacuum extractor can be a useful adjunct in certain circumstances, and its use has become widespread in American delivery suites. As with the obstetric forceps, which largely antedated its use, the vacuum extractor can lessen the overall risks of childbirth for both mother and infant.

The authors report no financial relationships relevant to this article.

CASE Three hours of pushing

C.A., age 29 years, is 40 weeks’ pregnant with her first child. After an unremarkable pregnancy, she arrives at the hospital for cervical ripening and induction of labor. Oxytocin is given, and labor progresses uneventfully. When C.A.’s cervix is dilated 8 cm, however, labor stalls. The physician orders placement of a pressure catheter and increases the dosage of oxytocin, and the cervix dilates fully. Although C.A. pushes well, the vertex descends only from +1 to +2 station (of 5 stations) after 3 hours.

How would you manage this delivery?

One option in C.A.’s case is operative vaginal delivery using the vacuum extractor, which has replaced the forceps as the most commonly used approach for operative vaginal delivery. Like the forceps, the vacuum extractor has vociferous detractors as well as supporters. Liberal use of cesarean section and questions regarding the safety of operative vaginal delivery vis-à-vis cesarean section have fueled the debate over its role in obstetric practice.

Among the benefits of vacuum extraction are its cost-effectiveness and shorter hospital stay (TABLE 1). It also obviates the need for cesarean section, including repeat cesarean. Risks include an increased incidence of genital tract trauma and a greater risk of fetal subgaleal hemorrhage.

We review 4 critical spheres of concern in regard to vacuum extraction:

1. Patient selection
2. Informed consent
3. Technique
4. Documentation

Increased understanding of these aspects of vacuum extraction will improve outcomes for the patient and limit medicolegal risk.

In the case of C.A., the physician offered 3 options:

• Continue maternal expulsive efforts to allow descent
• Attempt delivery by vacuum extraction
• Proceed to cesarean section on the basis of protracted descent.

Risks and benefits were reviewed with the patient, who chose to deliver by cesarean section. A 3,780-g infant in occiput posterior position was delivered safely.

TABLE 1

Delicate balance: Risks and benefits of operative vaginal delivery

WHO?	BENEFIT	RISK
Mother	Cost-effective Less blood loss Lower risk of febrile morbidity Maternal preference No need for cesarean section or repeat cesarean Shorter hospitalization and convalescence	Increased incidence of genital tract trauma Possible damage to pelvic floor, with urinary and anal incontinence
Fetus	Fewer respiratory difficulties at birth	Increased risk of subgaleal hemorrhage Association with shoulder dystocia

1. Patient selection: Maternal and fetal indications

Vacuum extraction may be justified for maternal or fetal indications.^1,2 Maternal indications include prolongation or arrest of the second stage of labor, or the need to shorten the second stage, for reasons such as maternal cardiac disease, complex congenital cardiovascular disorders, and maternal exhaustion.

No definitive time limit for the second stage of labor

There is more flexibility today than in the past about what constitutes a “safe” length of the second stage. Recommendations concerning when the mother should begin pushing—and for how long—have evolved from a strict time limit to a focus on progression. If the fetal heart rate (FHR) tracing is reassuring, the second stage no longer needs to be limited to 2 or 3 hours. On the contrary, if the patient is still able and willing to push, changes in positioning and further expectant management remain acceptable in contemporary practice.³ Otherwise, a trial of vacuum extraction may be appropriate.

Vacuum extraction is particularly useful when the mother has difficulty pushing because of exhaustion and the fetal head has descended enough that it distends the labia between contractions, as in outlet deliveries.

Fetal indications

Fetal indications for operative vaginal delivery include distress, jeopardy, or a “nonreassuring” FHR tracing. Such a tracing may include late and prolonged decelerations, baseline bradycardia or tachycardia with or without variable decelerations, or, occasionally, a normal baseline rate with diminished variability.

Use vacuum or forceps?

The choice depends on which device would achieve delivery in the safest manner with the lowest risk of fetal injury. With the vacuum, force is exerted directly on the fetal scalp and only secondarily on the fetal skull. This puts fetal vessels that traverse the subgaleal space at risk for injury (FIGURE). With forceps, force is exerted directly on the fetal skull and mitigated by the petrous bone. Little or no force is exerted on the fetal scalp, lessening the risk of traumatic injury such as potentially fatal subgaleal hemorrhage.

 

Indications and contraindications for vacuum extraction are similar, but not identical, to those for forceps delivery (TABLE 2).^2,3 The most important determinant for either device is the experience of the operator. You must be familiar with the instrument and technique before making any attempt to assist delivery. An inability to accurately assess fetal position or station, fetopelvic proportion, adequacy of labor, engagement of the fetal head, or any degree of malpresentation (including minor degrees of deflexion) is a contraindication to a trial of operative vaginal delivery.

Vacuum extraction should be reserved for fetuses at more than 34 weeks’ gestation because of the increased risk of intracranial hemorrhage associated with prematurity.

All decisions involving vacuum extraction should be made with caution. The adequacy of the pelvis, estimated fetal size, and any suggestions of fetopelvic disproportion are of particular significance.³

FIGURE

Subgaleal hemorrhage, a deadly complication

Blood can accumulate in a large potential space between the galea aponeurotica and the periosteum of the cranial bones after vacuum extraction. An infant with subgaleal hemorrhage will exhibit a boggy scalp, with swelling that crosses the suture lines and expands head circumferenceTABLE 2

Factors that predict success—or failure—of vacuum extraction

When a woman fits overlapping categories, the decision to use vacuum extraction—or not—may be a judgment call*
GOOD CANDIDACY
Multiparous
Term pregnancy
Occiput anterior position, well-flexed
Wide subpubic arch
Compliant
MARGINAL CANDIDACY
Primiparous
Post-term
Occiput posterior position
Average subpubic arch
Gestational diabetes
Arrest disorders in second stage
POOR CANDIDACY
Protraction disorders in second stage
Narrow subpubic arch
Uncertain position of fetal head
Deflexion or asynclitism
Anticipated large-for-gestational-age infant
Poor maternal compliance
* When faced with a good indication in a marginal candidate, we recommend delivery in a “double setup” situation in which preparations are made for both vacuum extraction and cesarean section. If the vacuum can be properly applied, the first application of traction is crucial. We will only proceed if significant descent is achieved. If the fetal head (not the scalp) can be advanced a full station, then we proceed cautiously. If not, ready access to cesarean section allows for completion of the delivery in a timely manner.

2. Informed consent: Elicit the patient’s desires

Thorough discussion with the patient and her family—to explain the reasoning behind the clinical decision to use the vacuum extractor and delineate the alternatives—is paramount. Moreover, the patient should be encouraged to actively participate in this discussion.

Among the alternatives to vacuum extraction are expectant observation and expedited delivery by cesarean section. Because patients increasingly are requesting elective cesarean section in the absence of obvious obstetric indications, this option should receive extra attention.

Most women still consider vaginal delivery an important milestone of female adulthood. When safety concerns arise and the situation makes vaginal delivery unwise, many women experience disappointment and postpartum depression over their “failed” attempt at vaginal delivery. These perceptions need to be addressed in discussions with the patient.

The risk–benefit equation

Vacuum extraction lessens the risk of maternal lacerations, either of the lower genital tract in the case of obstetric forceps, or of the cervix and lower uterine segment in the case of cesarean section. In addition, vacuum extraction can be performed comfortably in the absence of regional anesthesia.

Avoiding cesarean section can produce multiple benefits

Another maternal benefit of vacuum extraction is the decreased need for cesarean section. A reduction in the primary cesarean rate also lowers the need for repeat cesarean section, which can be more technically challenging than primary C-section due to the presence of dense scar tissue and intra-abdominal adhesions. Cesarean section also increases the risk of placenta accreta, increta, or percreta in subsequent pregnancies. These complications increase the likelihood of emergency hysterectomy, massive blood loss, and serious maternal morbidity and mortality.

Even in the absence of placenta accreta, both primary and repeat cesarean sections raise the risk of hemorrhage and febrile morbidity, prolong convalescence, and increase cost, compared with vaginal delivery. For these reasons, avoiding primary cesarean section can obviate the need for multiple surgical procedures and their attendant risks. The degree to which these factors favor vaginal delivery over cesarean section is subject to debate.

Maternal risks include pelvic floor trauma

Both vacuum extraction and forceps delivery increase the risk of anal sphincter injury and can impair fecal continence.⁴ Both methods also appear to increase trauma to the genital tract in comparison with spontaneous delivery and may predispose the woman to pelvic floor dysfunction, including urinary and anal incontinence.^5-10 However, anal sphincter trauma was less frequent after vacuum extraction than after forceps delivery.¹

Other maternal injuries associated with vacuum extraction include perineal lacerations and injuries to the vulva, vagina, and cervix. Vacuum extraction also has been implicated as a significant risk factor for postpartum hemorrhage¹¹ and genital-tract infection.¹

 

Fewer neonatal respiratory problems with vaginal delivery

Compared with cesarean section, vaginal delivery is thought to diminish the risk of intrapartum aspiration and respiratory problems in the newborn. It also may facilitate the transition from fetal to neonatal circulation and reduce the need for immediate resuscitation at birth.

Neonatal risks include soft-tissue injury and potential hemorrhage

Infants delivered by vacuum extraction have a significantly higher rate of intracranial hemorrhage, brachial plexus injuries, convulsions, central nervous system depression, and the need for mechanical ventilation, compared with spontaneously delivered infants (TABLE 3).^12,13

Although vacuum extraction is associated with a wide range of soft tissue injuries, they are often less serious than the fetal scalp injuries associated with obstetric forceps. Cup marks, bruising, and minor lacerations of the scalp and caput succedaneum are common fetal injuries, although the majority resolve without apparent sequelae.¹⁴

Subgaleal hemorrhage is the most serious neonatal complication of vacuum extraction, occurring in 1% to 3.8% of vacuum extractions (FIGURE).¹⁵ It coexists with neonatal coagulopathy in 19% to 29% of newborns¹⁶ and increases the risk of progression to hemorrhagic shock and death. Subgaleal hemorrhage has a mortality rate ranging from 2.7% to 22.8%.^15-17

Cephalhematoma is another complication associated with vacuum extraction. It involves an accumulation of blood beneath the periosteum of a cranial bone (usually the parietal bone), and it almost always resolves spontaneously. The incidence of cephalhematoma varies. It is significantly more common in deliveries involving vacuum extraction (9.8%) than in forceps deliveries (4.1%).¹⁸ Its incidence increases with the length of time the vacuum cup is applied and with paramedian application.¹⁸

Intracranial hemorrhage occurs in 1 of 860 vacuum extractions, 1 of 664 forceps deliveries, 1 of 954 cesarean deliveries, and 1 of 1,900 spontaneous deliveries.¹² Subdural hemorrhage is the most common form of intracranial hemorrhage and is almost invariably the result of birth trauma. However, asymptomatic subdural hematoma occurs in up to 6.1% of uncomplicated vaginal deliveries.¹⁹

Other, less common types of intracranial hemorrhage, such as subarachnoid, intraventricular, and intraparenchymal hemorrhage, have a more complex etiology, which includes birth asphyxia, hemorrhagic diathesis, infection, and vascular abnormalities.²⁰

Retinal hemorrhage also may occur after vacuum extraction, with an incidence of 49% to 77.8%, compared with 30.3% after forceps delivery, 30.4% after normal vaginal delivery, and 8.3% after cesarean delivery.²¹ It generally resolves spontaneously without any permanent damage.²²

TABLE 3

Vacuum extraction can injure the fetus

DIRECT INJURY
Cephalhematoma
Intracranial hemorrhage (parenchymal, subdural, intraventricular, subarachnoid)
Nerve injury
Scalp laceration, abrasion, ecchymoses, necrosis
Skull fracture
Subgaleal hemorrhage
INDIRECT INJURY
Anemia, hyperbilirubinemia
Brachial plexus injury
Scalp infection or abscess
SOURCE: O’Grady et al31

Shoulder dystocia and brachial plexus palsy

Vacuum extraction also is associated with shoulder dystocia and brachial plexus palsy, although the primary risk factor for these complications is thought to be increased fetal size.^23-25 The incidence of shoulder dystocia with vacuum extraction is 3.5%, compared with 1.5% for forceps delivery.²⁵

The risk of brachial plexus palsy also increases with vacuum extraction, especially as the duration of the procedure increases.²⁵

Less common complications associated with vacuum extraction are skull fractures, fetal hemorrhage from bleeding at the site of scalp electrodes, sepsis originating from infected scalp trauma, and corneal injury.

No long-term impairment

Long-term outcome studies of children delivered by vacuum extraction show no differences in physical or cognitive functioning or intelligence scores, compared with other modes of delivery.²⁶

3. Technique: Create conditions that ensure success

Certain prerequisites to vacuum extraction can assure successful application and strict adherence to protocol. These prerequisites include having an appropriate indication, thorough informed consent, proper maternal positioning, adequate anesthesia, and knowledge of fetal position and station (TABLE 4).¹ These objectives can be accomplished in the following steps:

1. After an informed consent discussion, assess maternal positioning and repeat the pelvic exam. Also ascertain the adequacy of anesthesia. Insert a bladder catheter.
2. Perform a “ghost” trial of vacuum extraction to visualize the procedure before the actual attempt.
3. Test the function of the vacuum.
4. Lubricate the vacuum cup with surgical soap or gel, insert it into the vagina, and maneuver it onto the fetal head. Place the vacuum extractor over the sagittal suture about 6 cm distal to the anterior fontanel and 2 cm proximal to the posterior fontanel. (The illustration on page 74 demonstrates positioning.) Apply a small degree of vacuum (approximately 20 mm Hg). Double-check application.
5. Gradually apply full vacuum (550–600 mm Hg, depending on cup size), allowing the scalp to mold to the extractor cup.
6. Apply 2-handed traction in concert with uterine contractions and supplemented by maternal pushing. Assuming there is no loss of vacuum (“pop-off” of the cup), the initial traction effort should produce a gain in station. If a “pop-off” occurs, a single additional attempt at delivery may be warranted.
7. As the head crowns, perform episiotomy as needed and slowly deliver the fetal head. Remove the vacuum cup.
8. After delivery of the placenta, inspect the vagina, cervix, and perineum closely.
9. Dictate a full operative note and annotate the delivery in the chart. See the section on documentation, below.

 

Vacuum extraction may fail for a number of reasons (TABLE 5).

TABLE 4

Perform these predelivery checks before applying traction

Is anesthesia adequate? Is maternal positioning correct?
Is the bladder empty?
Is the fetus in the proper attitude (flexion)?
Is fetal status reassuring?
Is the vacuum properly applied? The handle of the soft-cup extractor is parallel to the sagittal suture No maternal tissue is beneath the cup margin The middle of the cup is positioned over the point of cranial flexion (point F). This point lies in the midline above the sagittal suture. Cup margins should be about 3 cm distal to the posterior edge of the anterior fontanel
Has the patient been instructed on when and how long to push?
Are the proposed maneuvers appropriate?

TABLE 5

Why might vacuum extraction fail?

INSTRUMENT-RELATED
Pump failure
Vacuum leak
TECHNIQUE-RELATED
Failure to encourage maternal valsalva with traction efforts
Inappropriate intensity of traction
Incorrect axis of traction
Maternal tissue trapped beneath vacuum cup
Poor cup position
OBSTETRIC CONDITIONS
Congenital anomaly anencephaly ventriculomegaly
Fetal macrosomia
Incomplete cervical dilation
Position and attitude problems deflexion occiput posterior position asynclitism
Unappreciated cephalopelvic disproportion
SOURCE: Modified from Plauche et al32

Most important variable: Cup placement

The single most critical step in vacuum extraction is placement of the cup. It should be applied at the point of maximum fetal cranial flexion, which is proximal to the leading edge of the posterior fontanel.

Once full vacuum is achieved, encourage the mother to push with the next contraction, and apply steady traction in concert with her efforts.

The initial application of traction should be directed to maintain proper flexion of the fetal head, and should bring about descent of the fetal head. If there is no descent with the first application of traction, and correct technique and cup placement have been applied, abandon operative vaginal delivery (TABLE 6).

Do not make a further attempt to deliver the child using forceps, as the risk of intracranial hemorrhage appears to be highest in infants delivered using a combination of vacuum extraction and forceps.

TABLE 6

Repeat traction efforts reap a diminishing return

NUMBER OF TRACTION EFFORTS	SUCCESS RATE
	VACUUM EXTRACTION (N=433)	FORCEPS (N=555)
1 or 2	68.4%	38.4%
3 or 4	24.9%	48.6%
5 or more	6.7%	12.9%
Adapted from Sjostedt33

4. Documentation: The chart is the most important witness

The value of complete and contemporaneous notation cannot be overstated. The patient’s chart is the permanent repository of the record of delivery. It is without doubt the most important witness to the event and should be treated as such. Include a dictated operative note as well as notation in the chart itself. Notes should be legible and properly dated, with the time of day indicated.

When operative vaginal delivery is performed, record the following:

• indication for the procedure
• course of labor
• anesthesia
• personnel present
• instruments used
• position and station of the fetal head
• force and duration of traction
• complications, including how they were recognized and managed
• immediate condition of the newborn and all steps taken in resuscitation.

Minimizing medicolegal risk

The best way to prevent an accusation of medical malpractice is to develop strong clinical and interpersonal skills. These simple, intuitive suggestions may help:

• Understand the role of operative vaginal delivery in current practice.
• Develop a simple and interactive discussion model for use in labor and delivery with the patient and her family.
• Consider a woman’s preferences for delivery.
• Know the indications and contraindications for vacuum extraction.
• Use the checks and safeguards listed under 3. Technique: Create conditions that ensure success.
• Perform vacuum extraction in the cesarean section room. Stop the procedure at once if any problem arises, and proceed to cesarean delivery.
• Make all chart notations completely legible, and add dictated notes.

 

If you are a new physician or lack significant experience with vacuum extraction, ask for input, supervision, and education from more experienced clinicians. Also make it a point to ask about department guidelines and review the credentialing process. Once you become adept at vacuum extraction, mentor more junior colleagues.

Two critical concerns

When contemplating vacuum-assisted delivery, 2 risks are paramount:

• failure of the vacuum extractor to achieve delivery
• the potential for fetal and maternal injury.

Training must ensure appropriate case selection and technique. Vacuum extraction must be performed with the same precision and care used with forceps. If application of the device is incorrect, or if there is a wrong direction of traction, excessive traction, or traction in the presence of disproportion, the cup will slip or pop off, and vacuum delivery will fail, with the potential for traumatic fetal injury.

All risks must be discussed with the patient to fulfill informed consent, and the risks and benefits of alternative treatments should be part of the discussion. Active participation, in considering how best to approach delivery, is required of all parties concerned.

The vacuum extractor can be a useful adjunct in certain circumstances, and its use has become widespread in American delivery suites. As with the obstetric forceps, which largely antedated its use, the vacuum extractor can lessen the overall risks of childbirth for both mother and infant.

The authors report no financial relationships relevant to this article.

Although women produce only one tenth the amount of androgen that men do, testosterone and related androgen metabolites are as important to women throughout the lifespan as is estrogen. Androgens modulate a feeling of well-being, increase energy, support bone metabolism, and improve sexual function in women.^1-3 But too much androgen production, with elevated levels of testosterone and dehydroepiandrosterone (DHEA), can result in hirsutism, acne, and infertility in the setting of polycystic ovary syndrome (PCOS), all of which present clinical problems.

An equally complicated topic is androgen insufficiency in women. Not only is it difficult to diagnose, it is a major clinical issue to decide whether, when, and how to replace androgens in women. In this article, I look at androgen production throughout the female lifespan, particularly the relationship between estrogen and androgen. I also describe the evaluation of androgen insufficiency, which requires understanding of androgen physiology and ovarian function before and after menopause. These issues form the basis of the decision to replace androgen in women.

Androgen over the lifespan

In the premenopausal woman, androgen production is approximately equally divided between the adrenal gland and the ovaries. Androstenedione from both is converted to testosterone and then irreversibly to dihydrotestosterone (DHT). Androstenedione, testosterone, and even DHEA are secreted in equal quantities by the adrenals and ovaries. The only androgen that is predominantly adrenal is DHEAS, which is sulfated in the adrenal gland.

In premenopausal women, androstenedione is the precursor to testosterone, which is then metabolized to DHT, the androgen most active in hair follicles and implicated in hirsutism. It has been clear for many years that DHEA, although a weak androgen, is present in the greatest quantity in the circulation and is secreted during adrenarche, prior to menarche, beginning at ages 8 to 10. DHEAS peaks in young adulthood and begins to decline after age 40.⁴ The same is true for both total testosterone and free testosterone levels, which also decline in women after about age 25. Thus, peri- and postmenopausal women have approximately half the level of circulating androgens of women in their 20s (FIGURE 1, TABLE 1).⁵

FIGURE 1

Testosterone levels in women decline with aging
N=595
SOURCE: Davison S, et al⁵TABLE 1

How menopause affects plasma hormone levels

HORMONE	MEAN PLASMA LEVEL
	REPRODUCTIVE AGE* (N=15)	NATURALLY MENOPAUSAL (N=18)	OOPHORECTOMIZED (N=8)
Estrone (pg/mL)	58	49	48
Estradiol (pg/mL)	40	20†	18
Testosterone (ng/dL)	44	30†	12‡
DHT (ng/dL)	30	10†	<5‡
Androstenedione (ng/dL)	166	99†	64‡
DHEA (ng/dL)	542	197†	126§
DHT=dihydrotestosterone, DHEA=dehydroepiandrosterone
* Mean value during early follicular phase
† P<.01 for comparison with reproductive age
‡ P<.01 for comparison with naturally menopausal women
§ P<.05 for comparison with naturally menopausal women
SOURCE: Vermeulen18

It matters how menopause happens

Circulating androgen levels are greatly influenced by menopause—how much depends on whether it occurs naturally with the ovaries intact, or by surgical removal of the ovaries. Not only does estradiol diminish significantly in naturally menopausal women, but all androgens do as well. In young oophorectomized women, estrogen levels are similar to levels in naturally menopausal women, but androgen levels—including testosterone, DHT, and androstenedione—are significantly lower than in naturally menopausal women, demonstrating that the circulating levels of androgen after natural menopause are still significantly greater than those in oophorectomized women.⁶ Thus, the postmenopausal ovary contributes significantly to circulating levels of androgen.

Androgen physiology

Both androgens and estrogens circulate in the bloodstream tightly bound to the protein sex hormone-binding globulin (SHBG), and more loosely bound to albumin. The SHBG-bound fraction is unavailable for biologic activity. Therefore, the amount of SHBG a woman produces is a key determinant of her level of androgen bioactivity. For this reason, it is crucial to measure circulating SHBG.

In a feedback mechanism, SHBG production is regulated by androgen and estrogen levels, with estrogen stimulating SHBG production and testosterone decreasing it.⁷ In the normal woman, about 65% of testosterone is bound to SHBG and 30% is bound to albumin, leaving only 0.5% to 2% free and bioactively available.⁸ In postmenopausal women taking hormone replacement therapy, SHBG increases, but the addition of methyltestosterone lowers the overall levels of SHBG, even in the presence of estrogen, increasing the amount of bioavailable testosterone simply by lowering SHBG levels. Postmenopausal replacement with estrogen alone decreases the amount of bioavailable testosterone because of higher SHBG levels.

SHBG is synthesized in the liver, whose metabolism is increased by exposure to steroids. Therefore, oral forms of estrogen replacement, which stimulate the liver because of the “first pass” effect, result in a greater increase in SHBG than do transdermal estrogen preparations.

 

Elevated androgen levels have both ill and good effects

As I stated earlier, an appropriate level of androgen is optimal for women as well as men. Elevated androgen levels are problematic, in that they are the hallmark of PCOS, usually resulting from increased ovarian production of androgen. This elevation can cause anovulation, infertility, hirsutism, and other androgen-mediated physiologic effects. Androgen is also associated with elevated low-density lipoprotein and decreased high-density lipoprotein cholesterol, implying a possible relationship with cardiovascular disease. At the same time, however, elevated testosterone has been correlated with increased bone density in both the hip and the femoral neck.⁹

It is clear that appropriate androgen secretion, which does not elicit the side effects described above, is best for both the health and well-being of the woman.

How androgen affects female sexual function

We have known for years that androgen—not estrogen—is associated with satisfactory sexual function. Although estrogen replacement increases vaginal lubrication, it is androgen, most commonly in the form of oral methyltestosterone or injectable testosterone, that increases frequency of intercourse, desire, and sexual sensation (FIGURE 2).¹⁰ The definition of androgen insufficiency has been hotly debated, and is currently “a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen.”¹¹

FIGURE 2

How estrogen plus androgen affects sexual function
*P<.01; †P=.05
EE=esterified estrogens; MT=methyltestosterone
SOURCE: Sarrel PM, et al¹⁹

Assessing androgen levels

Clinical signs and symptoms of androgen insufficiency are important in establishing the diagnosis. They include a diminished sense of well-being, unexplained fatigue, decreased sexual desire, and thinning and loss of pubic hair.¹¹ Although it is possible to assess testosterone production and availability in women by measuring serum testosterone levels, a lack of consensus about the best measurement technique and interpretation of results makes it difficult to base the diagnosis of androgen insufficiency solely on serum levels.¹² Therefore, the diagnosis of androgen insufficiency is primarily a clinical diagnosis of symptoms.¹¹

How to measure testosterone

Obtain serum samples between 8 and 10 AM after day 8 and before day 20 of the normal menstrual cycle because testosterone is subject to diurnal variation, peaking in the early morning, as well as cyclic variation, peaking around midcycle.

Because free testosterone is the only bioavailable steroid, total testosterone and either free testosterone or SHBG must be measured to assess how much androgen is actually available. From total testosterone and SHBG, one can assess the free testosterone index as a measure of bioavailable androgen (the free testosterone index is a ratio of the amount of total testosterone divided by the SHBG level).¹¹ In fact, using the free testosterone index is preferable to the actual measurement of free testosterone because commercial assays lack the sensitivity and reliability to accurately measure the low levels of androgen found in women.

Several different testosterone assays exist, and the immunoassay for total testosterone is reasonably accurate. However, measurements of free testosterone are relatively inaccurate and poorly reproducible. Equilibrium dialysis is thought to be the gold standard for measuring free testosterone, but it is a difficult and time-consuming assay.¹²

Causes of low testosterone

In women, low testosterone secretion is usually the result of normal aging. Other conditions that alter testosterone production include oophorectomy, ovarian failure, adrenal insufficiency, hypopituitarism, and other forms of chronic illness.

Treatment with corticosteroids and estrogen therapy lowers active androgen levels in women.

What levels are cause for concern?

If androgen levels are at or below the 25th percentile of the normal range for reproductive-aged women, consider the possibility of androgen insufficiency and determine whether androgen replacement is in order.¹¹

When the signs and symptoms of testosterone insufficiency are present, one must first assess estrogen levels by measuring serum estradiol, obtaining vaginal cytology, or both, and by determining whether symptoms of estrogen insufficiency are present, such as hot flashes, night sweats, and vaginal dryness. If the patient is estrogen-insufficient, the first step in resolving her symptoms is estrogen replacement. If estrogen levels are adequate and there is no other reason for the patient’s symptoms of fatigue, lack of sexual desire, or low energy, a trial of testosterone is reasonable.

Treating androgen insufficiency

Current therapies include oral methyltestosterone combined with estrogen, and intramuscular testosterone propionate, testosterone cypionate, and testosterone enanthate. Subcutaneous implants of testosterone propionate are also available, as are transdermal preparations (TABLE 2). However, the transdermal formulations are designed for androgen insufficiency in men, and therefore deliver approximately 10 times as much androgen as women normally produce. Testosterone gel preparations are available that can be applied in lower levels to achieve normal female androgen levels.

 

TABLE 2

Testosterone therapies available now—or in the pipeline

Oral
Methyltestosterone Undecanoate
Intramuscular
Propionate Cypionate Enanthate
Subcutaneous (implant)
Propionate pellets Crystalline pellets
Transdermal
Patch Gel Emulsion Spray
Other
Vaginal ring Sublingual (in propylene glycol)

How long until relief?

It is clear from a number of studies^13,14 that estrogen plus methyltestosterone oral replacement improves sexual desire in women after 12 to 16 weeks, and that this improvement is based on an increase in bioavailable testosterone. A testosterone patch under development delivers 300 μg per day. When used with conjugated equine estrogens, this patch has been shown to increase bioavailable testosterone in women without ovaries who have very low androgen levels.³

In a 2005 study,¹⁵ more than 500 women with hypoactive sexual desire who had undergone a total abdominal hysterectomy–bilateral salpingo-oophorectomy were randomized to placebo or a testosterone patch that delivered 300 μg per day for 24 weeks. Not only did serum testosterone levels increase, but satisfying sexual activity and the numbers of sexual interactions and orgasms increased (FIGURE 3). Side effects of therapy included increased facial hair and acne, but there was no increase in serious adverse effects, and no increase in withdrawal from the study because of side effects. Unfortunately, this patch is in development and unavailable commercially in the United States.

FIGURE 3

Assessing testosterone status in women
Adapted from Braunstein GD²⁰
*Bachmann G, et al¹¹

Watch for side effects, and follow closely

Testosterone therapy is most appropriate for women who have undergone surgical menopause and for postmenopausal women who are dissatisfied with estrogen therapy because of symptoms such as decreased libido and a diminished sense of well-being, including headaches and fatigue. Side effects of testosterone therapy include hirsutism, acne, alopecia, worsening lipoproteins, and, in the case of methyltestosterone, the possibility of liver toxicity, so women receiving testosterone should be followed frequently and carefully to detect any of these effects.

Androgen insufficiency in a nutshell

Androgens in women engender a general sense of well-being, which includes elevated energy and mood and increased libido. It is appropriate to consider androgen replacement using oral methyltestosterone, androgen implants, or transdermal androgen gels in women with a clinical diagnosis of androgen insufficiency.

Before initiating androgen therapy, however, it is important to measure total androgen level and assess clinical symptoms. Also, monitor the incidence of side effects to ensure that the patient does not exceed normal female androgen levels. It is hoped that additional forms of androgen replacement for women will become available in the near future.

Although women produce only one tenth the amount of androgen that men do, testosterone and related androgen metabolites are as important to women throughout the lifespan as is estrogen. Androgens modulate a feeling of well-being, increase energy, support bone metabolism, and improve sexual function in women.^1-3 But too much androgen production, with elevated levels of testosterone and dehydroepiandrosterone (DHEA), can result in hirsutism, acne, and infertility in the setting of polycystic ovary syndrome (PCOS), all of which present clinical problems.

An equally complicated topic is androgen insufficiency in women. Not only is it difficult to diagnose, it is a major clinical issue to decide whether, when, and how to replace androgens in women. In this article, I look at androgen production throughout the female lifespan, particularly the relationship between estrogen and androgen. I also describe the evaluation of androgen insufficiency, which requires understanding of androgen physiology and ovarian function before and after menopause. These issues form the basis of the decision to replace androgen in women.

Androgen over the lifespan

In the premenopausal woman, androgen production is approximately equally divided between the adrenal gland and the ovaries. Androstenedione from both is converted to testosterone and then irreversibly to dihydrotestosterone (DHT). Androstenedione, testosterone, and even DHEA are secreted in equal quantities by the adrenals and ovaries. The only androgen that is predominantly adrenal is DHEAS, which is sulfated in the adrenal gland.

In premenopausal women, androstenedione is the precursor to testosterone, which is then metabolized to DHT, the androgen most active in hair follicles and implicated in hirsutism. It has been clear for many years that DHEA, although a weak androgen, is present in the greatest quantity in the circulation and is secreted during adrenarche, prior to menarche, beginning at ages 8 to 10. DHEAS peaks in young adulthood and begins to decline after age 40.⁴ The same is true for both total testosterone and free testosterone levels, which also decline in women after about age 25. Thus, peri- and postmenopausal women have approximately half the level of circulating androgens of women in their 20s (FIGURE 1, TABLE 1).⁵

FIGURE 1

Testosterone levels in women decline with aging
N=595
SOURCE: Davison S, et al⁵TABLE 1

How menopause affects plasma hormone levels

HORMONE	MEAN PLASMA LEVEL
	REPRODUCTIVE AGE* (N=15)	NATURALLY MENOPAUSAL (N=18)	OOPHORECTOMIZED (N=8)
Estrone (pg/mL)	58	49	48
Estradiol (pg/mL)	40	20†	18
Testosterone (ng/dL)	44	30†	12‡
DHT (ng/dL)	30	10†	<5‡
Androstenedione (ng/dL)	166	99†	64‡
DHEA (ng/dL)	542	197†	126§
DHT=dihydrotestosterone, DHEA=dehydroepiandrosterone
* Mean value during early follicular phase
† P<.01 for comparison with reproductive age
‡ P<.01 for comparison with naturally menopausal women
§ P<.05 for comparison with naturally menopausal women
SOURCE: Vermeulen18

It matters how menopause happens

Circulating androgen levels are greatly influenced by menopause—how much depends on whether it occurs naturally with the ovaries intact, or by surgical removal of the ovaries. Not only does estradiol diminish significantly in naturally menopausal women, but all androgens do as well. In young oophorectomized women, estrogen levels are similar to levels in naturally menopausal women, but androgen levels—including testosterone, DHT, and androstenedione—are significantly lower than in naturally menopausal women, demonstrating that the circulating levels of androgen after natural menopause are still significantly greater than those in oophorectomized women.⁶ Thus, the postmenopausal ovary contributes significantly to circulating levels of androgen.

Androgen physiology

Both androgens and estrogens circulate in the bloodstream tightly bound to the protein sex hormone-binding globulin (SHBG), and more loosely bound to albumin. The SHBG-bound fraction is unavailable for biologic activity. Therefore, the amount of SHBG a woman produces is a key determinant of her level of androgen bioactivity. For this reason, it is crucial to measure circulating SHBG.

In a feedback mechanism, SHBG production is regulated by androgen and estrogen levels, with estrogen stimulating SHBG production and testosterone decreasing it.⁷ In the normal woman, about 65% of testosterone is bound to SHBG and 30% is bound to albumin, leaving only 0.5% to 2% free and bioactively available.⁸ In postmenopausal women taking hormone replacement therapy, SHBG increases, but the addition of methyltestosterone lowers the overall levels of SHBG, even in the presence of estrogen, increasing the amount of bioavailable testosterone simply by lowering SHBG levels. Postmenopausal replacement with estrogen alone decreases the amount of bioavailable testosterone because of higher SHBG levels.

SHBG is synthesized in the liver, whose metabolism is increased by exposure to steroids. Therefore, oral forms of estrogen replacement, which stimulate the liver because of the “first pass” effect, result in a greater increase in SHBG than do transdermal estrogen preparations.

 

Elevated androgen levels have both ill and good effects

As I stated earlier, an appropriate level of androgen is optimal for women as well as men. Elevated androgen levels are problematic, in that they are the hallmark of PCOS, usually resulting from increased ovarian production of androgen. This elevation can cause anovulation, infertility, hirsutism, and other androgen-mediated physiologic effects. Androgen is also associated with elevated low-density lipoprotein and decreased high-density lipoprotein cholesterol, implying a possible relationship with cardiovascular disease. At the same time, however, elevated testosterone has been correlated with increased bone density in both the hip and the femoral neck.⁹

It is clear that appropriate androgen secretion, which does not elicit the side effects described above, is best for both the health and well-being of the woman.

How androgen affects female sexual function

We have known for years that androgen—not estrogen—is associated with satisfactory sexual function. Although estrogen replacement increases vaginal lubrication, it is androgen, most commonly in the form of oral methyltestosterone or injectable testosterone, that increases frequency of intercourse, desire, and sexual sensation (FIGURE 2).¹⁰ The definition of androgen insufficiency has been hotly debated, and is currently “a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen.”¹¹

FIGURE 2

How estrogen plus androgen affects sexual function
*P<.01; †P=.05
EE=esterified estrogens; MT=methyltestosterone
SOURCE: Sarrel PM, et al¹⁹

Assessing androgen levels

Clinical signs and symptoms of androgen insufficiency are important in establishing the diagnosis. They include a diminished sense of well-being, unexplained fatigue, decreased sexual desire, and thinning and loss of pubic hair.¹¹ Although it is possible to assess testosterone production and availability in women by measuring serum testosterone levels, a lack of consensus about the best measurement technique and interpretation of results makes it difficult to base the diagnosis of androgen insufficiency solely on serum levels.¹² Therefore, the diagnosis of androgen insufficiency is primarily a clinical diagnosis of symptoms.¹¹

How to measure testosterone

Obtain serum samples between 8 and 10 AM after day 8 and before day 20 of the normal menstrual cycle because testosterone is subject to diurnal variation, peaking in the early morning, as well as cyclic variation, peaking around midcycle.

Because free testosterone is the only bioavailable steroid, total testosterone and either free testosterone or SHBG must be measured to assess how much androgen is actually available. From total testosterone and SHBG, one can assess the free testosterone index as a measure of bioavailable androgen (the free testosterone index is a ratio of the amount of total testosterone divided by the SHBG level).¹¹ In fact, using the free testosterone index is preferable to the actual measurement of free testosterone because commercial assays lack the sensitivity and reliability to accurately measure the low levels of androgen found in women.

Several different testosterone assays exist, and the immunoassay for total testosterone is reasonably accurate. However, measurements of free testosterone are relatively inaccurate and poorly reproducible. Equilibrium dialysis is thought to be the gold standard for measuring free testosterone, but it is a difficult and time-consuming assay.¹²

Causes of low testosterone

In women, low testosterone secretion is usually the result of normal aging. Other conditions that alter testosterone production include oophorectomy, ovarian failure, adrenal insufficiency, hypopituitarism, and other forms of chronic illness.

Treatment with corticosteroids and estrogen therapy lowers active androgen levels in women.

What levels are cause for concern?

If androgen levels are at or below the 25th percentile of the normal range for reproductive-aged women, consider the possibility of androgen insufficiency and determine whether androgen replacement is in order.¹¹

When the signs and symptoms of testosterone insufficiency are present, one must first assess estrogen levels by measuring serum estradiol, obtaining vaginal cytology, or both, and by determining whether symptoms of estrogen insufficiency are present, such as hot flashes, night sweats, and vaginal dryness. If the patient is estrogen-insufficient, the first step in resolving her symptoms is estrogen replacement. If estrogen levels are adequate and there is no other reason for the patient’s symptoms of fatigue, lack of sexual desire, or low energy, a trial of testosterone is reasonable.

Treating androgen insufficiency

Current therapies include oral methyltestosterone combined with estrogen, and intramuscular testosterone propionate, testosterone cypionate, and testosterone enanthate. Subcutaneous implants of testosterone propionate are also available, as are transdermal preparations (TABLE 2). However, the transdermal formulations are designed for androgen insufficiency in men, and therefore deliver approximately 10 times as much androgen as women normally produce. Testosterone gel preparations are available that can be applied in lower levels to achieve normal female androgen levels.

 

TABLE 2

Testosterone therapies available now—or in the pipeline

Oral
Methyltestosterone Undecanoate
Intramuscular
Propionate Cypionate Enanthate
Subcutaneous (implant)
Propionate pellets Crystalline pellets
Transdermal
Patch Gel Emulsion Spray
Other
Vaginal ring Sublingual (in propylene glycol)

How long until relief?

It is clear from a number of studies^13,14 that estrogen plus methyltestosterone oral replacement improves sexual desire in women after 12 to 16 weeks, and that this improvement is based on an increase in bioavailable testosterone. A testosterone patch under development delivers 300 μg per day. When used with conjugated equine estrogens, this patch has been shown to increase bioavailable testosterone in women without ovaries who have very low androgen levels.³

In a 2005 study,¹⁵ more than 500 women with hypoactive sexual desire who had undergone a total abdominal hysterectomy–bilateral salpingo-oophorectomy were randomized to placebo or a testosterone patch that delivered 300 μg per day for 24 weeks. Not only did serum testosterone levels increase, but satisfying sexual activity and the numbers of sexual interactions and orgasms increased (FIGURE 3). Side effects of therapy included increased facial hair and acne, but there was no increase in serious adverse effects, and no increase in withdrawal from the study because of side effects. Unfortunately, this patch is in development and unavailable commercially in the United States.

FIGURE 3

Assessing testosterone status in women
Adapted from Braunstein GD²⁰
*Bachmann G, et al¹¹

Watch for side effects, and follow closely

Testosterone therapy is most appropriate for women who have undergone surgical menopause and for postmenopausal women who are dissatisfied with estrogen therapy because of symptoms such as decreased libido and a diminished sense of well-being, including headaches and fatigue. Side effects of testosterone therapy include hirsutism, acne, alopecia, worsening lipoproteins, and, in the case of methyltestosterone, the possibility of liver toxicity, so women receiving testosterone should be followed frequently and carefully to detect any of these effects.

Androgen insufficiency in a nutshell

Androgens in women engender a general sense of well-being, which includes elevated energy and mood and increased libido. It is appropriate to consider androgen replacement using oral methyltestosterone, androgen implants, or transdermal androgen gels in women with a clinical diagnosis of androgen insufficiency.

Before initiating androgen therapy, however, it is important to measure total androgen level and assess clinical symptoms. Also, monitor the incidence of side effects to ensure that the patient does not exceed normal female androgen levels. It is hoped that additional forms of androgen replacement for women will become available in the near future.

Although women produce only one tenth the amount of androgen that men do, testosterone and related androgen metabolites are as important to women throughout the lifespan as is estrogen. Androgens modulate a feeling of well-being, increase energy, support bone metabolism, and improve sexual function in women.^1-3 But too much androgen production, with elevated levels of testosterone and dehydroepiandrosterone (DHEA), can result in hirsutism, acne, and infertility in the setting of polycystic ovary syndrome (PCOS), all of which present clinical problems.

An equally complicated topic is androgen insufficiency in women. Not only is it difficult to diagnose, it is a major clinical issue to decide whether, when, and how to replace androgens in women. In this article, I look at androgen production throughout the female lifespan, particularly the relationship between estrogen and androgen. I also describe the evaluation of androgen insufficiency, which requires understanding of androgen physiology and ovarian function before and after menopause. These issues form the basis of the decision to replace androgen in women.

Androgen over the lifespan

In the premenopausal woman, androgen production is approximately equally divided between the adrenal gland and the ovaries. Androstenedione from both is converted to testosterone and then irreversibly to dihydrotestosterone (DHT). Androstenedione, testosterone, and even DHEA are secreted in equal quantities by the adrenals and ovaries. The only androgen that is predominantly adrenal is DHEAS, which is sulfated in the adrenal gland.

In premenopausal women, androstenedione is the precursor to testosterone, which is then metabolized to DHT, the androgen most active in hair follicles and implicated in hirsutism. It has been clear for many years that DHEA, although a weak androgen, is present in the greatest quantity in the circulation and is secreted during adrenarche, prior to menarche, beginning at ages 8 to 10. DHEAS peaks in young adulthood and begins to decline after age 40.⁴ The same is true for both total testosterone and free testosterone levels, which also decline in women after about age 25. Thus, peri- and postmenopausal women have approximately half the level of circulating androgens of women in their 20s (FIGURE 1, TABLE 1).⁵

FIGURE 1

Testosterone levels in women decline with aging
N=595
SOURCE: Davison S, et al⁵TABLE 1

How menopause affects plasma hormone levels

HORMONE	MEAN PLASMA LEVEL
	REPRODUCTIVE AGE* (N=15)	NATURALLY MENOPAUSAL (N=18)	OOPHORECTOMIZED (N=8)
Estrone (pg/mL)	58	49	48
Estradiol (pg/mL)	40	20†	18
Testosterone (ng/dL)	44	30†	12‡
DHT (ng/dL)	30	10†	<5‡
Androstenedione (ng/dL)	166	99†	64‡
DHEA (ng/dL)	542	197†	126§
DHT=dihydrotestosterone, DHEA=dehydroepiandrosterone
* Mean value during early follicular phase
† P<.01 for comparison with reproductive age
‡ P<.01 for comparison with naturally menopausal women
§ P<.05 for comparison with naturally menopausal women
SOURCE: Vermeulen18

It matters how menopause happens

Circulating androgen levels are greatly influenced by menopause—how much depends on whether it occurs naturally with the ovaries intact, or by surgical removal of the ovaries. Not only does estradiol diminish significantly in naturally menopausal women, but all androgens do as well. In young oophorectomized women, estrogen levels are similar to levels in naturally menopausal women, but androgen levels—including testosterone, DHT, and androstenedione—are significantly lower than in naturally menopausal women, demonstrating that the circulating levels of androgen after natural menopause are still significantly greater than those in oophorectomized women.⁶ Thus, the postmenopausal ovary contributes significantly to circulating levels of androgen.

Androgen physiology

Both androgens and estrogens circulate in the bloodstream tightly bound to the protein sex hormone-binding globulin (SHBG), and more loosely bound to albumin. The SHBG-bound fraction is unavailable for biologic activity. Therefore, the amount of SHBG a woman produces is a key determinant of her level of androgen bioactivity. For this reason, it is crucial to measure circulating SHBG.

In a feedback mechanism, SHBG production is regulated by androgen and estrogen levels, with estrogen stimulating SHBG production and testosterone decreasing it.⁷ In the normal woman, about 65% of testosterone is bound to SHBG and 30% is bound to albumin, leaving only 0.5% to 2% free and bioactively available.⁸ In postmenopausal women taking hormone replacement therapy, SHBG increases, but the addition of methyltestosterone lowers the overall levels of SHBG, even in the presence of estrogen, increasing the amount of bioavailable testosterone simply by lowering SHBG levels. Postmenopausal replacement with estrogen alone decreases the amount of bioavailable testosterone because of higher SHBG levels.

SHBG is synthesized in the liver, whose metabolism is increased by exposure to steroids. Therefore, oral forms of estrogen replacement, which stimulate the liver because of the “first pass” effect, result in a greater increase in SHBG than do transdermal estrogen preparations.

 

Elevated androgen levels have both ill and good effects

As I stated earlier, an appropriate level of androgen is optimal for women as well as men. Elevated androgen levels are problematic, in that they are the hallmark of PCOS, usually resulting from increased ovarian production of androgen. This elevation can cause anovulation, infertility, hirsutism, and other androgen-mediated physiologic effects. Androgen is also associated with elevated low-density lipoprotein and decreased high-density lipoprotein cholesterol, implying a possible relationship with cardiovascular disease. At the same time, however, elevated testosterone has been correlated with increased bone density in both the hip and the femoral neck.⁹

It is clear that appropriate androgen secretion, which does not elicit the side effects described above, is best for both the health and well-being of the woman.

How androgen affects female sexual function

We have known for years that androgen—not estrogen—is associated with satisfactory sexual function. Although estrogen replacement increases vaginal lubrication, it is androgen, most commonly in the form of oral methyltestosterone or injectable testosterone, that increases frequency of intercourse, desire, and sexual sensation (FIGURE 2).¹⁰ The definition of androgen insufficiency has been hotly debated, and is currently “a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen.”¹¹

FIGURE 2

How estrogen plus androgen affects sexual function
*P<.01; †P=.05
EE=esterified estrogens; MT=methyltestosterone
SOURCE: Sarrel PM, et al¹⁹

Assessing androgen levels

Clinical signs and symptoms of androgen insufficiency are important in establishing the diagnosis. They include a diminished sense of well-being, unexplained fatigue, decreased sexual desire, and thinning and loss of pubic hair.¹¹ Although it is possible to assess testosterone production and availability in women by measuring serum testosterone levels, a lack of consensus about the best measurement technique and interpretation of results makes it difficult to base the diagnosis of androgen insufficiency solely on serum levels.¹² Therefore, the diagnosis of androgen insufficiency is primarily a clinical diagnosis of symptoms.¹¹

How to measure testosterone

Obtain serum samples between 8 and 10 AM after day 8 and before day 20 of the normal menstrual cycle because testosterone is subject to diurnal variation, peaking in the early morning, as well as cyclic variation, peaking around midcycle.

Because free testosterone is the only bioavailable steroid, total testosterone and either free testosterone or SHBG must be measured to assess how much androgen is actually available. From total testosterone and SHBG, one can assess the free testosterone index as a measure of bioavailable androgen (the free testosterone index is a ratio of the amount of total testosterone divided by the SHBG level).¹¹ In fact, using the free testosterone index is preferable to the actual measurement of free testosterone because commercial assays lack the sensitivity and reliability to accurately measure the low levels of androgen found in women.

Several different testosterone assays exist, and the immunoassay for total testosterone is reasonably accurate. However, measurements of free testosterone are relatively inaccurate and poorly reproducible. Equilibrium dialysis is thought to be the gold standard for measuring free testosterone, but it is a difficult and time-consuming assay.¹²

Causes of low testosterone

In women, low testosterone secretion is usually the result of normal aging. Other conditions that alter testosterone production include oophorectomy, ovarian failure, adrenal insufficiency, hypopituitarism, and other forms of chronic illness.

Treatment with corticosteroids and estrogen therapy lowers active androgen levels in women.

What levels are cause for concern?

If androgen levels are at or below the 25th percentile of the normal range for reproductive-aged women, consider the possibility of androgen insufficiency and determine whether androgen replacement is in order.¹¹

When the signs and symptoms of testosterone insufficiency are present, one must first assess estrogen levels by measuring serum estradiol, obtaining vaginal cytology, or both, and by determining whether symptoms of estrogen insufficiency are present, such as hot flashes, night sweats, and vaginal dryness. If the patient is estrogen-insufficient, the first step in resolving her symptoms is estrogen replacement. If estrogen levels are adequate and there is no other reason for the patient’s symptoms of fatigue, lack of sexual desire, or low energy, a trial of testosterone is reasonable.

Treating androgen insufficiency

Current therapies include oral methyltestosterone combined with estrogen, and intramuscular testosterone propionate, testosterone cypionate, and testosterone enanthate. Subcutaneous implants of testosterone propionate are also available, as are transdermal preparations (TABLE 2). However, the transdermal formulations are designed for androgen insufficiency in men, and therefore deliver approximately 10 times as much androgen as women normally produce. Testosterone gel preparations are available that can be applied in lower levels to achieve normal female androgen levels.

 

TABLE 2

Testosterone therapies available now—or in the pipeline

Oral
Methyltestosterone Undecanoate
Intramuscular
Propionate Cypionate Enanthate
Subcutaneous (implant)
Propionate pellets Crystalline pellets
Transdermal
Patch Gel Emulsion Spray
Other
Vaginal ring Sublingual (in propylene glycol)

How long until relief?

It is clear from a number of studies^13,14 that estrogen plus methyltestosterone oral replacement improves sexual desire in women after 12 to 16 weeks, and that this improvement is based on an increase in bioavailable testosterone. A testosterone patch under development delivers 300 μg per day. When used with conjugated equine estrogens, this patch has been shown to increase bioavailable testosterone in women without ovaries who have very low androgen levels.³

In a 2005 study,¹⁵ more than 500 women with hypoactive sexual desire who had undergone a total abdominal hysterectomy–bilateral salpingo-oophorectomy were randomized to placebo or a testosterone patch that delivered 300 μg per day for 24 weeks. Not only did serum testosterone levels increase, but satisfying sexual activity and the numbers of sexual interactions and orgasms increased (FIGURE 3). Side effects of therapy included increased facial hair and acne, but there was no increase in serious adverse effects, and no increase in withdrawal from the study because of side effects. Unfortunately, this patch is in development and unavailable commercially in the United States.

FIGURE 3

Assessing testosterone status in women
Adapted from Braunstein GD²⁰
*Bachmann G, et al¹¹

Watch for side effects, and follow closely

Testosterone therapy is most appropriate for women who have undergone surgical menopause and for postmenopausal women who are dissatisfied with estrogen therapy because of symptoms such as decreased libido and a diminished sense of well-being, including headaches and fatigue. Side effects of testosterone therapy include hirsutism, acne, alopecia, worsening lipoproteins, and, in the case of methyltestosterone, the possibility of liver toxicity, so women receiving testosterone should be followed frequently and carefully to detect any of these effects.

Androgen insufficiency in a nutshell

Androgens in women engender a general sense of well-being, which includes elevated energy and mood and increased libido. It is appropriate to consider androgen replacement using oral methyltestosterone, androgen implants, or transdermal androgen gels in women with a clinical diagnosis of androgen insufficiency.

Before initiating androgen therapy, however, it is important to measure total androgen level and assess clinical symptoms. Also, monitor the incidence of side effects to ensure that the patient does not exceed normal female androgen levels. It is hoped that additional forms of androgen replacement for women will become available in the near future.

ObGyns and their patients are the beneficiaries of a steady stream of scientific data on issues relating to menopause. In last year’s Update, I focused on the question of whether menopausal hormone therapy (HT) increases the risk of breast cancer.¹ Because breast cancer continues to top the list of women’s concerns, I will use this year’s Update to assess what we have recently learned about HT and breast cancer, and to explore the latest data on nonhormonal management of vasomotor symptoms.

I am delighted that Dr. Michael McClung, an internationally recognized expert in skeletal health, has agreed to review current evidence on the prevention of osteoporotic fractures in menopausal women in the latter part of this article.

New WHI analysis confirms safety of short-term combination HT

Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen and progestin. Maturitas. 2006;55:103–115.

At the annual San Antonio Breast Cancer Symposium in December, investigators presented data showing that the incidence of breast cancer in US women decreased by 7% from 2002 to 2003, a striking decline that was most prominent among women aged 50 to 69 years. The presenters speculated that the plummeting rates of HT use following publication of the initial Women’s Health Initiative (WHI) findings in the summer of 2002 (in regard to the estrogen–progestin arm²) might be responsible for this decline.³

The major media attention that followed this presentation makes one thing clear: Concerns about developing breast cancer with HT use continue to fuel anxiety among women. Although secular trend data on the national breast cancer incidence can help generate hypotheses, they cannot explain the trends. What can shed light on the association between estrogen–progestin HT and breast cancer are important new data recently released by WHI investigators.

Women new to HT had no increased risk of breast cancer

In the 2006 subgroup analysis of WHI participants in the estrogen–progestin arm, investigators focused on HT use before enrollment in the trial. Recall that in this part of the WHI, 16,608 women with an intact uterus were randomized to conjugated equine estrogen plus medroxyprogesterone acetate or placebo. Use of the study medication was stopped after a mean follow-up of 5.6 years (mean exposure to HT: 4.4 years). Overall, the risk of invasive breast cancer was slightly higher with combination HT than placebo (hazard ratio [HR] 1.24; 95% confidence interval [CI] 1.01–1.54).²

In the 2006 report from the 2002 WHI study of estrogen–progestin HT versus placebo, investigators compared the risk of being diagnosed with breast cancer in 12,297 women who had not used HT prior to study enrollment with the risk in 4,311 participants who had previously used HT. Of the previous users, 42% reported less than 2 years of use prior to WHI enrollment, and 36% reported more than 4 years of HT prior to WHI enrollment.

The findings: Among WHI participants who had never before used HT, the use of estrogen–progestin HT in the study was not associated with an elevated risk of being diagnosed with breast cancer (HR 1.02; 95% CI 0.77–1.36). However, among previous HT users, the additional use of HT in the WHI study was associated with a risk nearly double that of placebo users (HR 1.96, 95% CI 1.17–3.27).

The reassuring results of this WHI subgroup analysis received little media attention in the United States, probably because the report appeared in a journal that has low readership in this country. WHI and other findings allow us to reassure women who have undergone hysterectomy that use of unopposed estrogen has little, if any, impact on breast cancer risk in menopausal women.^4,5 This new WHI subgroup analysis, along with a recent review of European and North American data,⁶ allows ObGyns to counsel women with an intact uterus that up to 5 years of combination estrogen–progestin hormone therapy also has little, if any, impact on breast cancer risk.

Not much to recommend among nonhormonal therapies

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy or placebo. Ann Intern Med. 2006;145:869–879.

 

Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med. 2006;355:2338–2347.

Grady D, Cohen B, Tice J, et al. Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial. Obstet Gynecol. 2007;109:823–830.

Loprinzi CL, Kugler JW, Barton DL, et al. Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. J Clin Oncol. 2007;25:308–312.

Since publication of the initial WHI findings in 2002,² interest in nonhormonal management of vasomotor symptoms has increased among menopausal women and their clinicians. The botanical black cohosh and “nutraceutical” soy or isoflavone supplements represent the nonprescription remedies most widely used for relief of hot flashes. Unfortunately, accumulating evidence does not support the efficacy of these popular remedies.

In a recent NIH-funded, randomized, double-blind, placebo-controlled clinical trial, Newton and colleagues compared the following interventions:

• black cohosh, 160 mg daily
  
• daily multibotanical supplement that included 200 mg of black cohosh and 9 other ingredients
  
• the multibotanical supplement plus counseling regarding dietary soy
  
• conjugated equine estrogen, 0.625 mg daily (with or without 2.5 mg of medroxyprogesterone acetate)
  
• placebo
  

The study involved 351 perimenopausal or postmenopausal women aged 45 to 55 years with 2 or more vasomotor symptoms daily.

The findings: At 3, 6, and 12 months, women allocated to estrogen (with or without progestin) had statistically significant relief of symptoms. In contrast, women allocated to botanical and/or herbal supplements experienced minimal relief, comparable to the effects of placebo.

The findings of this important study, as well as those of Grady, are discouraging: Black cohosh, botanicals, and encouraging increased soy intake are ineffective in the treatment of vasomotor symptoms.

Evidence on antidepressants is inconclusive

Selective serotonin reuptake inhibitors (SSRIs) and the antidepressant venlafaxine have been assessed for their effects on menopausal vasomotor symptoms, particularly in breast cancer survivors. In a recent review and also a randomized trial, Grady reports that the SSRIs citalopram and sertraline do not appear to be effective, and the findings in regard to the SSRI fluoxetine and venlafaxine have been inconsistent. Compared with placebo, the SSRI paroxetine has eased vasomotor symptoms to a modest degree in breast cancer survivors, but had little effect in women who have not had the disease.

Breast cancer survivors often take tamoxifen or aromatase inhibitors, medications that can induce or aggravate hot flashes. Breast cancer survivors also have a higher prevalence of mood disorders. These factors suggest that the experience and treatment of menopausal symptoms differ between breast cancer survivors and the general population.

Overall, Grady notes, for women with bothersome vasomotor symptoms who have no history of breast cancer, clinical trials of antidepressants have not been encouraging.

Gabapentin is more effective than antidepressants, but with a price

Clinical trials of gabapentin suggest that this anticonvulsant is moderately effective in the nonhormonal treatment of vasomotor symptoms, and the phase III trial by Loprinzi and colleagues finds it to be more effective therapy for vasomotor symptoms than antidepressants.

The drawback? This drug must be taken 2 or 3 times daily, and side effects (including fatigue) limit its attractiveness.

When deciding whom to treat, consider risk as well as BMD

Sanders KM, Nicholson GC, Watts JJ, et al. Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective? Bone. 2006;38:694–700.

The diagnosis of osteoporosis in postmenopausal women is now based on a threshold bone mineral density (BMD) T-score of –2.5. However, BMD is only one of several important risk factors for fracture, and most patients who experience a fracture related to osteoporosis do not have BMD values in the range consistent with osteoporosis, as Sanders and colleagues observe. Therefore, clinicians are faced with this question: Which patients who do not have osteoporosis should be treated to prevent fracture?

The World Health Organization (WHO) task force on fracture risk assessment, under the leadership of Professor John Kanis, has developed an algorithm to estimate fracture probability in individual patients.⁷ This algorithm is based on a sophisticated analysis of almost all of the large epidemiological studies performed worldwide that have assessed relationships between clinical risk factors and fracture risk. By including the 3 major risk factors (age, BMD, and fracture history), as well as weaker risk factors (family history of hip fracture, current smoking, excess alcohol intake, and history of chronic glucocorticoid use), the absolute risk of developing a fracture of the spine, wrist, hip, or shoulder over the next 10 years will be estimated. This information will be the basis for revised guidelines by the National Osteoporosis Foundation (NOF) and other organizations. The new guidelines will include recommendations for treating patients at or above a certain threshold of fracture risk rather than a certain BMD threshold. The new treatment threshold will be based on a combination of cost- and clinical effectiveness.

 

The WHO algorithm and revised NOF guidelines are expected later this year.

New paradigm will shift focus to older women

This revised approach will shift the focus of therapy from young postmenopausal women at low fracture risk toward older women who do not have osteoporosis but do have an increased risk of fracture by virtue of their age and other factors.⁸ This will direct therapy more appropriately to patients who stand to gain the most and in whom therapy has been proven to reduce fracture risk.

Despite concerns, bisphosphonates appear to be safe for the long term

Bisphosphonates are the most extensively studied and widely used treatment for osteoporosis. Alendronate, the first bisphosphonate approved for the treatment of osteoporosis in the United States, has been available for more than 11 years. In general, all 3 of the currently approved bisphosphonates are well tolerated, and studies following patients for 7 to 10 years have not demonstrated significant adverse events or evidence of skeletal harm with long-term use.^9-11 However, because the drugs accumulate in the skeleton, there is a theoretical concern that long-term use will lead to over-suppression of bone turnover.

Small series of patients receiving bisphosphonates have described unusual fractures, evidence of low formation, and poor fracture healing, suggesting skeletal harm in at least some patients.¹² Bone biopsies performed in patients who received alendronate for 10 years or risedronate for 5 years showed evidence of bone remodeling in all the biopsy samples.^11,13 There was no progressive inhibition of bone metabolism in those biopsies compared with biopsies taken from patients who had received shorter-term treatment.

These findings are consistent with bone-turnover marker data suggesting no progressive suppression of bone turnover with continued use.^10,11,13 Biochemical indices of bone resorption are reduced to the lower half of the normal premenopausal range within about 3 months of beginning therapy, and values remain at that new level as long as patients receive the drug.

Risk of osteonecrosis of the jaw is low in general population

Woo SB, Hellstein JW, Kalmar JR. Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753–761.

Bilezikian JP. Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med. 2006;355:2278–2281.

An association between bisphosphonate therapy and nonhealing lesions of the jaw (so-called osteonecrosis of the jaw) has been observed, but primarily affects patients with cancer-related bone diseases who receive high doses of intravenous therapy in addition to chemotherapy. Patients receiving oral doses of bisphosphonates for osteoporosis in Paget’s disease have also had these lesions, as Woo and colleagues point out.

There is much that we do not know about this clinical problem, including its pathogenesis, whether the risk increases with longer-term use, and whether stopping therapy reduces the risk of developing lesions or improves the outcome of lesions already present. We do know that the incidence of exposed bone in the jaw in patients receiving bisphosphonate therapy for osteoporosis is low, estimated to range from 1 in 1,000 to 1 in 100,000 patients, according to Bilezikian.

Risk is very small, compared with potential benefits

It is important to put this risk in perspective. Based on data from the alendronate Fracture Intervention Trials (FIT), we have estimates of hip and spine fracture risk in certain types of patients. For example, for women age 68 with a femoral neck T-score of –2.5 or lower and no vertebral fractures, the likelihood of a clinical fracture over a mean treatment interval of 4.2 years was 19.6%.¹⁴ In women age 71 with a femoral neck T-score of –2.5 and 1 or more vertebral fractures, spine and hip fractures occurred in 15% and 2.2% of subjects, respectively, over 2.9 years.¹⁵ In these populations, alendronate reduced the risk of both hip and spine fracture by about 50%. For women without a vertebral fracture, the absolute reduction in the risk of clinical fracture over 4.2 years was 6.5% (number needed to treat [NNT]=15). In patients with a vertebral fracture, the absolute reduction in the incidence of further spine and hip fracture was 8.6% over 2.9 years (NNT=12).

This information argues strongly that the concern about osteonecrosis of the jaw does not justify withholding bisphosphonate therapy from patients with osteoporosis. The risk of such lesions in otherwise healthy patients with osteoporosis is very low (much lower than the risk of fracture), and most lesions heal spontaneously when treatment is stopped.

Clinical recommendations

For patients using or considering bisphosphonate therapy for osteoporosis, the following measures may be helpful:

• Have regular dental checkups and routine preventive dental care.
  
• If invasive dental procedures are planned, such as tooth extraction or implants, complete the dental work and allow the bone to heal before beginning bisphosphonate therapy.
  
• If a patient on bisphosphonate therapy plans invasive dental work, stop treatment for 3 months before the procedure and do not restart it until the jaw lesion is healed. Although there is no firm evidence that this strategy is helpful, it is certain that discontinuing bisphosphonate for a few months does not harm the skeleton.
  
• If a patient on bisphosphonate develops exposed bone, stop the drug and consult a dentist or oral surgeon experienced in the care of these lesions.
  

 

Some can take a holiday from bisphosphonate therapy

Black DM, Schwartz AV, Ensrud KE, et al, for the FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-Term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–2938.

There is evidence that bone metabolism continues to be affected for some time when alendronate is stopped after 2 to 5 years of treatment, as Black and colleagues found in the Fracture Intervention Trial Long-Term Extension (FLEX) and others have demonstrated.¹⁰ This raises the possibility that patients can take a “drug holiday” after several years of treatment. (This study was also reported in the March issue of OBG Management in “Examining the Evidence,” with a commentary by Steven R. Goldstein, MD.)

The FLEX trial attempted to determine whether it is better to continue or stop alendronate after several years’ exposure. One thousand ninety-nine women who had taken alendronate for 3 to 6 years in the FIT trials were randomly assigned to 5 or 10 mg of alendronate daily or placebo. All subjects received 500 mg of calcium and small vitamin D supplements and were followed for an additional 5 years.

The 2 alendronate groups were pooled for the analyses. Patients who switched to placebo for 5 years had declines in BMD at the total hip (2.4%) and spine (3.7%), compared with those who continued alendronate. However, values at the end of 5 years without therapy remained at or above pretreatment levels. Indices of bone turnover increased modestly when therapy was discontinued, but again the rates of bone turnover remained substantially lower than pretreatment values.

Fractures were collected as an exploratory endpoint. Compared with women who stopped treatment, women who continued alendronate reduced their risk of developing a clinical vertebral fracture by 55% (from 5.3% in the placebo group to 2.4% in the alendronate group). No difference was observed in the incidence of nonvertebral fractures between the 2 groups.

Who should take a holiday, and who can stay put?

Unfortunately, this study does not clearly answer the question. Patients at high risk for spine fracture, including those with a previous fracture, appeared to fare better if they continued treatment. Patients at lower risk did equally well whether they stopped or continued alendronate. This suggests that it would be appropriate to stop treatment in women who are not at high risk, including women who do not have osteoporosis by BMD criteria and have not experienced a fragility fracture since menopause.

The reason for stopping therapy in patients at low risk is because there was no added benefit observed with continued treatment, not because of concerns about risk.

When should the holiday end?

If treatment is stopped, the clinical question of whether and when to restart treatment becomes a challenge. The changes in bone density after treatment is stopped are too small to discern in individual patients. In theory, monitoring one or more bone-turnover markers is a more sensitive way to determine when the effects of bisphosphonates on skeletal remodeling are dissipating, but this approach is backed by very little clinical experience.

Another unresolved issue is whether the response after stopping treatment is the same in patients taking risedronate, ibandronate, or lower doses of alendronate.

ObGyns and their patients are the beneficiaries of a steady stream of scientific data on issues relating to menopause. In last year’s Update, I focused on the question of whether menopausal hormone therapy (HT) increases the risk of breast cancer.¹ Because breast cancer continues to top the list of women’s concerns, I will use this year’s Update to assess what we have recently learned about HT and breast cancer, and to explore the latest data on nonhormonal management of vasomotor symptoms.

I am delighted that Dr. Michael McClung, an internationally recognized expert in skeletal health, has agreed to review current evidence on the prevention of osteoporotic fractures in menopausal women in the latter part of this article.

New WHI analysis confirms safety of short-term combination HT

Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen and progestin. Maturitas. 2006;55:103–115.

At the annual San Antonio Breast Cancer Symposium in December, investigators presented data showing that the incidence of breast cancer in US women decreased by 7% from 2002 to 2003, a striking decline that was most prominent among women aged 50 to 69 years. The presenters speculated that the plummeting rates of HT use following publication of the initial Women’s Health Initiative (WHI) findings in the summer of 2002 (in regard to the estrogen–progestin arm²) might be responsible for this decline.³

The major media attention that followed this presentation makes one thing clear: Concerns about developing breast cancer with HT use continue to fuel anxiety among women. Although secular trend data on the national breast cancer incidence can help generate hypotheses, they cannot explain the trends. What can shed light on the association between estrogen–progestin HT and breast cancer are important new data recently released by WHI investigators.

Women new to HT had no increased risk of breast cancer

In the 2006 subgroup analysis of WHI participants in the estrogen–progestin arm, investigators focused on HT use before enrollment in the trial. Recall that in this part of the WHI, 16,608 women with an intact uterus were randomized to conjugated equine estrogen plus medroxyprogesterone acetate or placebo. Use of the study medication was stopped after a mean follow-up of 5.6 years (mean exposure to HT: 4.4 years). Overall, the risk of invasive breast cancer was slightly higher with combination HT than placebo (hazard ratio [HR] 1.24; 95% confidence interval [CI] 1.01–1.54).²

In the 2006 report from the 2002 WHI study of estrogen–progestin HT versus placebo, investigators compared the risk of being diagnosed with breast cancer in 12,297 women who had not used HT prior to study enrollment with the risk in 4,311 participants who had previously used HT. Of the previous users, 42% reported less than 2 years of use prior to WHI enrollment, and 36% reported more than 4 years of HT prior to WHI enrollment.

The findings: Among WHI participants who had never before used HT, the use of estrogen–progestin HT in the study was not associated with an elevated risk of being diagnosed with breast cancer (HR 1.02; 95% CI 0.77–1.36). However, among previous HT users, the additional use of HT in the WHI study was associated with a risk nearly double that of placebo users (HR 1.96, 95% CI 1.17–3.27).

The reassuring results of this WHI subgroup analysis received little media attention in the United States, probably because the report appeared in a journal that has low readership in this country. WHI and other findings allow us to reassure women who have undergone hysterectomy that use of unopposed estrogen has little, if any, impact on breast cancer risk in menopausal women.^4,5 This new WHI subgroup analysis, along with a recent review of European and North American data,⁶ allows ObGyns to counsel women with an intact uterus that up to 5 years of combination estrogen–progestin hormone therapy also has little, if any, impact on breast cancer risk.

Not much to recommend among nonhormonal therapies

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy or placebo. Ann Intern Med. 2006;145:869–879.

 

Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med. 2006;355:2338–2347.

Grady D, Cohen B, Tice J, et al. Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial. Obstet Gynecol. 2007;109:823–830.

Loprinzi CL, Kugler JW, Barton DL, et al. Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. J Clin Oncol. 2007;25:308–312.

Since publication of the initial WHI findings in 2002,² interest in nonhormonal management of vasomotor symptoms has increased among menopausal women and their clinicians. The botanical black cohosh and “nutraceutical” soy or isoflavone supplements represent the nonprescription remedies most widely used for relief of hot flashes. Unfortunately, accumulating evidence does not support the efficacy of these popular remedies.

In a recent NIH-funded, randomized, double-blind, placebo-controlled clinical trial, Newton and colleagues compared the following interventions:

• black cohosh, 160 mg daily
  
• daily multibotanical supplement that included 200 mg of black cohosh and 9 other ingredients
  
• the multibotanical supplement plus counseling regarding dietary soy
  
• conjugated equine estrogen, 0.625 mg daily (with or without 2.5 mg of medroxyprogesterone acetate)
  
• placebo
  

The study involved 351 perimenopausal or postmenopausal women aged 45 to 55 years with 2 or more vasomotor symptoms daily.

The findings: At 3, 6, and 12 months, women allocated to estrogen (with or without progestin) had statistically significant relief of symptoms. In contrast, women allocated to botanical and/or herbal supplements experienced minimal relief, comparable to the effects of placebo.

The findings of this important study, as well as those of Grady, are discouraging: Black cohosh, botanicals, and encouraging increased soy intake are ineffective in the treatment of vasomotor symptoms.

Evidence on antidepressants is inconclusive

Selective serotonin reuptake inhibitors (SSRIs) and the antidepressant venlafaxine have been assessed for their effects on menopausal vasomotor symptoms, particularly in breast cancer survivors. In a recent review and also a randomized trial, Grady reports that the SSRIs citalopram and sertraline do not appear to be effective, and the findings in regard to the SSRI fluoxetine and venlafaxine have been inconsistent. Compared with placebo, the SSRI paroxetine has eased vasomotor symptoms to a modest degree in breast cancer survivors, but had little effect in women who have not had the disease.

Breast cancer survivors often take tamoxifen or aromatase inhibitors, medications that can induce or aggravate hot flashes. Breast cancer survivors also have a higher prevalence of mood disorders. These factors suggest that the experience and treatment of menopausal symptoms differ between breast cancer survivors and the general population.

Overall, Grady notes, for women with bothersome vasomotor symptoms who have no history of breast cancer, clinical trials of antidepressants have not been encouraging.

Gabapentin is more effective than antidepressants, but with a price

Clinical trials of gabapentin suggest that this anticonvulsant is moderately effective in the nonhormonal treatment of vasomotor symptoms, and the phase III trial by Loprinzi and colleagues finds it to be more effective therapy for vasomotor symptoms than antidepressants.

The drawback? This drug must be taken 2 or 3 times daily, and side effects (including fatigue) limit its attractiveness.

When deciding whom to treat, consider risk as well as BMD

Sanders KM, Nicholson GC, Watts JJ, et al. Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective? Bone. 2006;38:694–700.

The diagnosis of osteoporosis in postmenopausal women is now based on a threshold bone mineral density (BMD) T-score of –2.5. However, BMD is only one of several important risk factors for fracture, and most patients who experience a fracture related to osteoporosis do not have BMD values in the range consistent with osteoporosis, as Sanders and colleagues observe. Therefore, clinicians are faced with this question: Which patients who do not have osteoporosis should be treated to prevent fracture?

The World Health Organization (WHO) task force on fracture risk assessment, under the leadership of Professor John Kanis, has developed an algorithm to estimate fracture probability in individual patients.⁷ This algorithm is based on a sophisticated analysis of almost all of the large epidemiological studies performed worldwide that have assessed relationships between clinical risk factors and fracture risk. By including the 3 major risk factors (age, BMD, and fracture history), as well as weaker risk factors (family history of hip fracture, current smoking, excess alcohol intake, and history of chronic glucocorticoid use), the absolute risk of developing a fracture of the spine, wrist, hip, or shoulder over the next 10 years will be estimated. This information will be the basis for revised guidelines by the National Osteoporosis Foundation (NOF) and other organizations. The new guidelines will include recommendations for treating patients at or above a certain threshold of fracture risk rather than a certain BMD threshold. The new treatment threshold will be based on a combination of cost- and clinical effectiveness.

 

The WHO algorithm and revised NOF guidelines are expected later this year.

New paradigm will shift focus to older women

This revised approach will shift the focus of therapy from young postmenopausal women at low fracture risk toward older women who do not have osteoporosis but do have an increased risk of fracture by virtue of their age and other factors.⁸ This will direct therapy more appropriately to patients who stand to gain the most and in whom therapy has been proven to reduce fracture risk.

Despite concerns, bisphosphonates appear to be safe for the long term

Bisphosphonates are the most extensively studied and widely used treatment for osteoporosis. Alendronate, the first bisphosphonate approved for the treatment of osteoporosis in the United States, has been available for more than 11 years. In general, all 3 of the currently approved bisphosphonates are well tolerated, and studies following patients for 7 to 10 years have not demonstrated significant adverse events or evidence of skeletal harm with long-term use.^9-11 However, because the drugs accumulate in the skeleton, there is a theoretical concern that long-term use will lead to over-suppression of bone turnover.

Small series of patients receiving bisphosphonates have described unusual fractures, evidence of low formation, and poor fracture healing, suggesting skeletal harm in at least some patients.¹² Bone biopsies performed in patients who received alendronate for 10 years or risedronate for 5 years showed evidence of bone remodeling in all the biopsy samples.^11,13 There was no progressive inhibition of bone metabolism in those biopsies compared with biopsies taken from patients who had received shorter-term treatment.

These findings are consistent with bone-turnover marker data suggesting no progressive suppression of bone turnover with continued use.^10,11,13 Biochemical indices of bone resorption are reduced to the lower half of the normal premenopausal range within about 3 months of beginning therapy, and values remain at that new level as long as patients receive the drug.

Risk of osteonecrosis of the jaw is low in general population

Woo SB, Hellstein JW, Kalmar JR. Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753–761.

Bilezikian JP. Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med. 2006;355:2278–2281.

An association between bisphosphonate therapy and nonhealing lesions of the jaw (so-called osteonecrosis of the jaw) has been observed, but primarily affects patients with cancer-related bone diseases who receive high doses of intravenous therapy in addition to chemotherapy. Patients receiving oral doses of bisphosphonates for osteoporosis in Paget’s disease have also had these lesions, as Woo and colleagues point out.

There is much that we do not know about this clinical problem, including its pathogenesis, whether the risk increases with longer-term use, and whether stopping therapy reduces the risk of developing lesions or improves the outcome of lesions already present. We do know that the incidence of exposed bone in the jaw in patients receiving bisphosphonate therapy for osteoporosis is low, estimated to range from 1 in 1,000 to 1 in 100,000 patients, according to Bilezikian.

Risk is very small, compared with potential benefits

It is important to put this risk in perspective. Based on data from the alendronate Fracture Intervention Trials (FIT), we have estimates of hip and spine fracture risk in certain types of patients. For example, for women age 68 with a femoral neck T-score of –2.5 or lower and no vertebral fractures, the likelihood of a clinical fracture over a mean treatment interval of 4.2 years was 19.6%.¹⁴ In women age 71 with a femoral neck T-score of –2.5 and 1 or more vertebral fractures, spine and hip fractures occurred in 15% and 2.2% of subjects, respectively, over 2.9 years.¹⁵ In these populations, alendronate reduced the risk of both hip and spine fracture by about 50%. For women without a vertebral fracture, the absolute reduction in the risk of clinical fracture over 4.2 years was 6.5% (number needed to treat [NNT]=15). In patients with a vertebral fracture, the absolute reduction in the incidence of further spine and hip fracture was 8.6% over 2.9 years (NNT=12).

This information argues strongly that the concern about osteonecrosis of the jaw does not justify withholding bisphosphonate therapy from patients with osteoporosis. The risk of such lesions in otherwise healthy patients with osteoporosis is very low (much lower than the risk of fracture), and most lesions heal spontaneously when treatment is stopped.

Clinical recommendations

For patients using or considering bisphosphonate therapy for osteoporosis, the following measures may be helpful:

• Have regular dental checkups and routine preventive dental care.
  
• If invasive dental procedures are planned, such as tooth extraction or implants, complete the dental work and allow the bone to heal before beginning bisphosphonate therapy.
  
• If a patient on bisphosphonate therapy plans invasive dental work, stop treatment for 3 months before the procedure and do not restart it until the jaw lesion is healed. Although there is no firm evidence that this strategy is helpful, it is certain that discontinuing bisphosphonate for a few months does not harm the skeleton.
  
• If a patient on bisphosphonate develops exposed bone, stop the drug and consult a dentist or oral surgeon experienced in the care of these lesions.
  

 

Some can take a holiday from bisphosphonate therapy

Black DM, Schwartz AV, Ensrud KE, et al, for the FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-Term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–2938.

There is evidence that bone metabolism continues to be affected for some time when alendronate is stopped after 2 to 5 years of treatment, as Black and colleagues found in the Fracture Intervention Trial Long-Term Extension (FLEX) and others have demonstrated.¹⁰ This raises the possibility that patients can take a “drug holiday” after several years of treatment. (This study was also reported in the March issue of OBG Management in “Examining the Evidence,” with a commentary by Steven R. Goldstein, MD.)

The FLEX trial attempted to determine whether it is better to continue or stop alendronate after several years’ exposure. One thousand ninety-nine women who had taken alendronate for 3 to 6 years in the FIT trials were randomly assigned to 5 or 10 mg of alendronate daily or placebo. All subjects received 500 mg of calcium and small vitamin D supplements and were followed for an additional 5 years.

The 2 alendronate groups were pooled for the analyses. Patients who switched to placebo for 5 years had declines in BMD at the total hip (2.4%) and spine (3.7%), compared with those who continued alendronate. However, values at the end of 5 years without therapy remained at or above pretreatment levels. Indices of bone turnover increased modestly when therapy was discontinued, but again the rates of bone turnover remained substantially lower than pretreatment values.

Fractures were collected as an exploratory endpoint. Compared with women who stopped treatment, women who continued alendronate reduced their risk of developing a clinical vertebral fracture by 55% (from 5.3% in the placebo group to 2.4% in the alendronate group). No difference was observed in the incidence of nonvertebral fractures between the 2 groups.

Who should take a holiday, and who can stay put?

Unfortunately, this study does not clearly answer the question. Patients at high risk for spine fracture, including those with a previous fracture, appeared to fare better if they continued treatment. Patients at lower risk did equally well whether they stopped or continued alendronate. This suggests that it would be appropriate to stop treatment in women who are not at high risk, including women who do not have osteoporosis by BMD criteria and have not experienced a fragility fracture since menopause.

The reason for stopping therapy in patients at low risk is because there was no added benefit observed with continued treatment, not because of concerns about risk.

When should the holiday end?

If treatment is stopped, the clinical question of whether and when to restart treatment becomes a challenge. The changes in bone density after treatment is stopped are too small to discern in individual patients. In theory, monitoring one or more bone-turnover markers is a more sensitive way to determine when the effects of bisphosphonates on skeletal remodeling are dissipating, but this approach is backed by very little clinical experience.

Another unresolved issue is whether the response after stopping treatment is the same in patients taking risedronate, ibandronate, or lower doses of alendronate.