Expert Commentary

“Does cancer cause menorrhagia?” I asked on morning rounds recently. The response?

Blank stares. From students and residents.

“Well, what is menorrhagia?” I ask.

A resident regurgitates the textbook definition: “Abnormally heavy and prolonged menstrual bleeding lasting longer than 7 days or with blood loss exceeding 80 mL.”

“OK. What is metrorrhagia?”

Another textbook definition: “Abnormal uterine bleeding at irregular intervals.”

“Do you think cancer causes menorrhagia?”

Silence and sideways glances ensue. After a while, a junior resident says, barely audibly, “I guess so.”

I pounce: “Do you really believe that cancer causes heavy bleeding every 28 days?”

The junior resident has fallen into my trap, which isn’t so difficult to set or spring these days. It seems that contemporary medical training teaches residents how to regurgitate information on demand, but it doesn’t do so well at showing them how to apply their knowledge to common scenarios.

Pay attention to the backstory

In my residents’ world, all abnormal bleeding is reduced to “menometrorrhagia.” In fact, this term is so common it has been affectionately shortened by these residents to “menomet.” When I ask them what causes abnormal uterine bleeding, they recite the entire shopping list from UpToDate, with little or no understanding of how to determine which pathologies are likely, based on the patient’s bleeding pattern.

We go through the entities that might increase bleeding at the “normal” time—a large cavity secondary to multiparity; uterine hypertrophy as a result of myomata (without a submucosal component); adenomyosis; a polyp in synchrony with the phases of the menstrual cycle.

Then we go over things likely to cause bleeding at an abnormal time—anovulation and all its causes; polyps; submucous myomas; hyperplasia; and carcinoma.

Last, we discuss situations where there might be overlap between the two, and the need to get as much reliable information from the patient as possible. After all, a patient can tell you a lot. Let me give you an example.

CASE

A 50-year-old patient taking unopposed estrogen reports that she had no menses for 4 months, followed by an episode of staining. Transvaginal ultrasonography reveals that she has an endometrial echo of 8 mm. The patient says that she had vasomotor symptoms that disappeared just before the staining. She is not obese but is mildly plump, without a personal or family history of diabetes. She is parous, with one normal spontaneous delivery.

We all know that unopposed estrogen in some women is a risk factor for hyperplasia and adenocarcinoma of the endometrium. Simple hyperplasia can be reversed with progestin administration, and the rate of endometrial cancer is reduced when a progestin is added to the regimen of a woman taking exogenous estrogen.

CASE CONTINUED

If I believed that this patient had experienced anovulation for 5 months, I would have chosen to administer progestin. But the history she reports (the vasomotor symptoms and amenorrhea) suggests 4 months of little or no ovarian function, followed by a resurrection of some ovarian function. As a result of the information she provides, and the several follicles visible during sonographic assessment, I am considerably less concerned about the unopposed estrogen than I might otherwise have been, and I am able to fine-tune my clinical management accordingly.

This type of assessment requires careful extraction of relevant information (i.e., a thorough history) and an understanding of the nuances of physiology and pathology. These skills are, I believe, no longer being emphasized in medical education.

That is a problem.

Algorithms can be deceptively simple

Clinical pathways in which decision trees are dichotomous have become the mainstay of clinical practice. Using one such tree, we conclude that an endometrial echo of 4 mm or less in a woman who experiences postmenopausal bleeding carries a cancer risk that is so low, no biopsy is necessary. (Notice now that this is postmenopausal bleeding, not menorrhagia or metrorrhagia!) This conclusion is based on excellent prospective data, but the cutoff of 4 mm is somewhat arbitrary. A higher cutoff allows more cancers to escape detection, and a lower number results in more interventions, such as dilatation and curettage, hysteroscopy, or saline-infusion sonohysterography (and, I hope, not blind suction piston biopsy, unless you are sure the process is indeed global and not focal).

We have ultrasonography machines that produce measurements down to hundredths of a centimeter! Some nights I wake in a cold sweat, worried that a clinician will get an ultrasound report of a 3.94-mm endometrial echo and conclude that the patient is fine, or that a report of 4.03 mm will prompt a clinician to go all the way to hysterectomy, if all else fails, just to get a bit of tissue! Where is the thought process—the art of medicine?

When I give third-year medical students their first didactic lecture of the clerkship, I implore them to ask, “Where does that come from?” “Who is the exception?” “Why?” Our patients expect us to be able to think, to understand why we do what we do, to realize who the outlier is or may be. Otherwise, why get a medical degree?

Patients often consult a physician out of fear of being the numerator. Maybe only 1 in every 305 women 35 years old will deliver a chromosomally abnormal baby. Or maybe only 3 to 7 of every 100 postmenopausal women who experience uterine bleeding will have endometrial cancer. The odds may be in the patient’s favor, but she is afraid that she might turn out to be that 1, or those 3 to 7, in the numerator of the equation.

Enter the EHR

With so much of clinical practice designed to be carried out by algorithm, our students are learning what to do but not why—so who will design newer and better algorithms in the future? The likely source of those new algorithms: the electronic health or medical record.

Computer experts, who need to know little or no pathophysiology, will be able to mine outcomes databases. For instance, they might analyze an institution’s last 3,000 cases of proven ovarian torsion, including dozens of parameters such as white blood cell count, size of the mass on ultrasonography, body temperature, and number of hours the patient experienced pain. Then they will perform a regression analysis on this data and develop a receiver-operating-characteristic (ROC) curve with the best “fit” for a manageable number of parameters. The physician will plug the data into a handheld device and, depending on which side of the curve the patient falls, will take her to the operating room or manage her expectantly.

There will be little need, or even tolerance, for judgment or experience.

When I describe this scenario to a colleague—he’s the safety officer on labor and delivery—he says we need protocols to protect patients because so many clinicians who rely on judgment and experience are doing a mediocre job. I argue that medicine by protocol narrows the bandwidth. It may bring the bottom up, but it also brings the top down. More people will get better care, but the outlier probably won’t.

But why do people go to the doctor? For fear of being the outlier!

Can we fix this problem?

Probably not.

The entire medical field is moving toward enhanced care for the majority at the expense of the few. Patient-safety systems and algorithms are the wave of the future.

A drop in the bucket

I still give that pep talk to third-year medical students as they enter our rotation, in the hope that it will resonate with even one or two of them, who may resolve to develop and cultivate judgment and experience even within the system that is enveloping us.

As for the rest of the students, they’ll squirm uncomfortably in their seats, or get confused on morning rounds—and, maybe, assert that cancer indeed causes menorrhagia.

We want to hear from you! Tell us what you think.

“Does cancer cause menorrhagia?” I asked on morning rounds recently. The response?

Blank stares. From students and residents.

“Well, what is menorrhagia?” I ask.

A resident regurgitates the textbook definition: “Abnormally heavy and prolonged menstrual bleeding lasting longer than 7 days or with blood loss exceeding 80 mL.”

“OK. What is metrorrhagia?”

Another textbook definition: “Abnormal uterine bleeding at irregular intervals.”

“Do you think cancer causes menorrhagia?”

Silence and sideways glances ensue. After a while, a junior resident says, barely audibly, “I guess so.”

I pounce: “Do you really believe that cancer causes heavy bleeding every 28 days?”

The junior resident has fallen into my trap, which isn’t so difficult to set or spring these days. It seems that contemporary medical training teaches residents how to regurgitate information on demand, but it doesn’t do so well at showing them how to apply their knowledge to common scenarios.

Pay attention to the backstory

In my residents’ world, all abnormal bleeding is reduced to “menometrorrhagia.” In fact, this term is so common it has been affectionately shortened by these residents to “menomet.” When I ask them what causes abnormal uterine bleeding, they recite the entire shopping list from UpToDate, with little or no understanding of how to determine which pathologies are likely, based on the patient’s bleeding pattern.

We go through the entities that might increase bleeding at the “normal” time—a large cavity secondary to multiparity; uterine hypertrophy as a result of myomata (without a submucosal component); adenomyosis; a polyp in synchrony with the phases of the menstrual cycle.

Then we go over things likely to cause bleeding at an abnormal time—anovulation and all its causes; polyps; submucous myomas; hyperplasia; and carcinoma.

Last, we discuss situations where there might be overlap between the two, and the need to get as much reliable information from the patient as possible. After all, a patient can tell you a lot. Let me give you an example.

CASE

A 50-year-old patient taking unopposed estrogen reports that she had no menses for 4 months, followed by an episode of staining. Transvaginal ultrasonography reveals that she has an endometrial echo of 8 mm. The patient says that she had vasomotor symptoms that disappeared just before the staining. She is not obese but is mildly plump, without a personal or family history of diabetes. She is parous, with one normal spontaneous delivery.

We all know that unopposed estrogen in some women is a risk factor for hyperplasia and adenocarcinoma of the endometrium. Simple hyperplasia can be reversed with progestin administration, and the rate of endometrial cancer is reduced when a progestin is added to the regimen of a woman taking exogenous estrogen.

CASE CONTINUED

If I believed that this patient had experienced anovulation for 5 months, I would have chosen to administer progestin. But the history she reports (the vasomotor symptoms and amenorrhea) suggests 4 months of little or no ovarian function, followed by a resurrection of some ovarian function. As a result of the information she provides, and the several follicles visible during sonographic assessment, I am considerably less concerned about the unopposed estrogen than I might otherwise have been, and I am able to fine-tune my clinical management accordingly.

This type of assessment requires careful extraction of relevant information (i.e., a thorough history) and an understanding of the nuances of physiology and pathology. These skills are, I believe, no longer being emphasized in medical education.

That is a problem.

Algorithms can be deceptively simple

Clinical pathways in which decision trees are dichotomous have become the mainstay of clinical practice. Using one such tree, we conclude that an endometrial echo of 4 mm or less in a woman who experiences postmenopausal bleeding carries a cancer risk that is so low, no biopsy is necessary. (Notice now that this is postmenopausal bleeding, not menorrhagia or metrorrhagia!) This conclusion is based on excellent prospective data, but the cutoff of 4 mm is somewhat arbitrary. A higher cutoff allows more cancers to escape detection, and a lower number results in more interventions, such as dilatation and curettage, hysteroscopy, or saline-infusion sonohysterography (and, I hope, not blind suction piston biopsy, unless you are sure the process is indeed global and not focal).

We have ultrasonography machines that produce measurements down to hundredths of a centimeter! Some nights I wake in a cold sweat, worried that a clinician will get an ultrasound report of a 3.94-mm endometrial echo and conclude that the patient is fine, or that a report of 4.03 mm will prompt a clinician to go all the way to hysterectomy, if all else fails, just to get a bit of tissue! Where is the thought process—the art of medicine?

When I give third-year medical students their first didactic lecture of the clerkship, I implore them to ask, “Where does that come from?” “Who is the exception?” “Why?” Our patients expect us to be able to think, to understand why we do what we do, to realize who the outlier is or may be. Otherwise, why get a medical degree?

Patients often consult a physician out of fear of being the numerator. Maybe only 1 in every 305 women 35 years old will deliver a chromosomally abnormal baby. Or maybe only 3 to 7 of every 100 postmenopausal women who experience uterine bleeding will have endometrial cancer. The odds may be in the patient’s favor, but she is afraid that she might turn out to be that 1, or those 3 to 7, in the numerator of the equation.

Enter the EHR

With so much of clinical practice designed to be carried out by algorithm, our students are learning what to do but not why—so who will design newer and better algorithms in the future? The likely source of those new algorithms: the electronic health or medical record.

Computer experts, who need to know little or no pathophysiology, will be able to mine outcomes databases. For instance, they might analyze an institution’s last 3,000 cases of proven ovarian torsion, including dozens of parameters such as white blood cell count, size of the mass on ultrasonography, body temperature, and number of hours the patient experienced pain. Then they will perform a regression analysis on this data and develop a receiver-operating-characteristic (ROC) curve with the best “fit” for a manageable number of parameters. The physician will plug the data into a handheld device and, depending on which side of the curve the patient falls, will take her to the operating room or manage her expectantly.

There will be little need, or even tolerance, for judgment or experience.

When I describe this scenario to a colleague—he’s the safety officer on labor and delivery—he says we need protocols to protect patients because so many clinicians who rely on judgment and experience are doing a mediocre job. I argue that medicine by protocol narrows the bandwidth. It may bring the bottom up, but it also brings the top down. More people will get better care, but the outlier probably won’t.

But why do people go to the doctor? For fear of being the outlier!

Can we fix this problem?

Probably not.

The entire medical field is moving toward enhanced care for the majority at the expense of the few. Patient-safety systems and algorithms are the wave of the future.

A drop in the bucket

I still give that pep talk to third-year medical students as they enter our rotation, in the hope that it will resonate with even one or two of them, who may resolve to develop and cultivate judgment and experience even within the system that is enveloping us.

As for the rest of the students, they’ll squirm uncomfortably in their seats, or get confused on morning rounds—and, maybe, assert that cancer indeed causes menorrhagia.

We want to hear from you! Tell us what you think.

“Does cancer cause menorrhagia?” I asked on morning rounds recently. The response?

Blank stares. From students and residents.

“Well, what is menorrhagia?” I ask.

A resident regurgitates the textbook definition: “Abnormally heavy and prolonged menstrual bleeding lasting longer than 7 days or with blood loss exceeding 80 mL.”

“OK. What is metrorrhagia?”

Another textbook definition: “Abnormal uterine bleeding at irregular intervals.”

“Do you think cancer causes menorrhagia?”

Silence and sideways glances ensue. After a while, a junior resident says, barely audibly, “I guess so.”

I pounce: “Do you really believe that cancer causes heavy bleeding every 28 days?”

The junior resident has fallen into my trap, which isn’t so difficult to set or spring these days. It seems that contemporary medical training teaches residents how to regurgitate information on demand, but it doesn’t do so well at showing them how to apply their knowledge to common scenarios.

Pay attention to the backstory

In my residents’ world, all abnormal bleeding is reduced to “menometrorrhagia.” In fact, this term is so common it has been affectionately shortened by these residents to “menomet.” When I ask them what causes abnormal uterine bleeding, they recite the entire shopping list from UpToDate, with little or no understanding of how to determine which pathologies are likely, based on the patient’s bleeding pattern.

We go through the entities that might increase bleeding at the “normal” time—a large cavity secondary to multiparity; uterine hypertrophy as a result of myomata (without a submucosal component); adenomyosis; a polyp in synchrony with the phases of the menstrual cycle.

Then we go over things likely to cause bleeding at an abnormal time—anovulation and all its causes; polyps; submucous myomas; hyperplasia; and carcinoma.

Last, we discuss situations where there might be overlap between the two, and the need to get as much reliable information from the patient as possible. After all, a patient can tell you a lot. Let me give you an example.

CASE

A 50-year-old patient taking unopposed estrogen reports that she had no menses for 4 months, followed by an episode of staining. Transvaginal ultrasonography reveals that she has an endometrial echo of 8 mm. The patient says that she had vasomotor symptoms that disappeared just before the staining. She is not obese but is mildly plump, without a personal or family history of diabetes. She is parous, with one normal spontaneous delivery.

We all know that unopposed estrogen in some women is a risk factor for hyperplasia and adenocarcinoma of the endometrium. Simple hyperplasia can be reversed with progestin administration, and the rate of endometrial cancer is reduced when a progestin is added to the regimen of a woman taking exogenous estrogen.

CASE CONTINUED

If I believed that this patient had experienced anovulation for 5 months, I would have chosen to administer progestin. But the history she reports (the vasomotor symptoms and amenorrhea) suggests 4 months of little or no ovarian function, followed by a resurrection of some ovarian function. As a result of the information she provides, and the several follicles visible during sonographic assessment, I am considerably less concerned about the unopposed estrogen than I might otherwise have been, and I am able to fine-tune my clinical management accordingly.

This type of assessment requires careful extraction of relevant information (i.e., a thorough history) and an understanding of the nuances of physiology and pathology. These skills are, I believe, no longer being emphasized in medical education.

That is a problem.

Algorithms can be deceptively simple

Clinical pathways in which decision trees are dichotomous have become the mainstay of clinical practice. Using one such tree, we conclude that an endometrial echo of 4 mm or less in a woman who experiences postmenopausal bleeding carries a cancer risk that is so low, no biopsy is necessary. (Notice now that this is postmenopausal bleeding, not menorrhagia or metrorrhagia!) This conclusion is based on excellent prospective data, but the cutoff of 4 mm is somewhat arbitrary. A higher cutoff allows more cancers to escape detection, and a lower number results in more interventions, such as dilatation and curettage, hysteroscopy, or saline-infusion sonohysterography (and, I hope, not blind suction piston biopsy, unless you are sure the process is indeed global and not focal).

We have ultrasonography machines that produce measurements down to hundredths of a centimeter! Some nights I wake in a cold sweat, worried that a clinician will get an ultrasound report of a 3.94-mm endometrial echo and conclude that the patient is fine, or that a report of 4.03 mm will prompt a clinician to go all the way to hysterectomy, if all else fails, just to get a bit of tissue! Where is the thought process—the art of medicine?

When I give third-year medical students their first didactic lecture of the clerkship, I implore them to ask, “Where does that come from?” “Who is the exception?” “Why?” Our patients expect us to be able to think, to understand why we do what we do, to realize who the outlier is or may be. Otherwise, why get a medical degree?

Patients often consult a physician out of fear of being the numerator. Maybe only 1 in every 305 women 35 years old will deliver a chromosomally abnormal baby. Or maybe only 3 to 7 of every 100 postmenopausal women who experience uterine bleeding will have endometrial cancer. The odds may be in the patient’s favor, but she is afraid that she might turn out to be that 1, or those 3 to 7, in the numerator of the equation.

Enter the EHR

With so much of clinical practice designed to be carried out by algorithm, our students are learning what to do but not why—so who will design newer and better algorithms in the future? The likely source of those new algorithms: the electronic health or medical record.

Computer experts, who need to know little or no pathophysiology, will be able to mine outcomes databases. For instance, they might analyze an institution’s last 3,000 cases of proven ovarian torsion, including dozens of parameters such as white blood cell count, size of the mass on ultrasonography, body temperature, and number of hours the patient experienced pain. Then they will perform a regression analysis on this data and develop a receiver-operating-characteristic (ROC) curve with the best “fit” for a manageable number of parameters. The physician will plug the data into a handheld device and, depending on which side of the curve the patient falls, will take her to the operating room or manage her expectantly.

There will be little need, or even tolerance, for judgment or experience.

When I describe this scenario to a colleague—he’s the safety officer on labor and delivery—he says we need protocols to protect patients because so many clinicians who rely on judgment and experience are doing a mediocre job. I argue that medicine by protocol narrows the bandwidth. It may bring the bottom up, but it also brings the top down. More people will get better care, but the outlier probably won’t.

But why do people go to the doctor? For fear of being the outlier!

Can we fix this problem?

Probably not.

The entire medical field is moving toward enhanced care for the majority at the expense of the few. Patient-safety systems and algorithms are the wave of the future.

A drop in the bucket

I still give that pep talk to third-year medical students as they enter our rotation, in the hope that it will resonate with even one or two of them, who may resolve to develop and cultivate judgment and experience even within the system that is enveloping us.

As for the rest of the students, they’ll squirm uncomfortably in their seats, or get confused on morning rounds—and, maybe, assert that cancer indeed causes menorrhagia.

We want to hear from you! Tell us what you think.

Over the past 12 years, several studies have demonstrated a higher rate of cesarean delivery among nulliparous women with an unfavorable cervix who undergo induction of labor. However, these studies typically have compared induction of labor with spontaneous labor rather than with its appropriate counterpart—expectant management. In addition, in some cases, the increased rate of cesarean delivery among women who undergo induction of labor may be related to a comorbidity rather than elective induction.

In this retrospective cohort study, Osmundson and colleagues compared elective induction of labor at 39-0/7 to 40-5/7 weeks’ gestation with expectant management beyond 39 weeks. All women in the study were nulliparous, free of comorbidity, and carrying a singleton gestation; they also had an unfavorable cervix, as demonstrated by a modified Bishop score of less than 5.

(According to ACOG, the goal of induction of labor is to achieve vaginal delivery by stimulating uterine contractions before the onset of spontaneous labor.¹ Induction is elective when it is not associated with obstetric or medical complications.)

Although the rate of early term (37-0/7 to 38-6/7 weeks) induction increased significantly between 1991 and 2006, especially among non-Hispanic white women,² there is now strong evidence that early term delivery is associated with significantly higher neonatal, postneonatal, and infant mortality,³ compared with late term delivery (39 to 41 weeks). Therefore, elective induction should not be performed before 39 weeks’ gestation—and it wasn’t in the study by Osmundson and colleagues.

Strengths and weaknesses of the study

This study has a number of strengths:

• the a priori power calculation
• a review of each chart to ensure that no comorbidity was present
• availability of the Bishop score for each case
• documentation of the duration of labor and the time of delivery (i.e., whether it occurred during daytime hours or at night).

However, some weaknesses are also present:

• the retrospective design, with its inherent limitations
• lack of explanation as to why only 102 women met inclusion criteria when the study period was 2 years at a tertiary center (a flow diagram of total deliveries and the reasons for exclusion would have been useful)
• the fact that all inductions were performed using a Foley catheter balloon and oxytocin, thereby limiting appropriate assessment of resource utilization for other techniques, such as prostaglandin administration
• the small sample size, which prevents determination of whether expectant management is linked to uncommon complications such as macrosomia, shoulder dystocia, or meconium-aspiration syndrome.

We want to hear from you!  Tell us what you think.

Over the past 12 years, several studies have demonstrated a higher rate of cesarean delivery among nulliparous women with an unfavorable cervix who undergo induction of labor. However, these studies typically have compared induction of labor with spontaneous labor rather than with its appropriate counterpart—expectant management. In addition, in some cases, the increased rate of cesarean delivery among women who undergo induction of labor may be related to a comorbidity rather than elective induction.

In this retrospective cohort study, Osmundson and colleagues compared elective induction of labor at 39-0/7 to 40-5/7 weeks’ gestation with expectant management beyond 39 weeks. All women in the study were nulliparous, free of comorbidity, and carrying a singleton gestation; they also had an unfavorable cervix, as demonstrated by a modified Bishop score of less than 5.

(According to ACOG, the goal of induction of labor is to achieve vaginal delivery by stimulating uterine contractions before the onset of spontaneous labor.¹ Induction is elective when it is not associated with obstetric or medical complications.)

Although the rate of early term (37-0/7 to 38-6/7 weeks) induction increased significantly between 1991 and 2006, especially among non-Hispanic white women,² there is now strong evidence that early term delivery is associated with significantly higher neonatal, postneonatal, and infant mortality,³ compared with late term delivery (39 to 41 weeks). Therefore, elective induction should not be performed before 39 weeks’ gestation—and it wasn’t in the study by Osmundson and colleagues.

Strengths and weaknesses of the study

This study has a number of strengths:

• the a priori power calculation
• a review of each chart to ensure that no comorbidity was present
• availability of the Bishop score for each case
• documentation of the duration of labor and the time of delivery (i.e., whether it occurred during daytime hours or at night).

However, some weaknesses are also present:

• the retrospective design, with its inherent limitations
• lack of explanation as to why only 102 women met inclusion criteria when the study period was 2 years at a tertiary center (a flow diagram of total deliveries and the reasons for exclusion would have been useful)
• the fact that all inductions were performed using a Foley catheter balloon and oxytocin, thereby limiting appropriate assessment of resource utilization for other techniques, such as prostaglandin administration
• the small sample size, which prevents determination of whether expectant management is linked to uncommon complications such as macrosomia, shoulder dystocia, or meconium-aspiration syndrome.

We want to hear from you!  Tell us what you think.

Over the past 12 years, several studies have demonstrated a higher rate of cesarean delivery among nulliparous women with an unfavorable cervix who undergo induction of labor. However, these studies typically have compared induction of labor with spontaneous labor rather than with its appropriate counterpart—expectant management. In addition, in some cases, the increased rate of cesarean delivery among women who undergo induction of labor may be related to a comorbidity rather than elective induction.

In this retrospective cohort study, Osmundson and colleagues compared elective induction of labor at 39-0/7 to 40-5/7 weeks’ gestation with expectant management beyond 39 weeks. All women in the study were nulliparous, free of comorbidity, and carrying a singleton gestation; they also had an unfavorable cervix, as demonstrated by a modified Bishop score of less than 5.

(According to ACOG, the goal of induction of labor is to achieve vaginal delivery by stimulating uterine contractions before the onset of spontaneous labor.¹ Induction is elective when it is not associated with obstetric or medical complications.)

Although the rate of early term (37-0/7 to 38-6/7 weeks) induction increased significantly between 1991 and 2006, especially among non-Hispanic white women,² there is now strong evidence that early term delivery is associated with significantly higher neonatal, postneonatal, and infant mortality,³ compared with late term delivery (39 to 41 weeks). Therefore, elective induction should not be performed before 39 weeks’ gestation—and it wasn’t in the study by Osmundson and colleagues.

Strengths and weaknesses of the study

This study has a number of strengths:

• the a priori power calculation
• a review of each chart to ensure that no comorbidity was present
• availability of the Bishop score for each case
• documentation of the duration of labor and the time of delivery (i.e., whether it occurred during daytime hours or at night).

However, some weaknesses are also present:

• the retrospective design, with its inherent limitations
• lack of explanation as to why only 102 women met inclusion criteria when the study period was 2 years at a tertiary center (a flow diagram of total deliveries and the reasons for exclusion would have been useful)
• the fact that all inductions were performed using a Foley catheter balloon and oxytocin, thereby limiting appropriate assessment of resource utilization for other techniques, such as prostaglandin administration
• the small sample size, which prevents determination of whether expectant management is linked to uncommon complications such as macrosomia, shoulder dystocia, or meconium-aspiration syndrome.

We want to hear from you!  Tell us what you think.

The risks and benefits of bilateral oophorectomy at the time of hysterectomy for benign disease are the subject of ongoing discussion. (See, for example, an earlier article on the subject, “Remove the ovaries at hysterectomy? Here’s the lowdown on risks and benefits,” in the February 2010 issue of OBG MANAGEMENT.) There is uniform agreement that women who are at high risk of ovarian and breast cancer because of a significant family history or known BRCA mutation should strongly consider bilateral oophorectomy after completing childbearing. For women at average risk of ovarian or breast cancer, individualization of elective oophorectomy is recommended—but how can you do this for the patient sitting in your office?

Vitonis and colleagues analyzed multiple risk factors associated with ovarian cancer and developed a scoring system to help provide guidance for average-risk women and their physicians who need to make this important decision. This is the kind of mental modeling clinicians do daily in an abstract way, but this scoring system helps frame the associated risks and gives a mathematical value to inform the decision.

Risk factors in the scoring system are:

• Jewish ethnicity
• less than 1 year of oral contraceptive use
• nulliparity
• no breastfeeding
• no tubal ligation
• painful periods or endometriosis
• polycystic ovary syndrome or obesity
• talc use.

Subjects who had none or one of these risk factors were calculated to have a 1.2% lifetime risk of ovarian cancer (98.8% will not get ovarian cancer); the risk was 6.6% with a score of 5 or higher (93.4% will not get ovarian cancer).

Risk equation wasn’t fully explored

Noted by the authors, but not studied here, is the other side of this equation: namely, a woman’s risk factors for medical conditions that might be exacerbated by oophorectomy—including bone fracture, neurologic conditions, and, most important, cardiovascular disease. These conditions appear to be more common after oophorectomy and are considerably more prevalent causes of morbidity and mortality among women than is ovarian cancer.

Case-control design is a weakness

Vitonis and colleagues chose exclusion criteria wisely, but the case-control design of the study is a weakness because of inherent recall and selection biases. The authors should be commended for stating calculated risks as absolute risk rather than relative risk, which is usually misunderstood by the media and patients alike.

As the authors point out, their prototype needs to be validated in other populations and data sets, but it begins to frame the decision regarding oophorectomy for women undergoing hysterectomy for benign disease. However, we won’t have the complete picture until the other side of the equation is similarly analyzed—and that side concerns an individual woman’s risks for cardiovascular disease, neurologic conditions, and bone fracture.

We want to hear from you!  Tell us what you think.

The risks and benefits of bilateral oophorectomy at the time of hysterectomy for benign disease are the subject of ongoing discussion. (See, for example, an earlier article on the subject, “Remove the ovaries at hysterectomy? Here’s the lowdown on risks and benefits,” in the February 2010 issue of OBG MANAGEMENT.) There is uniform agreement that women who are at high risk of ovarian and breast cancer because of a significant family history or known BRCA mutation should strongly consider bilateral oophorectomy after completing childbearing. For women at average risk of ovarian or breast cancer, individualization of elective oophorectomy is recommended—but how can you do this for the patient sitting in your office?

Vitonis and colleagues analyzed multiple risk factors associated with ovarian cancer and developed a scoring system to help provide guidance for average-risk women and their physicians who need to make this important decision. This is the kind of mental modeling clinicians do daily in an abstract way, but this scoring system helps frame the associated risks and gives a mathematical value to inform the decision.

Risk factors in the scoring system are:

• Jewish ethnicity
• less than 1 year of oral contraceptive use
• nulliparity
• no breastfeeding
• no tubal ligation
• painful periods or endometriosis
• polycystic ovary syndrome or obesity
• talc use.

Subjects who had none or one of these risk factors were calculated to have a 1.2% lifetime risk of ovarian cancer (98.8% will not get ovarian cancer); the risk was 6.6% with a score of 5 or higher (93.4% will not get ovarian cancer).

Risk equation wasn’t fully explored

Noted by the authors, but not studied here, is the other side of this equation: namely, a woman’s risk factors for medical conditions that might be exacerbated by oophorectomy—including bone fracture, neurologic conditions, and, most important, cardiovascular disease. These conditions appear to be more common after oophorectomy and are considerably more prevalent causes of morbidity and mortality among women than is ovarian cancer.

Case-control design is a weakness

Vitonis and colleagues chose exclusion criteria wisely, but the case-control design of the study is a weakness because of inherent recall and selection biases. The authors should be commended for stating calculated risks as absolute risk rather than relative risk, which is usually misunderstood by the media and patients alike.

As the authors point out, their prototype needs to be validated in other populations and data sets, but it begins to frame the decision regarding oophorectomy for women undergoing hysterectomy for benign disease. However, we won’t have the complete picture until the other side of the equation is similarly analyzed—and that side concerns an individual woman’s risks for cardiovascular disease, neurologic conditions, and bone fracture.

We want to hear from you!  Tell us what you think.

The risks and benefits of bilateral oophorectomy at the time of hysterectomy for benign disease are the subject of ongoing discussion. (See, for example, an earlier article on the subject, “Remove the ovaries at hysterectomy? Here’s the lowdown on risks and benefits,” in the February 2010 issue of OBG MANAGEMENT.) There is uniform agreement that women who are at high risk of ovarian and breast cancer because of a significant family history or known BRCA mutation should strongly consider bilateral oophorectomy after completing childbearing. For women at average risk of ovarian or breast cancer, individualization of elective oophorectomy is recommended—but how can you do this for the patient sitting in your office?

Vitonis and colleagues analyzed multiple risk factors associated with ovarian cancer and developed a scoring system to help provide guidance for average-risk women and their physicians who need to make this important decision. This is the kind of mental modeling clinicians do daily in an abstract way, but this scoring system helps frame the associated risks and gives a mathematical value to inform the decision.

Risk factors in the scoring system are:

• Jewish ethnicity
• less than 1 year of oral contraceptive use
• nulliparity
• no breastfeeding
• no tubal ligation
• painful periods or endometriosis
• polycystic ovary syndrome or obesity
• talc use.

Subjects who had none or one of these risk factors were calculated to have a 1.2% lifetime risk of ovarian cancer (98.8% will not get ovarian cancer); the risk was 6.6% with a score of 5 or higher (93.4% will not get ovarian cancer).

Risk equation wasn’t fully explored

Noted by the authors, but not studied here, is the other side of this equation: namely, a woman’s risk factors for medical conditions that might be exacerbated by oophorectomy—including bone fracture, neurologic conditions, and, most important, cardiovascular disease. These conditions appear to be more common after oophorectomy and are considerably more prevalent causes of morbidity and mortality among women than is ovarian cancer.

Case-control design is a weakness

Vitonis and colleagues chose exclusion criteria wisely, but the case-control design of the study is a weakness because of inherent recall and selection biases. The authors should be commended for stating calculated risks as absolute risk rather than relative risk, which is usually misunderstood by the media and patients alike.

As the authors point out, their prototype needs to be validated in other populations and data sets, but it begins to frame the decision regarding oophorectomy for women undergoing hysterectomy for benign disease. However, we won’t have the complete picture until the other side of the equation is similarly analyzed—and that side concerns an individual woman’s risks for cardiovascular disease, neurologic conditions, and bone fracture.

We want to hear from you!  Tell us what you think.

This meta-analysis by Berghella and colleagues adds to the debate about the role of cervical-length measurement in determining candidacy for cerclage in an effort to reduce the rate of preterm birth. The authors are clearly passionate about the prevention of preterm birth—as we all are—but the conclusions they reach must be questioned.

First, it is misleading to report these results as Level-1 evidence. A meta-analysis can never, strictly speaking, be Level-1 evidence, although it may be based on an analysis of Level-1 evidence.

Sound confusing? Let’s take, as an example, the study of the role of calcium supplementation in the prevention of preeclampsia. In JAMA, in 1996, a meta-analysis fairly conclusively demonstrated that calcium supplementation was effective in preventing preeclampsia (odds ratio, 0.38; 95% CI, 0.22–0.65).¹ Yet, a subsequent large randomized trial failed to confirm the findings of this meta-analysis.²

The lesson here? Level-1 evidence consists of appropriately powered, large-scale, randomized clinical trials. To date, we lack such trials with respect to cervical-length measurement and indications for cerclage. In fact, two of the authors of this paper are “on the record” as saying this very thing.

A 2009 paper by Owen and coworkers demonstrated only that cerclage for a cervical length below 25 mm reduced previable birth and perinatal death, but did not prevent births before 35 weeks unless the cervical length was less than 15 mm—and that bit of information came from a secondary analysis of the data.³ In a follow-up study, Owen and coworkers concluded that cervical length did not predict preterm birth before 37, 35, or 28 weeks, whether or not cervical length was viewed as a continuum or was stratified.⁴ And in an earlier meta-analysis reported by Berghella and associates in 2005, the authors conclude that “…cerclage may reduce preterm birth, and a well-powered trial should be carried out on this group of patients.”⁵

We want to hear from you!  Tell us what you think.

This meta-analysis by Berghella and colleagues adds to the debate about the role of cervical-length measurement in determining candidacy for cerclage in an effort to reduce the rate of preterm birth. The authors are clearly passionate about the prevention of preterm birth—as we all are—but the conclusions they reach must be questioned.

First, it is misleading to report these results as Level-1 evidence. A meta-analysis can never, strictly speaking, be Level-1 evidence, although it may be based on an analysis of Level-1 evidence.

Sound confusing? Let’s take, as an example, the study of the role of calcium supplementation in the prevention of preeclampsia. In JAMA, in 1996, a meta-analysis fairly conclusively demonstrated that calcium supplementation was effective in preventing preeclampsia (odds ratio, 0.38; 95% CI, 0.22–0.65).¹ Yet, a subsequent large randomized trial failed to confirm the findings of this meta-analysis.²

The lesson here? Level-1 evidence consists of appropriately powered, large-scale, randomized clinical trials. To date, we lack such trials with respect to cervical-length measurement and indications for cerclage. In fact, two of the authors of this paper are “on the record” as saying this very thing.

A 2009 paper by Owen and coworkers demonstrated only that cerclage for a cervical length below 25 mm reduced previable birth and perinatal death, but did not prevent births before 35 weeks unless the cervical length was less than 15 mm—and that bit of information came from a secondary analysis of the data.³ In a follow-up study, Owen and coworkers concluded that cervical length did not predict preterm birth before 37, 35, or 28 weeks, whether or not cervical length was viewed as a continuum or was stratified.⁴ And in an earlier meta-analysis reported by Berghella and associates in 2005, the authors conclude that “…cerclage may reduce preterm birth, and a well-powered trial should be carried out on this group of patients.”⁵

We want to hear from you!  Tell us what you think.

This meta-analysis by Berghella and colleagues adds to the debate about the role of cervical-length measurement in determining candidacy for cerclage in an effort to reduce the rate of preterm birth. The authors are clearly passionate about the prevention of preterm birth—as we all are—but the conclusions they reach must be questioned.

First, it is misleading to report these results as Level-1 evidence. A meta-analysis can never, strictly speaking, be Level-1 evidence, although it may be based on an analysis of Level-1 evidence.

Sound confusing? Let’s take, as an example, the study of the role of calcium supplementation in the prevention of preeclampsia. In JAMA, in 1996, a meta-analysis fairly conclusively demonstrated that calcium supplementation was effective in preventing preeclampsia (odds ratio, 0.38; 95% CI, 0.22–0.65).¹ Yet, a subsequent large randomized trial failed to confirm the findings of this meta-analysis.²

The lesson here? Level-1 evidence consists of appropriately powered, large-scale, randomized clinical trials. To date, we lack such trials with respect to cervical-length measurement and indications for cerclage. In fact, two of the authors of this paper are “on the record” as saying this very thing.

A 2009 paper by Owen and coworkers demonstrated only that cerclage for a cervical length below 25 mm reduced previable birth and perinatal death, but did not prevent births before 35 weeks unless the cervical length was less than 15 mm—and that bit of information came from a secondary analysis of the data.³ In a follow-up study, Owen and coworkers concluded that cervical length did not predict preterm birth before 37, 35, or 28 weeks, whether or not cervical length was viewed as a continuum or was stratified.⁴ And in an earlier meta-analysis reported by Berghella and associates in 2005, the authors conclude that “…cerclage may reduce preterm birth, and a well-powered trial should be carried out on this group of patients.”⁵

We want to hear from you!  Tell us what you think.

Women who undergo treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 remain at higher risk of recurrent CIN 2 or 3 or invasive cancer than the population at large. A recent review of the literature suggests that the risk of developing invasive cancer remains 10 times higher for these women than for the general US population for at least 20 years after treatment.^1,2 The risk of CIN, on the other hand, declines rapidly over the first 2 years following treatment but remains above the population baseline for 6 to 10 years.^1,3

In its 2006 consensus guidelines, the American Society for Colposcopy and Cervical Pathology (ASCCP) recommends initial follow-up, after treatment for CIN 2 or 3, with HPV DNA testing at 6 to 12 months or with cytology alone or in combination with colposcopy at 6-month intervals until two consecutive negative results are obtained. After the initial follow-up, they recommend “routine” screening for the next 20 years. For many women, routine screening is cytology with or without HPV DNA testing every 3 years.⁴ ACOG, however, recommends annual screening after the initial post-treatment surveillance.⁴

Details of the trial

In this study, Melnikow and colleagues offer a cost-benefit analysis of post-treatment surveillance strategies.⁵ They evaluated 12 possible regimens—including yearly versus triennial screening—in a hypothetical cohort of 500,000 women who were treated for CIN 2 or 3 and followed from 30 to 85 years of age. They also compared women with the lowest and highest risk of recurrence, based on the initial diagnosis and treatment modality.³

They concluded that a conventional Pap test at 6 and 12 months after treatment, followed by annual conventional cytology, provides the most effective use of resources to reduce subsequent cervical cancers and cancer deaths. In patients who had the highest risk of recurrence, adding colposcopy at the initial post-treatment visit increased life expectancy and was highly valued by patients.

Not much offered here to inform clinical practice

This study offers useful information for those who determine health policy. For the practicing clinician, however, the study’s limitations pose significant obstacles to its usefulness in practice. For example, the authors excluded women who were initially treated with loop electrosurgical excision procedure (LEEP) who had positive margins. This eliminates a significant proportion of the post-treatment population. They also excluded surveillance strategies that included liquid-based cytology. They explained this exclusion by noting that liquid-based cytology has been shown to have similar sensitivity and lower specificity than conventional cytology but costs more. However, most clinicians in the United States prefer liquid-based cytology to the conventional Pap smear. Therefore, it is unlikely that most American providers will adopt the strategies that the authors found most cost-effective—i.e., those based on annual screening with the conventional Pap test.

The findings of this study could influence policy makers and insurers to encourage more widespread use of the conventional Pap test in post-treatment surveillance.

We want to hear from you!  Tell us what you think.

Women who undergo treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 remain at higher risk of recurrent CIN 2 or 3 or invasive cancer than the population at large. A recent review of the literature suggests that the risk of developing invasive cancer remains 10 times higher for these women than for the general US population for at least 20 years after treatment.^1,2 The risk of CIN, on the other hand, declines rapidly over the first 2 years following treatment but remains above the population baseline for 6 to 10 years.^1,3

In its 2006 consensus guidelines, the American Society for Colposcopy and Cervical Pathology (ASCCP) recommends initial follow-up, after treatment for CIN 2 or 3, with HPV DNA testing at 6 to 12 months or with cytology alone or in combination with colposcopy at 6-month intervals until two consecutive negative results are obtained. After the initial follow-up, they recommend “routine” screening for the next 20 years. For many women, routine screening is cytology with or without HPV DNA testing every 3 years.⁴ ACOG, however, recommends annual screening after the initial post-treatment surveillance.⁴

Details of the trial

In this study, Melnikow and colleagues offer a cost-benefit analysis of post-treatment surveillance strategies.⁵ They evaluated 12 possible regimens—including yearly versus triennial screening—in a hypothetical cohort of 500,000 women who were treated for CIN 2 or 3 and followed from 30 to 85 years of age. They also compared women with the lowest and highest risk of recurrence, based on the initial diagnosis and treatment modality.³

They concluded that a conventional Pap test at 6 and 12 months after treatment, followed by annual conventional cytology, provides the most effective use of resources to reduce subsequent cervical cancers and cancer deaths. In patients who had the highest risk of recurrence, adding colposcopy at the initial post-treatment visit increased life expectancy and was highly valued by patients.

Not much offered here to inform clinical practice

This study offers useful information for those who determine health policy. For the practicing clinician, however, the study’s limitations pose significant obstacles to its usefulness in practice. For example, the authors excluded women who were initially treated with loop electrosurgical excision procedure (LEEP) who had positive margins. This eliminates a significant proportion of the post-treatment population. They also excluded surveillance strategies that included liquid-based cytology. They explained this exclusion by noting that liquid-based cytology has been shown to have similar sensitivity and lower specificity than conventional cytology but costs more. However, most clinicians in the United States prefer liquid-based cytology to the conventional Pap smear. Therefore, it is unlikely that most American providers will adopt the strategies that the authors found most cost-effective—i.e., those based on annual screening with the conventional Pap test.

The findings of this study could influence policy makers and insurers to encourage more widespread use of the conventional Pap test in post-treatment surveillance.

We want to hear from you!  Tell us what you think.

Women who undergo treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 remain at higher risk of recurrent CIN 2 or 3 or invasive cancer than the population at large. A recent review of the literature suggests that the risk of developing invasive cancer remains 10 times higher for these women than for the general US population for at least 20 years after treatment.^1,2 The risk of CIN, on the other hand, declines rapidly over the first 2 years following treatment but remains above the population baseline for 6 to 10 years.^1,3

In its 2006 consensus guidelines, the American Society for Colposcopy and Cervical Pathology (ASCCP) recommends initial follow-up, after treatment for CIN 2 or 3, with HPV DNA testing at 6 to 12 months or with cytology alone or in combination with colposcopy at 6-month intervals until two consecutive negative results are obtained. After the initial follow-up, they recommend “routine” screening for the next 20 years. For many women, routine screening is cytology with or without HPV DNA testing every 3 years.⁴ ACOG, however, recommends annual screening after the initial post-treatment surveillance.⁴

Details of the trial

In this study, Melnikow and colleagues offer a cost-benefit analysis of post-treatment surveillance strategies.⁵ They evaluated 12 possible regimens—including yearly versus triennial screening—in a hypothetical cohort of 500,000 women who were treated for CIN 2 or 3 and followed from 30 to 85 years of age. They also compared women with the lowest and highest risk of recurrence, based on the initial diagnosis and treatment modality.³

They concluded that a conventional Pap test at 6 and 12 months after treatment, followed by annual conventional cytology, provides the most effective use of resources to reduce subsequent cervical cancers and cancer deaths. In patients who had the highest risk of recurrence, adding colposcopy at the initial post-treatment visit increased life expectancy and was highly valued by patients.

Not much offered here to inform clinical practice

This study offers useful information for those who determine health policy. For the practicing clinician, however, the study’s limitations pose significant obstacles to its usefulness in practice. For example, the authors excluded women who were initially treated with loop electrosurgical excision procedure (LEEP) who had positive margins. This eliminates a significant proportion of the post-treatment population. They also excluded surveillance strategies that included liquid-based cytology. They explained this exclusion by noting that liquid-based cytology has been shown to have similar sensitivity and lower specificity than conventional cytology but costs more. However, most clinicians in the United States prefer liquid-based cytology to the conventional Pap smear. Therefore, it is unlikely that most American providers will adopt the strategies that the authors found most cost-effective—i.e., those based on annual screening with the conventional Pap test.

The findings of this study could influence policy makers and insurers to encourage more widespread use of the conventional Pap test in post-treatment surveillance.

We want to hear from you!  Tell us what you think.

When the Women’s Health Initiative (WHI) published follow-up data on the association between estrogen-progestin hormone therapy (HT) and breast cancer last fall, it seemed, for a time, like another death knell had sounded for hormonal management of menopausal symptoms.¹ The data showed that breast cancers in women who have used oral estrogen-progestin therapy are more likely to be node-positive and carry a higher death rate than breast cancers in nonusers.

Since then, a new WHI analysis from the estrogen-alone arm has found a protective effect against breast cancer among hysterectomized users of unopposed conjugated equine estrogens (CEE).²

So what are clinicians to make of all the data? And how should you counsel your menopausal patients who report bothersome vasomotor symptoms? We put these questions to members of the OBG Management Virtual Board of Editors, and they responded with a not-so-surprising diversity of opinion. Presented here are excerpts of their reflections on the role of HT in clinical practice today.

For a closer look at data from the WHI and other studies, see the Update on Menopause, by Andrew M. Kaunitz, MD, on the facing page.

Hormone therapy is alive and kicking

To borrow from Mark Twain: Rumors of the death of HT have been greatly exaggerated. With every new spinoff report from the WHI, the tide of panic rises again.

In my private practice in gynecology, I see many patients who seek my care because another physician (usually another gynecologist) has declined to prescribe HT. Sometimes the HT is refused because the patient has reached 5 years of therapy, and the doctor is simply not comfortable continuing.

What is the guiding principle here? Beneficence? Paternalism (or maternalism)? Risk-aversion? All pharmaceutical therapies have risks. Penicillin can cause anaphylaxis; should we advise patients to avoid antibiotics?

When I counsel women about treatment of vasomotor symptoms, I review herbal and botanical remedies and neurotransmitter modulators as well as estrogen and progestin HT options. I believe that these are all valid options, and I take time to give the patient realistic expectations of efficacy and risks for each one, so that she can make a well-informed decision. But which is the most effective for relief of vasomotor symptoms?

Yes, it’s still HT.

In 2011, we have reached an age of enlightenment with regard to HT. We are using lower dosages of estrogen than ever to address menopausal symptoms. We are preferentially prescribing non-oral HT to reduce thromboembolic complications. To prevent endometrial hyperplasia, we are looking to native (dare I say “bioidentical”?) progesterone, as it appears that different progestins carry different levels of breast cancer risk.³

An enlightened approach means addressing the patient’s symptoms while minimizing the risk of adverse effects. Let’s not regress back to the age of panic.

Dr. Spencer reports no relevant financial relationships.

Patients lack information

As a staff physician in Specialized Women’s Health at the Cleveland Clinic, I manage menopausal women on a regular basis. I find that many of these patients—and their physicians—are poorly informed about the actual risks and benefits of HT. They are unaware of the difference between a prevention trial and a risk trial. And they grossly overestimate the risk of an adverse effect. For example, women who used combination estrogen-progestin in the WHI experienced an increase of 8 cases of breast cancer for every 10,000 woman-years of use. In contrast, women who do not exercise regularly suffer an increase of 35 cases of breast cancer for every 10,000 woman-years of use. In short, the use of HT in the average woman poses far less risk of breast cancer than a poor lifestyle does.

Furthermore, women are not aware that we have a great deal of evidence that early initiation of HT minimizes cardiovascular risk. They are unaware that this early initiation of therapy may well confer a decrease in overall mortality as high as 30%. Patients do not realize that the WHI studied only oral HT and that the use of lower-dose transdermal estrogen most likely minimizes the risks of blood clots, stroke, and hypertension.

I believe that we have allowed the sensationalized coverage of the WHI to cloud the actual data showing that the risks of HT are small. There appears to be some gender bias involved. We allow men to have a drug marketed to them that carries a risk of blindness, heart attack, hypertension, and 4-hour erections—we simply conclude that the benefit is worth the risk. Why don’t we look at HT in the same risk-benefit light? Perhaps it’s because we do not believe that treating a woman’s disabling vasomotor symptoms; her silent, progressive bone loss; or her painful vaginal dryness is worthy of our medical attention.

When we approach the problem of hypertension, we do not prescribe the same dosage of the same medication for all patients. Nor do we assume that any medical path is risk-free. My approach to the menopausal patient is the same: I treat her symptoms as I would any other medical condition that I manage. I conduct an individualized risk-benefit assessment, taking into account the patient’s family history, cardiovascular and lipid status, and risks of breast cancer and osteoporosis. Each patient is prescribed a unique dosage individualized for her symptomatology. And I reevaluate the patient routinely and make any necessary adjustment in the drug or dosage, or both.

As clinicians, we are charged with guiding our patients through the media frenzy to help them differentiate reality and hype. Our patients deserve evidence-based management of their real menopausal symptoms.

Dr. Volkar reports no relevant financial relationships.

Some patients demand HT

HT still plays a significant role in my practice. At every annual visit, I review and document the updated risks and benefits of HT for the patient, as well as the alternatives. In recent years, there has been a decline in patient interest in hormones, but it hasn’t been as significant as I expected: My patients tend to be more interested in quality of life than the research I quote to them on the complications of HT.

Patients who have new-onset vasomotor instability seldom request HT as first-line therapy. Usually, they request guidance and recommendations for over-the-counter remedies out of concern about and fear of HT. The only patients who specifically request HT are symptomatic patients who have not responded to nonprescription treatment and established patients doing well on HT.

As expected, I have observed a significant increase in symptomatic urogenital atrophy in patients who are not taking systemic HT, so I am prescribing more local vaginal estrogen than ever before.

Despite my annual review of the HT warnings, most of my established patients demand to continue using HT, often commenting, “Doc, are you trying to ruin my marriage?” or “Doc, I need my hormones or I might kill somebody.” These particular patients are not fearful of HT—they are fearful of life without it.

As long as HT is FDA-approved and available for use, I will continue to prescribe it for patients when it is appropriate. However, as more potential adverse effects come to light, I am giving strong consideration to having the patient sign a consent form each time I start or renew HT, for obvious liability concerns.

Dr. McGrath reports no relevant financial relationships.

Hormones pose a real legal risk

I have not prescribed HT since 2002. The reason is simple: No woman is going to sue me for not prescribing hormones for menopausal symptoms. She may not be happy. She may switch to another ObGyn. But she will not sue.

Forget about medical literature and scientific data. Every 6 months, it seems, some new article comes out with new recommendations. We ObGyns are like puppets dangling at the end of a string, swinging from one side to another, depending on which way the medical winds blow. Unfortunately, in this day and age, we no longer work for the patients, but for the lawyers.

So heed the following recommendation, and you may get some unhappy patients, but you won’t get sued: Do not prescribe hormones for menopausal symptoms. No woman has died from lack of hormones, but all you need is one case of breast cancer, or a fatal heart attack, stroke, or pulmonary embolism, for some lawyer to link the catastrophe to HT, and there goes your practice.

It’s just not worth it.

Dr. Zandieh reports no relevant financial relationships.

Many women turn to alternative therapies

Many of my patients pursue alternative interventions that do not involve formal estrogen supplementation. These options include both lifestyle changes and phytoestrogens (plant-based supplements with estrogen-like properties). Phytoestrogen products often include black cohosh or soy isoflavones such as genistein that claim SERM-like activity (selective estrogen receptor modulator) to manage hot flashes, night sweats, vaginal dryness, and other menopausal symptoms.

Despite research showing a lack of effectiveness for most phytoestrogen-based products, a surprisingly large percentage of patients utilize these products, often without the knowledge of their provider. It is important to ask about these products because they can interfere with other medications and, in the case of black cohosh, may be contraindicated in patients who have liver disorders.

Although data have been lacking with respect to the use of phytoestrogen-based products, some of these formulations may provide a level of effectiveness for a variety of patients.

Despite the botanical nature of these products, I counsel my patients that there is a potential for estrogen-like activity. Therefore, these products may carry some of the same risks as the estrogen they seek to avoid.

Dr. Bernick reports that he is a consultant for vitaWebMD.

New data make it easier to tailor HT

I completed my ObGyn residency during the mid-1990s, at a time when it was common to begin almost every menopausal woman on HT. As data from the WHI trial and Heart and Estrogen/progestin Replacement Study (HERS) exploded in the media, a small percentage of my patients stopped taking their hormones immediately.^4,5 The majority of my patients turned to me for interpretation of the studies and guidance on how they applied to their particular clinical scenario.

I believe that my patients are better served by having an extensive discussion of their general health and behavioral habits as a means of addressing their menopausal symptoms. I must admit, before the WHI and HERS trials, I gave this kind of counseling short shrift. Now, when I talk with patients, I find it easiest to discuss HT from a risk-benefit standpoint in light of the data to date. Before the WHI and HERS trials, I did not treat hysterectomized women any differently than those who had an intact uterus. Nor did I think in terms of initiating treatment in early versus late menopause or pay much attention to risk factors for breast cancer or heart disease. Now, we have data on these considerations that enable me to more accurately determine a woman’s unique risk-benefit profile as she contemplates HT. ACOG’s analysis and perspective have also helped.⁶

Once beyond this first level of discussion, if the patient elects to initiate HT, the focus shifts to “What dosage and for how long?” At her annual visit, we revisit “the numbers” and discuss how they apply to her case. Most important, I assess how HT is affecting her quality of life. I explain to my patients that the concept of the lowest dosage for the shortest duration is one we should embrace not only with HT but with all of their medications on a yearly basis.

Today, my patients run the spectrum of HT use. I have 80-year-old hysterectomized patients with a 30-year history of HT use who look at me pointedly and say, “You’re not gonna stop my hormones, are you?” And I have 52-year-old patients who proudly inform me that their symptoms are manageable without HT now that they have started yoga.

Dr. delRosario reports no relevant financial relationships.

More patients are declining HT

I routinely advise my patients about the increased risk of breast cancer and positive nodes when I prescribe estrogen-progestin HT, based on the recent publication from the WHI study.¹ I tell them straight up that it is a defined risk, but short-term usage of HT for vasomotor symptoms may be acceptable, along with yearly mammograms. They are comfortable knowing the risks and are declining, in increasing numbers, to start or maintain HT.

Alternatives that I recommend are multivitamins and supplemental vitamin D and daily calcium for osteopenia prevention. I suggest using a serotonin reuptake inhibitor for vasomotor symptom control.

Dr. Schnee reports no relevant financial relationships.

Individualizing therapy is a priority

I doubt that any gynecologist in active practice has forgotten the day in July 2002 when the startling news about the WHI study broke. I remember clearly that I was inundated with questions from anxious women—as well as my residents—wondering about the immediate implications. Suddenly, what had been a panacea for menopausal vasomotor symptoms had become a deadly poison, and women wanted to know with certainty whether they would develop breast cancer.

Since that time, as small aliquots of new information have been published periodically, we have learned to look at HT in a new light. Not all the news is positive, and not all of it is negative—and we are certainly far from the last word on this controversy.

My practice with a Federally Qualified Health Care Center brings patients of different ethnic and racial groups to my office. Most of them (~55%) have Spanish as their primary language, and a significant minority (~30%) are English-speaking. My patients are generally not forthcoming about symptoms that they consider a “normal” part of menopause. I therefore question perimenopausal and menopausal women specifically about vasomotor symptoms and vaginal dryness and dyspareunia. The options I offer them depend on the most troubling symptoms.

Besides estrogen, I offer fluoxetine and desvenlafaxine for vasomotor symptoms. For vaginal dryness and dyspareunia, I offer short-term local conjugated estrogen cream. My patients tend to be more accepting of the estrogen cream than the antidepressants. For perimenopausal women who also need contraception, I offer the low-dose oral contraceptive. Of course, I also suggest lifestyle adjustments such as avoidance of caffeine and increased physical activity.

Numerous reports have noted that over-weight and obese women experience more hot flushes and vasomotor symptoms than their counterparts of normal weight, but I find that thin Caucasian women complain of hot flushes most often. These patients are generally aware of HT but reluctant to use it. Many of these women are taking St. John’s wort or black cohosh as self-medication but do not necessarily report this use. Now I specifically ask about these remedies.

In short, I listen actively, take a thorough history, try to be culturally sensitive, and individualize my advice and pharmacotherapy to suit each patient’s needs.

Dr. Joshi reports no relevant financial relationships.

Transdermal and vaginal estrogen are mainstays

Denying a woman HT when she is suffering from vasomotor symptoms is heartless. I typically recommend vaginal administration of estrogen and progesterone. Reports from the WHI suggest that it is best to avoid a first pass through the liver, and oral medroxyprogesterone acetate is implicated in unwanted heart and breast effects of HT, so I generally prescribe transdermal estrogen, the vaginal ring, or estrogen cream to relieve symptoms. A Prometrium capsule inserted vaginally twice a week protects the endometrium nicely. In my practice, an endometrial sample verified benign endometrium in every case of breakthrough bleeding with this program.

If a patient cannot take estrogen because of breast cancer or concerns about it, I typically offer oral gabapentin for vasomotor symptoms and local tamoxifen (one tablet, ground up, with KY jelly, inserted vaginally twice weekly) for symptoms in the pudendal region. This local tamoxifen improves clinical appearance, vaginal pH, and the cytologic cornification index.

Dr. Shirley reports no relevant financial relationships.

A turn away from hormones

Very few of my patients accept hormonal therapy for their menopausal symptoms these days. A couple of patients have asked for bioidentical hormones, and a few others have been candidates for a low-dose oral contraceptive. Some patients ask about blood tests to determine their menopausal status, but they usually agree with me after I explain why these tests are not helpful.

In my practice, the most common menopausal symptom is vaginal dryness—but I usually have to ask about it before the patient acknowledges the problem. I recommend vaginal lubricants more often than local estrogen, and I try to keep a good supply of lubricants on hand.

Overall, patients are fearful of hormones. I try to counsel them that the benefits and risks of hormones vary according to age and route of administration. I rarely prescribe combination estrogen-progestin HT anymore. And I prefer the transdermal route rather than oral administration. In women who have a uterus, I prescribe quarterly progesterone (Prometrium). Otherwise, I recommend unopposed estrogen.

Dr. Goyle reports no relevant financial relationships.

Stress the benefits of HT!

You only get one shot! One shot to sell symptomatic menopausal women on the benefits and use of estrogen. If you drop the ball by not anticipating and explaining the side effects, your patient will quit and buy the junk over the counter, which is usually worse than useless! If you are a firm believer in the four “S”s of HT—sleep, sex, skin, and sanity—you must be positive and stress them to your patient.

Sleep is obviously better when the patient doesn’t wake up drenched in sweat. Sex is better because it doesn’t hurt. (Ask your patient whether she would like a plum or a prune for a vagina! She will instantly grasp the physiologic concept!) Skin is better because of the slowdown in collagen loss. Sanity is improved because of the increase in well being, improved thought processes, and enjoyment of life.

For heaven’s sakes, don’t stop HT after 5 or 6 years! Keep it going with gels, patches, or intravaginal cream forever. After all, women spend more than one third of their life in the postmenopausal phase—make it a wonderful life! Your patients will be appreciative. More important, they will reward you by coming back to see you year after year and singing your praises.

Dr. Franklin reports no relevant financial relationships.

Scare headlines grab attention

Saul R. Berg, MD
Pittsburgh, Pa

I believe that the tide will turn in regard to HT in the not-too-distant future. It takes time for the real truth to get out. In the meantime, scare headlines tend to grab attention.

I hope that, in the near future, we will be able to genetically identify women who should not use HT. Until then, I discuss the risks and benefits of HT with my patients and honor their decision. Transdermal estrogen and bimonthly or quarterly progestin—I typically use Prometrium—are my preference.

At present, there don’t seem to be any outstanding alternatives to hormonal therapy.

Dr. Berg reports no relevant financial relationships.

INSTANT POLL
How do you counsel and treat your menopausal patients who report bothersome vasomotor symptoms?
To enter your response, click here.

We want to hear from you! Tell us what you think.

When the Women’s Health Initiative (WHI) published follow-up data on the association between estrogen-progestin hormone therapy (HT) and breast cancer last fall, it seemed, for a time, like another death knell had sounded for hormonal management of menopausal symptoms.¹ The data showed that breast cancers in women who have used oral estrogen-progestin therapy are more likely to be node-positive and carry a higher death rate than breast cancers in nonusers.

Since then, a new WHI analysis from the estrogen-alone arm has found a protective effect against breast cancer among hysterectomized users of unopposed conjugated equine estrogens (CEE).²

So what are clinicians to make of all the data? And how should you counsel your menopausal patients who report bothersome vasomotor symptoms? We put these questions to members of the OBG Management Virtual Board of Editors, and they responded with a not-so-surprising diversity of opinion. Presented here are excerpts of their reflections on the role of HT in clinical practice today.

For a closer look at data from the WHI and other studies, see the Update on Menopause, by Andrew M. Kaunitz, MD, on the facing page.

Hormone therapy is alive and kicking

To borrow from Mark Twain: Rumors of the death of HT have been greatly exaggerated. With every new spinoff report from the WHI, the tide of panic rises again.

In my private practice in gynecology, I see many patients who seek my care because another physician (usually another gynecologist) has declined to prescribe HT. Sometimes the HT is refused because the patient has reached 5 years of therapy, and the doctor is simply not comfortable continuing.

What is the guiding principle here? Beneficence? Paternalism (or maternalism)? Risk-aversion? All pharmaceutical therapies have risks. Penicillin can cause anaphylaxis; should we advise patients to avoid antibiotics?

When I counsel women about treatment of vasomotor symptoms, I review herbal and botanical remedies and neurotransmitter modulators as well as estrogen and progestin HT options. I believe that these are all valid options, and I take time to give the patient realistic expectations of efficacy and risks for each one, so that she can make a well-informed decision. But which is the most effective for relief of vasomotor symptoms?

Yes, it’s still HT.

In 2011, we have reached an age of enlightenment with regard to HT. We are using lower dosages of estrogen than ever to address menopausal symptoms. We are preferentially prescribing non-oral HT to reduce thromboembolic complications. To prevent endometrial hyperplasia, we are looking to native (dare I say “bioidentical”?) progesterone, as it appears that different progestins carry different levels of breast cancer risk.³

An enlightened approach means addressing the patient’s symptoms while minimizing the risk of adverse effects. Let’s not regress back to the age of panic.

Dr. Spencer reports no relevant financial relationships.

Patients lack information

As a staff physician in Specialized Women’s Health at the Cleveland Clinic, I manage menopausal women on a regular basis. I find that many of these patients—and their physicians—are poorly informed about the actual risks and benefits of HT. They are unaware of the difference between a prevention trial and a risk trial. And they grossly overestimate the risk of an adverse effect. For example, women who used combination estrogen-progestin in the WHI experienced an increase of 8 cases of breast cancer for every 10,000 woman-years of use. In contrast, women who do not exercise regularly suffer an increase of 35 cases of breast cancer for every 10,000 woman-years of use. In short, the use of HT in the average woman poses far less risk of breast cancer than a poor lifestyle does.

Furthermore, women are not aware that we have a great deal of evidence that early initiation of HT minimizes cardiovascular risk. They are unaware that this early initiation of therapy may well confer a decrease in overall mortality as high as 30%. Patients do not realize that the WHI studied only oral HT and that the use of lower-dose transdermal estrogen most likely minimizes the risks of blood clots, stroke, and hypertension.

I believe that we have allowed the sensationalized coverage of the WHI to cloud the actual data showing that the risks of HT are small. There appears to be some gender bias involved. We allow men to have a drug marketed to them that carries a risk of blindness, heart attack, hypertension, and 4-hour erections—we simply conclude that the benefit is worth the risk. Why don’t we look at HT in the same risk-benefit light? Perhaps it’s because we do not believe that treating a woman’s disabling vasomotor symptoms; her silent, progressive bone loss; or her painful vaginal dryness is worthy of our medical attention.

When we approach the problem of hypertension, we do not prescribe the same dosage of the same medication for all patients. Nor do we assume that any medical path is risk-free. My approach to the menopausal patient is the same: I treat her symptoms as I would any other medical condition that I manage. I conduct an individualized risk-benefit assessment, taking into account the patient’s family history, cardiovascular and lipid status, and risks of breast cancer and osteoporosis. Each patient is prescribed a unique dosage individualized for her symptomatology. And I reevaluate the patient routinely and make any necessary adjustment in the drug or dosage, or both.

As clinicians, we are charged with guiding our patients through the media frenzy to help them differentiate reality and hype. Our patients deserve evidence-based management of their real menopausal symptoms.

Dr. Volkar reports no relevant financial relationships.

Some patients demand HT

HT still plays a significant role in my practice. At every annual visit, I review and document the updated risks and benefits of HT for the patient, as well as the alternatives. In recent years, there has been a decline in patient interest in hormones, but it hasn’t been as significant as I expected: My patients tend to be more interested in quality of life than the research I quote to them on the complications of HT.

Patients who have new-onset vasomotor instability seldom request HT as first-line therapy. Usually, they request guidance and recommendations for over-the-counter remedies out of concern about and fear of HT. The only patients who specifically request HT are symptomatic patients who have not responded to nonprescription treatment and established patients doing well on HT.

As expected, I have observed a significant increase in symptomatic urogenital atrophy in patients who are not taking systemic HT, so I am prescribing more local vaginal estrogen than ever before.

Despite my annual review of the HT warnings, most of my established patients demand to continue using HT, often commenting, “Doc, are you trying to ruin my marriage?” or “Doc, I need my hormones or I might kill somebody.” These particular patients are not fearful of HT—they are fearful of life without it.

As long as HT is FDA-approved and available for use, I will continue to prescribe it for patients when it is appropriate. However, as more potential adverse effects come to light, I am giving strong consideration to having the patient sign a consent form each time I start or renew HT, for obvious liability concerns.

Dr. McGrath reports no relevant financial relationships.

Hormones pose a real legal risk

I have not prescribed HT since 2002. The reason is simple: No woman is going to sue me for not prescribing hormones for menopausal symptoms. She may not be happy. She may switch to another ObGyn. But she will not sue.

Forget about medical literature and scientific data. Every 6 months, it seems, some new article comes out with new recommendations. We ObGyns are like puppets dangling at the end of a string, swinging from one side to another, depending on which way the medical winds blow. Unfortunately, in this day and age, we no longer work for the patients, but for the lawyers.

So heed the following recommendation, and you may get some unhappy patients, but you won’t get sued: Do not prescribe hormones for menopausal symptoms. No woman has died from lack of hormones, but all you need is one case of breast cancer, or a fatal heart attack, stroke, or pulmonary embolism, for some lawyer to link the catastrophe to HT, and there goes your practice.

It’s just not worth it.

Dr. Zandieh reports no relevant financial relationships.

Many women turn to alternative therapies

Many of my patients pursue alternative interventions that do not involve formal estrogen supplementation. These options include both lifestyle changes and phytoestrogens (plant-based supplements with estrogen-like properties). Phytoestrogen products often include black cohosh or soy isoflavones such as genistein that claim SERM-like activity (selective estrogen receptor modulator) to manage hot flashes, night sweats, vaginal dryness, and other menopausal symptoms.

Despite research showing a lack of effectiveness for most phytoestrogen-based products, a surprisingly large percentage of patients utilize these products, often without the knowledge of their provider. It is important to ask about these products because they can interfere with other medications and, in the case of black cohosh, may be contraindicated in patients who have liver disorders.

Although data have been lacking with respect to the use of phytoestrogen-based products, some of these formulations may provide a level of effectiveness for a variety of patients.

Despite the botanical nature of these products, I counsel my patients that there is a potential for estrogen-like activity. Therefore, these products may carry some of the same risks as the estrogen they seek to avoid.

Dr. Bernick reports that he is a consultant for vitaWebMD.

New data make it easier to tailor HT

I completed my ObGyn residency during the mid-1990s, at a time when it was common to begin almost every menopausal woman on HT. As data from the WHI trial and Heart and Estrogen/progestin Replacement Study (HERS) exploded in the media, a small percentage of my patients stopped taking their hormones immediately.^4,5 The majority of my patients turned to me for interpretation of the studies and guidance on how they applied to their particular clinical scenario.

I believe that my patients are better served by having an extensive discussion of their general health and behavioral habits as a means of addressing their menopausal symptoms. I must admit, before the WHI and HERS trials, I gave this kind of counseling short shrift. Now, when I talk with patients, I find it easiest to discuss HT from a risk-benefit standpoint in light of the data to date. Before the WHI and HERS trials, I did not treat hysterectomized women any differently than those who had an intact uterus. Nor did I think in terms of initiating treatment in early versus late menopause or pay much attention to risk factors for breast cancer or heart disease. Now, we have data on these considerations that enable me to more accurately determine a woman’s unique risk-benefit profile as she contemplates HT. ACOG’s analysis and perspective have also helped.⁶

Once beyond this first level of discussion, if the patient elects to initiate HT, the focus shifts to “What dosage and for how long?” At her annual visit, we revisit “the numbers” and discuss how they apply to her case. Most important, I assess how HT is affecting her quality of life. I explain to my patients that the concept of the lowest dosage for the shortest duration is one we should embrace not only with HT but with all of their medications on a yearly basis.

Today, my patients run the spectrum of HT use. I have 80-year-old hysterectomized patients with a 30-year history of HT use who look at me pointedly and say, “You’re not gonna stop my hormones, are you?” And I have 52-year-old patients who proudly inform me that their symptoms are manageable without HT now that they have started yoga.

Dr. delRosario reports no relevant financial relationships.

More patients are declining HT

I routinely advise my patients about the increased risk of breast cancer and positive nodes when I prescribe estrogen-progestin HT, based on the recent publication from the WHI study.¹ I tell them straight up that it is a defined risk, but short-term usage of HT for vasomotor symptoms may be acceptable, along with yearly mammograms. They are comfortable knowing the risks and are declining, in increasing numbers, to start or maintain HT.

Alternatives that I recommend are multivitamins and supplemental vitamin D and daily calcium for osteopenia prevention. I suggest using a serotonin reuptake inhibitor for vasomotor symptom control.

Dr. Schnee reports no relevant financial relationships.

Individualizing therapy is a priority

I doubt that any gynecologist in active practice has forgotten the day in July 2002 when the startling news about the WHI study broke. I remember clearly that I was inundated with questions from anxious women—as well as my residents—wondering about the immediate implications. Suddenly, what had been a panacea for menopausal vasomotor symptoms had become a deadly poison, and women wanted to know with certainty whether they would develop breast cancer.

Since that time, as small aliquots of new information have been published periodically, we have learned to look at HT in a new light. Not all the news is positive, and not all of it is negative—and we are certainly far from the last word on this controversy.

My practice with a Federally Qualified Health Care Center brings patients of different ethnic and racial groups to my office. Most of them (~55%) have Spanish as their primary language, and a significant minority (~30%) are English-speaking. My patients are generally not forthcoming about symptoms that they consider a “normal” part of menopause. I therefore question perimenopausal and menopausal women specifically about vasomotor symptoms and vaginal dryness and dyspareunia. The options I offer them depend on the most troubling symptoms.

Besides estrogen, I offer fluoxetine and desvenlafaxine for vasomotor symptoms. For vaginal dryness and dyspareunia, I offer short-term local conjugated estrogen cream. My patients tend to be more accepting of the estrogen cream than the antidepressants. For perimenopausal women who also need contraception, I offer the low-dose oral contraceptive. Of course, I also suggest lifestyle adjustments such as avoidance of caffeine and increased physical activity.

Numerous reports have noted that over-weight and obese women experience more hot flushes and vasomotor symptoms than their counterparts of normal weight, but I find that thin Caucasian women complain of hot flushes most often. These patients are generally aware of HT but reluctant to use it. Many of these women are taking St. John’s wort or black cohosh as self-medication but do not necessarily report this use. Now I specifically ask about these remedies.

In short, I listen actively, take a thorough history, try to be culturally sensitive, and individualize my advice and pharmacotherapy to suit each patient’s needs.

Dr. Joshi reports no relevant financial relationships.

Transdermal and vaginal estrogen are mainstays

Denying a woman HT when she is suffering from vasomotor symptoms is heartless. I typically recommend vaginal administration of estrogen and progesterone. Reports from the WHI suggest that it is best to avoid a first pass through the liver, and oral medroxyprogesterone acetate is implicated in unwanted heart and breast effects of HT, so I generally prescribe transdermal estrogen, the vaginal ring, or estrogen cream to relieve symptoms. A Prometrium capsule inserted vaginally twice a week protects the endometrium nicely. In my practice, an endometrial sample verified benign endometrium in every case of breakthrough bleeding with this program.

If a patient cannot take estrogen because of breast cancer or concerns about it, I typically offer oral gabapentin for vasomotor symptoms and local tamoxifen (one tablet, ground up, with KY jelly, inserted vaginally twice weekly) for symptoms in the pudendal region. This local tamoxifen improves clinical appearance, vaginal pH, and the cytologic cornification index.

Dr. Shirley reports no relevant financial relationships.

A turn away from hormones

Very few of my patients accept hormonal therapy for their menopausal symptoms these days. A couple of patients have asked for bioidentical hormones, and a few others have been candidates for a low-dose oral contraceptive. Some patients ask about blood tests to determine their menopausal status, but they usually agree with me after I explain why these tests are not helpful.

In my practice, the most common menopausal symptom is vaginal dryness—but I usually have to ask about it before the patient acknowledges the problem. I recommend vaginal lubricants more often than local estrogen, and I try to keep a good supply of lubricants on hand.

Overall, patients are fearful of hormones. I try to counsel them that the benefits and risks of hormones vary according to age and route of administration. I rarely prescribe combination estrogen-progestin HT anymore. And I prefer the transdermal route rather than oral administration. In women who have a uterus, I prescribe quarterly progesterone (Prometrium). Otherwise, I recommend unopposed estrogen.

Dr. Goyle reports no relevant financial relationships.

Stress the benefits of HT!

You only get one shot! One shot to sell symptomatic menopausal women on the benefits and use of estrogen. If you drop the ball by not anticipating and explaining the side effects, your patient will quit and buy the junk over the counter, which is usually worse than useless! If you are a firm believer in the four “S”s of HT—sleep, sex, skin, and sanity—you must be positive and stress them to your patient.

Sleep is obviously better when the patient doesn’t wake up drenched in sweat. Sex is better because it doesn’t hurt. (Ask your patient whether she would like a plum or a prune for a vagina! She will instantly grasp the physiologic concept!) Skin is better because of the slowdown in collagen loss. Sanity is improved because of the increase in well being, improved thought processes, and enjoyment of life.

For heaven’s sakes, don’t stop HT after 5 or 6 years! Keep it going with gels, patches, or intravaginal cream forever. After all, women spend more than one third of their life in the postmenopausal phase—make it a wonderful life! Your patients will be appreciative. More important, they will reward you by coming back to see you year after year and singing your praises.

Dr. Franklin reports no relevant financial relationships.

Scare headlines grab attention

Saul R. Berg, MD
Pittsburgh, Pa

I believe that the tide will turn in regard to HT in the not-too-distant future. It takes time for the real truth to get out. In the meantime, scare headlines tend to grab attention.

I hope that, in the near future, we will be able to genetically identify women who should not use HT. Until then, I discuss the risks and benefits of HT with my patients and honor their decision. Transdermal estrogen and bimonthly or quarterly progestin—I typically use Prometrium—are my preference.

At present, there don’t seem to be any outstanding alternatives to hormonal therapy.

Dr. Berg reports no relevant financial relationships.

INSTANT POLL
How do you counsel and treat your menopausal patients who report bothersome vasomotor symptoms?
To enter your response, click here.

We want to hear from you! Tell us what you think.

When the Women’s Health Initiative (WHI) published follow-up data on the association between estrogen-progestin hormone therapy (HT) and breast cancer last fall, it seemed, for a time, like another death knell had sounded for hormonal management of menopausal symptoms.¹ The data showed that breast cancers in women who have used oral estrogen-progestin therapy are more likely to be node-positive and carry a higher death rate than breast cancers in nonusers.

Since then, a new WHI analysis from the estrogen-alone arm has found a protective effect against breast cancer among hysterectomized users of unopposed conjugated equine estrogens (CEE).²

So what are clinicians to make of all the data? And how should you counsel your menopausal patients who report bothersome vasomotor symptoms? We put these questions to members of the OBG Management Virtual Board of Editors, and they responded with a not-so-surprising diversity of opinion. Presented here are excerpts of their reflections on the role of HT in clinical practice today.

For a closer look at data from the WHI and other studies, see the Update on Menopause, by Andrew M. Kaunitz, MD, on the facing page.

Hormone therapy is alive and kicking

To borrow from Mark Twain: Rumors of the death of HT have been greatly exaggerated. With every new spinoff report from the WHI, the tide of panic rises again.

In my private practice in gynecology, I see many patients who seek my care because another physician (usually another gynecologist) has declined to prescribe HT. Sometimes the HT is refused because the patient has reached 5 years of therapy, and the doctor is simply not comfortable continuing.

What is the guiding principle here? Beneficence? Paternalism (or maternalism)? Risk-aversion? All pharmaceutical therapies have risks. Penicillin can cause anaphylaxis; should we advise patients to avoid antibiotics?

When I counsel women about treatment of vasomotor symptoms, I review herbal and botanical remedies and neurotransmitter modulators as well as estrogen and progestin HT options. I believe that these are all valid options, and I take time to give the patient realistic expectations of efficacy and risks for each one, so that she can make a well-informed decision. But which is the most effective for relief of vasomotor symptoms?

Yes, it’s still HT.

In 2011, we have reached an age of enlightenment with regard to HT. We are using lower dosages of estrogen than ever to address menopausal symptoms. We are preferentially prescribing non-oral HT to reduce thromboembolic complications. To prevent endometrial hyperplasia, we are looking to native (dare I say “bioidentical”?) progesterone, as it appears that different progestins carry different levels of breast cancer risk.³

An enlightened approach means addressing the patient’s symptoms while minimizing the risk of adverse effects. Let’s not regress back to the age of panic.

Dr. Spencer reports no relevant financial relationships.

Patients lack information

As a staff physician in Specialized Women’s Health at the Cleveland Clinic, I manage menopausal women on a regular basis. I find that many of these patients—and their physicians—are poorly informed about the actual risks and benefits of HT. They are unaware of the difference between a prevention trial and a risk trial. And they grossly overestimate the risk of an adverse effect. For example, women who used combination estrogen-progestin in the WHI experienced an increase of 8 cases of breast cancer for every 10,000 woman-years of use. In contrast, women who do not exercise regularly suffer an increase of 35 cases of breast cancer for every 10,000 woman-years of use. In short, the use of HT in the average woman poses far less risk of breast cancer than a poor lifestyle does.

Furthermore, women are not aware that we have a great deal of evidence that early initiation of HT minimizes cardiovascular risk. They are unaware that this early initiation of therapy may well confer a decrease in overall mortality as high as 30%. Patients do not realize that the WHI studied only oral HT and that the use of lower-dose transdermal estrogen most likely minimizes the risks of blood clots, stroke, and hypertension.

I believe that we have allowed the sensationalized coverage of the WHI to cloud the actual data showing that the risks of HT are small. There appears to be some gender bias involved. We allow men to have a drug marketed to them that carries a risk of blindness, heart attack, hypertension, and 4-hour erections—we simply conclude that the benefit is worth the risk. Why don’t we look at HT in the same risk-benefit light? Perhaps it’s because we do not believe that treating a woman’s disabling vasomotor symptoms; her silent, progressive bone loss; or her painful vaginal dryness is worthy of our medical attention.

When we approach the problem of hypertension, we do not prescribe the same dosage of the same medication for all patients. Nor do we assume that any medical path is risk-free. My approach to the menopausal patient is the same: I treat her symptoms as I would any other medical condition that I manage. I conduct an individualized risk-benefit assessment, taking into account the patient’s family history, cardiovascular and lipid status, and risks of breast cancer and osteoporosis. Each patient is prescribed a unique dosage individualized for her symptomatology. And I reevaluate the patient routinely and make any necessary adjustment in the drug or dosage, or both.

As clinicians, we are charged with guiding our patients through the media frenzy to help them differentiate reality and hype. Our patients deserve evidence-based management of their real menopausal symptoms.

Dr. Volkar reports no relevant financial relationships.

Some patients demand HT

HT still plays a significant role in my practice. At every annual visit, I review and document the updated risks and benefits of HT for the patient, as well as the alternatives. In recent years, there has been a decline in patient interest in hormones, but it hasn’t been as significant as I expected: My patients tend to be more interested in quality of life than the research I quote to them on the complications of HT.

Patients who have new-onset vasomotor instability seldom request HT as first-line therapy. Usually, they request guidance and recommendations for over-the-counter remedies out of concern about and fear of HT. The only patients who specifically request HT are symptomatic patients who have not responded to nonprescription treatment and established patients doing well on HT.

As expected, I have observed a significant increase in symptomatic urogenital atrophy in patients who are not taking systemic HT, so I am prescribing more local vaginal estrogen than ever before.

Despite my annual review of the HT warnings, most of my established patients demand to continue using HT, often commenting, “Doc, are you trying to ruin my marriage?” or “Doc, I need my hormones or I might kill somebody.” These particular patients are not fearful of HT—they are fearful of life without it.

As long as HT is FDA-approved and available for use, I will continue to prescribe it for patients when it is appropriate. However, as more potential adverse effects come to light, I am giving strong consideration to having the patient sign a consent form each time I start or renew HT, for obvious liability concerns.

Dr. McGrath reports no relevant financial relationships.

Hormones pose a real legal risk

I have not prescribed HT since 2002. The reason is simple: No woman is going to sue me for not prescribing hormones for menopausal symptoms. She may not be happy. She may switch to another ObGyn. But she will not sue.

Forget about medical literature and scientific data. Every 6 months, it seems, some new article comes out with new recommendations. We ObGyns are like puppets dangling at the end of a string, swinging from one side to another, depending on which way the medical winds blow. Unfortunately, in this day and age, we no longer work for the patients, but for the lawyers.

So heed the following recommendation, and you may get some unhappy patients, but you won’t get sued: Do not prescribe hormones for menopausal symptoms. No woman has died from lack of hormones, but all you need is one case of breast cancer, or a fatal heart attack, stroke, or pulmonary embolism, for some lawyer to link the catastrophe to HT, and there goes your practice.

It’s just not worth it.

Dr. Zandieh reports no relevant financial relationships.

Many women turn to alternative therapies

Many of my patients pursue alternative interventions that do not involve formal estrogen supplementation. These options include both lifestyle changes and phytoestrogens (plant-based supplements with estrogen-like properties). Phytoestrogen products often include black cohosh or soy isoflavones such as genistein that claim SERM-like activity (selective estrogen receptor modulator) to manage hot flashes, night sweats, vaginal dryness, and other menopausal symptoms.

Despite research showing a lack of effectiveness for most phytoestrogen-based products, a surprisingly large percentage of patients utilize these products, often without the knowledge of their provider. It is important to ask about these products because they can interfere with other medications and, in the case of black cohosh, may be contraindicated in patients who have liver disorders.

Although data have been lacking with respect to the use of phytoestrogen-based products, some of these formulations may provide a level of effectiveness for a variety of patients.

Despite the botanical nature of these products, I counsel my patients that there is a potential for estrogen-like activity. Therefore, these products may carry some of the same risks as the estrogen they seek to avoid.

Dr. Bernick reports that he is a consultant for vitaWebMD.

New data make it easier to tailor HT

I completed my ObGyn residency during the mid-1990s, at a time when it was common to begin almost every menopausal woman on HT. As data from the WHI trial and Heart and Estrogen/progestin Replacement Study (HERS) exploded in the media, a small percentage of my patients stopped taking their hormones immediately.^4,5 The majority of my patients turned to me for interpretation of the studies and guidance on how they applied to their particular clinical scenario.

I believe that my patients are better served by having an extensive discussion of their general health and behavioral habits as a means of addressing their menopausal symptoms. I must admit, before the WHI and HERS trials, I gave this kind of counseling short shrift. Now, when I talk with patients, I find it easiest to discuss HT from a risk-benefit standpoint in light of the data to date. Before the WHI and HERS trials, I did not treat hysterectomized women any differently than those who had an intact uterus. Nor did I think in terms of initiating treatment in early versus late menopause or pay much attention to risk factors for breast cancer or heart disease. Now, we have data on these considerations that enable me to more accurately determine a woman’s unique risk-benefit profile as she contemplates HT. ACOG’s analysis and perspective have also helped.⁶

Once beyond this first level of discussion, if the patient elects to initiate HT, the focus shifts to “What dosage and for how long?” At her annual visit, we revisit “the numbers” and discuss how they apply to her case. Most important, I assess how HT is affecting her quality of life. I explain to my patients that the concept of the lowest dosage for the shortest duration is one we should embrace not only with HT but with all of their medications on a yearly basis.

Today, my patients run the spectrum of HT use. I have 80-year-old hysterectomized patients with a 30-year history of HT use who look at me pointedly and say, “You’re not gonna stop my hormones, are you?” And I have 52-year-old patients who proudly inform me that their symptoms are manageable without HT now that they have started yoga.

Dr. delRosario reports no relevant financial relationships.

More patients are declining HT

I routinely advise my patients about the increased risk of breast cancer and positive nodes when I prescribe estrogen-progestin HT, based on the recent publication from the WHI study.¹ I tell them straight up that it is a defined risk, but short-term usage of HT for vasomotor symptoms may be acceptable, along with yearly mammograms. They are comfortable knowing the risks and are declining, in increasing numbers, to start or maintain HT.

Alternatives that I recommend are multivitamins and supplemental vitamin D and daily calcium for osteopenia prevention. I suggest using a serotonin reuptake inhibitor for vasomotor symptom control.

Dr. Schnee reports no relevant financial relationships.

Individualizing therapy is a priority

I doubt that any gynecologist in active practice has forgotten the day in July 2002 when the startling news about the WHI study broke. I remember clearly that I was inundated with questions from anxious women—as well as my residents—wondering about the immediate implications. Suddenly, what had been a panacea for menopausal vasomotor symptoms had become a deadly poison, and women wanted to know with certainty whether they would develop breast cancer.

Since that time, as small aliquots of new information have been published periodically, we have learned to look at HT in a new light. Not all the news is positive, and not all of it is negative—and we are certainly far from the last word on this controversy.

My practice with a Federally Qualified Health Care Center brings patients of different ethnic and racial groups to my office. Most of them (~55%) have Spanish as their primary language, and a significant minority (~30%) are English-speaking. My patients are generally not forthcoming about symptoms that they consider a “normal” part of menopause. I therefore question perimenopausal and menopausal women specifically about vasomotor symptoms and vaginal dryness and dyspareunia. The options I offer them depend on the most troubling symptoms.

Besides estrogen, I offer fluoxetine and desvenlafaxine for vasomotor symptoms. For vaginal dryness and dyspareunia, I offer short-term local conjugated estrogen cream. My patients tend to be more accepting of the estrogen cream than the antidepressants. For perimenopausal women who also need contraception, I offer the low-dose oral contraceptive. Of course, I also suggest lifestyle adjustments such as avoidance of caffeine and increased physical activity.

Numerous reports have noted that over-weight and obese women experience more hot flushes and vasomotor symptoms than their counterparts of normal weight, but I find that thin Caucasian women complain of hot flushes most often. These patients are generally aware of HT but reluctant to use it. Many of these women are taking St. John’s wort or black cohosh as self-medication but do not necessarily report this use. Now I specifically ask about these remedies.

In short, I listen actively, take a thorough history, try to be culturally sensitive, and individualize my advice and pharmacotherapy to suit each patient’s needs.

Dr. Joshi reports no relevant financial relationships.

Transdermal and vaginal estrogen are mainstays

Denying a woman HT when she is suffering from vasomotor symptoms is heartless. I typically recommend vaginal administration of estrogen and progesterone. Reports from the WHI suggest that it is best to avoid a first pass through the liver, and oral medroxyprogesterone acetate is implicated in unwanted heart and breast effects of HT, so I generally prescribe transdermal estrogen, the vaginal ring, or estrogen cream to relieve symptoms. A Prometrium capsule inserted vaginally twice a week protects the endometrium nicely. In my practice, an endometrial sample verified benign endometrium in every case of breakthrough bleeding with this program.

If a patient cannot take estrogen because of breast cancer or concerns about it, I typically offer oral gabapentin for vasomotor symptoms and local tamoxifen (one tablet, ground up, with KY jelly, inserted vaginally twice weekly) for symptoms in the pudendal region. This local tamoxifen improves clinical appearance, vaginal pH, and the cytologic cornification index.

Dr. Shirley reports no relevant financial relationships.

A turn away from hormones

Very few of my patients accept hormonal therapy for their menopausal symptoms these days. A couple of patients have asked for bioidentical hormones, and a few others have been candidates for a low-dose oral contraceptive. Some patients ask about blood tests to determine their menopausal status, but they usually agree with me after I explain why these tests are not helpful.

In my practice, the most common menopausal symptom is vaginal dryness—but I usually have to ask about it before the patient acknowledges the problem. I recommend vaginal lubricants more often than local estrogen, and I try to keep a good supply of lubricants on hand.

Overall, patients are fearful of hormones. I try to counsel them that the benefits and risks of hormones vary according to age and route of administration. I rarely prescribe combination estrogen-progestin HT anymore. And I prefer the transdermal route rather than oral administration. In women who have a uterus, I prescribe quarterly progesterone (Prometrium). Otherwise, I recommend unopposed estrogen.

Dr. Goyle reports no relevant financial relationships.

Stress the benefits of HT!

You only get one shot! One shot to sell symptomatic menopausal women on the benefits and use of estrogen. If you drop the ball by not anticipating and explaining the side effects, your patient will quit and buy the junk over the counter, which is usually worse than useless! If you are a firm believer in the four “S”s of HT—sleep, sex, skin, and sanity—you must be positive and stress them to your patient.

Sleep is obviously better when the patient doesn’t wake up drenched in sweat. Sex is better because it doesn’t hurt. (Ask your patient whether she would like a plum or a prune for a vagina! She will instantly grasp the physiologic concept!) Skin is better because of the slowdown in collagen loss. Sanity is improved because of the increase in well being, improved thought processes, and enjoyment of life.

For heaven’s sakes, don’t stop HT after 5 or 6 years! Keep it going with gels, patches, or intravaginal cream forever. After all, women spend more than one third of their life in the postmenopausal phase—make it a wonderful life! Your patients will be appreciative. More important, they will reward you by coming back to see you year after year and singing your praises.

Dr. Franklin reports no relevant financial relationships.

Scare headlines grab attention

Saul R. Berg, MD
Pittsburgh, Pa

I believe that the tide will turn in regard to HT in the not-too-distant future. It takes time for the real truth to get out. In the meantime, scare headlines tend to grab attention.

I hope that, in the near future, we will be able to genetically identify women who should not use HT. Until then, I discuss the risks and benefits of HT with my patients and honor their decision. Transdermal estrogen and bimonthly or quarterly progestin—I typically use Prometrium—are my preference.

At present, there don’t seem to be any outstanding alternatives to hormonal therapy.

Dr. Berg reports no relevant financial relationships.

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Approximately 13 million preterm births occur annually worldwide.¹ Depending on the geographic locale, PPROM is responsible for 16% to 40% of these births.²

The clinical approach to PPROM is one of the most contentious issues in obstetrics, with disagreement on virtually every aspect of it. Under debate are the lower and upper limits of the gestational age range at which intervention is warranted, as well as the use of ancillary interventions such as corticosteroids and antibiotics. Briery and colleagues add to the scientific debate now by asking whether 17P would be effective as cotreatment (with antibiotics) to prolong latency after PPROM.

According to their findings, the answer to this question is “No.”

Details of the trial

Briery and colleagues conducted a placebo-controlled, double-blind, randomized clinical trial of women with a singleton gestation complicated by PPROM. Excluded from the study were women whose pregnancy involved additional fetal or placental complications.

All women included in the study received antibiotics according to a protocol from the National Institutes of Health; they also were given betamethasone for fetal maturation. Tocolytics were not used. Because randomization did not occur until after each woman was transferred from the labor and delivery unit to the high-risk floor, we can assume that no participants were manifesting uterine contractions.

Women received weekly injections of 17P or placebo until 34 weeks’ gestation or delivery. The primary outcome was the interval from study entry to delivery.

One woman had a pregnancy of 23.5 weeks’ duration at randomization; the remainder had gestations that were 24 weeks or older. There were no other differences in demographics, cervical dilatation, gestational age at study entry, or reasons for delivery between the two study groups.

Study design may have been unrealistic

The authors calculated that they needed a sample size of 56 patients to detect a 50% increase in latency, based on population data from their institution showing that 80% of patients who have PPROM deliver within 7 days. Such a calculation may have set an unrealistic—albeit logistically convenient—goal, rendering the study underpowered to detect smaller effects. Note, for example, that when antibiotics are given to women who have PPROM, prolongation of the latency period is only 33% (pooled effect from a recent meta-analysis).³ Even so, given the findings of Briery and colleagues, latency improvement after 17P administration would appear to be unlikely even in a larger study. There was not even a trend toward a longer interval to delivery (mean of 11.2 days with 17P vs 14.5 days with placebo).

Only secondary prevention of preterm birth is effective

The indications for progesterone supplementation in pregnancy are still evolving as part of a sustained scientific effort to prevent preterm labor and delivery. Strategies to prevent preterm delivery can be categorized as primary, secondary, or tertiary, as can strategies for other public health concerns.

Because any number of variables—known and unknown—may trigger preterm labor, identifying them and providing primary preventive strategies in the entire pregnant population remain elusive tasks.

Tertiary prevention—i.e., treatment given to already symptomatic individuals—is also notoriously ineffective. There are no data supporting the use of progesterone as primary prevention (in low-risk women) or tertiary prevention (e.g., tocolytic). ACOG made note of this in 2003, and its conclusions remain valid today.⁴ According to a 2010 Cochrane review, there is insufficient evidence to advocate progestational agents as tocolytic agents for women who present with threatened or established preterm labor.⁵

In light of these data, the results reported by Briery and colleagues are hardly surprising. In women who may have already entered the irreversible phase of parturition (manifesting uterine contractions; presenting with advanced, painless cervical dilatation; or after PPROM), progesterone will remain ineffective. The only applicable use of prophylactic progesterone in pregnancy is as secondary prevention.⁴ In contrast to primary and tertiary prevention, the secondary level of prevention—i.e., an intervention aimed at minimizing the risk of preterm birth in women who are identified as having an elevated risk—is supported by several systematic reviews of randomized, controlled trials.^6,7 According to these reviews, progesterone certainly is effective in high-risk pregnant women who have a short cervix or a history of spontaneous preterm birth. The same cannot be said about women who have PPROM.

We want to hear from you!  Tell us what you think.

Approximately 13 million preterm births occur annually worldwide.¹ Depending on the geographic locale, PPROM is responsible for 16% to 40% of these births.²

The clinical approach to PPROM is one of the most contentious issues in obstetrics, with disagreement on virtually every aspect of it. Under debate are the lower and upper limits of the gestational age range at which intervention is warranted, as well as the use of ancillary interventions such as corticosteroids and antibiotics. Briery and colleagues add to the scientific debate now by asking whether 17P would be effective as cotreatment (with antibiotics) to prolong latency after PPROM.

According to their findings, the answer to this question is “No.”

Details of the trial

Briery and colleagues conducted a placebo-controlled, double-blind, randomized clinical trial of women with a singleton gestation complicated by PPROM. Excluded from the study were women whose pregnancy involved additional fetal or placental complications.

All women included in the study received antibiotics according to a protocol from the National Institutes of Health; they also were given betamethasone for fetal maturation. Tocolytics were not used. Because randomization did not occur until after each woman was transferred from the labor and delivery unit to the high-risk floor, we can assume that no participants were manifesting uterine contractions.

Women received weekly injections of 17P or placebo until 34 weeks’ gestation or delivery. The primary outcome was the interval from study entry to delivery.

One woman had a pregnancy of 23.5 weeks’ duration at randomization; the remainder had gestations that were 24 weeks or older. There were no other differences in demographics, cervical dilatation, gestational age at study entry, or reasons for delivery between the two study groups.

Study design may have been unrealistic

The authors calculated that they needed a sample size of 56 patients to detect a 50% increase in latency, based on population data from their institution showing that 80% of patients who have PPROM deliver within 7 days. Such a calculation may have set an unrealistic—albeit logistically convenient—goal, rendering the study underpowered to detect smaller effects. Note, for example, that when antibiotics are given to women who have PPROM, prolongation of the latency period is only 33% (pooled effect from a recent meta-analysis).³ Even so, given the findings of Briery and colleagues, latency improvement after 17P administration would appear to be unlikely even in a larger study. There was not even a trend toward a longer interval to delivery (mean of 11.2 days with 17P vs 14.5 days with placebo).

Only secondary prevention of preterm birth is effective

The indications for progesterone supplementation in pregnancy are still evolving as part of a sustained scientific effort to prevent preterm labor and delivery. Strategies to prevent preterm delivery can be categorized as primary, secondary, or tertiary, as can strategies for other public health concerns.

Because any number of variables—known and unknown—may trigger preterm labor, identifying them and providing primary preventive strategies in the entire pregnant population remain elusive tasks.

Tertiary prevention—i.e., treatment given to already symptomatic individuals—is also notoriously ineffective. There are no data supporting the use of progesterone as primary prevention (in low-risk women) or tertiary prevention (e.g., tocolytic). ACOG made note of this in 2003, and its conclusions remain valid today.⁴ According to a 2010 Cochrane review, there is insufficient evidence to advocate progestational agents as tocolytic agents for women who present with threatened or established preterm labor.⁵

In light of these data, the results reported by Briery and colleagues are hardly surprising. In women who may have already entered the irreversible phase of parturition (manifesting uterine contractions; presenting with advanced, painless cervical dilatation; or after PPROM), progesterone will remain ineffective. The only applicable use of prophylactic progesterone in pregnancy is as secondary prevention.⁴ In contrast to primary and tertiary prevention, the secondary level of prevention—i.e., an intervention aimed at minimizing the risk of preterm birth in women who are identified as having an elevated risk—is supported by several systematic reviews of randomized, controlled trials.^6,7 According to these reviews, progesterone certainly is effective in high-risk pregnant women who have a short cervix or a history of spontaneous preterm birth. The same cannot be said about women who have PPROM.

We want to hear from you!  Tell us what you think.

Approximately 13 million preterm births occur annually worldwide.¹ Depending on the geographic locale, PPROM is responsible for 16% to 40% of these births.²

The clinical approach to PPROM is one of the most contentious issues in obstetrics, with disagreement on virtually every aspect of it. Under debate are the lower and upper limits of the gestational age range at which intervention is warranted, as well as the use of ancillary interventions such as corticosteroids and antibiotics. Briery and colleagues add to the scientific debate now by asking whether 17P would be effective as cotreatment (with antibiotics) to prolong latency after PPROM.

According to their findings, the answer to this question is “No.”

Details of the trial

Briery and colleagues conducted a placebo-controlled, double-blind, randomized clinical trial of women with a singleton gestation complicated by PPROM. Excluded from the study were women whose pregnancy involved additional fetal or placental complications.

All women included in the study received antibiotics according to a protocol from the National Institutes of Health; they also were given betamethasone for fetal maturation. Tocolytics were not used. Because randomization did not occur until after each woman was transferred from the labor and delivery unit to the high-risk floor, we can assume that no participants were manifesting uterine contractions.

Women received weekly injections of 17P or placebo until 34 weeks’ gestation or delivery. The primary outcome was the interval from study entry to delivery.

One woman had a pregnancy of 23.5 weeks’ duration at randomization; the remainder had gestations that were 24 weeks or older. There were no other differences in demographics, cervical dilatation, gestational age at study entry, or reasons for delivery between the two study groups.

Study design may have been unrealistic

The authors calculated that they needed a sample size of 56 patients to detect a 50% increase in latency, based on population data from their institution showing that 80% of patients who have PPROM deliver within 7 days. Such a calculation may have set an unrealistic—albeit logistically convenient—goal, rendering the study underpowered to detect smaller effects. Note, for example, that when antibiotics are given to women who have PPROM, prolongation of the latency period is only 33% (pooled effect from a recent meta-analysis).³ Even so, given the findings of Briery and colleagues, latency improvement after 17P administration would appear to be unlikely even in a larger study. There was not even a trend toward a longer interval to delivery (mean of 11.2 days with 17P vs 14.5 days with placebo).

Only secondary prevention of preterm birth is effective

The indications for progesterone supplementation in pregnancy are still evolving as part of a sustained scientific effort to prevent preterm labor and delivery. Strategies to prevent preterm delivery can be categorized as primary, secondary, or tertiary, as can strategies for other public health concerns.

Because any number of variables—known and unknown—may trigger preterm labor, identifying them and providing primary preventive strategies in the entire pregnant population remain elusive tasks.

Tertiary prevention—i.e., treatment given to already symptomatic individuals—is also notoriously ineffective. There are no data supporting the use of progesterone as primary prevention (in low-risk women) or tertiary prevention (e.g., tocolytic). ACOG made note of this in 2003, and its conclusions remain valid today.⁴ According to a 2010 Cochrane review, there is insufficient evidence to advocate progestational agents as tocolytic agents for women who present with threatened or established preterm labor.⁵

In light of these data, the results reported by Briery and colleagues are hardly surprising. In women who may have already entered the irreversible phase of parturition (manifesting uterine contractions; presenting with advanced, painless cervical dilatation; or after PPROM), progesterone will remain ineffective. The only applicable use of prophylactic progesterone in pregnancy is as secondary prevention.⁴ In contrast to primary and tertiary prevention, the secondary level of prevention—i.e., an intervention aimed at minimizing the risk of preterm birth in women who are identified as having an elevated risk—is supported by several systematic reviews of randomized, controlled trials.^6,7 According to these reviews, progesterone certainly is effective in high-risk pregnant women who have a short cervix or a history of spontaneous preterm birth. The same cannot be said about women who have PPROM.

We want to hear from you!  Tell us what you think.