There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

Pelvic floor disorders (PFDs) affect many pregnant and newly postpartum women. These conditions, including urinary incontinence, anal incontinence, and pelvic organ prolapse (POP), can be overshadowed by common pregnancy and postpartum concerns (TABLE 1).¹ With the use of a few quick screening questions, however, PFDs easily can be identified in this at-risk population. Active management need not be delayed until after delivery for women experiencing bother, as options exist for women with PFDs during pregnancy as well as postpartum.

In this article, we discuss the common PFDs that obstetric clinicians face in the context of case scenarios and review how you can be better equipped to care for affected individuals.

CASE 1 Screening

A 30-year-old woman (G1P1) presents for her routine postpartum visit after an operative vaginal delivery with a second-degree laceration.

How would you screen this patient for PFDs?

Why screening for PFDs matters

While there are no validated PFD screening tools for this patient population, clinicians can ask a series of brief open-ended questions as part of the review of systems to efficiently evaluate for the common PFDs in peripartum patients (see “Screening questions to evaluate patients for peripartum pelvic floor disorders” below).

Pelvic floor disorders in the peripartum period can have a significant negative impact. In pregnancy, nearly half of women report psychological strain due to the presence of bowel, bladder, prolapse, or sexual dysfunction symptoms.² Postpartum, PFDs have negative effects on overall health, well-being, and self-esteem, with significantly increased rates of postpartum depression in women who experience urinary incontinence.^3,4 Proactively inquiring about PFD symptoms, providing anticipatory guidance, and recommending treatment options can positively impact a patient in multiple domains.

CASE 2 Stress urinary incontinence

A 27-year-old woman (G1P1) presents 2 months following spontaneous vaginal delivery with symptoms of urine leakage with laughing and running. Her urinary incontinence has been improving since delivery, but it continues to be bothersome.

What would you recommend for this patient?

Conservative SUI management strategies in pregnancy

Urinary tract symptoms are common in pregnancy, with up to 41.8% of women reporting urinary symptom distress in the third trimester.⁵ During pregnancy, estrogen and progesterone decrease urethral pressure that, together with increased intra-abdominal pressure from the gravid uterus, can cause or worsen stress urinary incontinence (SUI).⁶

During pregnancy, women should be offered conservative therapies for SUI. For women who can perform a pelvic floor contraction (a Kegel exercise), self-guided pelvic floor muscle exercises (PFMEs) may be helpful (see “Pelvic floor muscle exercises” below). We recommend that women start with 1 to 2 sets of 10 Kegel exercises per day and that they hold the squeeze for 2 to 3 seconds, working up to holding for 10 seconds. The goal is to strengthen and improve muscle control so that the Kegel squeeze can be paired with activities that cause SUI.

For women who are unable to perform a Kegel exercise or are not improving with a home PFME regimen, referral to pelvic floor physical therapy (PFPT) can be considered. While data support the efficacy of PFPT for SUI treatment in nonpregnant women,⁷ data are lacking on PFME in pregnancy.

In women without urinary incontinence, PFME in early pregnancy can prevent the onset of incontinence in late pregnancy and the postpartum period.⁸ By contrast, the same 2020 Cochrane Review found no evidence that antenatal pelvic floor muscle therapy in incontinent women decreases incontinence in mid- or late-pregnancy or in the postpartum period.⁸ As the quality of this evidence is very low and there is no evidence of harm with PFME, we continue to recommend it for women with bothersome SUI.

Incontinence pessaries or vaginal inserts (such as Poise Impressa bladder supports) can be helpful for SUI treatment. An incontinence pessary can be fitted in the office, and fitting kits are available for both. Pessaries can safely be used in pregnancy, but there are no data on the efficacy of pessaries for treating SUI in pregnancy. In nonpregnant women, evidence demonstrates 63% satisfaction 3 months post–pessary placement for SUI.⁷

We do not recommend invasive procedures for the treatment of SUI during pregnancy or in the first 6 months following delivery. There is no evidence that elective cesarean delivery prevents persistent SUI postpartum.⁹

Continue to: Managing SUI in the postpartum period...

Managing SUI in the postpartum period

After the first 6 months postpartum and exhaustion of conservative measures, we offer surgical interventions for women with persistent, bothersome incontinence. Surgery for SUI typically is not recommended until childbearing is complete, but it can be considered if the patient’s bother is significant.

For women with bothersome SUI who still desire future pregnancy, management options include periurethral bulking, a retropubic urethropexy (Burch procedure), or a midurethral sling procedure. Women who undergo an anti-incontinence procedure have an increased risk for urinary retention during a subsequent pregnancy.¹⁰ Most women with a midurethral sling will continue to be continent following an obstetric delivery.

Anticipatory guidance

At 3 months postpartum, the incidence of urinary incontinence is 6% to 40%, depending on parity and delivery type. Postpartum urinary incontinence is most common after instrumented vaginal delivery (32%) followed by spontaneous vaginal delivery (28%) and cesarean delivery (15%). The mean prevalence of any type of urinary incontinence is 33% at 3 months postpartum, and only small changes in the rate of urinary incontinence occur over the first postpartum year.¹¹ While urinary incontinence is common postpartum, it should not be considered normal. We counsel that symptoms may improve spontaneously, but treatment can be initiated if the patient experiences significant bother.

A longitudinal cohort study that followed women from 3 months to 12 years postpartum found that, of women with urinary incontinence at 3 months postpartum, 76% continued to report incontinence at 12 years postpartum.¹² We recommend that women be counseled that, even when symptoms resolve, they remain at increased risk for urinary incontinence in the future. Invasive therapies should be used to treat bothersome urinary incontinence, not to prevent future incontinence.

CASE 3 Fecal incontinence

A 24-year-old woman (G1P1) presents 3 weeks postpartum following a forceps-assisted vaginal delivery complicated by a 3c laceration. She reports fecal urgency, inability to control flatus, and once-daily fecal incontinence.

How would you evaluate these symptoms?

Steps in evaluation

The initial evaluation should include an inquiry regarding the patient’s stool consistency and bowel regimen. The Bristol stool form scale can be used to help patients describe their typical bowel movements (TABLE 2).¹³ During healing, the goal is to achieve a Bristol type 4 stool, both to avoid straining and to improve continence, as loose stool is the most difficult to control.

A physical examination can evaluate healing and sphincter integrity; it should include inspection of the distal vagina and perineal body and a digital rectal exam. Anal canal resting tone and squeeze strength should be evaluated, and the digital rectal examination scoring system (DRESS) can be useful for quantification (TABLE 3).¹⁴ Lack of tone at rest in the anterolateral portion of the sphincter complex can indicate an internal anal sphincter defect, as 80% of the resting tone comes from this muscle (FIGURE).¹⁵

The rectovaginal septum should be assessed given the increased risk of rectovaginal fistula in women with obstetric anal sphincter injury (OASI). The patient should be instructed to contract the anal sphincter, allowing evaluation of muscular contraction. Lack of contraction anteriolaterally may indicate external anal sphincter separation.

Continue to: Conservative options for improving fecal incontinence symptoms...

Conservative options for improving fecal incontinence symptoms

The patient can be counseled regarding stool bulking, first with insoluble fiber supplementation and cessation of stool softeners if she is incontinent of liquid stool. If these measures are not effective, use of a constipating agent, such as loperamide, can improve stool consistency and thereby decrease incontinence episodes. PFPT with biofeedback can be offered as well. While typically we do not recommend initiating PFPT before 6 weeks postpartum, so the initial phases of healing can occur, early referral enables the patient to avoid a delay in access to care.

The patient also can be counseled about a referral to a pelvic floor specialist for further evaluation. A variety of peripartum pelvic floor disorder clinics are being established by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) physicians. These clinics provide the benefit of comprehensive care for pelvic floor disorders in this unique population.

When conservative measures fail. If a patient has persistent bowel control issues despite conservative measures, a referral to an FPMRS physician should be initiated.

Delivery route in future pregnancies

The risk of a subsequent OASI is low. While this means that many women can safely pursue a future vaginal delivery, a scheduled cesarean delivery is indicated for women with persistent bowel control issues, wound healing complications, and those who experienced psychological trauma from their delivery.¹⁶ We recommend a shared-decision making approach, reviewing modifiable and nonmodifiable risk factors to help determine whether or not a future vaginal birth is appropriate. It is important to highlight that a cesarean delivery does not protect against fecal incontinence in women with a history of OASI; however, there is benefit in preventing worsening of anal incontinence, if present.¹⁷

CASE 4 Uterovaginal prolapse

A 36-year-old woman (G3P3) presents for her routine postpartum visit at 6 weeks after a spontaneous vaginal delivery without lacerations. She reports a persistent feeling of vaginal pressure and fullness. She thinks she felt a bulge with wiping after a bowel movement.

What options are available for this patient?

Prolapse in the peripartum population

Previous studies have revealed an increased prevalence of POP in pregnant women on examination compared with their nulligravid counterparts (47.6% vs 0%).¹⁸ With the changes in the hormonal milieu in pregnancy, as well as the weight of the gravid uterus on the pelvic floor, it is not surprising that pregnancy may be the inciting event to expose even transient defects in pelvic organ support.¹⁹

It is well established that increasing parity and, to a lesser extent, larger babies are associated with increased risk for future POP and surgery for prolapse. In the first year postpartum, nearly one-third of women have stage 2 or greater prolapse on exam, with studies demonstrating an increased prevalence of postpartum POP in women who delivered vaginally compared with those who delivered by cesarean.^20,21

Initial evaluation

Diagnosis can be made during a routine pelvic exam by having the patient perform a Valsalva maneuver while in the lithotomy position. Using half of a speculum permits evaluation of the anterior and posterior vaginal walls separately, and Valsalva during a bimanual exam can aid in evaluating descensus of the uterus and cervix.

Excellent free patient education resources available online through the American Urogynecologic Society and the International Urogynecological Association can be used to direct counseling.

Continue to: Treatments you can offer for POP...

For pregnant or postpartum patients with bothersome prolapse, initial management options include pessary fitting and/or PFPT referral. In pregnancy, women often can be successfully fitted with a pessary for POP; however, as expulsion is a common issue, selection of a stiffer or space-occupying device may be more efficacious.

Often, early onset POP in pregnancy resolves as the gravid uterus lifts out of the pelvis in the second trimester, at which time the pessary can be discontinued. In the postpartum period, a pessary fitting can be undertaken similarly to that in nonpregnant patients. While data are lacking in the peripartum population, evidence supports the positive impact of PFPT on improving POP symptom bother.²² Additionally, for postpartum women who experience OASI, PFPT can produce significant improvement in subjective POP and associated bother.²³

Impact of future childbearing wishes on treatment

The desire for future childbearing does not preclude treatment of patients experiencing bother from POP after conservative management options have failed. Both vaginal native tissue and mesh-augmented uterine-sparing repairs are performed by many FPMRS specialists and are associated with good outcomes. As with SUI, we do not recommend invasive treatment for POP during pregnancy or before 6 months postpartum.

In conclusion

Obstetric specialists play an essential role in caring for women with PFDs in the peripartum period. Basic evaluation, counseling, and management can be initiated using many of the resources already available in an obstetric ambulatory practice. Important adjunctive resources include those available for both providers and patients through the American Urogynecologic Society and the International Urogynecological Association. In addition, clinicians can partner with pelvic floor specialists through the growing number of FPMRS-run peripartum pelvic floor disorder clinics across the country and pelvic floor physical therapists.

If these specialty clinics and therapists are not available in your area, FPMRS specialists, urologists, gastroenterologists, and/or colorectal surgeons can aid in patient diagnosis and management to reach the ultimate goal of improving PFDs in this at-risk population. ●

Pelvic floor disorders (PFDs) affect many pregnant and newly postpartum women. These conditions, including urinary incontinence, anal incontinence, and pelvic organ prolapse (POP), can be overshadowed by common pregnancy and postpartum concerns (TABLE 1).¹ With the use of a few quick screening questions, however, PFDs easily can be identified in this at-risk population. Active management need not be delayed until after delivery for women experiencing bother, as options exist for women with PFDs during pregnancy as well as postpartum.

In this article, we discuss the common PFDs that obstetric clinicians face in the context of case scenarios and review how you can be better equipped to care for affected individuals.

CASE 1 Screening

A 30-year-old woman (G1P1) presents for her routine postpartum visit after an operative vaginal delivery with a second-degree laceration.

How would you screen this patient for PFDs?

Why screening for PFDs matters

While there are no validated PFD screening tools for this patient population, clinicians can ask a series of brief open-ended questions as part of the review of systems to efficiently evaluate for the common PFDs in peripartum patients (see “Screening questions to evaluate patients for peripartum pelvic floor disorders” below).

Pelvic floor disorders in the peripartum period can have a significant negative impact. In pregnancy, nearly half of women report psychological strain due to the presence of bowel, bladder, prolapse, or sexual dysfunction symptoms.² Postpartum, PFDs have negative effects on overall health, well-being, and self-esteem, with significantly increased rates of postpartum depression in women who experience urinary incontinence.^3,4 Proactively inquiring about PFD symptoms, providing anticipatory guidance, and recommending treatment options can positively impact a patient in multiple domains.

CASE 2 Stress urinary incontinence

A 27-year-old woman (G1P1) presents 2 months following spontaneous vaginal delivery with symptoms of urine leakage with laughing and running. Her urinary incontinence has been improving since delivery, but it continues to be bothersome.

What would you recommend for this patient?

Conservative SUI management strategies in pregnancy

Urinary tract symptoms are common in pregnancy, with up to 41.8% of women reporting urinary symptom distress in the third trimester.⁵ During pregnancy, estrogen and progesterone decrease urethral pressure that, together with increased intra-abdominal pressure from the gravid uterus, can cause or worsen stress urinary incontinence (SUI).⁶

During pregnancy, women should be offered conservative therapies for SUI. For women who can perform a pelvic floor contraction (a Kegel exercise), self-guided pelvic floor muscle exercises (PFMEs) may be helpful (see “Pelvic floor muscle exercises” below). We recommend that women start with 1 to 2 sets of 10 Kegel exercises per day and that they hold the squeeze for 2 to 3 seconds, working up to holding for 10 seconds. The goal is to strengthen and improve muscle control so that the Kegel squeeze can be paired with activities that cause SUI.

For women who are unable to perform a Kegel exercise or are not improving with a home PFME regimen, referral to pelvic floor physical therapy (PFPT) can be considered. While data support the efficacy of PFPT for SUI treatment in nonpregnant women,⁷ data are lacking on PFME in pregnancy.

In women without urinary incontinence, PFME in early pregnancy can prevent the onset of incontinence in late pregnancy and the postpartum period.⁸ By contrast, the same 2020 Cochrane Review found no evidence that antenatal pelvic floor muscle therapy in incontinent women decreases incontinence in mid- or late-pregnancy or in the postpartum period.⁸ As the quality of this evidence is very low and there is no evidence of harm with PFME, we continue to recommend it for women with bothersome SUI.

Incontinence pessaries or vaginal inserts (such as Poise Impressa bladder supports) can be helpful for SUI treatment. An incontinence pessary can be fitted in the office, and fitting kits are available for both. Pessaries can safely be used in pregnancy, but there are no data on the efficacy of pessaries for treating SUI in pregnancy. In nonpregnant women, evidence demonstrates 63% satisfaction 3 months post–pessary placement for SUI.⁷

We do not recommend invasive procedures for the treatment of SUI during pregnancy or in the first 6 months following delivery. There is no evidence that elective cesarean delivery prevents persistent SUI postpartum.⁹

Continue to: Managing SUI in the postpartum period...

Managing SUI in the postpartum period

After the first 6 months postpartum and exhaustion of conservative measures, we offer surgical interventions for women with persistent, bothersome incontinence. Surgery for SUI typically is not recommended until childbearing is complete, but it can be considered if the patient’s bother is significant.

For women with bothersome SUI who still desire future pregnancy, management options include periurethral bulking, a retropubic urethropexy (Burch procedure), or a midurethral sling procedure. Women who undergo an anti-incontinence procedure have an increased risk for urinary retention during a subsequent pregnancy.¹⁰ Most women with a midurethral sling will continue to be continent following an obstetric delivery.

Anticipatory guidance

At 3 months postpartum, the incidence of urinary incontinence is 6% to 40%, depending on parity and delivery type. Postpartum urinary incontinence is most common after instrumented vaginal delivery (32%) followed by spontaneous vaginal delivery (28%) and cesarean delivery (15%). The mean prevalence of any type of urinary incontinence is 33% at 3 months postpartum, and only small changes in the rate of urinary incontinence occur over the first postpartum year.¹¹ While urinary incontinence is common postpartum, it should not be considered normal. We counsel that symptoms may improve spontaneously, but treatment can be initiated if the patient experiences significant bother.

A longitudinal cohort study that followed women from 3 months to 12 years postpartum found that, of women with urinary incontinence at 3 months postpartum, 76% continued to report incontinence at 12 years postpartum.¹² We recommend that women be counseled that, even when symptoms resolve, they remain at increased risk for urinary incontinence in the future. Invasive therapies should be used to treat bothersome urinary incontinence, not to prevent future incontinence.

CASE 3 Fecal incontinence

A 24-year-old woman (G1P1) presents 3 weeks postpartum following a forceps-assisted vaginal delivery complicated by a 3c laceration. She reports fecal urgency, inability to control flatus, and once-daily fecal incontinence.

How would you evaluate these symptoms?

Steps in evaluation

The initial evaluation should include an inquiry regarding the patient’s stool consistency and bowel regimen. The Bristol stool form scale can be used to help patients describe their typical bowel movements (TABLE 2).¹³ During healing, the goal is to achieve a Bristol type 4 stool, both to avoid straining and to improve continence, as loose stool is the most difficult to control.

A physical examination can evaluate healing and sphincter integrity; it should include inspection of the distal vagina and perineal body and a digital rectal exam. Anal canal resting tone and squeeze strength should be evaluated, and the digital rectal examination scoring system (DRESS) can be useful for quantification (TABLE 3).¹⁴ Lack of tone at rest in the anterolateral portion of the sphincter complex can indicate an internal anal sphincter defect, as 80% of the resting tone comes from this muscle (FIGURE).¹⁵

The rectovaginal septum should be assessed given the increased risk of rectovaginal fistula in women with obstetric anal sphincter injury (OASI). The patient should be instructed to contract the anal sphincter, allowing evaluation of muscular contraction. Lack of contraction anteriolaterally may indicate external anal sphincter separation.

Continue to: Conservative options for improving fecal incontinence symptoms...

Conservative options for improving fecal incontinence symptoms

The patient can be counseled regarding stool bulking, first with insoluble fiber supplementation and cessation of stool softeners if she is incontinent of liquid stool. If these measures are not effective, use of a constipating agent, such as loperamide, can improve stool consistency and thereby decrease incontinence episodes. PFPT with biofeedback can be offered as well. While typically we do not recommend initiating PFPT before 6 weeks postpartum, so the initial phases of healing can occur, early referral enables the patient to avoid a delay in access to care.

The patient also can be counseled about a referral to a pelvic floor specialist for further evaluation. A variety of peripartum pelvic floor disorder clinics are being established by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) physicians. These clinics provide the benefit of comprehensive care for pelvic floor disorders in this unique population.

When conservative measures fail. If a patient has persistent bowel control issues despite conservative measures, a referral to an FPMRS physician should be initiated.

Delivery route in future pregnancies

The risk of a subsequent OASI is low. While this means that many women can safely pursue a future vaginal delivery, a scheduled cesarean delivery is indicated for women with persistent bowel control issues, wound healing complications, and those who experienced psychological trauma from their delivery.¹⁶ We recommend a shared-decision making approach, reviewing modifiable and nonmodifiable risk factors to help determine whether or not a future vaginal birth is appropriate. It is important to highlight that a cesarean delivery does not protect against fecal incontinence in women with a history of OASI; however, there is benefit in preventing worsening of anal incontinence, if present.¹⁷

CASE 4 Uterovaginal prolapse

A 36-year-old woman (G3P3) presents for her routine postpartum visit at 6 weeks after a spontaneous vaginal delivery without lacerations. She reports a persistent feeling of vaginal pressure and fullness. She thinks she felt a bulge with wiping after a bowel movement.

What options are available for this patient?

Prolapse in the peripartum population

Previous studies have revealed an increased prevalence of POP in pregnant women on examination compared with their nulligravid counterparts (47.6% vs 0%).¹⁸ With the changes in the hormonal milieu in pregnancy, as well as the weight of the gravid uterus on the pelvic floor, it is not surprising that pregnancy may be the inciting event to expose even transient defects in pelvic organ support.¹⁹

It is well established that increasing parity and, to a lesser extent, larger babies are associated with increased risk for future POP and surgery for prolapse. In the first year postpartum, nearly one-third of women have stage 2 or greater prolapse on exam, with studies demonstrating an increased prevalence of postpartum POP in women who delivered vaginally compared with those who delivered by cesarean.^20,21

Initial evaluation

Diagnosis can be made during a routine pelvic exam by having the patient perform a Valsalva maneuver while in the lithotomy position. Using half of a speculum permits evaluation of the anterior and posterior vaginal walls separately, and Valsalva during a bimanual exam can aid in evaluating descensus of the uterus and cervix.

Excellent free patient education resources available online through the American Urogynecologic Society and the International Urogynecological Association can be used to direct counseling.

Continue to: Treatments you can offer for POP...

For pregnant or postpartum patients with bothersome prolapse, initial management options include pessary fitting and/or PFPT referral. In pregnancy, women often can be successfully fitted with a pessary for POP; however, as expulsion is a common issue, selection of a stiffer or space-occupying device may be more efficacious.

Often, early onset POP in pregnancy resolves as the gravid uterus lifts out of the pelvis in the second trimester, at which time the pessary can be discontinued. In the postpartum period, a pessary fitting can be undertaken similarly to that in nonpregnant patients. While data are lacking in the peripartum population, evidence supports the positive impact of PFPT on improving POP symptom bother.²² Additionally, for postpartum women who experience OASI, PFPT can produce significant improvement in subjective POP and associated bother.²³

Impact of future childbearing wishes on treatment

The desire for future childbearing does not preclude treatment of patients experiencing bother from POP after conservative management options have failed. Both vaginal native tissue and mesh-augmented uterine-sparing repairs are performed by many FPMRS specialists and are associated with good outcomes. As with SUI, we do not recommend invasive treatment for POP during pregnancy or before 6 months postpartum.

In conclusion

Obstetric specialists play an essential role in caring for women with PFDs in the peripartum period. Basic evaluation, counseling, and management can be initiated using many of the resources already available in an obstetric ambulatory practice. Important adjunctive resources include those available for both providers and patients through the American Urogynecologic Society and the International Urogynecological Association. In addition, clinicians can partner with pelvic floor specialists through the growing number of FPMRS-run peripartum pelvic floor disorder clinics across the country and pelvic floor physical therapists.

If these specialty clinics and therapists are not available in your area, FPMRS specialists, urologists, gastroenterologists, and/or colorectal surgeons can aid in patient diagnosis and management to reach the ultimate goal of improving PFDs in this at-risk population. ●

Pelvic floor disorders (PFDs) affect many pregnant and newly postpartum women. These conditions, including urinary incontinence, anal incontinence, and pelvic organ prolapse (POP), can be overshadowed by common pregnancy and postpartum concerns (TABLE 1).¹ With the use of a few quick screening questions, however, PFDs easily can be identified in this at-risk population. Active management need not be delayed until after delivery for women experiencing bother, as options exist for women with PFDs during pregnancy as well as postpartum.

In this article, we discuss the common PFDs that obstetric clinicians face in the context of case scenarios and review how you can be better equipped to care for affected individuals.

CASE 1 Screening

A 30-year-old woman (G1P1) presents for her routine postpartum visit after an operative vaginal delivery with a second-degree laceration.

How would you screen this patient for PFDs?

Why screening for PFDs matters

While there are no validated PFD screening tools for this patient population, clinicians can ask a series of brief open-ended questions as part of the review of systems to efficiently evaluate for the common PFDs in peripartum patients (see “Screening questions to evaluate patients for peripartum pelvic floor disorders” below).

Pelvic floor disorders in the peripartum period can have a significant negative impact. In pregnancy, nearly half of women report psychological strain due to the presence of bowel, bladder, prolapse, or sexual dysfunction symptoms.² Postpartum, PFDs have negative effects on overall health, well-being, and self-esteem, with significantly increased rates of postpartum depression in women who experience urinary incontinence.^3,4 Proactively inquiring about PFD symptoms, providing anticipatory guidance, and recommending treatment options can positively impact a patient in multiple domains.

CASE 2 Stress urinary incontinence

A 27-year-old woman (G1P1) presents 2 months following spontaneous vaginal delivery with symptoms of urine leakage with laughing and running. Her urinary incontinence has been improving since delivery, but it continues to be bothersome.

What would you recommend for this patient?

Conservative SUI management strategies in pregnancy

Urinary tract symptoms are common in pregnancy, with up to 41.8% of women reporting urinary symptom distress in the third trimester.⁵ During pregnancy, estrogen and progesterone decrease urethral pressure that, together with increased intra-abdominal pressure from the gravid uterus, can cause or worsen stress urinary incontinence (SUI).⁶

During pregnancy, women should be offered conservative therapies for SUI. For women who can perform a pelvic floor contraction (a Kegel exercise), self-guided pelvic floor muscle exercises (PFMEs) may be helpful (see “Pelvic floor muscle exercises” below). We recommend that women start with 1 to 2 sets of 10 Kegel exercises per day and that they hold the squeeze for 2 to 3 seconds, working up to holding for 10 seconds. The goal is to strengthen and improve muscle control so that the Kegel squeeze can be paired with activities that cause SUI.

For women who are unable to perform a Kegel exercise or are not improving with a home PFME regimen, referral to pelvic floor physical therapy (PFPT) can be considered. While data support the efficacy of PFPT for SUI treatment in nonpregnant women,⁷ data are lacking on PFME in pregnancy.

In women without urinary incontinence, PFME in early pregnancy can prevent the onset of incontinence in late pregnancy and the postpartum period.⁸ By contrast, the same 2020 Cochrane Review found no evidence that antenatal pelvic floor muscle therapy in incontinent women decreases incontinence in mid- or late-pregnancy or in the postpartum period.⁸ As the quality of this evidence is very low and there is no evidence of harm with PFME, we continue to recommend it for women with bothersome SUI.

Incontinence pessaries or vaginal inserts (such as Poise Impressa bladder supports) can be helpful for SUI treatment. An incontinence pessary can be fitted in the office, and fitting kits are available for both. Pessaries can safely be used in pregnancy, but there are no data on the efficacy of pessaries for treating SUI in pregnancy. In nonpregnant women, evidence demonstrates 63% satisfaction 3 months post–pessary placement for SUI.⁷

We do not recommend invasive procedures for the treatment of SUI during pregnancy or in the first 6 months following delivery. There is no evidence that elective cesarean delivery prevents persistent SUI postpartum.⁹

Continue to: Managing SUI in the postpartum period...

Managing SUI in the postpartum period

After the first 6 months postpartum and exhaustion of conservative measures, we offer surgical interventions for women with persistent, bothersome incontinence. Surgery for SUI typically is not recommended until childbearing is complete, but it can be considered if the patient’s bother is significant.

For women with bothersome SUI who still desire future pregnancy, management options include periurethral bulking, a retropubic urethropexy (Burch procedure), or a midurethral sling procedure. Women who undergo an anti-incontinence procedure have an increased risk for urinary retention during a subsequent pregnancy.¹⁰ Most women with a midurethral sling will continue to be continent following an obstetric delivery.

Anticipatory guidance

At 3 months postpartum, the incidence of urinary incontinence is 6% to 40%, depending on parity and delivery type. Postpartum urinary incontinence is most common after instrumented vaginal delivery (32%) followed by spontaneous vaginal delivery (28%) and cesarean delivery (15%). The mean prevalence of any type of urinary incontinence is 33% at 3 months postpartum, and only small changes in the rate of urinary incontinence occur over the first postpartum year.¹¹ While urinary incontinence is common postpartum, it should not be considered normal. We counsel that symptoms may improve spontaneously, but treatment can be initiated if the patient experiences significant bother.

A longitudinal cohort study that followed women from 3 months to 12 years postpartum found that, of women with urinary incontinence at 3 months postpartum, 76% continued to report incontinence at 12 years postpartum.¹² We recommend that women be counseled that, even when symptoms resolve, they remain at increased risk for urinary incontinence in the future. Invasive therapies should be used to treat bothersome urinary incontinence, not to prevent future incontinence.

CASE 3 Fecal incontinence

A 24-year-old woman (G1P1) presents 3 weeks postpartum following a forceps-assisted vaginal delivery complicated by a 3c laceration. She reports fecal urgency, inability to control flatus, and once-daily fecal incontinence.

How would you evaluate these symptoms?

Steps in evaluation

The initial evaluation should include an inquiry regarding the patient’s stool consistency and bowel regimen. The Bristol stool form scale can be used to help patients describe their typical bowel movements (TABLE 2).¹³ During healing, the goal is to achieve a Bristol type 4 stool, both to avoid straining and to improve continence, as loose stool is the most difficult to control.

A physical examination can evaluate healing and sphincter integrity; it should include inspection of the distal vagina and perineal body and a digital rectal exam. Anal canal resting tone and squeeze strength should be evaluated, and the digital rectal examination scoring system (DRESS) can be useful for quantification (TABLE 3).¹⁴ Lack of tone at rest in the anterolateral portion of the sphincter complex can indicate an internal anal sphincter defect, as 80% of the resting tone comes from this muscle (FIGURE).¹⁵

The rectovaginal septum should be assessed given the increased risk of rectovaginal fistula in women with obstetric anal sphincter injury (OASI). The patient should be instructed to contract the anal sphincter, allowing evaluation of muscular contraction. Lack of contraction anteriolaterally may indicate external anal sphincter separation.

Continue to: Conservative options for improving fecal incontinence symptoms...

Conservative options for improving fecal incontinence symptoms

The patient can be counseled regarding stool bulking, first with insoluble fiber supplementation and cessation of stool softeners if she is incontinent of liquid stool. If these measures are not effective, use of a constipating agent, such as loperamide, can improve stool consistency and thereby decrease incontinence episodes. PFPT with biofeedback can be offered as well. While typically we do not recommend initiating PFPT before 6 weeks postpartum, so the initial phases of healing can occur, early referral enables the patient to avoid a delay in access to care.

The patient also can be counseled about a referral to a pelvic floor specialist for further evaluation. A variety of peripartum pelvic floor disorder clinics are being established by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) physicians. These clinics provide the benefit of comprehensive care for pelvic floor disorders in this unique population.

When conservative measures fail. If a patient has persistent bowel control issues despite conservative measures, a referral to an FPMRS physician should be initiated.

Delivery route in future pregnancies

The risk of a subsequent OASI is low. While this means that many women can safely pursue a future vaginal delivery, a scheduled cesarean delivery is indicated for women with persistent bowel control issues, wound healing complications, and those who experienced psychological trauma from their delivery.¹⁶ We recommend a shared-decision making approach, reviewing modifiable and nonmodifiable risk factors to help determine whether or not a future vaginal birth is appropriate. It is important to highlight that a cesarean delivery does not protect against fecal incontinence in women with a history of OASI; however, there is benefit in preventing worsening of anal incontinence, if present.¹⁷

CASE 4 Uterovaginal prolapse

A 36-year-old woman (G3P3) presents for her routine postpartum visit at 6 weeks after a spontaneous vaginal delivery without lacerations. She reports a persistent feeling of vaginal pressure and fullness. She thinks she felt a bulge with wiping after a bowel movement.

What options are available for this patient?

Prolapse in the peripartum population

Previous studies have revealed an increased prevalence of POP in pregnant women on examination compared with their nulligravid counterparts (47.6% vs 0%).¹⁸ With the changes in the hormonal milieu in pregnancy, as well as the weight of the gravid uterus on the pelvic floor, it is not surprising that pregnancy may be the inciting event to expose even transient defects in pelvic organ support.¹⁹

It is well established that increasing parity and, to a lesser extent, larger babies are associated with increased risk for future POP and surgery for prolapse. In the first year postpartum, nearly one-third of women have stage 2 or greater prolapse on exam, with studies demonstrating an increased prevalence of postpartum POP in women who delivered vaginally compared with those who delivered by cesarean.^20,21

Initial evaluation

Diagnosis can be made during a routine pelvic exam by having the patient perform a Valsalva maneuver while in the lithotomy position. Using half of a speculum permits evaluation of the anterior and posterior vaginal walls separately, and Valsalva during a bimanual exam can aid in evaluating descensus of the uterus and cervix.

Excellent free patient education resources available online through the American Urogynecologic Society and the International Urogynecological Association can be used to direct counseling.

Continue to: Treatments you can offer for POP...

For pregnant or postpartum patients with bothersome prolapse, initial management options include pessary fitting and/or PFPT referral. In pregnancy, women often can be successfully fitted with a pessary for POP; however, as expulsion is a common issue, selection of a stiffer or space-occupying device may be more efficacious.

Often, early onset POP in pregnancy resolves as the gravid uterus lifts out of the pelvis in the second trimester, at which time the pessary can be discontinued. In the postpartum period, a pessary fitting can be undertaken similarly to that in nonpregnant patients. While data are lacking in the peripartum population, evidence supports the positive impact of PFPT on improving POP symptom bother.²² Additionally, for postpartum women who experience OASI, PFPT can produce significant improvement in subjective POP and associated bother.²³

Impact of future childbearing wishes on treatment

The desire for future childbearing does not preclude treatment of patients experiencing bother from POP after conservative management options have failed. Both vaginal native tissue and mesh-augmented uterine-sparing repairs are performed by many FPMRS specialists and are associated with good outcomes. As with SUI, we do not recommend invasive treatment for POP during pregnancy or before 6 months postpartum.

In conclusion

Obstetric specialists play an essential role in caring for women with PFDs in the peripartum period. Basic evaluation, counseling, and management can be initiated using many of the resources already available in an obstetric ambulatory practice. Important adjunctive resources include those available for both providers and patients through the American Urogynecologic Society and the International Urogynecological Association. In addition, clinicians can partner with pelvic floor specialists through the growing number of FPMRS-run peripartum pelvic floor disorder clinics across the country and pelvic floor physical therapists.

If these specialty clinics and therapists are not available in your area, FPMRS specialists, urologists, gastroenterologists, and/or colorectal surgeons can aid in patient diagnosis and management to reach the ultimate goal of improving PFDs in this at-risk population. ●

Raghuraman N, Temming LA, Doering MM, et al. Maternal oxygen supplementation compared with room air for intrauterine resuscitation: a systematic review and meta-analysis. JAMA Pediatr. January 4, 2021. doi:10.1001/jamapediatrics.2020.5351.

EXPERT COMMENTARY

Maternal oxygen supplementation is widely used in labor for nonreassuring fetal heart rate (FHR) tracings, although its efficacy is uncertain for preventing fetal acidosis, operative intervention, or sequelae of neonatal encephalopathy. Recently, Raghuraman and colleagues reported the results of a systematic review and meta-analysis that included 16 randomized controlled trials. A total of 1,078 women were included in the oxygen group and 974 in the room air group. The primary outcome was umbilical artery pH; 14 trials reported on this outcome.

After analyzing the pooled and stratified results of the effect of maternal oxygen supplementation versus room air on umbilical artery gas measures, the authors concluded that peripartum oxygen supplementation is not associated with clinically relevant improvement in umbilical artery pH. They acknowledged, however, that the published studies were heterogeneous, lacked data on the association of oxygen supplementation with neonatal outcome, and did not assess oxygen use for abnormal FHR tracings, except for one trial with category II FHR tracings.

Effects of O₂ supplementation

As maternal arterial hemoglobin is nearly saturated under normal conditions, maternal hyperoxia produces only modest increases in umbilical vein Po₂ and O₂ content during maternal normoxemia but greater effects during maternal hypoxemia (FIGURE).¹ Maternal O₂ supplementation will impact fetal oxygenation depending on the extent of O₂ supplementation and the normality of maternal, placental, and fetal O₂ transport steps.²

Fetal hypoxemia and acidosis can result from an interruption or an impairment of the mother-to-placenta-to-fetus oxygen pathway. With some interruptions of the oxygen pathway, such as placental abruption and complete cord occlusion–induced bradycardia, there would be less impact of maternal hyperoxia. By contrast, with other oxygen pathway impairments, such as reduced oxygen transfer with placental insufficiency, maternal hyperoxia can be of greater value by increasing maternal uterine artery and vein Po₂ and, thus, the placental O₂ transfer.

Continue to: Circumstances that may benefit from O₂ supplementation...

Late FHR decelerations reflect impairment of oxygen transfer and thus represent the heart rate pattern that is most likely to benefit from maternal hyperoxia. However, recurrent late decelerations occur in less than 2% of low-risk patients in labor,³ and severe levels of acidosis (umbilical artery pH <7.0 or base deficit [BD] ≥12 mmol/L) occur in only 1% to 2% of near-term or term deliveries.^4,5

Variable decelerations also reflect fetal hypoxia and are much more common than late decelerations, so they also may benefit from O₂ supplementation. Regardless, O₂ supplementation should be seen only as a temporizing strategy while other resuscitative actions are initiated, including preparation for operative delivery, if indicated.

In a prior study by Raghuraman and colleagues (1 of only 4 studies that met selection criteria of oxygen supplementation for patients in labor), newborns of patients not receiving oxygen demonstrated 95% confidence limits of umbilical artery pH (7.24–7.28) and BD (2.9–4.3) well within the normal range.⁶ Thus, the low prevalence of cases in which a benefit might be anticipated and the low incidence of severe acidosis challenges the design of prospective studies to detect statistically and clinically significant changes in blood gas measures and newborn outcomes.

The normal mild fetal acidosis that develops during labor is likely a result of recurrent interruption of uterine placental blood flow during uterine contractions⁷ and is unlikely to benefit from maternal hyperoxia. Similarly, as placental oxygen transfer is predominantly flow rather than diffusion limited,⁸ oxygen supplementation is unlikely to improve severe variable FHR decelerations. Thus, a randomized study of hyperoxia in unselected laboring patients is unlikely to have a measurable effect on clinically significant acidosis.

Oxygen transport pathway guides treatment

For the present, an understanding of oxygen transport can guide clinical oxygen use. Thus, mothers with relative hypoxemia will unquestionably benefit with supplemental oxygen administration. Similarly, fetuses at risk for placental dysfunction (for example, growth restriction, postterm) and particularly those manifesting evidence of impaired oxygen transport (that is, late decelerations) may be most likely to benefit from the increased O₂ gradient. For patients with reduced maternal uterine perfusion (such as hypotension or hypovolemia), pressors and/or fluid volume are likely to be more effective, while amnioinfusion is of greater value for umbilical cord compression patterns. A reduction in uterine activity may be of benefit to all fetuses exhibiting compromise. Due to the modest impact on fetal oxygen content, maternal hyperoxia does not produce significant fetal oxidative stress as measured by fetal malondialdehyde levels. 

Raghuraman N, Temming LA, Doering MM, et al. Maternal oxygen supplementation compared with room air for intrauterine resuscitation: a systematic review and meta-analysis. JAMA Pediatr. January 4, 2021. doi:10.1001/jamapediatrics.2020.5351.

EXPERT COMMENTARY

Maternal oxygen supplementation is widely used in labor for nonreassuring fetal heart rate (FHR) tracings, although its efficacy is uncertain for preventing fetal acidosis, operative intervention, or sequelae of neonatal encephalopathy. Recently, Raghuraman and colleagues reported the results of a systematic review and meta-analysis that included 16 randomized controlled trials. A total of 1,078 women were included in the oxygen group and 974 in the room air group. The primary outcome was umbilical artery pH; 14 trials reported on this outcome.

After analyzing the pooled and stratified results of the effect of maternal oxygen supplementation versus room air on umbilical artery gas measures, the authors concluded that peripartum oxygen supplementation is not associated with clinically relevant improvement in umbilical artery pH. They acknowledged, however, that the published studies were heterogeneous, lacked data on the association of oxygen supplementation with neonatal outcome, and did not assess oxygen use for abnormal FHR tracings, except for one trial with category II FHR tracings.

Effects of O₂ supplementation

As maternal arterial hemoglobin is nearly saturated under normal conditions, maternal hyperoxia produces only modest increases in umbilical vein Po₂ and O₂ content during maternal normoxemia but greater effects during maternal hypoxemia (FIGURE).¹ Maternal O₂ supplementation will impact fetal oxygenation depending on the extent of O₂ supplementation and the normality of maternal, placental, and fetal O₂ transport steps.²

Fetal hypoxemia and acidosis can result from an interruption or an impairment of the mother-to-placenta-to-fetus oxygen pathway. With some interruptions of the oxygen pathway, such as placental abruption and complete cord occlusion–induced bradycardia, there would be less impact of maternal hyperoxia. By contrast, with other oxygen pathway impairments, such as reduced oxygen transfer with placental insufficiency, maternal hyperoxia can be of greater value by increasing maternal uterine artery and vein Po₂ and, thus, the placental O₂ transfer.

Continue to: Circumstances that may benefit from O₂ supplementation...

Late FHR decelerations reflect impairment of oxygen transfer and thus represent the heart rate pattern that is most likely to benefit from maternal hyperoxia. However, recurrent late decelerations occur in less than 2% of low-risk patients in labor,³ and severe levels of acidosis (umbilical artery pH <7.0 or base deficit [BD] ≥12 mmol/L) occur in only 1% to 2% of near-term or term deliveries.^4,5

Variable decelerations also reflect fetal hypoxia and are much more common than late decelerations, so they also may benefit from O₂ supplementation. Regardless, O₂ supplementation should be seen only as a temporizing strategy while other resuscitative actions are initiated, including preparation for operative delivery, if indicated.

In a prior study by Raghuraman and colleagues (1 of only 4 studies that met selection criteria of oxygen supplementation for patients in labor), newborns of patients not receiving oxygen demonstrated 95% confidence limits of umbilical artery pH (7.24–7.28) and BD (2.9–4.3) well within the normal range.⁶ Thus, the low prevalence of cases in which a benefit might be anticipated and the low incidence of severe acidosis challenges the design of prospective studies to detect statistically and clinically significant changes in blood gas measures and newborn outcomes.

The normal mild fetal acidosis that develops during labor is likely a result of recurrent interruption of uterine placental blood flow during uterine contractions⁷ and is unlikely to benefit from maternal hyperoxia. Similarly, as placental oxygen transfer is predominantly flow rather than diffusion limited,⁸ oxygen supplementation is unlikely to improve severe variable FHR decelerations. Thus, a randomized study of hyperoxia in unselected laboring patients is unlikely to have a measurable effect on clinically significant acidosis.

Oxygen transport pathway guides treatment

For the present, an understanding of oxygen transport can guide clinical oxygen use. Thus, mothers with relative hypoxemia will unquestionably benefit with supplemental oxygen administration. Similarly, fetuses at risk for placental dysfunction (for example, growth restriction, postterm) and particularly those manifesting evidence of impaired oxygen transport (that is, late decelerations) may be most likely to benefit from the increased O₂ gradient. For patients with reduced maternal uterine perfusion (such as hypotension or hypovolemia), pressors and/or fluid volume are likely to be more effective, while amnioinfusion is of greater value for umbilical cord compression patterns. A reduction in uterine activity may be of benefit to all fetuses exhibiting compromise. Due to the modest impact on fetal oxygen content, maternal hyperoxia does not produce significant fetal oxidative stress as measured by fetal malondialdehyde levels. 

Raghuraman N, Temming LA, Doering MM, et al. Maternal oxygen supplementation compared with room air for intrauterine resuscitation: a systematic review and meta-analysis. JAMA Pediatr. January 4, 2021. doi:10.1001/jamapediatrics.2020.5351.

EXPERT COMMENTARY

Maternal oxygen supplementation is widely used in labor for nonreassuring fetal heart rate (FHR) tracings, although its efficacy is uncertain for preventing fetal acidosis, operative intervention, or sequelae of neonatal encephalopathy. Recently, Raghuraman and colleagues reported the results of a systematic review and meta-analysis that included 16 randomized controlled trials. A total of 1,078 women were included in the oxygen group and 974 in the room air group. The primary outcome was umbilical artery pH; 14 trials reported on this outcome.

After analyzing the pooled and stratified results of the effect of maternal oxygen supplementation versus room air on umbilical artery gas measures, the authors concluded that peripartum oxygen supplementation is not associated with clinically relevant improvement in umbilical artery pH. They acknowledged, however, that the published studies were heterogeneous, lacked data on the association of oxygen supplementation with neonatal outcome, and did not assess oxygen use for abnormal FHR tracings, except for one trial with category II FHR tracings.

Effects of O₂ supplementation

As maternal arterial hemoglobin is nearly saturated under normal conditions, maternal hyperoxia produces only modest increases in umbilical vein Po₂ and O₂ content during maternal normoxemia but greater effects during maternal hypoxemia (FIGURE).¹ Maternal O₂ supplementation will impact fetal oxygenation depending on the extent of O₂ supplementation and the normality of maternal, placental, and fetal O₂ transport steps.²

Fetal hypoxemia and acidosis can result from an interruption or an impairment of the mother-to-placenta-to-fetus oxygen pathway. With some interruptions of the oxygen pathway, such as placental abruption and complete cord occlusion–induced bradycardia, there would be less impact of maternal hyperoxia. By contrast, with other oxygen pathway impairments, such as reduced oxygen transfer with placental insufficiency, maternal hyperoxia can be of greater value by increasing maternal uterine artery and vein Po₂ and, thus, the placental O₂ transfer.

Continue to: Circumstances that may benefit from O₂ supplementation...

Late FHR decelerations reflect impairment of oxygen transfer and thus represent the heart rate pattern that is most likely to benefit from maternal hyperoxia. However, recurrent late decelerations occur in less than 2% of low-risk patients in labor,³ and severe levels of acidosis (umbilical artery pH <7.0 or base deficit [BD] ≥12 mmol/L) occur in only 1% to 2% of near-term or term deliveries.^4,5

Variable decelerations also reflect fetal hypoxia and are much more common than late decelerations, so they also may benefit from O₂ supplementation. Regardless, O₂ supplementation should be seen only as a temporizing strategy while other resuscitative actions are initiated, including preparation for operative delivery, if indicated.

In a prior study by Raghuraman and colleagues (1 of only 4 studies that met selection criteria of oxygen supplementation for patients in labor), newborns of patients not receiving oxygen demonstrated 95% confidence limits of umbilical artery pH (7.24–7.28) and BD (2.9–4.3) well within the normal range.⁶ Thus, the low prevalence of cases in which a benefit might be anticipated and the low incidence of severe acidosis challenges the design of prospective studies to detect statistically and clinically significant changes in blood gas measures and newborn outcomes.

The normal mild fetal acidosis that develops during labor is likely a result of recurrent interruption of uterine placental blood flow during uterine contractions⁷ and is unlikely to benefit from maternal hyperoxia. Similarly, as placental oxygen transfer is predominantly flow rather than diffusion limited,⁸ oxygen supplementation is unlikely to improve severe variable FHR decelerations. Thus, a randomized study of hyperoxia in unselected laboring patients is unlikely to have a measurable effect on clinically significant acidosis.

Oxygen transport pathway guides treatment

For the present, an understanding of oxygen transport can guide clinical oxygen use. Thus, mothers with relative hypoxemia will unquestionably benefit with supplemental oxygen administration. Similarly, fetuses at risk for placental dysfunction (for example, growth restriction, postterm) and particularly those manifesting evidence of impaired oxygen transport (that is, late decelerations) may be most likely to benefit from the increased O₂ gradient. For patients with reduced maternal uterine perfusion (such as hypotension or hypovolemia), pressors and/or fluid volume are likely to be more effective, while amnioinfusion is of greater value for umbilical cord compression patterns. A reduction in uterine activity may be of benefit to all fetuses exhibiting compromise. Due to the modest impact on fetal oxygen content, maternal hyperoxia does not produce significant fetal oxidative stress as measured by fetal malondialdehyde levels. 

Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol. 2021;224:187.e1-187.e10.

EXPERT COMMENTARY

Counseling patients regarding treatment of HMB requires a realistic discussion about the risks of intervention and the expected outcomes. In addition to decreasing menstrual blood loss, treatment benefits of the LNG-IUS include a reversible form of intervention, minimal discomfort with placement in an office environment with an awake patient, and a reliable form of contraception. Abnormal uterine bleeding (AUB) and progesterone-related adverse effects historically have been associated with LNG-IUS use and can lead to patient desires for device removal or additional intervention.

Similarly, in addition to endometrial ablation (EA) decreasing menstrual blood loss, its benefits include avoiding a hysterectomy with an outpatient procedure. Endometrial ablation does require a desire for no future pregnancies while using a reliable form of contraception. Risks of EA include failure to improve HMB or worsening pelvic pain that requires additional intervention, such as hysterectomy. Historically, clinical data suggest failure is more likely for women less than 40 years of age or with adenomyosis at the time of ablation.

Results of a long-term RCT by Beelen and colleagues may aid gynecologists in counseling patients on the risks and benefits of these 2 treatment options.

Details of the study

Performed between 2012 and 2016, this multicenter RCT evaluated primary intervention of the LNG-IUS in 132 women versus EA in 138 women. The women were older than age 34, did not want a future pregnancy, and had other etiologies of AUB eliminated.

The primary outcome was blood loss after 24 months as assessed with a Pictorial Blood Loss Assessment Chart (PBAC) score.

Secondary outcomes included controlled bleeding, defined as a PBAC score not exceeding 75 points; complications and reinterventions within 24 months; amenorrhea; spotting; dysmenorrhea; presence of clots; duration of blood loss; satisfaction with treatment; QoL; and sexual function.

The statistical null hypothesis of the trial was noninferiority of LNG-IUS treatment compared with EA treatment.

Results. Regarding the primary outcome, the mean PBAC score at 2 years was 64.8 for the LNG-IUS treatment group and 14.2 for the EA group. Importantly, however, the authors could not demonstrate noninferiority of the LNG-IUS compared with EA as a primary intervention for HMB.

For the secondary outcomes, there was no significant difference between groups, with both groups having a significant decrease in HMB at 3 months with PBAC scores that did not exceed 75 points: 60% in the LNG-IUS group and 83% in the EA group. In the LNG-IUS group, 35% of women received additional medical or surgical intervention versus 20% in the EA group.

Study strengths and limitations

Strengths of this study include its multicenter design, with 26 hospitals, and the long-term follow-up of 24 months. During the follow-up period, women were allowed to receive a reintervention as clinically indicated; thus, outcomes reflect results that are not from only a single designated intervention. For example, of the women in the LNG-IUS group, 34 received a surgical intervention, 31 (24%) underwent EA, and 9 (7%) underwent a hysterectomy. However, 6 of the 9 who underwent hysterectomy had a preceding EA, and these 6 women are not reported as surgical intervention of EA since the original designation for intervention was the LNG-IUS.

Notably, the patients and physicians were not blinded to the intervention, and the study excluded patients who wanted a future pregnancy. ●

Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol. 2021;224:187.e1-187.e10.

EXPERT COMMENTARY

Counseling patients regarding treatment of HMB requires a realistic discussion about the risks of intervention and the expected outcomes. In addition to decreasing menstrual blood loss, treatment benefits of the LNG-IUS include a reversible form of intervention, minimal discomfort with placement in an office environment with an awake patient, and a reliable form of contraception. Abnormal uterine bleeding (AUB) and progesterone-related adverse effects historically have been associated with LNG-IUS use and can lead to patient desires for device removal or additional intervention.

Similarly, in addition to endometrial ablation (EA) decreasing menstrual blood loss, its benefits include avoiding a hysterectomy with an outpatient procedure. Endometrial ablation does require a desire for no future pregnancies while using a reliable form of contraception. Risks of EA include failure to improve HMB or worsening pelvic pain that requires additional intervention, such as hysterectomy. Historically, clinical data suggest failure is more likely for women less than 40 years of age or with adenomyosis at the time of ablation.

Results of a long-term RCT by Beelen and colleagues may aid gynecologists in counseling patients on the risks and benefits of these 2 treatment options.

Details of the study

Performed between 2012 and 2016, this multicenter RCT evaluated primary intervention of the LNG-IUS in 132 women versus EA in 138 women. The women were older than age 34, did not want a future pregnancy, and had other etiologies of AUB eliminated.

The primary outcome was blood loss after 24 months as assessed with a Pictorial Blood Loss Assessment Chart (PBAC) score.

Secondary outcomes included controlled bleeding, defined as a PBAC score not exceeding 75 points; complications and reinterventions within 24 months; amenorrhea; spotting; dysmenorrhea; presence of clots; duration of blood loss; satisfaction with treatment; QoL; and sexual function.

The statistical null hypothesis of the trial was noninferiority of LNG-IUS treatment compared with EA treatment.

Results. Regarding the primary outcome, the mean PBAC score at 2 years was 64.8 for the LNG-IUS treatment group and 14.2 for the EA group. Importantly, however, the authors could not demonstrate noninferiority of the LNG-IUS compared with EA as a primary intervention for HMB.

For the secondary outcomes, there was no significant difference between groups, with both groups having a significant decrease in HMB at 3 months with PBAC scores that did not exceed 75 points: 60% in the LNG-IUS group and 83% in the EA group. In the LNG-IUS group, 35% of women received additional medical or surgical intervention versus 20% in the EA group.

Study strengths and limitations

Strengths of this study include its multicenter design, with 26 hospitals, and the long-term follow-up of 24 months. During the follow-up period, women were allowed to receive a reintervention as clinically indicated; thus, outcomes reflect results that are not from only a single designated intervention. For example, of the women in the LNG-IUS group, 34 received a surgical intervention, 31 (24%) underwent EA, and 9 (7%) underwent a hysterectomy. However, 6 of the 9 who underwent hysterectomy had a preceding EA, and these 6 women are not reported as surgical intervention of EA since the original designation for intervention was the LNG-IUS.

Notably, the patients and physicians were not blinded to the intervention, and the study excluded patients who wanted a future pregnancy. ●

Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol. 2021;224:187.e1-187.e10.

EXPERT COMMENTARY

Counseling patients regarding treatment of HMB requires a realistic discussion about the risks of intervention and the expected outcomes. In addition to decreasing menstrual blood loss, treatment benefits of the LNG-IUS include a reversible form of intervention, minimal discomfort with placement in an office environment with an awake patient, and a reliable form of contraception. Abnormal uterine bleeding (AUB) and progesterone-related adverse effects historically have been associated with LNG-IUS use and can lead to patient desires for device removal or additional intervention.

Similarly, in addition to endometrial ablation (EA) decreasing menstrual blood loss, its benefits include avoiding a hysterectomy with an outpatient procedure. Endometrial ablation does require a desire for no future pregnancies while using a reliable form of contraception. Risks of EA include failure to improve HMB or worsening pelvic pain that requires additional intervention, such as hysterectomy. Historically, clinical data suggest failure is more likely for women less than 40 years of age or with adenomyosis at the time of ablation.

Results of a long-term RCT by Beelen and colleagues may aid gynecologists in counseling patients on the risks and benefits of these 2 treatment options.

Details of the study

Performed between 2012 and 2016, this multicenter RCT evaluated primary intervention of the LNG-IUS in 132 women versus EA in 138 women. The women were older than age 34, did not want a future pregnancy, and had other etiologies of AUB eliminated.

The primary outcome was blood loss after 24 months as assessed with a Pictorial Blood Loss Assessment Chart (PBAC) score.

Secondary outcomes included controlled bleeding, defined as a PBAC score not exceeding 75 points; complications and reinterventions within 24 months; amenorrhea; spotting; dysmenorrhea; presence of clots; duration of blood loss; satisfaction with treatment; QoL; and sexual function.

The statistical null hypothesis of the trial was noninferiority of LNG-IUS treatment compared with EA treatment.

Results. Regarding the primary outcome, the mean PBAC score at 2 years was 64.8 for the LNG-IUS treatment group and 14.2 for the EA group. Importantly, however, the authors could not demonstrate noninferiority of the LNG-IUS compared with EA as a primary intervention for HMB.

For the secondary outcomes, there was no significant difference between groups, with both groups having a significant decrease in HMB at 3 months with PBAC scores that did not exceed 75 points: 60% in the LNG-IUS group and 83% in the EA group. In the LNG-IUS group, 35% of women received additional medical or surgical intervention versus 20% in the EA group.

Study strengths and limitations

Strengths of this study include its multicenter design, with 26 hospitals, and the long-term follow-up of 24 months. During the follow-up period, women were allowed to receive a reintervention as clinically indicated; thus, outcomes reflect results that are not from only a single designated intervention. For example, of the women in the LNG-IUS group, 34 received a surgical intervention, 31 (24%) underwent EA, and 9 (7%) underwent a hysterectomy. However, 6 of the 9 who underwent hysterectomy had a preceding EA, and these 6 women are not reported as surgical intervention of EA since the original designation for intervention was the LNG-IUS.

Notably, the patients and physicians were not blinded to the intervention, and the study excluded patients who wanted a future pregnancy. ●

For women with a Bishop score ≤6, CR is an important first step in planned induction of labor (IOL). CR is believed to reduce the length of labor induction and increase the probability of a vaginal delivery. Historically, CR has been undertaken on a labor unit. However, with an increased rate of labor induction, the resources of the modern labor unit are incredibly stressed. Compounding the problem is the nursing shortage caused by the COVID-19 pandemic, which has resulted in staff being unavailable as they recover from a respiratory infection or are quarantined after an exposure. The COVID-19 pandemic also has motivated many patients to avoid the hospital as much as possible.

Office-based ambulatory CR is an alternative to inpatient CR and has the potential to reduce the use of labor unit resources. When CR is initiated in the office, the patient either is sent home overnight to return to the labor unit for IOL in the morning or is sent home in the morning to return for IOL in the evening or at night. A secondary benefit of office- and home-based CR is that it may increase patient satisfaction with the process of CR. This editorial summarizes the literature supporting office-based ambulatory CR.

Mechanical methods of CR

Contemporary mechanical methods of CR include the transcervical insertion of a Foley catheter, Cook double-balloon CR catheter, Dilapan-S, or laminaria. There are many publications reporting the feasibility of office-based ambulatory CR with transcervical balloon catheters and very few publications reporting on the use of Dilapan-S or laminaria for ambulatory CR.

Foley catheter

Many studies have investigated the effectiveness of transcervical Foley catheter for ambulatory CR. Policiano and colleagues compared the effectiveness of ambulatory versus inpatient Foley catheter CR.¹ A total of 130 women with a Bishop score <6 at ≥41 weeks’ gestation were randomly assigned to outpatient or inpatient CR with a transcervical Foley catheter (Covidian Dover Silicon coated latex Foley catheter 16 Fr/5.3 mm diameter). The Foley catheter bulb was distended with 40 mL of a sterile saline solution. The end of the Foley was taped to the patient’s inner thigh. Manual traction was gently applied to the catheter every 6 hours. If the catheter was extruded, the Bishop score was assessed. For a Bishop score <6, the patient was given additional inpatient misoprostol (25 µg vaginally every 4 hours for up to 5 doses). For a Bishop score ≥6, intravenous oxytocin IOL was initiated. At 24 hours if the Foley catheter was still in situ, it was removed. Women were excluded from the study for the following factors: noncephalic presentation, spontaneous labor, hydramnios, nonreassuring cardiotocography (CTG), multiple pregnancy, ruptured membranes, active vaginal bleeding, Streptococcus group B infection, and HIV infection. Prostaglandin CR was not used if the woman had a previous cesarean delivery. No prophylactic antibiotics were administered. After placement of the Foley catheter, reassuring CTG was documented prior to sending the patient home.

Outpatient, compared with inpatient, CR resulted in a mean reduction of 10 hours in the time from admission to delivery. The time from insertion of the Foley catheter to delivery in the outpatient group was 38.2 hours, and 44.9 hours for the inpatient group (P<.01). The cesarean delivery rates were similar in both groups—28% and 38%, respectively. Three cases of chorioamnionitis occurred in each group. These study results support the feasibility of office-based ambulatory CR with a transcervical Foley.

Ausbeck and colleagues randomly assigned 126 nulliparous women with a Bishop score <5, at a gestational age ranging from 39 weeks and 0 days through 41 weeks and 6 days, to outpatient overnight CR or inpatient CR with a transcervical Foley catheter.² Breech presentation and multiple gestation pregnancies were excluded from the study. The investigators utilized a 16 French Foley catheter and filled the balloon with 30 mL of sterile water. The Foley was taped to the woman’s inner thigh on slight tension. After placement of the Foley catheter at least 20 minutes of CTG monitoring was performed. The women in the outpatient group were given the contact number for the labor unit and advised that they could take acetaminophen for pain. They were advised that they could stay at home if the Foley catheter was expelled. They were admitted to the labor unit at the time scheduled for their IOL.

The mean time from admission to delivery was reduced by 4.3 hours in the outpatient compared with the inpatient CR group (17.4 vs 21.7 hours; P<.01). In the outpatient CR group, 22% of the women were admitted to labor before the time of the scheduled IOL. The cesarean delivery rates were similar in the outpatient and inpatient CR groups (24% vs 33%, P = .32). In the outpatient and inpatient groups, chorioamnionitis was diagnosed in 22% and 13% (P = .16) of the women. The authors concluded that outpatient CR with a transcervical Foley catheter reduced the time from admission to delivery.

Other research groups also have confirmed the feasibility of outpatient CR with a transcervical Foley catheter.^3-5

Placement of the Foley catheter can be performed digitally without direct visualization of the cervix or by direct visualization using a vaginal speculum. After placement of the speculum, the cervix is cleansed with a povidone-iodine solution and a sterile ring forceps is used to grasp the catheter and guide it through the cervical os. In one small study, self-reported pain was similar for both digital and direct visualization methods for placement of the balloon catheter.⁶ When using Foley catheter CR, filling the standard Foley catheter balloon with 60 mL of fluid, rather than 30 to 40 mL of fluid, is rarely associated with balloon rupture and may result in more effective CR.^6,7

Continue to: Double-balloon catheter...

The Cook double-balloon catheter for CR is meant to create pressure on both sides of the cervix, facilitating CR. Studies have reported that the Cook double-balloon catheter can be used for outpatient CR. In one study, 48 women with a low-risk pregnancy, at 37 to 42 weeks’ gestation and a Bishop score <7 were randomly assigned to outpatient or inpatient double-balloon CR.⁸ Both balloons were filled with 70 to 80 mL of sterile water. CTG monitoring was performed for 20 minutes before and after balloon placement. The women in the outpatient CR group were instructed to return to the labor unit the next day at 8 AM for IOL or earlier if they had regular uterine contractions, rupture of membranes, or vaginal bleeding. Seven percent of the women in the outpatient group returned to the labor unit before 8 AM. After removal of the balloon catheter, women in the outpatient and inpatient groups needed additional misoprostol CR in 12% and 13% of cases, respectively. Outcomes were similar in the two groups, but the study was not powered to identify small differences between the groups.

In another study of outpatient CR with the Cook double-balloon catheter, 695 women with a Bishop score <7, at ≥37 weeks’ gestation, were randomly assigned to outpatient CR with a double-balloon catheter or inpatient CR with dinoprostone (PGE₂) (2 mg dinoprostone vaginal gel [Prostin] or dinoprostone 10 mg controlled-release tape (Cervidil).⁹ Women assigned to dinoprostone CR had CTG monitoring prior to commencing PGE₂ CR and at least 30 min of CTG monitoring after insertion of the vaginal PGE₂. Women assigned to balloon CR were not admitted to the hospital. CTG was performed prior to insertion of the balloon. After insertion, the two balloons on the catheter were each filled with 80 mL of saline. After catheter insertion CTG monitoring was not routinely performed. The women in the double-balloon catheter group returned to the labor unit 12 hours after insertion to initiate IOL. The primary outcome was composite neonatal morbidity and mortality, including admission to a neonatal intensive care unit (NICU), intubation, cardiac compressions, acidemia, hypoxic ischemic encephalopathy, seizure, infection, pulmonary hypertension, stillbirth, or death.

There was no significant difference in the rate of the primary outcome in the catheter versus the PGE₂ group (18.6% and 25.8%; P = .07). Admission to the NICU occurred at rates of 12.6% and 15.5% in the catheter and PGE₂ groups. Umbilical cord arterial pH <7.00 at birth occurred at a rate of 3.5% in the catheter group and 9.2% in the PGE₂ group. The cesarean delivery rates in the catheter and PGE groups were 32.6% and 25.8%, respectively (P = .24). The investigators concluded that outpatient CR using a double-balloon catheter is safe and feasible for nulliparous women.

Two systematic reviews and meta-analyses reported that outcomes were similar when using the Foley or double-balloon catheter for CR.^10,11 The Cook double-balloon CR kit includes a stylet, which can facilitate passing the catheter through the cervix.

Continue to: Dilapan-S and laminaria...

There are many published studies using Dilapan-S and laminaria for cervical preparation prior to uterine evacuation.¹² There are few published studies using Dilapan-S or laminaria for CR prior to IOL. In a pilot study, 21 patients were randomly assigned to outpatient versus inpatient Dilapan-S for CR the night prior to scheduled oxytocin IOL.¹³ The length of time from initiation of oxytocin to delivery in the outpatient and inpatient groups was similar (11 vs 14 hours, respectively). The outpatient compared with the inpatient group had a shorter length of hospitalization until delivery (51 vs 70 hours).

In other studies of Dilapan-S for CR, the patients remained in the hospital once the dilators were inserted. In one small trial, 41 women were randomized to CR with Dilapan-S or laminaria. As many dilators as could be comfortably tolerated by the patient were inserted.¹⁴ The mean numbers of Dilapan-S and laminaria dilators inserted were 4.3 and 9.7, respectively. The morning after the insertion of the dilators, oxytocin IOL was initiated. The times from initiation of oxytocin to delivery for the women in the Dilapan-S and laminaria groups were 11.6 and 15.5 hours, respectively.

An observational study reported on outcomes with Dilapan-S for CR on inpatients.¹⁵ In the study 444 women scheduled for IOL at 37 to 40 weeks’ gestation, with a mean baseline Bishop score of 2.9, had Dilapan-S placed for approximately 15 hours prior to oxytocin IOL. The mean number of Dilapan-S dilators that were inserted was 3.8. The study protocol prohibited placing more than 5 cervical dilator devices. The mean Bishop score after removal of the dilators was 6.5. The most common adverse effects of Dilapan-S CR were bleeding (2.7%) and pain (0.2%). The cesarean delivery rate in the cohort was 30.1%. An Apgar score <7 at 5 minutes was recorded for 3 newborns. An umbilical artery pH of <7.10 was observed in 8 newborns.

In a randomized trial performed on inpatients, 419 women undergoing CR were assigned to a Foley balloon or Dilapan-S.¹⁶ The vaginal delivery rates were similar in the groups—76% for Foley and 81% for Dilapan-S. Maternal and neonatal adverse effects were similar between the two groups. Compared with Foley catheter, women assigned to Dilapan-S reported greater satisfaction with their CR experience, more sleep, and more ability to perform daily activities.

Misoprostol and dinoprostone

Both misoprostol and dinoprostone are effective for outpatient CR. However, a Cochrane systematic review and meta-analysis concluded that balloon CR, compared with prostaglandin CR, is probably associated with a lower risk of uterine hyperstimulation with concerning fetal heart rate changes.¹⁷ Because misoprostol and dinoprostone occasionally can cause uterine hyperstimulation with fetal heart changes, many experts recommend CTG monitoring both before and after administration of misoprostol or dinoprostone for CR.

In a trial of outpatient versus inpatient vaginal PGE₂ CR, 425 women at 37 to 42 weeks’ gestation were assigned randomly to outpatient or inpatient CR.¹⁸ All women had CTG monitoring for 20 minutes before and after vaginal placement of the PGE₂ gel. The PGE₂ dose was 2 mg for nulliparous and 1 mg for parous women. The cesarean delivery rates were similar in the outpatient and inpatient groups—22.3% and 22.9%, respectively. Among the women randomized to outpatient CR, 27 women (13%) could not be discharged home after administration of the vaginal PGE₂ because of frequent uterine contractions or an abnormal fetal heart rate pattern. In addition, 64 women (30%) in the outpatient group returned to the hospital before scheduled induction because of frequent contractions. Maternal and neonatal complications were similar in the two groups. The investigators concluded that, at the dose and route of prostaglandin utilized in this study, the resultant rates of abnormal fetal heart rate pattern and frequent contractions might reduce the clinical utility of outpatient vaginal prostaglandin CR.

Another study also reported a greater rate of uterine tachysystole with vaginal PGE₂ compared with a Foley catheter for CR (9% vs 0%).¹⁹ In a Cochrane systematic review of vaginal prostaglandin for CR, compared with placebo, vaginal prostaglandins were associated with a significantly greater rate of uterine hyperstimulation with fetal heart rate changes (4.8% vs 1.0%).²⁰ Other studies also reported the feasibility of outpatient CR with vaginal prostaglandin.^21,22

Both oral and vaginal misoprostol have been utilized for outpatient CR. In one study, 87 women with singleton pregnancy at 40 to 42 weeks’ gestation with a Bishop score <6 were randomized to outpatient CR with oral misoprostol (100 µg) or placebo.²³ Following administration of the oral misoprostol, the women had 2 hours of CTG monitoring. The treatment was repeated daily for up to 3 days if there was no change in the cervix. If labor occurred, the patient was admitted to the labor unit for oxytocin IOL. The times from first dose of misoprostol or placebo to delivery were 46 and 84 hours (P<.001), respectively.

In another study, 49 women ≥40 weeks’ gestation with a Bishop score <5 were randomly assigned to receive outpatient oral misoprostol 25 µg or 50 µg.²⁴ The dose could be repeated every 3 days over 9 days if ripening or labor had not been achieved. The women had CTG before administration of oral misoprostol. After the misoprostol dose, they had 2 hours of CTG monitoring. The number of doses received by the women assigned to the 50 µg group were 83%, 13%, and 4% for 1, 2, and 3 doses, respectively. The number of doses received by the women assigned to the 25 µg group were 58%, 26%, and 16% for 1, 2, and 3 doses, respectively. The mean intervals from initiation of CR to delivery in the 25 µg and the 50 µg groups were 3.9 and 2.5 days, respectively. The investigators reported no maternal or newborn adverse events, although the study was not powered to detect infrequent events.

Many studies have reported on the feasibility of outpatient CR with vaginal misoprostol.^25-30 In one study, 77 women at 40 weeks’ gestation and a Bishop score ≤8 were randomized to a single dose of vaginal misoprostol 25 µg or gentle cervical examination (control).²⁵ The women had 1 hour of CTG monitoring after the intervention. If they had regular contractions they were admitted to the birthing unit. If they had no regular contractions they were discharged home. For nulliparous women, the time from intervention to delivery in the misoprostol group was 4.9 days, and 8.1 days in the control group. For parous women, the times from intervention to delivery in the two groups were 3.8 and 6.9 days, respectively.

Continue to: Inclusion and exclusion criteria for outpatient CR...

Inclusion and exclusion criteria for outpatient CR

Outpatient CR should be limited to low-risk women with a singleton gestation, who have reliable access to transportation from home to the labor unit and have a clear understanding of the instructions for outpatient CR. Patient characteristics that may be utilized to offer office-based CR include:

• singleton pregnancy at 39 weeks’ and 0 days’ gestation through 40 weeks’ and 6 days’ gestation
• cephalic presentation
• Bishop score ≤6.

Women who should be excluded from outpatient CR include those with:

• contraindications to vaginal delivery
• fetal growth restriction
• abnormal umbilical artery Doppler results
• oligo- or polyhydramnios
• multiple gestation
• major fetal anomaly
• recent nonreactive fetal heart rate tracing
• maternal report of decreased fetal movement
• abnormal biophysical profile
• prior cesarean delivery
• recent vaginal bleeding
• gestational diabetes requiring medication treatment
• significant hypertension.

Practices should establish their own inclusion and exclusion criteria for ambulatory CR.

Safety of office-based ambulatory CR among low-risk women

Safety is a complex concept with experts often disagreeing on what level of safety is required to accept a new medical procedure. Establishing the safety of office-based ambulatory CR among low-risk women would require a very large cohort or randomized studies with at least a thousand participants. Only a few large studies focused on the safety of CR have been reported. Sciscione and colleagues reported a large observational study of inpatient transcervical Foley catheter for CR involving 1,905 women.³¹ They reported no adverse outcomes among term, singleton, uncomplicated pregnancies. They calculated that the 95% confidence interval (CI) for an adverse event was between 0.0% and 0.2%. In a meta-analysis of 26 studies including 5,563 women, the risk of chorioamnionitis during IOL was equivalent with pre-IOL Foley catheter CR (7.2%) or prostaglandin CR (7.2%) (relative risk, 0.96; 95% CI, 0.66–1.38).³²

Two systematic reviews have reported that, compared with balloon CR, misoprostol CR is associated with an increased risk of uterine tachysystole.^33-34 In a large retrospective study, compared with inpatient CR, outpatient CR with dinoprostone vaginal insert was not associated with an increased risk of newborn admission to the neonatal intensive care unit or a low Apgar score at 5 minutes after birth.³⁵

Will you consider office-based CR in your obstetric practice?

As reviewed in this editorial, evolving data suggest that it is feasible to initiate CR in the office ambulatory setting prior to admission to the labor unit for additional CR or IOL. Many women prefer to complete CR at home after initiation in the office, rather than have CR in a labor unit or hospital setting.³⁶ The transcervical balloon catheter has the most published data supporting the feasibility of ambulatory CR. Compared with misoprostol, the transcervical balloon catheter is associated with a low rate of uterine tachysystole. It may be a preferred method for outpatient CR. If placement of a transcervical balloon catheter is challenging, for example when the patient has a tightly closed cervix, oral misoprostol ambulatory CR may be an option if CTG monitoring is available in the office.

During the COVID pandemic, many in-person office visits have transitioned to virtual visits with the patient in their home. Historically, most cases of CR have been performed on labor and delivery units. It may be time for your practice to consider office-based ambulatory CR for low-risk women planning an IOL. Office-based ambulatory CR is a win for labor nurses who generally prefer to manage laboring patients rather than patients undergoing prolonged in-hospital CR. Outpatient CR is also a win for low-risk patients who prefer to be at home rather than in a labor unit. ●

For women with a Bishop score ≤6, CR is an important first step in planned induction of labor (IOL). CR is believed to reduce the length of labor induction and increase the probability of a vaginal delivery. Historically, CR has been undertaken on a labor unit. However, with an increased rate of labor induction, the resources of the modern labor unit are incredibly stressed. Compounding the problem is the nursing shortage caused by the COVID-19 pandemic, which has resulted in staff being unavailable as they recover from a respiratory infection or are quarantined after an exposure. The COVID-19 pandemic also has motivated many patients to avoid the hospital as much as possible.

Office-based ambulatory CR is an alternative to inpatient CR and has the potential to reduce the use of labor unit resources. When CR is initiated in the office, the patient either is sent home overnight to return to the labor unit for IOL in the morning or is sent home in the morning to return for IOL in the evening or at night. A secondary benefit of office- and home-based CR is that it may increase patient satisfaction with the process of CR. This editorial summarizes the literature supporting office-based ambulatory CR.

Mechanical methods of CR

Contemporary mechanical methods of CR include the transcervical insertion of a Foley catheter, Cook double-balloon CR catheter, Dilapan-S, or laminaria. There are many publications reporting the feasibility of office-based ambulatory CR with transcervical balloon catheters and very few publications reporting on the use of Dilapan-S or laminaria for ambulatory CR.

Foley catheter

Many studies have investigated the effectiveness of transcervical Foley catheter for ambulatory CR. Policiano and colleagues compared the effectiveness of ambulatory versus inpatient Foley catheter CR.¹ A total of 130 women with a Bishop score <6 at ≥41 weeks’ gestation were randomly assigned to outpatient or inpatient CR with a transcervical Foley catheter (Covidian Dover Silicon coated latex Foley catheter 16 Fr/5.3 mm diameter). The Foley catheter bulb was distended with 40 mL of a sterile saline solution. The end of the Foley was taped to the patient’s inner thigh. Manual traction was gently applied to the catheter every 6 hours. If the catheter was extruded, the Bishop score was assessed. For a Bishop score <6, the patient was given additional inpatient misoprostol (25 µg vaginally every 4 hours for up to 5 doses). For a Bishop score ≥6, intravenous oxytocin IOL was initiated. At 24 hours if the Foley catheter was still in situ, it was removed. Women were excluded from the study for the following factors: noncephalic presentation, spontaneous labor, hydramnios, nonreassuring cardiotocography (CTG), multiple pregnancy, ruptured membranes, active vaginal bleeding, Streptococcus group B infection, and HIV infection. Prostaglandin CR was not used if the woman had a previous cesarean delivery. No prophylactic antibiotics were administered. After placement of the Foley catheter, reassuring CTG was documented prior to sending the patient home.

Outpatient, compared with inpatient, CR resulted in a mean reduction of 10 hours in the time from admission to delivery. The time from insertion of the Foley catheter to delivery in the outpatient group was 38.2 hours, and 44.9 hours for the inpatient group (P<.01). The cesarean delivery rates were similar in both groups—28% and 38%, respectively. Three cases of chorioamnionitis occurred in each group. These study results support the feasibility of office-based ambulatory CR with a transcervical Foley.

Ausbeck and colleagues randomly assigned 126 nulliparous women with a Bishop score <5, at a gestational age ranging from 39 weeks and 0 days through 41 weeks and 6 days, to outpatient overnight CR or inpatient CR with a transcervical Foley catheter.² Breech presentation and multiple gestation pregnancies were excluded from the study. The investigators utilized a 16 French Foley catheter and filled the balloon with 30 mL of sterile water. The Foley was taped to the woman’s inner thigh on slight tension. After placement of the Foley catheter at least 20 minutes of CTG monitoring was performed. The women in the outpatient group were given the contact number for the labor unit and advised that they could take acetaminophen for pain. They were advised that they could stay at home if the Foley catheter was expelled. They were admitted to the labor unit at the time scheduled for their IOL.

The mean time from admission to delivery was reduced by 4.3 hours in the outpatient compared with the inpatient CR group (17.4 vs 21.7 hours; P<.01). In the outpatient CR group, 22% of the women were admitted to labor before the time of the scheduled IOL. The cesarean delivery rates were similar in the outpatient and inpatient CR groups (24% vs 33%, P = .32). In the outpatient and inpatient groups, chorioamnionitis was diagnosed in 22% and 13% (P = .16) of the women. The authors concluded that outpatient CR with a transcervical Foley catheter reduced the time from admission to delivery.

Other research groups also have confirmed the feasibility of outpatient CR with a transcervical Foley catheter.^3-5

Placement of the Foley catheter can be performed digitally without direct visualization of the cervix or by direct visualization using a vaginal speculum. After placement of the speculum, the cervix is cleansed with a povidone-iodine solution and a sterile ring forceps is used to grasp the catheter and guide it through the cervical os. In one small study, self-reported pain was similar for both digital and direct visualization methods for placement of the balloon catheter.⁶ When using Foley catheter CR, filling the standard Foley catheter balloon with 60 mL of fluid, rather than 30 to 40 mL of fluid, is rarely associated with balloon rupture and may result in more effective CR.^6,7

Continue to: Double-balloon catheter...

The Cook double-balloon catheter for CR is meant to create pressure on both sides of the cervix, facilitating CR. Studies have reported that the Cook double-balloon catheter can be used for outpatient CR. In one study, 48 women with a low-risk pregnancy, at 37 to 42 weeks’ gestation and a Bishop score <7 were randomly assigned to outpatient or inpatient double-balloon CR.⁸ Both balloons were filled with 70 to 80 mL of sterile water. CTG monitoring was performed for 20 minutes before and after balloon placement. The women in the outpatient CR group were instructed to return to the labor unit the next day at 8 AM for IOL or earlier if they had regular uterine contractions, rupture of membranes, or vaginal bleeding. Seven percent of the women in the outpatient group returned to the labor unit before 8 AM. After removal of the balloon catheter, women in the outpatient and inpatient groups needed additional misoprostol CR in 12% and 13% of cases, respectively. Outcomes were similar in the two groups, but the study was not powered to identify small differences between the groups.

In another study of outpatient CR with the Cook double-balloon catheter, 695 women with a Bishop score <7, at ≥37 weeks’ gestation, were randomly assigned to outpatient CR with a double-balloon catheter or inpatient CR with dinoprostone (PGE₂) (2 mg dinoprostone vaginal gel [Prostin] or dinoprostone 10 mg controlled-release tape (Cervidil).⁹ Women assigned to dinoprostone CR had CTG monitoring prior to commencing PGE₂ CR and at least 30 min of CTG monitoring after insertion of the vaginal PGE₂. Women assigned to balloon CR were not admitted to the hospital. CTG was performed prior to insertion of the balloon. After insertion, the two balloons on the catheter were each filled with 80 mL of saline. After catheter insertion CTG monitoring was not routinely performed. The women in the double-balloon catheter group returned to the labor unit 12 hours after insertion to initiate IOL. The primary outcome was composite neonatal morbidity and mortality, including admission to a neonatal intensive care unit (NICU), intubation, cardiac compressions, acidemia, hypoxic ischemic encephalopathy, seizure, infection, pulmonary hypertension, stillbirth, or death.

There was no significant difference in the rate of the primary outcome in the catheter versus the PGE₂ group (18.6% and 25.8%; P = .07). Admission to the NICU occurred at rates of 12.6% and 15.5% in the catheter and PGE₂ groups. Umbilical cord arterial pH <7.00 at birth occurred at a rate of 3.5% in the catheter group and 9.2% in the PGE₂ group. The cesarean delivery rates in the catheter and PGE groups were 32.6% and 25.8%, respectively (P = .24). The investigators concluded that outpatient CR using a double-balloon catheter is safe and feasible for nulliparous women.

Two systematic reviews and meta-analyses reported that outcomes were similar when using the Foley or double-balloon catheter for CR.^10,11 The Cook double-balloon CR kit includes a stylet, which can facilitate passing the catheter through the cervix.

Continue to: Dilapan-S and laminaria...

There are many published studies using Dilapan-S and laminaria for cervical preparation prior to uterine evacuation.¹² There are few published studies using Dilapan-S or laminaria for CR prior to IOL. In a pilot study, 21 patients were randomly assigned to outpatient versus inpatient Dilapan-S for CR the night prior to scheduled oxytocin IOL.¹³ The length of time from initiation of oxytocin to delivery in the outpatient and inpatient groups was similar (11 vs 14 hours, respectively). The outpatient compared with the inpatient group had a shorter length of hospitalization until delivery (51 vs 70 hours).

In other studies of Dilapan-S for CR, the patients remained in the hospital once the dilators were inserted. In one small trial, 41 women were randomized to CR with Dilapan-S or laminaria. As many dilators as could be comfortably tolerated by the patient were inserted.¹⁴ The mean numbers of Dilapan-S and laminaria dilators inserted were 4.3 and 9.7, respectively. The morning after the insertion of the dilators, oxytocin IOL was initiated. The times from initiation of oxytocin to delivery for the women in the Dilapan-S and laminaria groups were 11.6 and 15.5 hours, respectively.

An observational study reported on outcomes with Dilapan-S for CR on inpatients.¹⁵ In the study 444 women scheduled for IOL at 37 to 40 weeks’ gestation, with a mean baseline Bishop score of 2.9, had Dilapan-S placed for approximately 15 hours prior to oxytocin IOL. The mean number of Dilapan-S dilators that were inserted was 3.8. The study protocol prohibited placing more than 5 cervical dilator devices. The mean Bishop score after removal of the dilators was 6.5. The most common adverse effects of Dilapan-S CR were bleeding (2.7%) and pain (0.2%). The cesarean delivery rate in the cohort was 30.1%. An Apgar score <7 at 5 minutes was recorded for 3 newborns. An umbilical artery pH of <7.10 was observed in 8 newborns.

In a randomized trial performed on inpatients, 419 women undergoing CR were assigned to a Foley balloon or Dilapan-S.¹⁶ The vaginal delivery rates were similar in the groups—76% for Foley and 81% for Dilapan-S. Maternal and neonatal adverse effects were similar between the two groups. Compared with Foley catheter, women assigned to Dilapan-S reported greater satisfaction with their CR experience, more sleep, and more ability to perform daily activities.

Misoprostol and dinoprostone

Both misoprostol and dinoprostone are effective for outpatient CR. However, a Cochrane systematic review and meta-analysis concluded that balloon CR, compared with prostaglandin CR, is probably associated with a lower risk of uterine hyperstimulation with concerning fetal heart rate changes.¹⁷ Because misoprostol and dinoprostone occasionally can cause uterine hyperstimulation with fetal heart changes, many experts recommend CTG monitoring both before and after administration of misoprostol or dinoprostone for CR.

In a trial of outpatient versus inpatient vaginal PGE₂ CR, 425 women at 37 to 42 weeks’ gestation were assigned randomly to outpatient or inpatient CR.¹⁸ All women had CTG monitoring for 20 minutes before and after vaginal placement of the PGE₂ gel. The PGE₂ dose was 2 mg for nulliparous and 1 mg for parous women. The cesarean delivery rates were similar in the outpatient and inpatient groups—22.3% and 22.9%, respectively. Among the women randomized to outpatient CR, 27 women (13%) could not be discharged home after administration of the vaginal PGE₂ because of frequent uterine contractions or an abnormal fetal heart rate pattern. In addition, 64 women (30%) in the outpatient group returned to the hospital before scheduled induction because of frequent contractions. Maternal and neonatal complications were similar in the two groups. The investigators concluded that, at the dose and route of prostaglandin utilized in this study, the resultant rates of abnormal fetal heart rate pattern and frequent contractions might reduce the clinical utility of outpatient vaginal prostaglandin CR.

Another study also reported a greater rate of uterine tachysystole with vaginal PGE₂ compared with a Foley catheter for CR (9% vs 0%).¹⁹ In a Cochrane systematic review of vaginal prostaglandin for CR, compared with placebo, vaginal prostaglandins were associated with a significantly greater rate of uterine hyperstimulation with fetal heart rate changes (4.8% vs 1.0%).²⁰ Other studies also reported the feasibility of outpatient CR with vaginal prostaglandin.^21,22

Both oral and vaginal misoprostol have been utilized for outpatient CR. In one study, 87 women with singleton pregnancy at 40 to 42 weeks’ gestation with a Bishop score <6 were randomized to outpatient CR with oral misoprostol (100 µg) or placebo.²³ Following administration of the oral misoprostol, the women had 2 hours of CTG monitoring. The treatment was repeated daily for up to 3 days if there was no change in the cervix. If labor occurred, the patient was admitted to the labor unit for oxytocin IOL. The times from first dose of misoprostol or placebo to delivery were 46 and 84 hours (P<.001), respectively.

In another study, 49 women ≥40 weeks’ gestation with a Bishop score <5 were randomly assigned to receive outpatient oral misoprostol 25 µg or 50 µg.²⁴ The dose could be repeated every 3 days over 9 days if ripening or labor had not been achieved. The women had CTG before administration of oral misoprostol. After the misoprostol dose, they had 2 hours of CTG monitoring. The number of doses received by the women assigned to the 50 µg group were 83%, 13%, and 4% for 1, 2, and 3 doses, respectively. The number of doses received by the women assigned to the 25 µg group were 58%, 26%, and 16% for 1, 2, and 3 doses, respectively. The mean intervals from initiation of CR to delivery in the 25 µg and the 50 µg groups were 3.9 and 2.5 days, respectively. The investigators reported no maternal or newborn adverse events, although the study was not powered to detect infrequent events.

Many studies have reported on the feasibility of outpatient CR with vaginal misoprostol.^25-30 In one study, 77 women at 40 weeks’ gestation and a Bishop score ≤8 were randomized to a single dose of vaginal misoprostol 25 µg or gentle cervical examination (control).²⁵ The women had 1 hour of CTG monitoring after the intervention. If they had regular contractions they were admitted to the birthing unit. If they had no regular contractions they were discharged home. For nulliparous women, the time from intervention to delivery in the misoprostol group was 4.9 days, and 8.1 days in the control group. For parous women, the times from intervention to delivery in the two groups were 3.8 and 6.9 days, respectively.

Continue to: Inclusion and exclusion criteria for outpatient CR...

Inclusion and exclusion criteria for outpatient CR

Outpatient CR should be limited to low-risk women with a singleton gestation, who have reliable access to transportation from home to the labor unit and have a clear understanding of the instructions for outpatient CR. Patient characteristics that may be utilized to offer office-based CR include:

• singleton pregnancy at 39 weeks’ and 0 days’ gestation through 40 weeks’ and 6 days’ gestation
• cephalic presentation
• Bishop score ≤6.

Women who should be excluded from outpatient CR include those with:

• contraindications to vaginal delivery
• fetal growth restriction
• abnormal umbilical artery Doppler results
• oligo- or polyhydramnios
• multiple gestation
• major fetal anomaly
• recent nonreactive fetal heart rate tracing
• maternal report of decreased fetal movement
• abnormal biophysical profile
• prior cesarean delivery
• recent vaginal bleeding
• gestational diabetes requiring medication treatment
• significant hypertension.

Practices should establish their own inclusion and exclusion criteria for ambulatory CR.

Safety of office-based ambulatory CR among low-risk women

Safety is a complex concept with experts often disagreeing on what level of safety is required to accept a new medical procedure. Establishing the safety of office-based ambulatory CR among low-risk women would require a very large cohort or randomized studies with at least a thousand participants. Only a few large studies focused on the safety of CR have been reported. Sciscione and colleagues reported a large observational study of inpatient transcervical Foley catheter for CR involving 1,905 women.³¹ They reported no adverse outcomes among term, singleton, uncomplicated pregnancies. They calculated that the 95% confidence interval (CI) for an adverse event was between 0.0% and 0.2%. In a meta-analysis of 26 studies including 5,563 women, the risk of chorioamnionitis during IOL was equivalent with pre-IOL Foley catheter CR (7.2%) or prostaglandin CR (7.2%) (relative risk, 0.96; 95% CI, 0.66–1.38).³²

Two systematic reviews have reported that, compared with balloon CR, misoprostol CR is associated with an increased risk of uterine tachysystole.^33-34 In a large retrospective study, compared with inpatient CR, outpatient CR with dinoprostone vaginal insert was not associated with an increased risk of newborn admission to the neonatal intensive care unit or a low Apgar score at 5 minutes after birth.³⁵

Will you consider office-based CR in your obstetric practice?

As reviewed in this editorial, evolving data suggest that it is feasible to initiate CR in the office ambulatory setting prior to admission to the labor unit for additional CR or IOL. Many women prefer to complete CR at home after initiation in the office, rather than have CR in a labor unit or hospital setting.³⁶ The transcervical balloon catheter has the most published data supporting the feasibility of ambulatory CR. Compared with misoprostol, the transcervical balloon catheter is associated with a low rate of uterine tachysystole. It may be a preferred method for outpatient CR. If placement of a transcervical balloon catheter is challenging, for example when the patient has a tightly closed cervix, oral misoprostol ambulatory CR may be an option if CTG monitoring is available in the office.

During the COVID pandemic, many in-person office visits have transitioned to virtual visits with the patient in their home. Historically, most cases of CR have been performed on labor and delivery units. It may be time for your practice to consider office-based ambulatory CR for low-risk women planning an IOL. Office-based ambulatory CR is a win for labor nurses who generally prefer to manage laboring patients rather than patients undergoing prolonged in-hospital CR. Outpatient CR is also a win for low-risk patients who prefer to be at home rather than in a labor unit. ●

For women with a Bishop score ≤6, CR is an important first step in planned induction of labor (IOL). CR is believed to reduce the length of labor induction and increase the probability of a vaginal delivery. Historically, CR has been undertaken on a labor unit. However, with an increased rate of labor induction, the resources of the modern labor unit are incredibly stressed. Compounding the problem is the nursing shortage caused by the COVID-19 pandemic, which has resulted in staff being unavailable as they recover from a respiratory infection or are quarantined after an exposure. The COVID-19 pandemic also has motivated many patients to avoid the hospital as much as possible.

Office-based ambulatory CR is an alternative to inpatient CR and has the potential to reduce the use of labor unit resources. When CR is initiated in the office, the patient either is sent home overnight to return to the labor unit for IOL in the morning or is sent home in the morning to return for IOL in the evening or at night. A secondary benefit of office- and home-based CR is that it may increase patient satisfaction with the process of CR. This editorial summarizes the literature supporting office-based ambulatory CR.

Mechanical methods of CR

Contemporary mechanical methods of CR include the transcervical insertion of a Foley catheter, Cook double-balloon CR catheter, Dilapan-S, or laminaria. There are many publications reporting the feasibility of office-based ambulatory CR with transcervical balloon catheters and very few publications reporting on the use of Dilapan-S or laminaria for ambulatory CR.

Foley catheter

Many studies have investigated the effectiveness of transcervical Foley catheter for ambulatory CR. Policiano and colleagues compared the effectiveness of ambulatory versus inpatient Foley catheter CR.¹ A total of 130 women with a Bishop score <6 at ≥41 weeks’ gestation were randomly assigned to outpatient or inpatient CR with a transcervical Foley catheter (Covidian Dover Silicon coated latex Foley catheter 16 Fr/5.3 mm diameter). The Foley catheter bulb was distended with 40 mL of a sterile saline solution. The end of the Foley was taped to the patient’s inner thigh. Manual traction was gently applied to the catheter every 6 hours. If the catheter was extruded, the Bishop score was assessed. For a Bishop score <6, the patient was given additional inpatient misoprostol (25 µg vaginally every 4 hours for up to 5 doses). For a Bishop score ≥6, intravenous oxytocin IOL was initiated. At 24 hours if the Foley catheter was still in situ, it was removed. Women were excluded from the study for the following factors: noncephalic presentation, spontaneous labor, hydramnios, nonreassuring cardiotocography (CTG), multiple pregnancy, ruptured membranes, active vaginal bleeding, Streptococcus group B infection, and HIV infection. Prostaglandin CR was not used if the woman had a previous cesarean delivery. No prophylactic antibiotics were administered. After placement of the Foley catheter, reassuring CTG was documented prior to sending the patient home.

Outpatient, compared with inpatient, CR resulted in a mean reduction of 10 hours in the time from admission to delivery. The time from insertion of the Foley catheter to delivery in the outpatient group was 38.2 hours, and 44.9 hours for the inpatient group (P<.01). The cesarean delivery rates were similar in both groups—28% and 38%, respectively. Three cases of chorioamnionitis occurred in each group. These study results support the feasibility of office-based ambulatory CR with a transcervical Foley.

Ausbeck and colleagues randomly assigned 126 nulliparous women with a Bishop score <5, at a gestational age ranging from 39 weeks and 0 days through 41 weeks and 6 days, to outpatient overnight CR or inpatient CR with a transcervical Foley catheter.² Breech presentation and multiple gestation pregnancies were excluded from the study. The investigators utilized a 16 French Foley catheter and filled the balloon with 30 mL of sterile water. The Foley was taped to the woman’s inner thigh on slight tension. After placement of the Foley catheter at least 20 minutes of CTG monitoring was performed. The women in the outpatient group were given the contact number for the labor unit and advised that they could take acetaminophen for pain. They were advised that they could stay at home if the Foley catheter was expelled. They were admitted to the labor unit at the time scheduled for their IOL.

The mean time from admission to delivery was reduced by 4.3 hours in the outpatient compared with the inpatient CR group (17.4 vs 21.7 hours; P<.01). In the outpatient CR group, 22% of the women were admitted to labor before the time of the scheduled IOL. The cesarean delivery rates were similar in the outpatient and inpatient CR groups (24% vs 33%, P = .32). In the outpatient and inpatient groups, chorioamnionitis was diagnosed in 22% and 13% (P = .16) of the women. The authors concluded that outpatient CR with a transcervical Foley catheter reduced the time from admission to delivery.

Other research groups also have confirmed the feasibility of outpatient CR with a transcervical Foley catheter.^3-5

Placement of the Foley catheter can be performed digitally without direct visualization of the cervix or by direct visualization using a vaginal speculum. After placement of the speculum, the cervix is cleansed with a povidone-iodine solution and a sterile ring forceps is used to grasp the catheter and guide it through the cervical os. In one small study, self-reported pain was similar for both digital and direct visualization methods for placement of the balloon catheter.⁶ When using Foley catheter CR, filling the standard Foley catheter balloon with 60 mL of fluid, rather than 30 to 40 mL of fluid, is rarely associated with balloon rupture and may result in more effective CR.^6,7

Continue to: Double-balloon catheter...

The Cook double-balloon catheter for CR is meant to create pressure on both sides of the cervix, facilitating CR. Studies have reported that the Cook double-balloon catheter can be used for outpatient CR. In one study, 48 women with a low-risk pregnancy, at 37 to 42 weeks’ gestation and a Bishop score <7 were randomly assigned to outpatient or inpatient double-balloon CR.⁸ Both balloons were filled with 70 to 80 mL of sterile water. CTG monitoring was performed for 20 minutes before and after balloon placement. The women in the outpatient CR group were instructed to return to the labor unit the next day at 8 AM for IOL or earlier if they had regular uterine contractions, rupture of membranes, or vaginal bleeding. Seven percent of the women in the outpatient group returned to the labor unit before 8 AM. After removal of the balloon catheter, women in the outpatient and inpatient groups needed additional misoprostol CR in 12% and 13% of cases, respectively. Outcomes were similar in the two groups, but the study was not powered to identify small differences between the groups.

In another study of outpatient CR with the Cook double-balloon catheter, 695 women with a Bishop score <7, at ≥37 weeks’ gestation, were randomly assigned to outpatient CR with a double-balloon catheter or inpatient CR with dinoprostone (PGE₂) (2 mg dinoprostone vaginal gel [Prostin] or dinoprostone 10 mg controlled-release tape (Cervidil).⁹ Women assigned to dinoprostone CR had CTG monitoring prior to commencing PGE₂ CR and at least 30 min of CTG monitoring after insertion of the vaginal PGE₂. Women assigned to balloon CR were not admitted to the hospital. CTG was performed prior to insertion of the balloon. After insertion, the two balloons on the catheter were each filled with 80 mL of saline. After catheter insertion CTG monitoring was not routinely performed. The women in the double-balloon catheter group returned to the labor unit 12 hours after insertion to initiate IOL. The primary outcome was composite neonatal morbidity and mortality, including admission to a neonatal intensive care unit (NICU), intubation, cardiac compressions, acidemia, hypoxic ischemic encephalopathy, seizure, infection, pulmonary hypertension, stillbirth, or death.

There was no significant difference in the rate of the primary outcome in the catheter versus the PGE₂ group (18.6% and 25.8%; P = .07). Admission to the NICU occurred at rates of 12.6% and 15.5% in the catheter and PGE₂ groups. Umbilical cord arterial pH <7.00 at birth occurred at a rate of 3.5% in the catheter group and 9.2% in the PGE₂ group. The cesarean delivery rates in the catheter and PGE groups were 32.6% and 25.8%, respectively (P = .24). The investigators concluded that outpatient CR using a double-balloon catheter is safe and feasible for nulliparous women.

Two systematic reviews and meta-analyses reported that outcomes were similar when using the Foley or double-balloon catheter for CR.^10,11 The Cook double-balloon CR kit includes a stylet, which can facilitate passing the catheter through the cervix.

Continue to: Dilapan-S and laminaria...

There are many published studies using Dilapan-S and laminaria for cervical preparation prior to uterine evacuation.¹² There are few published studies using Dilapan-S or laminaria for CR prior to IOL. In a pilot study, 21 patients were randomly assigned to outpatient versus inpatient Dilapan-S for CR the night prior to scheduled oxytocin IOL.¹³ The length of time from initiation of oxytocin to delivery in the outpatient and inpatient groups was similar (11 vs 14 hours, respectively). The outpatient compared with the inpatient group had a shorter length of hospitalization until delivery (51 vs 70 hours).

In other studies of Dilapan-S for CR, the patients remained in the hospital once the dilators were inserted. In one small trial, 41 women were randomized to CR with Dilapan-S or laminaria. As many dilators as could be comfortably tolerated by the patient were inserted.¹⁴ The mean numbers of Dilapan-S and laminaria dilators inserted were 4.3 and 9.7, respectively. The morning after the insertion of the dilators, oxytocin IOL was initiated. The times from initiation of oxytocin to delivery for the women in the Dilapan-S and laminaria groups were 11.6 and 15.5 hours, respectively.

An observational study reported on outcomes with Dilapan-S for CR on inpatients.¹⁵ In the study 444 women scheduled for IOL at 37 to 40 weeks’ gestation, with a mean baseline Bishop score of 2.9, had Dilapan-S placed for approximately 15 hours prior to oxytocin IOL. The mean number of Dilapan-S dilators that were inserted was 3.8. The study protocol prohibited placing more than 5 cervical dilator devices. The mean Bishop score after removal of the dilators was 6.5. The most common adverse effects of Dilapan-S CR were bleeding (2.7%) and pain (0.2%). The cesarean delivery rate in the cohort was 30.1%. An Apgar score <7 at 5 minutes was recorded for 3 newborns. An umbilical artery pH of <7.10 was observed in 8 newborns.

In a randomized trial performed on inpatients, 419 women undergoing CR were assigned to a Foley balloon or Dilapan-S.¹⁶ The vaginal delivery rates were similar in the groups—76% for Foley and 81% for Dilapan-S. Maternal and neonatal adverse effects were similar between the two groups. Compared with Foley catheter, women assigned to Dilapan-S reported greater satisfaction with their CR experience, more sleep, and more ability to perform daily activities.

Misoprostol and dinoprostone

Both misoprostol and dinoprostone are effective for outpatient CR. However, a Cochrane systematic review and meta-analysis concluded that balloon CR, compared with prostaglandin CR, is probably associated with a lower risk of uterine hyperstimulation with concerning fetal heart rate changes.¹⁷ Because misoprostol and dinoprostone occasionally can cause uterine hyperstimulation with fetal heart changes, many experts recommend CTG monitoring both before and after administration of misoprostol or dinoprostone for CR.

In a trial of outpatient versus inpatient vaginal PGE₂ CR, 425 women at 37 to 42 weeks’ gestation were assigned randomly to outpatient or inpatient CR.¹⁸ All women had CTG monitoring for 20 minutes before and after vaginal placement of the PGE₂ gel. The PGE₂ dose was 2 mg for nulliparous and 1 mg for parous women. The cesarean delivery rates were similar in the outpatient and inpatient groups—22.3% and 22.9%, respectively. Among the women randomized to outpatient CR, 27 women (13%) could not be discharged home after administration of the vaginal PGE₂ because of frequent uterine contractions or an abnormal fetal heart rate pattern. In addition, 64 women (30%) in the outpatient group returned to the hospital before scheduled induction because of frequent contractions. Maternal and neonatal complications were similar in the two groups. The investigators concluded that, at the dose and route of prostaglandin utilized in this study, the resultant rates of abnormal fetal heart rate pattern and frequent contractions might reduce the clinical utility of outpatient vaginal prostaglandin CR.

Another study also reported a greater rate of uterine tachysystole with vaginal PGE₂ compared with a Foley catheter for CR (9% vs 0%).¹⁹ In a Cochrane systematic review of vaginal prostaglandin for CR, compared with placebo, vaginal prostaglandins were associated with a significantly greater rate of uterine hyperstimulation with fetal heart rate changes (4.8% vs 1.0%).²⁰ Other studies also reported the feasibility of outpatient CR with vaginal prostaglandin.^21,22

Both oral and vaginal misoprostol have been utilized for outpatient CR. In one study, 87 women with singleton pregnancy at 40 to 42 weeks’ gestation with a Bishop score <6 were randomized to outpatient CR with oral misoprostol (100 µg) or placebo.²³ Following administration of the oral misoprostol, the women had 2 hours of CTG monitoring. The treatment was repeated daily for up to 3 days if there was no change in the cervix. If labor occurred, the patient was admitted to the labor unit for oxytocin IOL. The times from first dose of misoprostol or placebo to delivery were 46 and 84 hours (P<.001), respectively.

In another study, 49 women ≥40 weeks’ gestation with a Bishop score <5 were randomly assigned to receive outpatient oral misoprostol 25 µg or 50 µg.²⁴ The dose could be repeated every 3 days over 9 days if ripening or labor had not been achieved. The women had CTG before administration of oral misoprostol. After the misoprostol dose, they had 2 hours of CTG monitoring. The number of doses received by the women assigned to the 50 µg group were 83%, 13%, and 4% for 1, 2, and 3 doses, respectively. The number of doses received by the women assigned to the 25 µg group were 58%, 26%, and 16% for 1, 2, and 3 doses, respectively. The mean intervals from initiation of CR to delivery in the 25 µg and the 50 µg groups were 3.9 and 2.5 days, respectively. The investigators reported no maternal or newborn adverse events, although the study was not powered to detect infrequent events.

Many studies have reported on the feasibility of outpatient CR with vaginal misoprostol.^25-30 In one study, 77 women at 40 weeks’ gestation and a Bishop score ≤8 were randomized to a single dose of vaginal misoprostol 25 µg or gentle cervical examination (control).²⁵ The women had 1 hour of CTG monitoring after the intervention. If they had regular contractions they were admitted to the birthing unit. If they had no regular contractions they were discharged home. For nulliparous women, the time from intervention to delivery in the misoprostol group was 4.9 days, and 8.1 days in the control group. For parous women, the times from intervention to delivery in the two groups were 3.8 and 6.9 days, respectively.

Continue to: Inclusion and exclusion criteria for outpatient CR...

Inclusion and exclusion criteria for outpatient CR

Outpatient CR should be limited to low-risk women with a singleton gestation, who have reliable access to transportation from home to the labor unit and have a clear understanding of the instructions for outpatient CR. Patient characteristics that may be utilized to offer office-based CR include:

• singleton pregnancy at 39 weeks’ and 0 days’ gestation through 40 weeks’ and 6 days’ gestation
• cephalic presentation
• Bishop score ≤6.

Women who should be excluded from outpatient CR include those with:

• contraindications to vaginal delivery
• fetal growth restriction
• abnormal umbilical artery Doppler results
• oligo- or polyhydramnios
• multiple gestation
• major fetal anomaly
• recent nonreactive fetal heart rate tracing
• maternal report of decreased fetal movement
• abnormal biophysical profile
• prior cesarean delivery
• recent vaginal bleeding
• gestational diabetes requiring medication treatment
• significant hypertension.

Practices should establish their own inclusion and exclusion criteria for ambulatory CR.

Safety of office-based ambulatory CR among low-risk women

Safety is a complex concept with experts often disagreeing on what level of safety is required to accept a new medical procedure. Establishing the safety of office-based ambulatory CR among low-risk women would require a very large cohort or randomized studies with at least a thousand participants. Only a few large studies focused on the safety of CR have been reported. Sciscione and colleagues reported a large observational study of inpatient transcervical Foley catheter for CR involving 1,905 women.³¹ They reported no adverse outcomes among term, singleton, uncomplicated pregnancies. They calculated that the 95% confidence interval (CI) for an adverse event was between 0.0% and 0.2%. In a meta-analysis of 26 studies including 5,563 women, the risk of chorioamnionitis during IOL was equivalent with pre-IOL Foley catheter CR (7.2%) or prostaglandin CR (7.2%) (relative risk, 0.96; 95% CI, 0.66–1.38).³²

Two systematic reviews have reported that, compared with balloon CR, misoprostol CR is associated with an increased risk of uterine tachysystole.^33-34 In a large retrospective study, compared with inpatient CR, outpatient CR with dinoprostone vaginal insert was not associated with an increased risk of newborn admission to the neonatal intensive care unit or a low Apgar score at 5 minutes after birth.³⁵

Will you consider office-based CR in your obstetric practice?

As reviewed in this editorial, evolving data suggest that it is feasible to initiate CR in the office ambulatory setting prior to admission to the labor unit for additional CR or IOL. Many women prefer to complete CR at home after initiation in the office, rather than have CR in a labor unit or hospital setting.³⁶ The transcervical balloon catheter has the most published data supporting the feasibility of ambulatory CR. Compared with misoprostol, the transcervical balloon catheter is associated with a low rate of uterine tachysystole. It may be a preferred method for outpatient CR. If placement of a transcervical balloon catheter is challenging, for example when the patient has a tightly closed cervix, oral misoprostol ambulatory CR may be an option if CTG monitoring is available in the office.

During the COVID pandemic, many in-person office visits have transitioned to virtual visits with the patient in their home. Historically, most cases of CR have been performed on labor and delivery units. It may be time for your practice to consider office-based ambulatory CR for low-risk women planning an IOL. Office-based ambulatory CR is a win for labor nurses who generally prefer to manage laboring patients rather than patients undergoing prolonged in-hospital CR. Outpatient CR is also a win for low-risk patients who prefer to be at home rather than in a labor unit. ●

PHYSICIAN LEADERSHIP: RACIAL DISPARITIES AND RACISM. WHERE DO WE GO FROM HERE?

BIFTU MENGESHA, MD, MAS; KAVITA SHAH ARORA, MD, MBE, MS; AND BARBARA LEVY, MD

(COMMENTARY; AUGUST 2020)

Political diatribe paints a huge swath

I read the above referenced article with equal measure of angst and offense, amazement and incredulity, irritation and, some would say, typical white male denial. The authors have succumbed to the zeitgeist currently enveloping our country and painted us all with one huge swath of the same proverbial brush—inappropriately.

No doubt certain reforms are needed in our society and perhaps within areas of medicine. I am for anything that improves all peoples’ lives and health. The country is rightfully clamoring for equality. That means equality for all, however. But by way of one small example of systemic overreaction, many articles now are replete with comments about “Black people and Brown people and white people.” Adjectives have been turned into proper nouns, but applied only to some groups, not all. That foments continued inequity, not equality.

The authors implore us to strive for “engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.” In my view, the best way I can do that is not by words but actions, and that is to do what I am trained to do, which is take care of patients the best I can regardless of their color or creed. I have always done that, and everyone I work with does as well. For the authors to imply I (we) don’t is at a minimum offensive and pejorative, and flat wrong.

I agree to a certain extent that our health care contributes to poor, or at least less desirable, outcomes. But so do the actions or inactions of our patients. I do not agree that it is a racial issue. It affects all people. I see it every day. I am probably in the minority of physicians who think we should go to a single-payor system (note I did not say free). But to state that the system creates poor outcomes only for “Blacks, Indigenous, and Latinx,” I disagree. Tennessee has TennCare (Medicaid) and almost anyone can get it, and if they are pregnant they certainly can. Access is not an issue. All people have to do is avail themselves of it. It does not matter the race!

The authors call for the implementation “of system-wide intersectional and antiracist practices” to address “racism, sexism, gender discrimination, economic and social injustice.” They are preaching to the wrong crowd. If I (we) pursued all these lofty goals, I (we) would not have time to care for the very patients they are now lamenting don’t have enough care or proper care.

I facilitate conversations on a regular basis with my black patients as well as my white patients. I recently asked a patient if she distrusted me because I am a white male. It is enlightening to hear patient comments, which are mostly along the lines of “the world has gone crazy.” That is a polite interpretation of their comments. Maybe they say what they think I want to hear, but I don’t think so.

“Repair what we have broken…” by “uplifting their voices and redistributing our power to them.” I don’t see how I (we) have broken anything. If taking care of all comers as best as one can has broken something, then I am guilty. Regarding that I need to examine how “we have eroded the trust of the very communities we care for” and that we are guilty of “medical experimentation on and exploitation of Black and Brown bodies,” what are we to examine? How have I (we) eroded the trust? Present-day physicians had nothing to do with things like the Tuskegee Institute experiment, and I hardly see how blaming us today for that abominable episode in our HISTORY is a valid point. Implying that we add to that distrust by not giving the same pain relief to certain people because of race is just preposterous. Further, asking to let others lead, for example, on the medical executive committee or in positions such as chief of service or chief of staff usually are not something one “gets” to be, but something one usually is “talked into.” There is not a racial barrier to those roles, at least at my institution, and once again the brush has inappropriately painted us all.

I understand the general gestalt of this article and agree with its basic premises. But while well meaning, this political diatribe belongs in the halls of Congress, not in the halls of our hospitals or the pages of a medical journal. I am tired of being told, directly or indirectly, that I am a racist by TV news, newspapers, social media, professional sports teams, and now by my medical journals. I would ask the authors to be careful who they throw under the bus.

Scott Peters, MD

Oak Ridge, Tennessee

Continue to: Drs. Mengesha, Arora, and Levy respond...

We appreciate the opportunity to respond to Dr. Peters. Our article brings long overdue awareness to systemic and structural problems that result in disproportionately inequitable outcomes for people of color. We are not debating the morality of individuals or talking about racism as an inherently “bad” trait that some people have, but rather recognizing the impact of social structures on health and well-being in which we all—Black, Brown, and White—live. We all have inherent biases, recognized or unrecognized, that impact our actions, decisions, and behaviors. We are humans with upbringing, backgrounds, and learned frameworks influenced by our sociocultural context that conditions our responses to a given situation. This is also woven into our hospitals, exam rooms, and even our medical journals. It constantly influences the health, well-being, and livelihood of patients—nothing that we do in medicine is in isolation of this greater context. Our health care system is steeped in this sociocultural context and impacts all patients in intersecting ways, whether that be by race, class, gender, or other social identities. And while we did not create the system in which we operate, we now have abundant evidence that shows it continually delivers inequitable outcomes particularly for people of color.

We are very clear that physicians and health care professionals strive to provide the very best care for each and every patient. We do not discount the hard work and good intentions of our colleagues. And while some individual patient behaviors may somewhat modify outcomes, we also strongly disagree with the premise that patients are to blame for poor or less desirable outcomes they face. Instead, our position is focused on the impact that the systems we work in are creating barriers to equitable care at levels of influence above a single individual, and that it is our collective professional responsibility to acknowledge and take action to lessen those barriers.

System-wide changes would not be at the expense of patient care, and physicians cannot and in fact should not shoulder these changes alone. Our current paradigm of training does not give us the capacity to do so, and a single individual cannot make such a large system change alone. The change we are advocating for requires collaboration within multidisciplinary and interprofessional teams, long-term planning, and incremental but intentional change. This is not dissimilar to the recognition over 20 years ago by the Institute of Medicine (now the National Academy of Medicine) that “to err is human.” Our eyes were opened to the structural issues resulting in medical errors, and very slowly our profession has acknowledged the necessity to recognize, report, and analyze the root causes of those errors. We do so because it is critically important to ensure that the same error never happens again. It is part of the commitment to honor our oath to “do no harm.” Similarly, racial inequities in health outcomes should also be “never events” as there is no biological basis or individual blame for these inequities, but rather systemic and structural processes (which is de facto racism) that contribute to disproportionately worse outcomes.

Disparities in COVID-19 vaccination rates for people of color is a current example that illustrates the deep distrust in our health care system that historical events, like Tuskegee, have created. In Tennessee, for example, 7% of COVID-19 vaccines have been administered to Black people despite the fact that they make up 15% of cases, 18% of deaths, and 16% of the total population.1 There are other ongoing systemic issues, including inequities in distribution, prioritization, and access, that are contributing to the lower vaccination rates among people of color; however, as physicians and advocates for our patients, it is crucial for us to acknowledge the fear of, and resistance to, government-sponsored health programs which has resulted from events like Tuskegee.

We are advocating for building our systems to help support all of the social and societal determinants of health our patients are faced with, including racism, while they are receiving care from us. Patients are faced with undue morbidity and mortality because of our health care system’s ineffectiveness in incorporating this as a part of systemic care delivery to all. We must work together alongside other health care professionals, public health and policy agencies, and community advocates to stop this deadly cycle. There will be no improvement and no end in sight unless we work together toward this common goal.

Reference 

1. Ndugga N, Pham O, Hill L, et al. Latest data on COVID-19 vaccinations: race/ethnicity. Kaiser Family Foundation website. February 1, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/latest-data-covid-19-vaccinations-cases-deaths-race-ethnicity/. Accessed February 11, 2021.

PHYSICIAN LEADERSHIP: RACIAL DISPARITIES AND RACISM. WHERE DO WE GO FROM HERE?

BIFTU MENGESHA, MD, MAS; KAVITA SHAH ARORA, MD, MBE, MS; AND BARBARA LEVY, MD

(COMMENTARY; AUGUST 2020)

Political diatribe paints a huge swath

I read the above referenced article with equal measure of angst and offense, amazement and incredulity, irritation and, some would say, typical white male denial. The authors have succumbed to the zeitgeist currently enveloping our country and painted us all with one huge swath of the same proverbial brush—inappropriately.

No doubt certain reforms are needed in our society and perhaps within areas of medicine. I am for anything that improves all peoples’ lives and health. The country is rightfully clamoring for equality. That means equality for all, however. But by way of one small example of systemic overreaction, many articles now are replete with comments about “Black people and Brown people and white people.” Adjectives have been turned into proper nouns, but applied only to some groups, not all. That foments continued inequity, not equality.

The authors implore us to strive for “engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.” In my view, the best way I can do that is not by words but actions, and that is to do what I am trained to do, which is take care of patients the best I can regardless of their color or creed. I have always done that, and everyone I work with does as well. For the authors to imply I (we) don’t is at a minimum offensive and pejorative, and flat wrong.

I agree to a certain extent that our health care contributes to poor, or at least less desirable, outcomes. But so do the actions or inactions of our patients. I do not agree that it is a racial issue. It affects all people. I see it every day. I am probably in the minority of physicians who think we should go to a single-payor system (note I did not say free). But to state that the system creates poor outcomes only for “Blacks, Indigenous, and Latinx,” I disagree. Tennessee has TennCare (Medicaid) and almost anyone can get it, and if they are pregnant they certainly can. Access is not an issue. All people have to do is avail themselves of it. It does not matter the race!

The authors call for the implementation “of system-wide intersectional and antiracist practices” to address “racism, sexism, gender discrimination, economic and social injustice.” They are preaching to the wrong crowd. If I (we) pursued all these lofty goals, I (we) would not have time to care for the very patients they are now lamenting don’t have enough care or proper care.

I facilitate conversations on a regular basis with my black patients as well as my white patients. I recently asked a patient if she distrusted me because I am a white male. It is enlightening to hear patient comments, which are mostly along the lines of “the world has gone crazy.” That is a polite interpretation of their comments. Maybe they say what they think I want to hear, but I don’t think so.

“Repair what we have broken…” by “uplifting their voices and redistributing our power to them.” I don’t see how I (we) have broken anything. If taking care of all comers as best as one can has broken something, then I am guilty. Regarding that I need to examine how “we have eroded the trust of the very communities we care for” and that we are guilty of “medical experimentation on and exploitation of Black and Brown bodies,” what are we to examine? How have I (we) eroded the trust? Present-day physicians had nothing to do with things like the Tuskegee Institute experiment, and I hardly see how blaming us today for that abominable episode in our HISTORY is a valid point. Implying that we add to that distrust by not giving the same pain relief to certain people because of race is just preposterous. Further, asking to let others lead, for example, on the medical executive committee or in positions such as chief of service or chief of staff usually are not something one “gets” to be, but something one usually is “talked into.” There is not a racial barrier to those roles, at least at my institution, and once again the brush has inappropriately painted us all.

I understand the general gestalt of this article and agree with its basic premises. But while well meaning, this political diatribe belongs in the halls of Congress, not in the halls of our hospitals or the pages of a medical journal. I am tired of being told, directly or indirectly, that I am a racist by TV news, newspapers, social media, professional sports teams, and now by my medical journals. I would ask the authors to be careful who they throw under the bus.

Scott Peters, MD

Oak Ridge, Tennessee

Continue to: Drs. Mengesha, Arora, and Levy respond...

We appreciate the opportunity to respond to Dr. Peters. Our article brings long overdue awareness to systemic and structural problems that result in disproportionately inequitable outcomes for people of color. We are not debating the morality of individuals or talking about racism as an inherently “bad” trait that some people have, but rather recognizing the impact of social structures on health and well-being in which we all—Black, Brown, and White—live. We all have inherent biases, recognized or unrecognized, that impact our actions, decisions, and behaviors. We are humans with upbringing, backgrounds, and learned frameworks influenced by our sociocultural context that conditions our responses to a given situation. This is also woven into our hospitals, exam rooms, and even our medical journals. It constantly influences the health, well-being, and livelihood of patients—nothing that we do in medicine is in isolation of this greater context. Our health care system is steeped in this sociocultural context and impacts all patients in intersecting ways, whether that be by race, class, gender, or other social identities. And while we did not create the system in which we operate, we now have abundant evidence that shows it continually delivers inequitable outcomes particularly for people of color.

We are very clear that physicians and health care professionals strive to provide the very best care for each and every patient. We do not discount the hard work and good intentions of our colleagues. And while some individual patient behaviors may somewhat modify outcomes, we also strongly disagree with the premise that patients are to blame for poor or less desirable outcomes they face. Instead, our position is focused on the impact that the systems we work in are creating barriers to equitable care at levels of influence above a single individual, and that it is our collective professional responsibility to acknowledge and take action to lessen those barriers.

System-wide changes would not be at the expense of patient care, and physicians cannot and in fact should not shoulder these changes alone. Our current paradigm of training does not give us the capacity to do so, and a single individual cannot make such a large system change alone. The change we are advocating for requires collaboration within multidisciplinary and interprofessional teams, long-term planning, and incremental but intentional change. This is not dissimilar to the recognition over 20 years ago by the Institute of Medicine (now the National Academy of Medicine) that “to err is human.” Our eyes were opened to the structural issues resulting in medical errors, and very slowly our profession has acknowledged the necessity to recognize, report, and analyze the root causes of those errors. We do so because it is critically important to ensure that the same error never happens again. It is part of the commitment to honor our oath to “do no harm.” Similarly, racial inequities in health outcomes should also be “never events” as there is no biological basis or individual blame for these inequities, but rather systemic and structural processes (which is de facto racism) that contribute to disproportionately worse outcomes.

Disparities in COVID-19 vaccination rates for people of color is a current example that illustrates the deep distrust in our health care system that historical events, like Tuskegee, have created. In Tennessee, for example, 7% of COVID-19 vaccines have been administered to Black people despite the fact that they make up 15% of cases, 18% of deaths, and 16% of the total population.1 There are other ongoing systemic issues, including inequities in distribution, prioritization, and access, that are contributing to the lower vaccination rates among people of color; however, as physicians and advocates for our patients, it is crucial for us to acknowledge the fear of, and resistance to, government-sponsored health programs which has resulted from events like Tuskegee.

We are advocating for building our systems to help support all of the social and societal determinants of health our patients are faced with, including racism, while they are receiving care from us. Patients are faced with undue morbidity and mortality because of our health care system’s ineffectiveness in incorporating this as a part of systemic care delivery to all. We must work together alongside other health care professionals, public health and policy agencies, and community advocates to stop this deadly cycle. There will be no improvement and no end in sight unless we work together toward this common goal.

Reference 

1. Ndugga N, Pham O, Hill L, et al. Latest data on COVID-19 vaccinations: race/ethnicity. Kaiser Family Foundation website. February 1, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/latest-data-covid-19-vaccinations-cases-deaths-race-ethnicity/. Accessed February 11, 2021.

PHYSICIAN LEADERSHIP: RACIAL DISPARITIES AND RACISM. WHERE DO WE GO FROM HERE?

BIFTU MENGESHA, MD, MAS; KAVITA SHAH ARORA, MD, MBE, MS; AND BARBARA LEVY, MD

(COMMENTARY; AUGUST 2020)

Political diatribe paints a huge swath

I read the above referenced article with equal measure of angst and offense, amazement and incredulity, irritation and, some would say, typical white male denial. The authors have succumbed to the zeitgeist currently enveloping our country and painted us all with one huge swath of the same proverbial brush—inappropriately.

No doubt certain reforms are needed in our society and perhaps within areas of medicine. I am for anything that improves all peoples’ lives and health. The country is rightfully clamoring for equality. That means equality for all, however. But by way of one small example of systemic overreaction, many articles now are replete with comments about “Black people and Brown people and white people.” Adjectives have been turned into proper nouns, but applied only to some groups, not all. That foments continued inequity, not equality.

The authors implore us to strive for “engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.” In my view, the best way I can do that is not by words but actions, and that is to do what I am trained to do, which is take care of patients the best I can regardless of their color or creed. I have always done that, and everyone I work with does as well. For the authors to imply I (we) don’t is at a minimum offensive and pejorative, and flat wrong.

I agree to a certain extent that our health care contributes to poor, or at least less desirable, outcomes. But so do the actions or inactions of our patients. I do not agree that it is a racial issue. It affects all people. I see it every day. I am probably in the minority of physicians who think we should go to a single-payor system (note I did not say free). But to state that the system creates poor outcomes only for “Blacks, Indigenous, and Latinx,” I disagree. Tennessee has TennCare (Medicaid) and almost anyone can get it, and if they are pregnant they certainly can. Access is not an issue. All people have to do is avail themselves of it. It does not matter the race!

The authors call for the implementation “of system-wide intersectional and antiracist practices” to address “racism, sexism, gender discrimination, economic and social injustice.” They are preaching to the wrong crowd. If I (we) pursued all these lofty goals, I (we) would not have time to care for the very patients they are now lamenting don’t have enough care or proper care.

I facilitate conversations on a regular basis with my black patients as well as my white patients. I recently asked a patient if she distrusted me because I am a white male. It is enlightening to hear patient comments, which are mostly along the lines of “the world has gone crazy.” That is a polite interpretation of their comments. Maybe they say what they think I want to hear, but I don’t think so.

“Repair what we have broken…” by “uplifting their voices and redistributing our power to them.” I don’t see how I (we) have broken anything. If taking care of all comers as best as one can has broken something, then I am guilty. Regarding that I need to examine how “we have eroded the trust of the very communities we care for” and that we are guilty of “medical experimentation on and exploitation of Black and Brown bodies,” what are we to examine? How have I (we) eroded the trust? Present-day physicians had nothing to do with things like the Tuskegee Institute experiment, and I hardly see how blaming us today for that abominable episode in our HISTORY is a valid point. Implying that we add to that distrust by not giving the same pain relief to certain people because of race is just preposterous. Further, asking to let others lead, for example, on the medical executive committee or in positions such as chief of service or chief of staff usually are not something one “gets” to be, but something one usually is “talked into.” There is not a racial barrier to those roles, at least at my institution, and once again the brush has inappropriately painted us all.

I understand the general gestalt of this article and agree with its basic premises. But while well meaning, this political diatribe belongs in the halls of Congress, not in the halls of our hospitals or the pages of a medical journal. I am tired of being told, directly or indirectly, that I am a racist by TV news, newspapers, social media, professional sports teams, and now by my medical journals. I would ask the authors to be careful who they throw under the bus.

Scott Peters, MD

Oak Ridge, Tennessee

Continue to: Drs. Mengesha, Arora, and Levy respond...

We appreciate the opportunity to respond to Dr. Peters. Our article brings long overdue awareness to systemic and structural problems that result in disproportionately inequitable outcomes for people of color. We are not debating the morality of individuals or talking about racism as an inherently “bad” trait that some people have, but rather recognizing the impact of social structures on health and well-being in which we all—Black, Brown, and White—live. We all have inherent biases, recognized or unrecognized, that impact our actions, decisions, and behaviors. We are humans with upbringing, backgrounds, and learned frameworks influenced by our sociocultural context that conditions our responses to a given situation. This is also woven into our hospitals, exam rooms, and even our medical journals. It constantly influences the health, well-being, and livelihood of patients—nothing that we do in medicine is in isolation of this greater context. Our health care system is steeped in this sociocultural context and impacts all patients in intersecting ways, whether that be by race, class, gender, or other social identities. And while we did not create the system in which we operate, we now have abundant evidence that shows it continually delivers inequitable outcomes particularly for people of color.

We are very clear that physicians and health care professionals strive to provide the very best care for each and every patient. We do not discount the hard work and good intentions of our colleagues. And while some individual patient behaviors may somewhat modify outcomes, we also strongly disagree with the premise that patients are to blame for poor or less desirable outcomes they face. Instead, our position is focused on the impact that the systems we work in are creating barriers to equitable care at levels of influence above a single individual, and that it is our collective professional responsibility to acknowledge and take action to lessen those barriers.

System-wide changes would not be at the expense of patient care, and physicians cannot and in fact should not shoulder these changes alone. Our current paradigm of training does not give us the capacity to do so, and a single individual cannot make such a large system change alone. The change we are advocating for requires collaboration within multidisciplinary and interprofessional teams, long-term planning, and incremental but intentional change. This is not dissimilar to the recognition over 20 years ago by the Institute of Medicine (now the National Academy of Medicine) that “to err is human.” Our eyes were opened to the structural issues resulting in medical errors, and very slowly our profession has acknowledged the necessity to recognize, report, and analyze the root causes of those errors. We do so because it is critically important to ensure that the same error never happens again. It is part of the commitment to honor our oath to “do no harm.” Similarly, racial inequities in health outcomes should also be “never events” as there is no biological basis or individual blame for these inequities, but rather systemic and structural processes (which is de facto racism) that contribute to disproportionately worse outcomes.

Disparities in COVID-19 vaccination rates for people of color is a current example that illustrates the deep distrust in our health care system that historical events, like Tuskegee, have created. In Tennessee, for example, 7% of COVID-19 vaccines have been administered to Black people despite the fact that they make up 15% of cases, 18% of deaths, and 16% of the total population.1 There are other ongoing systemic issues, including inequities in distribution, prioritization, and access, that are contributing to the lower vaccination rates among people of color; however, as physicians and advocates for our patients, it is crucial for us to acknowledge the fear of, and resistance to, government-sponsored health programs which has resulted from events like Tuskegee.

We are advocating for building our systems to help support all of the social and societal determinants of health our patients are faced with, including racism, while they are receiving care from us. Patients are faced with undue morbidity and mortality because of our health care system’s ineffectiveness in incorporating this as a part of systemic care delivery to all. We must work together alongside other health care professionals, public health and policy agencies, and community advocates to stop this deadly cycle. There will be no improvement and no end in sight unless we work together toward this common goal.

Reference 

1. Ndugga N, Pham O, Hill L, et al. Latest data on COVID-19 vaccinations: race/ethnicity. Kaiser Family Foundation website. February 1, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/latest-data-covid-19-vaccinations-cases-deaths-race-ethnicity/. Accessed February 11, 2021.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Almost one in four men and women diagnosed with kidney stones have osteoporosis or a history of fracture at the time of their diagnosis, yet fewer than 10% undergo bone mineral density (BMD) screening, a retrospective analysis of a Veterans Health Administration database shows.

kgerakis/Getty Images

Because the majority of those analyzed in the VA dataset were men, this means that middle-aged and older men with kidney stones have about the same risk for osteoporosis as postmenopausal women do, but BMD screening for such men is not currently recommended, the study notes.

“These findings suggest that the risk of osteoporosis or fractures in patients with kidney stone disease is not restricted to postmenopausal women but is also observed in men, a group that is less well recognized to be at risk,” Calyani Ganesan, MD, of Stanford (Calif.) University and colleagues say in their article, published online March 3 in the Journal of Bone and Mineral Research.

“We hope this work raises awareness regarding the possibility of reduced bone strength in patients with kidney stones, [and] in our future work, we hope to identify which patients with kidney stones are at higher risk for osteoporosis or fracture to help guide bone density screening efforts by clinicians in this population,” Dr. Ganesan added in a statement.
 

VA dataset: Just 9.1% had DXA after kidney stone diagnosed

A total of 531,431 patients with a history of kidney stone disease were identified in the VA dataset. Of these, 23.6% either had been diagnosed with osteoporosis or had a history of fracture around the time of their kidney stone diagnosis. The most common diagnosis was a non-hip fracture, seen in 19% of patients, Dr. Ganesan and colleagues note, followed by osteoporosis in 6.1%, and hip fracture in 2.1%.

The mean age of the patients who concurrently had received a diagnosis of kidney stone disease and osteoporosis or had a fracture history was 64.2 years. In this cohort, more than 91% were men. The majority of the patients were White.

Among some 462,681 patients who had no prior history of either osteoporosis or fracture before their diagnosis of kidney stones, only 9.1% had undergone dual-energy x-ray absorptiometry (DXA) screening for BMD in the 5 years after their kidney stone diagnosis.

“Of those who completed DXA ... 20% were subsequently diagnosed with osteoporosis,” the authors note – 19% with non-hip fracture, and 2.4% with hip fracture.

Importantly, 85% of patients with kidney stone disease who were screened with DXA and were later diagnosed with osteoporosis were men.

“Given that almost 20% of patients in our cohort had a non-hip fracture, we contend that osteoporosis is underdiagnosed and undertreated in older men with kidney stone disease,” the authors stress.

Perform DXA screen in older men, even in absence of hypercalciuria

The authors also explain that the most common metabolic abnormality associated with kidney stones is high urine calcium excretion, or hypercalciuria.

“In a subset of patients with kidney stones, dysregulated calcium homeostasis may be present in which calcium is resorbed from bone and excreted into the urine, which can lead to osteoporosis and the formation of calcium stones,” they explain.

However, when they carried out a 24-hour assessment of urine calcium excretion on a small subset of patients with kidney stones, “we found no correlation between osteoporosis and the level of 24-hour urine calcium excretion,” they point out.

Even when the authors excluded patients who were taking a thiazide diuretic – a class of drugs that decreases urine calcium excretion – there was no correlation between osteoporosis and the level of 24-hour urine calcium excretion.

The investigators suggest it is possible that, in the majority of patients with kidney stones, the cause of hypercalciuria is more closely related to overabsorption of calcium from the gut, not to overresorption of calcium from the bone.

“Nonetheless, our findings indicate that patients with kidney stone disease could benefit from DXA screening even in the absence of hypercalciuria,” they state.

“And our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle-aged and older men, for whom efforts to mitigate risks of osteoporosis and fractures are not commonly emphasized,” they reaffirm.

The study was funded by the VA Merit Review and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Almost one in four men and women diagnosed with kidney stones have osteoporosis or a history of fracture at the time of their diagnosis, yet fewer than 10% undergo bone mineral density (BMD) screening, a retrospective analysis of a Veterans Health Administration database shows.

kgerakis/Getty Images

Because the majority of those analyzed in the VA dataset were men, this means that middle-aged and older men with kidney stones have about the same risk for osteoporosis as postmenopausal women do, but BMD screening for such men is not currently recommended, the study notes.

“These findings suggest that the risk of osteoporosis or fractures in patients with kidney stone disease is not restricted to postmenopausal women but is also observed in men, a group that is less well recognized to be at risk,” Calyani Ganesan, MD, of Stanford (Calif.) University and colleagues say in their article, published online March 3 in the Journal of Bone and Mineral Research.

“We hope this work raises awareness regarding the possibility of reduced bone strength in patients with kidney stones, [and] in our future work, we hope to identify which patients with kidney stones are at higher risk for osteoporosis or fracture to help guide bone density screening efforts by clinicians in this population,” Dr. Ganesan added in a statement.
 

VA dataset: Just 9.1% had DXA after kidney stone diagnosed

A total of 531,431 patients with a history of kidney stone disease were identified in the VA dataset. Of these, 23.6% either had been diagnosed with osteoporosis or had a history of fracture around the time of their kidney stone diagnosis. The most common diagnosis was a non-hip fracture, seen in 19% of patients, Dr. Ganesan and colleagues note, followed by osteoporosis in 6.1%, and hip fracture in 2.1%.

The mean age of the patients who concurrently had received a diagnosis of kidney stone disease and osteoporosis or had a fracture history was 64.2 years. In this cohort, more than 91% were men. The majority of the patients were White.

Among some 462,681 patients who had no prior history of either osteoporosis or fracture before their diagnosis of kidney stones, only 9.1% had undergone dual-energy x-ray absorptiometry (DXA) screening for BMD in the 5 years after their kidney stone diagnosis.

“Of those who completed DXA ... 20% were subsequently diagnosed with osteoporosis,” the authors note – 19% with non-hip fracture, and 2.4% with hip fracture.

Importantly, 85% of patients with kidney stone disease who were screened with DXA and were later diagnosed with osteoporosis were men.

“Given that almost 20% of patients in our cohort had a non-hip fracture, we contend that osteoporosis is underdiagnosed and undertreated in older men with kidney stone disease,” the authors stress.

Perform DXA screen in older men, even in absence of hypercalciuria

The authors also explain that the most common metabolic abnormality associated with kidney stones is high urine calcium excretion, or hypercalciuria.

“In a subset of patients with kidney stones, dysregulated calcium homeostasis may be present in which calcium is resorbed from bone and excreted into the urine, which can lead to osteoporosis and the formation of calcium stones,” they explain.

However, when they carried out a 24-hour assessment of urine calcium excretion on a small subset of patients with kidney stones, “we found no correlation between osteoporosis and the level of 24-hour urine calcium excretion,” they point out.

Even when the authors excluded patients who were taking a thiazide diuretic – a class of drugs that decreases urine calcium excretion – there was no correlation between osteoporosis and the level of 24-hour urine calcium excretion.

The investigators suggest it is possible that, in the majority of patients with kidney stones, the cause of hypercalciuria is more closely related to overabsorption of calcium from the gut, not to overresorption of calcium from the bone.

“Nonetheless, our findings indicate that patients with kidney stone disease could benefit from DXA screening even in the absence of hypercalciuria,” they state.

“And our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle-aged and older men, for whom efforts to mitigate risks of osteoporosis and fractures are not commonly emphasized,” they reaffirm.

The study was funded by the VA Merit Review and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Almost one in four men and women diagnosed with kidney stones have osteoporosis or a history of fracture at the time of their diagnosis, yet fewer than 10% undergo bone mineral density (BMD) screening, a retrospective analysis of a Veterans Health Administration database shows.

kgerakis/Getty Images

Because the majority of those analyzed in the VA dataset were men, this means that middle-aged and older men with kidney stones have about the same risk for osteoporosis as postmenopausal women do, but BMD screening for such men is not currently recommended, the study notes.

“These findings suggest that the risk of osteoporosis or fractures in patients with kidney stone disease is not restricted to postmenopausal women but is also observed in men, a group that is less well recognized to be at risk,” Calyani Ganesan, MD, of Stanford (Calif.) University and colleagues say in their article, published online March 3 in the Journal of Bone and Mineral Research.

“We hope this work raises awareness regarding the possibility of reduced bone strength in patients with kidney stones, [and] in our future work, we hope to identify which patients with kidney stones are at higher risk for osteoporosis or fracture to help guide bone density screening efforts by clinicians in this population,” Dr. Ganesan added in a statement.
 

VA dataset: Just 9.1% had DXA after kidney stone diagnosed

A total of 531,431 patients with a history of kidney stone disease were identified in the VA dataset. Of these, 23.6% either had been diagnosed with osteoporosis or had a history of fracture around the time of their kidney stone diagnosis. The most common diagnosis was a non-hip fracture, seen in 19% of patients, Dr. Ganesan and colleagues note, followed by osteoporosis in 6.1%, and hip fracture in 2.1%.

The mean age of the patients who concurrently had received a diagnosis of kidney stone disease and osteoporosis or had a fracture history was 64.2 years. In this cohort, more than 91% were men. The majority of the patients were White.

Among some 462,681 patients who had no prior history of either osteoporosis or fracture before their diagnosis of kidney stones, only 9.1% had undergone dual-energy x-ray absorptiometry (DXA) screening for BMD in the 5 years after their kidney stone diagnosis.

“Of those who completed DXA ... 20% were subsequently diagnosed with osteoporosis,” the authors note – 19% with non-hip fracture, and 2.4% with hip fracture.

Importantly, 85% of patients with kidney stone disease who were screened with DXA and were later diagnosed with osteoporosis were men.

“Given that almost 20% of patients in our cohort had a non-hip fracture, we contend that osteoporosis is underdiagnosed and undertreated in older men with kidney stone disease,” the authors stress.

Perform DXA screen in older men, even in absence of hypercalciuria

The authors also explain that the most common metabolic abnormality associated with kidney stones is high urine calcium excretion, or hypercalciuria.

“In a subset of patients with kidney stones, dysregulated calcium homeostasis may be present in which calcium is resorbed from bone and excreted into the urine, which can lead to osteoporosis and the formation of calcium stones,” they explain.

However, when they carried out a 24-hour assessment of urine calcium excretion on a small subset of patients with kidney stones, “we found no correlation between osteoporosis and the level of 24-hour urine calcium excretion,” they point out.

Even when the authors excluded patients who were taking a thiazide diuretic – a class of drugs that decreases urine calcium excretion – there was no correlation between osteoporosis and the level of 24-hour urine calcium excretion.

The investigators suggest it is possible that, in the majority of patients with kidney stones, the cause of hypercalciuria is more closely related to overabsorption of calcium from the gut, not to overresorption of calcium from the bone.

“Nonetheless, our findings indicate that patients with kidney stone disease could benefit from DXA screening even in the absence of hypercalciuria,” they state.

“And our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle-aged and older men, for whom efforts to mitigate risks of osteoporosis and fractures are not commonly emphasized,” they reaffirm.

The study was funded by the VA Merit Review and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.