Meeting NewsPerspective

Custom-compounded bioidentical HT for menopause symptoms may yield ‘abnormally high’ hormone levels

Pellet hormone therapy, a solid custom-compounded bioidentical estrogen therapy that is inserted under the skin, may be less safe than FDA-approved HT therapies for postmenopausal women, according to findings presented at the North American Menopause Society annual meeting.

Xuezhi (Daniel) Jiang

Researchers found substantially increased serum estradiol and total testosterone levels associated with pellet HT.

“While recent prescription rates for custom-compounded bioidentical HT now approach those of FDA-approved hormone prescriptions, the majority of women are either misinformed or unaware that there is no evidence to support the safety of custom-compounded bioidentical HT; the long-term clinical sequelae of [this] HT and abnormally higher estradiol and total testosterone levels are still largely unknown,” Xuezhi (Daniel) Jiang, MD, PhD, FACOG, NCMP, associate professor of obstetrics and gynecology at Sidney Kimmel Medical College of Thomas Jefferson University and director of clinical research in the department of obstetrics and gynecology at Reading Hospital of Tower Health in West Reading, Pennsylvania, told Endocrine Today. “We are in urgent need of future prospective studies to help develop a clinical guideline for safety monitoring in women on custom-compounded bioidentical HT.”

Using data from the Reading Hospital electronic medical record system, Jiang and colleagues retrospectively reviewed serum estradiol and total testosterone levels for 384 postmenopausal women who used pellet HT and 155 postmenopausal women who used HT approved by the FDA.

The researchers found that treatment lasted an average of 3.92 years for pellet HT and 3.33 years for FDA-approved HT (P < .0001). The average number of serum estradiol assessments during treatment was 6.81 for pellet HT and 0.39 for FDA-approved HT. Similarly, the average number of total testosterone assessments during treatment was 4.98 for pellet HT and 0.14 for FDA-approved HT.

Mean serum estradiol and total testosterone levels for women using pellet HT were 237.7 pg/mL and 192.84 pg/mL, respectively, compared with 93.45 pg/mL and 15.59 pg/mL for women using FDA-approved HT (P < .00001 for both).

According to Jiang, there was also a “significantly higher incidence of side effects” with pellet HT.

“It raises a red flag to clinicians who prescribe custom-compounded bioidentical HT that women on pellet [HT] need to be carefully monitored for their serum estradiol and total testosterone levels before an evidence-based clinical guideline is issued,” Jiang said. “It raises a red flag to women who are on, or consider to be on, pellet [HT] that custom-compounded bioidentical HT may not be as safe as compounding companies have claimed. The majority of women are not aware that many FDA-approved hormone products are, in fact, bioidentical to endogenous human reproductive hormones. In addition, many individualized options for hormone therapy are available to women using FDA-approved products with many dosages/delivery options available.” – by Phil Neuffer

Reference:

Jiang X, et al. Abstract S-14. Presented at: North American Menopause Society Annual Meeting; Sept. 25-28, 2019; Chicago.

For more information:

Xuezhi (Daniel) Jiang, MD, PhD, FACOG, NCMP, can be reached at Daniel.Jiang@towerhealth.org.

Disclosure: Jiang reports no relevant financial disclosures.

Pellet hormone therapy, a solid custom-compounded bioidentical estrogen therapy that is inserted under the skin, may be less safe than FDA-approved HT therapies for postmenopausal women, according to findings presented at the North American Menopause Society annual meeting.

Xuezhi (Daniel) Jiang

Researchers found substantially increased serum estradiol and total testosterone levels associated with pellet HT.

“While recent prescription rates for custom-compounded bioidentical HT now approach those of FDA-approved hormone prescriptions, the majority of women are either misinformed or unaware that there is no evidence to support the safety of custom-compounded bioidentical HT; the long-term clinical sequelae of [this] HT and abnormally higher estradiol and total testosterone levels are still largely unknown,” Xuezhi (Daniel) Jiang, MD, PhD, FACOG, NCMP, associate professor of obstetrics and gynecology at Sidney Kimmel Medical College of Thomas Jefferson University and director of clinical research in the department of obstetrics and gynecology at Reading Hospital of Tower Health in West Reading, Pennsylvania, told Endocrine Today. “We are in urgent need of future prospective studies to help develop a clinical guideline for safety monitoring in women on custom-compounded bioidentical HT.”

Using data from the Reading Hospital electronic medical record system, Jiang and colleagues retrospectively reviewed serum estradiol and total testosterone levels for 384 postmenopausal women who used pellet HT and 155 postmenopausal women who used HT approved by the FDA.

The researchers found that treatment lasted an average of 3.92 years for pellet HT and 3.33 years for FDA-approved HT (P < .0001). The average number of serum estradiol assessments during treatment was 6.81 for pellet HT and 0.39 for FDA-approved HT. Similarly, the average number of total testosterone assessments during treatment was 4.98 for pellet HT and 0.14 for FDA-approved HT.

Mean serum estradiol and total testosterone levels for women using pellet HT were 237.7 pg/mL and 192.84 pg/mL, respectively, compared with 93.45 pg/mL and 15.59 pg/mL for women using FDA-approved HT (P < .00001 for both).

According to Jiang, there was also a “significantly higher incidence of side effects” with pellet HT.

“It raises a red flag to clinicians who prescribe custom-compounded bioidentical HT that women on pellet [HT] need to be carefully monitored for their serum estradiol and total testosterone levels before an evidence-based clinical guideline is issued,” Jiang said. “It raises a red flag to women who are on, or consider to be on, pellet [HT] that custom-compounded bioidentical HT may not be as safe as compounding companies have claimed. The majority of women are not aware that many FDA-approved hormone products are, in fact, bioidentical to endogenous human reproductive hormones. In addition, many individualized options for hormone therapy are available to women using FDA-approved products with many dosages/delivery options available.” – by Phil Neuffer

Reference:

Jiang X, et al. Abstract S-14. Presented at: North American Menopause Society Annual Meeting; Sept. 25-28, 2019; Chicago.

For more information:

Xuezhi (Daniel) Jiang, MD, PhD, FACOG, NCMP, can be reached at Daniel.Jiang@towerhealth.org.

Disclosure: Jiang reports no relevant financial disclosures.

    Perspective
    JoAnn E. Manson

    JoAnn E. Manson

    Jiang and colleagues’ study adds important data to the growing concerns about custom-compounded bioidentical hormone therapy (cBHT). These findings stand in stark contrast to the perception of many women that cBHT is safer and more effective than FDA-regulated hormone therapy, fostered by aggressive cBHT marketing campaigns and the absence of patient package inserts or labeling of these products. FDA-regulated HT, on the other hand, has an extensive patient package insert and “black box” warning, with class labeling of all menopausal HT products.

    Additional alarming data suggest that prescription rates for cBHT are now approaching 50% of all HT prescribed in the U.S. Repeated laboratory measurements of sex hormones among women on cBHT also contribute to escalating health care costs, often incurred by the patient herself.

    Given that a wide variety of FDA-approved products are available containing “bioidentical” hormones (estradiol and/or progesterone) in a broad range of dosages, what accounts for the soaring rates of cBHT use in the U.S.? Why do these products have such appeal, and why are they being prescribed at such high rates? 

    Despite the appearance of “customized content” based on repeated salivary or blood-based hormonal testing, there is no clear evidence that sex hormone levels correlate with efficacy of treatment or symptom response to treatment. It is well established that the cBHT lacks the standardization of dose, purity of content and stringent quality control of FDA-approved products. Nonetheless, cBHT is perceived as “natural” and safer than FDA-approved products, despite lack of evidence for these claims.

    Of great concern, surveys suggest that 10% to 50% of women mistakenly believe that cBHT is FDA-approved, and two-thirds are uncertain about its regulation. The lack of information on the absence of FDA approval and the lack of a patient package insert regarding the medication’s risks — as required for FDA-approved HT — are very likely contributing to this misperception and false sense of safety. Compounded products should have similar labeling requirements.

    The bottom line is that clinicians should be cautious about prescribing cBHT and limit prescriptions to clinical scenarios where other options are not available. In addition, patients need to be informed that there are many FDA-approved bioidentical HT options in a wide variety of doses and that cBHT is not FDA regulated. It’s important for patients to be told the truth about these issues so they can make informed choices.

    • JoAnn E. Manson, MD, DrPH
    • Chief, Division of Preventive Medicine
      Brigham and Women's Hospital
      Professor of Medicine
      Michael and Lee Bell Professor of Women's Health
      Harvard Medical School

    Disclosures: Manson reports no relevant financial disclosures.

    See more from North American Menopause Society