Safety and efficacy of non-FDA approved menopause therapies


At the 2023 ACOG Annual Clinical & Scientific Meeting, the safety and efficacy of compounded bioidentical hormone therapy for menopause were discussed.

Safety and efficacy of non-FDA approved menopause therapies | Image Credit: © Pixel-Shot - © Pixel-Shot -

Safety and efficacy of non-FDA approved menopause therapies | Image Credit: © Pixel-Shot - © Pixel-Shot -

Non-FDA-approved approaches to menopausal hormone therapy are not safer than FDA-approved products, according to data presented by Robert P. Kauffman, MD, NCMP, at the 2023 American Academy of Obstetricians and Gynecologists Annual Clinical & Scientific Meeting. 

Ineffective therapies and dubious product promotion are often seen in medicine, including vitamins for dementia, multiple prescription medications for weight loss, antioxidants and diets for cancer, and hydroxychloroquine and ivermectin for COVID-19. The ob-gyn field is also affected, with black cohosh and herbals promoted for menopausal vasomotor symptoms (VMS) despite no data indicating efficacy.

Compounded Bioidentical Hormone Therapy (cBHT) is a bioidentical, meaning it has the same hormone structure as the index hormone. However, this product has received little to no FDA oversight, unlike FDA-approved products for estradiol, progesterone, and testosterone. 

Types of cBHT include pills, creams, and pellets. These products see 26 million to 33 million prescriptions per year, with use seen in about 41% of women in the United States. The cost is often higher than that of FDA-approved products and is rarely covered by third party payers.

It is commonly believed that natural products are safer. A study known as the Women’s Health Initiative measured cardiovascular disease and breast cancer in patients taking hormone therapies, but the initial results were surrounded by misinterpretations, leading to demonization in the media.

A reassuring subgroup analysis went largely unignored in comparison. Because of this, conjugated equine estrogens receive stigma to this day, despite not being associated with increased risks of adverse outcomes. On the other hand, a rise has been seen in promotions of cBHT.

Promotions for cBHT include claiming less risk than conventional hormone therapy (HT), ability to treat hormone imbalance, anti-aging effects, decreased breast cancer risk, weight loss, and fertility enhancement. This has increased overall cBHT use, but most US and international women’s health organizations recommend against use outside of narrow indications.

Systemic estrogen has been proven more effective for treating VMS than non-hormonal treatments, with a lower dose needed to achieve goals. There are multiple well-studied FDA-approved products with positive safety data and a favorable benefit to risk ratio, such as raloxifene (Evista; Reddy's Laboratories), ospemifene (Osphena; Shionogi), and bazedoxifene (Conbriza; Wyeth Pharmaceuticals).

Androgen in premenopausal women has also not had a replacement with clear benefits, and dehydroepiandrosterone supplementation has not been associated with consistent benefits. FDA concerns for testosterone treatment in menopause include hirsutism, cardiovascular disease, breast cancer, diabetes, and deep vein thrombosis.

Currently, testosterone administration over physiologic levels is not recommended. Short-term use is not associated with increased breast cancer risk, but data on long-term use remains unclear. Women with hormone-sensitive breast cancer should remain cautious.

The primary issue cBHT faces is a lack of properly conducted randomized control trials measuring safety and efficacy. Compounding has been associated with multiple quality deficits, including the presence of impurities and lack of sterility. 

Data on absorption, distribution, and metabolism of compounding is also lacking. Estradiol pellets, another alternative to FDA-approved therapies, have been associated with years of elevated estradiol and uterine bleeding. 

When examining overall safety data, cBHT tabs, creams, and pellets fail to receive the same federal oversite as FDA-approved options. One study found side effects of compounded pellets included mood swings, anxiety, mastalgia, acne, weight gain, and abnormal uterine bleeding. The rate of side effects was 57.6% in the pellet group compared to 14.8% for FDA-approved products.

When examining peer-reviewed literature, investigators found no papers indicating cream or pellets are safer, more effective, or less likely to lead to side effects than FDA-approved products. Claims of cBHT preventing Alzheimer’s disease, increasing length and quality of life, and decreasing risks of breast cancer, sexually transmitted diseases, and stroke are also unproven.

Reviews have concluded evidence supporting cBHT use in women with menopause is insufficient, and practitioners have a duty to inform patients of this fact. Only those with a documented allergy to an active ingredient should use cBHT. In the future, morewell-designed trial of cBHT should be performed.


Kauffman RP. The non-FDA-approved approach to menopausal hormone therapy. Is it safe? Is it ethical?Presented at: 2023 Annual Clinical & Scientific Meeting. May 19-21. Baltimore, Maryland.

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