Elevated levels
Average peak serum estradiol was significantly higher in the pellet treatment group than in the conventional therapy group (237.70 pg/mL vs. 93.45 pg/mL), as was average peak serum testosterone (192.84 ng/dL vs. 15.59 ng/dL), the researchers reported. Patients on FDA-approved treatments were less likely to have had their hormone levels measured. How concentrations of hormone levels correlate with side effects is unclear, Dr. Jiang said.
The study was limited by its single-institution, retrospective design, and some patient characteristics differed between the treatment groups, the authors noted.
Still, “clinicians ought to be mindful of fully counseling patients on side effects identified in the current study,” Dr. Jiang and coauthors concluded. Clinicians also need to discuss potential risks of breast cancer, endometrial cancer, and cardiovascular disease with patients.
Many primary care clinicians rely on outdated information from the Women’s Health Initiative, published in 2002 and 2004, in their understanding of postmenopausal hormonal therapy and its risks and benefits, Dr. Jiang said. And some patients consider custom-compounded hormone therapy to be safer and more natural, “which is totally misleading.”
Pellets and other custom-compounded medicine containing testosterone may make patients feel better and more energetic, Dr. Jiang acknowledged. “That’s a reason why patients ... tend to stay on, even though they have side effects. The only issue is the safety.”
Additional questions remain. The researchers recently started to examine rates of breast cancer and abnormal breast pathology and mammogram results. “It’s a long journey,” he said.
Plenty of approved options
Custom-compounded medicines are not FDA approved and are not recommended by medical menopause societies, Dr. Jiang said. Meanwhile, plenty of approved hormone therapies, including bioidentical treatments, have safety data and are available.
A 2020 consensus study report from the National Academies of Sciences, Engineering, and Medicine that examined the use of compounded hormonal therapy and provides guidance for clinicians is a good start in addressing this major issue, he added.
A committee determined “there is insufficient evidence to support the overall clinical utility of [compounded bioidentical hormone therapies] as treatment for menopause and male hypogonadism symptoms.”
If an FDA-approved option is available, “I would always go with an FDA-approved product before I would go with a compounded product,” Dr. Winer said. A 2012 fungal meningitis outbreak linked to a compounding pharmacy highlighted risks associated with poor quality compounded drugs.
“I think at least now it is recognized that compounding is an issue that has got to be dealt with,” Dr. Winer said. “It is just that it is so widespread and it is sometimes under the radar ... that I think it is really hard for the FDA to get a handle on it.”
Dr. Winer has seen patients on compounded treatments who are underdosed and patients who are overdosed. “I’ve also seen patients who do quite well with it, but I’m not happy continuing it because tomorrow there may be inconsistency in potency or quality resulting in a different clinical response,” she said.
Nevertheless, compounded pharmacies are needed, Dr. Winer said. If she wants to give natural progesterone that is FDA approved but happens to be made with peanut oil, she will have a compounding pharmacy make it with canola oil instead if a patient has a peanut allergy, for example. Other patients need dosages that are so low that they are not available as FDA-approved products.
Dr. Jiang and Dr. Kauffman had no relevant financial disclosures. Dr. Winer has done work with AbbVie (related to endometriosis), TherapeuticsMD (related to a menopause bioidentical hormonal pill and vaginal estrogen product), and Biogix (related to an antioxidant supplement for menopause symptoms).
*This story was updated on 6/22/2021.