With seemingly ageless celebrities touting the benefits of bioidentical, compounded hormones, and the cloud of the Women’s Health Initiative still obscuring the view, both physicians and patients want to know the truth about natural hormone replacement.
But as in so many areas of life, the truth can be many things to many people, Dr. Jan L. Shifren shared at the annual meeting of the North American Menopause Society (NAMS).
"For a woman with bothersome menopausal symptoms and concerns about potential hormone therapy [HT] risks, ‘bioHT’ may mean a formulation of hormones with all of the benefits and no risks, as it’s ‘natural’ and contains no package insert with a black box warning," said Dr. Shifren, director of the menopause program at Massachusetts General Hospital, Boston. "For a bioHT practitioner, it may mean a way of helping menopausal women disenfranchised with the medical establishment, while providing a steady source of income. For a clinician or pharmacist practicing within the current standard of care, an FDA inspector, or a lawyer for a women with endometrial cancer associated with its use, bioHT may mean something quite different!"
Dr. Jan L. Shifren
Bioidentical hormones are typically plant-based compounds with a molecular structure identical to that of the corresponding human hormone. Dosing is individual and based on a woman’s salivary hormone levels. Prescriptions are pharmacist compounded, typically in a topical preparation, but sometimes in an oral tablet or injected pellet.
All of this may sound reasonable at first glance, Dr. Shifren said. But science and money just keep getting in the way of the celebrity endorsements.
"Hormone therapy should be guided by symptoms. There are no data to support the use of blood or saliva measurements to improve treatment efficacy," Dr. Shifren said. Serum hormone levels constantly fluctuate – not only within the menstrual cycle, but also within a single day, "so it’s impossible to ‘match’ any individual woman’s ‘ideal’ hormone levels."
Additionally, Dr. Shifren said, salivary levels don’t even correspond to serum levels.
Safety is one of the biggest problems with such compounds. Because their manufacture is in the hands of a single individual, there’s no quality oversight. Women can’t count on getting the correct prescribed dose of hormone – and sometimes not even close to it.
A recent study commissioned by MORE magazine examined the exact hormone content in 12 bioHT prescriptions, which were filled by 12 pharmacies. Two pharmacies were retail stores and 10 were online companies.
Flora Research Labs analyzed the medications with mass spectrometry. The values varied widely: 96%-260% of the prescribed estrogen dose and 60%-80% of the prescribed progesterone dose.
"None of these would have met FDA standards," Dr. Shifren said. "The purity, bioavailability, and dose-to-dose consistency of any given prescription is an unknown."
Concern about the safety of conventional HT frequently drives women to seek out what they consider a more natural alternative. Although much more data have emerged, the original furor over the Women’s Health Initiative still casts HT in a negative light for many, Dr. Shifren said.
For women in good health, who start combination estrogen/progesterone HT early in menopause, at the lowest effective dose, the increased risks of cardiovascular disease and cancer are negligible. A 2010 British study of 15,710 cases and almost 60,000 controls found that low-dose transdermal HT had no effect on stroke risk. High-dose patch estrogen increased the risk by 89%, and both low- and high-dose oral estrogen increased the risk by 69%; however, each of those increases translated to an absolute increase of only about 1 stroke per year (BMJ 2010;340:c2519 [doi: 10.1136/bmj.c2519]).
A 2008 French study of almost 81,000 women found no significant associations between breast cancer and route of HT administration. However, the study did conclude that the combination of estrogen and progesterone was probably the safest, with a risk ratio of 1.0. Estrogen plus dydrogesterone resulted in a nonsignificant risk increase (relative risk, 1.16). Estrogen in combination with other progestogens carried a significant 69% risk increase (Breast Cancer Res. Treat. 2008;107:103-11).
Finally, Dr. Shifren said, it’s just about impossible to take profit out of the picture. Compounding HT sales are reaching more than $2 billion per year now.
"Many practitioners who prescribe compounded hormones also sell them, or benefit financially from relationships with compounders. This poses a potential conflict of interest and violates standards of professional ethical conduct," she said.
Dr. Shifren provides research consulting for New England Research Institutes.