Is FDA-Approved Bioidentical Hormone Replacement Therapy Safe?

The news that menopausal hormone therapy had the potential to cause higher rates of breast cancer, cardiovascular disease, and overall harm rocked women and physicians across the country. The study arm used progesterone and Premarin, because it was the most commonly prescribed form of estrogen and is still prescribed more than a million times a year in the U.S. It’s a mixture of more than 50 different estrogens from horse pee. (Premarin” comes from the words “pregnant mare urine”—if you’re skeptical, try crushing a pill and sniffing it.)

The dour findings of the Women’s Health Initiative (combined with some high-profile celebrity endorsements) saw interest shift to “bioidentical hormones,” made from plants rather than a horse source. They are marketed as being safer and more effective. No wonder estimates peg the annual number of prescriptions at 30 million a year, constituting a billion-dollar industry.

One reason patients may believe compounded hormone therapy is safer is that, thanks to a legal loophole, they are not mandated to provide the FDA insert required for commercial products warning about side effects. Purchased at regular pharmacies, hormones have a prominent black box with an all-caps “WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER, AND PROBABLE DEMENTIA.” There’s no evidence that bioidentical hormones are any safer, but the missing laundry list of side effects may give patients a false sense of security. Another appeal is customized dosing based on saliva hormone testing, but such tests are considered to be unreliable and so recommended against, since the only people who profit are the ones trying to sell you the tests.

Custom-compounded hormones are not FDA-approved, have not been shown to be safer or more effective, and may lack standardization of quality, purity, and dose. When the FDA or muckraking journalists have filled the same prescriptions in compounding pharmacies in different states, a third of the stated estrogen contents were off up as much as 250 percent. No wonder all the major American medical societies that counsel physicians on treating menopausal women recommend against compounded hormones, including the American College of Obstetrics and Gynecology, the Endocrine Society, and the North American Menopause Society. Characterizing the pushback they got from their 2020 review recommending against the use of bioidentical hormones, the National Academies of Sciences, Engineering, and Medicine concluded, “It is clear from these communications that many clinicians, compounding pharmacists, and patients hold minimum, if any, concerns regarding the medication’s safety and effectiveness.”

Now, as of 2019, there are pee-free FDA-approved bioidentical hormones that skirt the standardization concerns of compounded preparations, but that just brings us back to square one, since they are considered to have the same risk/benefit profile. The multibillion-dollar compounded hormone industry is considered a “leading source of disinformation,” but the same could be said of Big Pharma. With so many billions of dollars at stake, it’s hard to know who to trust. When in doubt, I turn to The Medical Letter on Drugs and Therapeutics, considered one of the least biased sources in medicine. It’s kind of like the Consumer Reports of the drug world—and, in fact, was actually co-founded by the co-founder of the publisher of Consumer Reports more than 50 years ago. As The Medical Letter used to brag on their website, it “does not accept grants—from any source; donations—from anyone; [or] funding—from any entity.” They won’t let their work be used for promotional purposes, and they don’t accept any advertising. In their review of the evidence, they concluded, “There is no acceptable evidence that bio-identical hormones are safer.”

So, how do you treat menopausal symptoms like hot flashes? The American College of Obstetricians and Gynecologists suggests palliative measures, such as “consuming cool drinks,” but is there really no way to treat hot flashes without the cancer, clots, and coronaries? Thankfully there is, as I cover in a video series that starts with Menopausal Hot Flashes Are Not Inevitable and then moves from prevention to treatment.