Use of Unapproved Menopausal Hormone Therapy Skyrockets

Miriam E. Tucker

October 16, 2014

UPDATED October 22, 2014 // Editor's note: A comment from the International Academy of Compounding Pharmacists has been added.

NATIONAL HARBOR, Maryland — Anywhere from 1 million to 2.5 million women in the United States — about 2% of the female population older than 40 years — are using "bioidentical" compounded menopausal hormone therapy not approved by the US Food and Drug Administration (FDA), new data show.

These products now make up nearly 40% of all menopausal hormones used in the United States, at an out-of-pocket cost of $1 billion to $2 billion annually. What's more, 86% of women don't know that what they're taking isn't FDA-approved, according to data from two posters presented here at the annual meeting of the North American Menopause Society (NAMS) 2014 Annual Meeting.

Bioidentical compounded therapy typically refers to a combination of hormones — such as estradiol, estrone, and progesterone — that are supposedly "customized" for the patient on the basis of blood or salivary measurements, explained JoAnn Pinkerton, MD, professor of obstetrics and gynecology at the University of Virginia in Charlottesville, who was involved in one of the studies. The process has not been validated, the doses are not standardized, and the compounded products have not been demonstrated to be safe or effective in randomized controlled trials, she told Medscape Medical News.

Many of the prescriptions are written by so-called "anti-aging" doctors, but ob/gyns and primary care physicians are also prescribing them, she noted.

"Our summation is that a lot of women are doing this. It's important, if you are prescribing, to first prescribe something that's FDA-approved. If you can't do that for sensitivity reasons or because there's a special need, you need to educate the woman about the unique risks, and that includes the fact that the FDA doesn't regulate these products, monitor them, or oversee them," Dr Pinkerton told Medscape Medical News.

In addition to the general lack of data, specific risks associated with these products include recently identified issues with compounding pharmacies; nonsterile processing has led to deaths related to fungal infection. There is also evidence suggesting that the progesterone doses in some of these products aren't high enough to protect women with intact uteri from cancer, Dr Pinkerton continued.

"The findings of the studies presented at the recent [NAMS] meeting about the use of compounded hormone replacement therapy are quite consistent with what physicians and pharmacists already know — many patients have misconceptions or a lack of knowledge about their medicines," a spokesperson for the International Academy of Compounding Pharmacists (IACP) told Medscape Medical News when asked for comment on the studies. "It is incumbent upon prescribers and pharmacists, regardless of whether a [hormone therapy] regimen is compounded or manufactured, to fully educate consumers about the benefits and risks of all medications, how they should be taken, and what types of side effects to look for and when to report those."

Major Shift Since WHI

In the first study, data from American women 40 years and older who responded to an internet survey, conducted by Rose Research, were analyzed by Ginger Constantine, MD, from EndoRheum Consultants in Media, Pennsylvania, and colleagues.

The researchers looked for trends in the use of compounded non-FDA approved hormone therapy after the 2001 publication of the Women's Health Initiative (WHI), which scared many physicians and patients into seeking alternatives to menopausal hormone therapy. Prior to the WHI, approximately 17.9 million women were taking FDA-approved menopausal hormone therapy, totaling $3.9 billion in sales, and compounded hormone use was unusual.

Of the 17,825 survey respondents, 5% reported using any type of menopausal hormone therapy, and those women used an average of 1.7 products per month.

On the basis of those data and data from the 2012 census, Dr Constantine and colleagues estimated that 3.7 million women in the United States used some form of menopausal hormone therapy in 2013.

That translates into 57 million to 75 million menopausal hormone therapy prescriptions annually, based on national prescribing data from Source Healthcare Analytics Prescription Data from 1998 to 2013. Of those, 36 million prescriptions were for FDA-approved products, leaving an estimated 21 million to 39 million annual prescriptions for unapproved compounded hormone therapy.

The researchers also estimated that approximately 1 million to 2.5 million American women are taking the compounded products.

Survey respondents reported paying an average $49 out of pocket per month for the compounded hormone therapy, indicating that the total amount spent on unregulated unapproved hormone therapies ranges from $1 billion to $2 billion annually.

In the second study, data from the Rose Research survey and from a smaller survey conducted by Harris Interactive were analyzed by Dr Pinkerton and Nanette Santoro, MD, professor of obstetrics and gynecology at the University of Colorado at Denver.

Of the 801 respondents to the Harris Interactive survey, 76% did not know whether "bioidentical hormone therapies compounded at a specialty pharmacy" were FDA-approved, and 10% thought they were FDA-approved.

Of the 1771 ever-users of menopausal hormone therapy who responded to the Rose Research survey, 27% didn't know whether the product they were using had been compounded.

"Huge Knowledge Gap"

"There's a huge knowledge gap," said Dr Pinkerton. "We as providers have to educate our patients about the safety of FDA-approved products, the good and bad about hormone therapy and the fact that custom compounding has those same risks, plus the unique risk related to the lack of monitoring and overseeing, and the fact that there are no randomized clinical trial data to show that these products are safe or effective," she told Medscape Medical News.

"How are women to know, when their healthcare provider is a source of information to them about their health, when that provider is using a treatment that has not been subject to FDA testing? That's very troubling," said Pauline Maki, MD, professor of psychiatry and psychology at the University of Illinois in Chicago, and incoming president of NAMS.

The term "bioidentical" has come to be associated with these unapproved compounded products, but the FDA-approved oral estradiol is also bioidentical, she told Medscape Medical News.

"Bioidentical just means similar to what's in your body. It's like putting 'gluten-free' on grapes," she said.

But using the same term does not mean that physicians should consider the unapproved and approved agents equivalent. "I know exactly what's in that FDA-approved tablet and I know what the clinical trial data look like for that tablet," she said. "With these compounded products, they're relabeling them and repacking them in nonstandard doses without rigorous scientific evaluation. It's the same thing, but less safe," Dr Maki warned.

"There are other nonhormonal alternatives for hot flashes, such as certain antidepressants and gabapentin (off-label, but at least FDA-approved). While nothing is quite as effective as hormonal therapy for moderate to severe hot flashes, Dr Maki noted, "the key is to give women a choice when they have options."

TherapeuticsMD supported the Rose Research and the Harris Interactive surveys. Dr Pinkerton reports consulting for, conducting research for, and/or receiving travel fees from Pfizer, Depomed, Noven, Shionogi, NovoNordisk, TherapeuticsMD; and conducting multicenter research for Depomed, Endoceutics, and Bionova. All of her fees go to her institution. Dr Constantine reports consulting for TherapeuticsMD and Shionogi. Dr Santoro reports receiving grant/research support from Bayer Healthcare and owning stock in MenoGeniX. Coauthors on Dr. Constantine's studies are employees of TherapeuticsMD. Dr Maki is an advisor to Pfizer.

North American Menopause Society (NAMS) 2014 Annual Meeting: Abstracts P-79 and P-89. Presented October 16, 2014.

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