According to an Endocrine Society Scientific Statement, patients need to be counseled about the risks of custom-compounded bioidentical hormones. The preferred treatments should have been vetted by the U.S. Food and Drug Administration, not Oprah.

Physicians may need to take time to explain to patients the potential risks of using “bioidentical hormone” formulations made by compounding pharmacies, say the authors of an Endocrine Society scientific statement.

Many practitioners and patients find the subject confusing because of misleading information from the Internet and endorsements for alternative menopausal replacement hormones from celebrities such as Oprah Winfrey and Suzanne Somers. The compounded formulations are touted as “natural” and tailored to an individual’s needs, but “bioidentical hormones” is better understood as a marketing term to sell products that are not approved by the Food and Drug Administration (FDA), according to Nanette Santoro, MD, chair of the task force that wrote the scientific statement.

Patients need to understand that FDA-approved hormones from pharmaceutical companies offer protections of purity, controlled manufacturing processes, and evidence from clinical trials that products from less-regulated compounding pharmacies do not. In addition, many of the newer FDA-approved formulations can be described as bioidentical because they are the same molecules as hormones found in the body.

Unknown Manufacturing Conditions

Patients are attracted to that “natural” label, but they can’t know the conditions under which the formulations are produced. An extreme example of the danger of the less-regulated environment of compounding pharmacies occurred in 2012, when more than 60 people died from fungal meningitis after receiving injections of tainted steroids supplied by the New England Compounding Center. The head of that pharmacy was recently found guilty of racketeering charges.

“The message that we would like to get to women and to prescribers is that they should only consider a compounded hormone therapy if they can’t tolerate a government-approved therapy, or if they need a dose or formulation that is not commonly available in a government-approved therapy.” – JoAnn Pinkerton, MD, executive director, North American Menopause Society; professor, obstetrics and gynecology, University of Virginia Health System

But another worrisome problem is that compounding pharmacists can, for example, introduce excipients with unknown effects on absorption of the hormone.

“The conditions under which it is produced and the exact excipients that are put into that substance are going to affect its absorption, and may affect whether or not it causes you harm,” says Santoro, who chairs the department of obstetrics and gynecology at the University of Colorado Anschutz Medical Campus, Aurora. “No matter how carefully it is prepared, it is impossible to know the product’s pharmacokinetics. So, I don’t know if my patient is getting a peak at one hour, two hours, five hours, six hours, or never because the excipient is blocking absorption.”

Millions of Women?

The number of women using these products appears to be huge, according to a study by Santoro and JoAnn Pinkerton, MD, executive director of the North American Menopause Society and professor of obstetrics and gynecology at the University of Virginia Health System. The study estimated that 1 million to 2.5 million U.S. women aged 40 years or older are using compounded hormone therapy. “It seems to be a bigger part of the market than we thought before. A quarter to a third of the market for hormone therapy products is in the custom-compounded realm,” Santoro says.

The study also found that many women are not aware that the custom-compounded products have not been evaluated by the FDA. “These custom-compounded products require prescriptions,” Pinkerton says. “Many women believe that if they are given a prescription, it means that the product is government-approved. So, when asked in the survey, many women couldn’t tell whether or not what they were taking was a government-approved or nongovernment-approved therapy.”

The Myth of Saliva Testing

Another tactic used by compounded products marketers is the notion that through saliva testing, they can provide each individual a perfect match of hormone needs, another claim that the scientific statement seeks to knock down. “The custom compounders for menopause [hormones say that] ‘everybody is a special snowflake, and you need your special recipe of hormones, and we can do that for you,’” Santoro says.

“The scientific statement makes the point that salivary testing unreliable,” Pinkerton says. “Patients pay significant costs to receive data that they believe is individualized to them, when in reality, dosing for hormone therapy is done based on symptoms, not based on blood levels or salivary testing,”

A patient whose hot flashes are gone is on the correct dose, Santoro agrees: “Only in rare cases, if they are outliers on the pharmacokinetic curve, do you need to measure blood levels. Saliva testing adds a level of complexity that doesn’t need to be there.”

Thyroid Hormones

In addition to the menopausal hormones, thyroid insufficiency is the other main condition for which bioidentical hormones are marketed. Santoro says that “somewhere between 1 in 10 to 1 in 20 people do not do well” on replacement of levothyroxine (T4), and some seem to do better with a combination of T4 and triiodothyronine (T3). She says that marketers in the bioidentical field seize on this to push “the belief that if you got it from a biological source it is better. That has led to people taking things like porcine thyroid” because it contains both T4 and T3.

Treatment guidelines from organizations like the American Thyroid Association recommend avoiding these “natural” extracts from pig thyroid glands because they raise safety concerns — in particular because of their ratio of T4 to T3, with T3 levels being much too high. And it should be noted that the standard drugs for replacing T4 and T3 are in fact bioidentical — the exact same molecules as the hormones.

Successful Communication

Santoro and Pinkerton regularly encounter patients who request compounded bioidentical hormones, often because they are afraid of traditional hormone therapy.

Part of their worry stems from the spin that the compounding marketers put on the preliminary release of results from the Women’s Health Initiative more than a decade ago about risks of menopausal hormone replacement therapy. One fallout from the WHI was that FDA-approved estrogen therapies must include boxed warnings about potential dangers. The less-regulated compounded therapies are not required to include these warnings, which can lead women to make the unwarranted assumption that they have no risks.

“A lot of these marketers build on a small truth and then make it much more broadly applicable in an inappropriate way,” Santoro says, such as claiming that women experienced problems because they were not using “natural products.”

For example, the fourth hit from a Google search of the term, “bioidentical hormones,” turns up a website that makes the false statement: “There is an overwhelmingly large body of evidence that supports the claim that bioidentical hormone therapy is safer and more effective than synthetic hormone replacement.” There is in fact no such evidence, the scientific statement emphasizes.

“There are reasons to use compounding, but there is not a reason for a third of American women to be using it as a preferred form of hormone therapy. Maybe 1% of people will have a reaction to all forms of hormone therapy and might do better with compounding.” – Nanette Santoro, MD, chair, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora

Santoro and Pinkerton both explain to patients influenced by such claims that there are FDA-approved products that can be defined as “bioidentical.” “I know it is going to be another 10 minutes of education added to the visit,” Santoro says. “I have to explain that what they are getting is much more reliable if we use an FDA-approved compound, so I feel much more comfortable giving that to them. There are real safety issues and efficacy issues with using something that is compounded, so it would not be my first recommendation for them, it would be my last, if nothing else worked.”

“The message that we would like to get to women and to prescribers is that they should only consider a compounded hormone therapy if they can’t tolerate a government-approved therapy, or if they need a dose or formulation that is not commonly available in a government-approved therapy,” Pinkerton says. “The majority of women are very willing to try a government-approved bioidentical hormone therapy once they understand that it is available, and the difference in the safety between government-approved vs. compounded.”

“There are reasons to use compounding, but there is not a reason for a third of American women to be using it as a preferred form of hormone therapy,” Santoro says. “Maybe 1% of people will have a reaction to all forms of hormone therapy and might do better with compounding.”

A Consensus

In addition to the Endocrine Society’s statement, Pinkerton says that “the majority of the key medical societies, including the North American Menopause Society, American Congress of Obstetrics and Gynecology, and American Society for Reproductive Medicine, as well as several international societies, all recommend the use of government-approved hormone formulations that provide many options without the unique risks of compounded hormone therapy.”

“Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement” was published in The Journal of Clinical Endocrinology & Metabolism in April 2016.

Seaborg is a freelance writer based in Charlottesville, Va. He wrote about the increase in hip fractures in the May issue.