Bioidentical Hormones Revisited

Recently, I was browsing through an online discussion board about the pros and cons of hormone replacement therapy. I ran across this comment from a participant: “I’m going to try bioidentical hormones like Suzanne Somers. I’ve heard they’re safer.”

Whoa! I thought. Let’s do some objective homework first, and weigh the risks before you jump in.

Celebrity endorsements notwithstanding, bioidentical hormone replacement therapy (bHRT) is neither the miracle cure nor fountain of youth touted by Ms. Somers. Nor is it some kind of snake oil concocted by salacious quacks or unscrupulous doctors and pharmacists.

The truth is, of course, much more nuanced.

As a physician, I’d always opt for more treatment choices when it comes to helping women with the unpleasantries of menopause. I want more drugs in the arsenal, more ways to treat hot flashes, sleeplessness, and loss of libido. However, the entire topic of bioidentical hormones is so laden with emotion and misinformation that it takes a very fine point to tease fact from hyperbole.

We laid the groundwork on bioidenticals before, but the issue continues to befuddle and mislead, so let’s circle back and fill in some gaps.

Any hormone therapy, whether bioidentical or synthetic, is only intended to ease menopausal symptoms. Hormones were never meant to keep your memory sharp or your hair shiny or your skin taut. Hormones are not a fountain of youth. The latest medical guidelines state that hormones should be taken at the lowest possible dose for the shortest period of time needed to ease symptoms. This is because hormones, whether bioidentical or synthetic, are drugs and they interact with other systems in the body, sometimes in ways that are not well understood.

Point #1. Menopause isn’t a disease; it’s a natural transition. Hormone therapy is intended neither to keep your hormones “in harmony” nor to keep menopause at bay indefinitely. Hormone therapy is intended to ease the symptoms of the menopausal transition when they are interfering with your life.

Next, bioidenticals aren’t necessarily “natural” and therefore “safer.” The marketing message that hooks women is that bioidentical hormones are derived from “natural” sources and are therefore safer than hormones from other sources.

Bioidenticals are estrogens that are indeed made from plant sources, but they are processed (synthesized, if you will) to create a hormone that can be absorbed by humans. “All plant-derived hormone preparations, whether they come from a compounding pharmacy or a large commercial pharmacy, require a chemical process to synthesize the final product,” writes Dr. Oz in this article.

With bioidenticals, however, you end up with a molecule that is exactly like (identical to) human hormones, whereas non-bioidentical hormones are similar but not identical.

Any hormone, whether those your body produces or those you ingest, affects your body. Also, the delivery method, whether a patch, pill, or vaginal cream, also affects the way your body absorbs and responds to the hormone.

Point #2: Don’t equate “bio” with something “natural” and therefore risk free. Taking any hormone involves some risk. (Decisions about hormone therapy need to be based on careful consideration for each individual—understanding both the potential risks and benefits for that woman.) Bioidentical hormones are so-called because the molecule is identical to the human hormone and because they are derived from plant sources, even though they must be synthesized to be useful.

“So ‘natural’ doesn’t necessarily equal ‘safe’—and may simply be a euphemism for ‘unregulated,’” according to this article in the Harvard Women’s Health Watch.

You can, we should note, get bioidentical hormones that are FDA approved and regulated. Many familiar brands of hormonal rings, creams, patches, pills, and gels are both commercially manufactured by pharmaceutical companies and bioidentical. These include Estrace, Femring, Vivelle, Vagifem, and Prometrium, and more. You know what you’re getting with these products.

You know that the active ingredient is in the form and dosage that the label says it is. That kind of uniformity and “safety” is the assurance provided by FDA testing and approval.

Point #3: Many major brands of commercially manufactured hormones are both bioidentical and FDA approved.

Next, let’s understand what “custom-compounding” means. Many bioidenticals are touted as natural, safe, and custom-made just for you to bring your hormones back in balance. Custom-compounded drugs are made in small, customized batches by pharmacies that specialize in custom-compounding. They can be prescribed by a clinician.

Custom-compounding is very helpful when a patient needs a special dosage of a medication, or a different delivery method, or is allergic to a filler in a commercial drug. Maybe, for example, you need a lower dose of progesterone than is commercially available, or you need it in a vaginal cream, and the big pharmas only make it for administering orally.

However, neither the process nor the product is FDA-regulated or approved, and in fact, studies have shown that they are much less consistent than commercial products. In a few highly publicized cases, contaminated medications distributed by custom-compounders have been responsible for serious illness, infection, and death. An example is the outbreak of fungal meningitis in the fall of 2012.

The problem with custom-compounded hormones arises with claims of customized products that are safe, natural, and that will restore hormonal balance, among other things.

In actuality, it’s not possible to accurately pinpoint hormonal levels in an individual because they are constantly changing. The hypothalamus, pituitary and ovaries (the HPO axis, as we call it) work in a very integrated and precise way to direct hormone production. Our replacements aren’t able to replicate that concert of events, but we can do a good job of replacing the hormones more consistently, which many women prefer to the ‘ups and downs’ we’re familiar with. The only way to determine an effective dose is through symptom control—the lowest dose that relieves a woman’s symptoms. “Salivary and blood testing of hormone levels used by custom compounders is meaningless for midlife women as their hormone levels vary throughout the day, and from day to day” is the North American Menopause Society position.

“This doesn’t mean that you shouldn’t consider compounded hormones. Just realize that, in a real sense, you’re going to be an experiment of one,” says the Harvard Medical Watch article.

Also realize that custom-compounded drugs usually aren’t covered by insurance, and the regimen of testing and compounding gets expensive very quickly.

Point #4. Custom-compounding of drugs is a time-honored practice of making drugs in small batches or according to specific needs (while the processes and products aren’t subject to federal regulation or oversight). Claims that these products are healthier, safer, or somehow contain properties lacking in commercial products should be viewed with suspicion.

Q: What should I know about Estrace?

Estrace is a bio-identical form of estradiol, a plant-based version of the same estrogen made by our ovaries. It comes in two forms—oral (systemic) and vaginal (localized). I use very little oral estrogen in my practice, because we've learned that transdermal estrogen (delivered by patch, gel, or spray or other forms that deliver it through the skin) is safer than oral. Because it's not metabolized by the liver, it doesn't carry the same risk of thrombosis.

Vaginal Estrace is great from a therapeutic perspective—that is, it's very effective for treating vaginal atrophy. Because it's a cream, though, many of my patients don't love it: Some find creams messy to apply. It's important to find a form of localized hormones that each patient will actually use!

Bioidentical Hormones: Flap? Or No Flap?

Suzanne Somers touts them in her bestselling book, Ageless: The Naked Truth about Bioidentical Hormones. Oprah promotes their use. On the other hand, the Harvard Medical School, the North American Menopause Society, and the Endocrine Society take a more cautionary position toward compounded bioidentical hormones. And I find that many of my patients are just confused.

So what are bioidentical hormones and what’s all the controversy surrounding them?

We’ve written a lot on Middlesexmd.com about the importance of estrogen to vaginal health and sexual function. We’ve also discussed various options for replacing estrogen and enhancing vaginal comfort. And we explored the latest thinking about hormone replacement therapy (HRT).

In a nutshell, estrogen is critical to sexual comfort and function, and that’s the hormone we lose during menopause. Most therapies revolve around replacing estrogen to treat menopausal symptoms.

For many years, Premarin was the estrogen replacement of choice. This is a synthetic estrogen made from the urine of pregnant mares, which, according to the Harvard Women’s Health Watch,  “contains a mix of estrogens (some unique to horses), steroids, and various other substances.”

Bioidentical hormones, on the other hand, are defined by the Endocrine Society as “compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body.” Bioidentical hormones are usually extracted from plant sources.

Moderation in all things.Pharmaceutical companies manufacture many brands of bioidentical estrogens, such as Vivelle, Elestrin, Divigel, Evamist and one brand of bioidentical progesterone (Prometrium). These are FDA-approved bioidentical hormones. About 95 percent of my patients are on these FDA-approved bioidentical hormones. All hormones, whether they are synthetic or bioidentical, are labeled with the black-box warnings mandated since the massive Women’s Health Initiative study linked slightly higher rates of breast cancer, blood clots, and heart disease to hormone replacement therapy.

So far, so good.

Confusion enters in when bioidentical hormones are custom-compounded by pharmacies. Sometimes there are good reasons for a doctor to prescribe a custom-compounded hormone, if a patient is allergic to some agent in the FDA-approved hormones, for example, or if her dosage can be lower than those produced by pharmaceutical companies.

But hormones made by custom compounders aren’t subject to FDA oversight, nor must they adhere to FDA-approved processes. These custom hormones don’t come with black-box warnings because they don’t fall under the FDA umbrella.

In actual practice, there may not be that much difference between custom hormones and FDA-approved hormones. According to the Harvard Women’s Health Watch, in a 2001 random test of 37 hormone products from 12 compounding pharmacies, almost one-quarter (24 percent) were less potent than prescribed, while 2 percent of FDA-approved products were less potent.

The other problem with custom compounds is cost. Health insurance usually doesn’t cover them, so the regimen gets expensive very quickly.

While custom compounds may be a helpful option for some women, the controversy surrounds the claims about them made by celebrities like Suzanne Somers and even by some clinicians.

In the introduction to her book, Somers writes, “This new approach to health [bioidentical hormone replacement therapy] gives you back your lean body, shining hair, and thick skin, provided you are eating correctly and exercising in moderation. This new medicine allows your brain to work perfectly and offers the greatest defense against cancer, heart attack, and Alzheimer’s disease. Don’t you want that?”

Well, who wouldn’t? But like most claims that sounds too good to be true, so is this one.

The truth is that bioidentical compounds, no matter how “natural and safe” they may sound, are still drugs. There’s no scientific evidence that their effect is any different than synthetic hormones. Also, because hormonal levels vary from day to day, even from hour to hour, attempting to customize hormonal treatments is tricky business. “There’s no stable ‘normal’ value at all for salivary or blood levels of these hormones or levels that correlate with symptoms,” says the Harvard Women’s Health Watch.

The current medical advice is to take the lowest possible dosage of any hormone—synthetic or bioidentical—for the shortest period of time to alleviate menopausal symptoms. There is, unfortunately, no way to turn back the clock—"natural" or otherwise. In the meantime, the hormones that work for a woman can significantly improve her quality of life.