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Intriguing concepts arise in the world of hormones
Judy Foreman -- Medical Matters
Originally published December 16, 2005

True confession time: Just when I thought I had made peace with the Great Post-Menopausal Hormone Decision - in my case, sticking with very low dose oral hormones, despite the risks revealed in a 2002 study - I have plunged into the murk again.

This time, my curiosity and my game plan are focused on "bioidentical" hormones, which are synthesized from soy and yams. They are made to be very similar to the hormones your body already produces - much more similar, for instance, than the hormones post-menopausal woman swallowed in pills like Prempro and Premarin.

Proponents argue that this close similarity means bioidentical hormones won't have the dangerous side effects of oral hormones such as Prempro. The 2002 study found that Prempro modestly increased the risk of breast cancer, heart disease, stroke and blood clots.

But some mainstream researchers are leery. Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital in Boston, called the research on bioidentical hormones "very, very sparse" and warned that women should not flock to them.

"We need to be cautious about not repeating the debacle that occurred with conventional hormone therapy," said Manson, a leader in the 2002 research on standard hormone replacement therapy.

In a September newsletter, doctors from the Mayo Clinic similarly warned that "hormones aren't safer or better just because they're labeled natural or bioidentical."

So why am I even considering replacing oral hormones with something "bioidentical"?

Because I like the way they're delivered. The only way to get a "bioidentical" substance - that is, an exact chemical match to something the body already makes - into the system is non-orally, chiefly through the skin, via patches, creams, lotions or gels. Medicines taken orally don't enter the bloodstream in the same form that you take them because they pass first through the liver, where their chemical structure is altered. Medicines taken transdermally do not pass through the liver first en route to the bloodstream and hence, are not altered.

When a woman takes oral estradiol, the hormone that declines precipitously at menopause, it is converted in the liver to estrone, a weaker hormone, said Dr. Alan Altman, a menopause specialist in private practice in Brookline. By contrast, when estradiol is taken transdermally, it gets right into the bloodstream as estradiol.

The transdermal form does not appear to increase certain cardiovascular risk factors, such as blood clotting proteins, triglycerides and C-reactive protein, as oral estradiol does, hormone specialists say. And, there may also be another advantage to taking transdermal estrogen. Research suggests that oral estrogen reduces the amount of available testosterone and therefore sex drive, while transdermal does not.

For the moment, at least, "non-oral is the way to go," said Dr. Carolyn Shaak, medical director of WomanWell in Needham, Mass., and a longtime proponent of bioidentical hormones. "If you want to duplicate the function of the ovary, you want to use a non-oral delivery system."

Bioidentical hormones can either be made by drug companies or, as proponents prefer, on a patient-by-patient basis by a "compounding" pharmacist, who follows a doctor's prescription to deliver a precise dose. The compounded versions are safer and more effective than standard hormones cooked up by the big pharmaceutical companies, proponents say.

Dr. Steven F. Hotze, who owns a compounding pharmacy in Houston and has treated thousands of patients with bioidentical hormones, has no doubts about the superiority of these products. His patients, he said, "come in on Premarin and are sick. We put them on bioidentical hormones and they get well. Hello? Come talk to my patients!"

Compelling words, to be sure. But there's actually no hard proof that compounded hormones, which are not approved by the U.S. Food and Drug Administration, are safe and effective.

In late October, a review committee of the American College of Obstetricians and Gynecologists found that "there is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies."

The group cited a government analysis of 29 product samples (not all of them hormones) from 12 compounding pharmacies. It found that one-third of the products flunked quality tests, with many not even containing the proper amount of the active ingredients.

You don't have to go to a compounding pharmacy to get many of these products. There have long been FDA-approved estradiol patches on the market. And in the last year or so, one FDA-approved cream (Estrasorb) and an FDA-approved gel (Estrogel) have also become available.

There are also FDA-approved vaginal rings that deliver estradiol, one called Estring, which combats only vaginal dryness; and another, Femring, which goes to the whole body and addresses more symptoms.
Things get trickier with the other menopausal hormones, testosterone and progesterone. A testosterone patch for women is in the works, but at the moment, the only way for women to get testosterone is to use small amounts of approved male products "off-label" or to use a compounded testosterone cream, which means doses may vary from application to application.

For progesterone, which women who still have a uterus must take to offset the risk of uterine cancer from estrogen, a good solution is micronized progesterone, sold as Prometrium, a pill that may carry less cardiovascular risk than the synthetic progesterone sold as Provera.

Needless to say, the growing popularity of non-oral approaches to hormone replacement is not lost on big drug companies, some of which are already making patches and creams.

Wyeth Pharmaceuticals, which makes the pill Premarin, went so far as to file a citizens' petition to the FDA in October to address what a company spokeswoman called "the growing and unlawful manufacture and marketing of so-called bioidentical hormone replacement therapy."

The reaction to that in the bioidentical world is also no surprise. As Hotze, the Houston bioidentical guru, put it: "They're putting pressure on the FDA to drive us little guys out of business. It's a big monopoly push."

As for me, my path through the murk is getting clearer. I'm switching from Premarin to an estrogen patch. I could have switched to a compounded cream, but I feel safer with an FDA-approved product.

But, as we all know by now, hormone therapy is a moving target. So stay tuned!



Judy Foreman's column appears every other week. Past columns are available at myhealthsense.com.