Hormone Replacement Therapy: Marketing of Beauty-Focused Drug Stirs Debate over Women's Safety

Before the current controversy over hormone replacement therapy, many women and their doctors devoutly believed -- with scant scientific evidence -- that the drugs could not only ease menopause symptoms but also hold a bit of aging at bay, keeping skin smooth and young looking. That belief has been so pervasive that the pharmaceutical firm Pfizer started testing a drug called FemHRT in hundreds of American and Canadian women to see if that's the case.

Now it's a new world for hormone therapy, and amid growing concerns over the safety of the drugs, Pfizer's timing couldn't be worse.

FemHRT may soon come under tighter federal restrictions as regulators reassess all hormone medications. Pfizer says its form of HRT, and its skin study, are safe. But some doctors, researchers and women's health activists wonder whether Pfizer's beauty-focused trial is inappropriate -- or even obsolete.

"My concern is that pharmaceutical companies are looking for other ways to market these drugs," said Dr. Garnet Anderson, co-principal investigator of the major study that recently exposed new HRT risks.

"That's the wrong public health approach." It's hardly unusual for pharmaceutical companies to test their drugs after approval, looking for new benefits of the medicine. If those new "indications" get federal approval, drug makers can use them to differentiate their products in the marketplace.

But these days, the existence of Pfizer's FemHRT skin trial is touching a nerve. Scientists have long wanted to know whether hormones really do offer beauty benefits. But the trial infuriates some women's health advocates, who see it as yet another example of the drug industry capitalizing on women's fear of aging to sell more of a product whose risks are only now being quantified.

"Realistically, there's just too much concern on the part of health care providers and consumers about known risks," said Dr. Hector Medina, an obstetrician-gynecologist at El Camino Medical Group who has prescribed FemHRT to his patients. "To address whether cosmetic end points are reached or not really seems a little bit superfluous." Such concerns reflect just how much the beliefs surrounding HRT drugs and menopause treatment are shifting, changing the marketplace for companies such as Pfizer almost overnight.

In July, a massive federal trial of Prempro, a combination hormone therapy of estrogen and progesterone used by millions of women and made by Wyeth, a competitor of Pfizer, was shut down because of small but significant risks of breast cancer, stroke and heart disease.

In August, federal regulators announced a "major reassessment" of all hormone therapies for menopausal women, a move that could profoundly change how they are marketed and prescribed. The influential American College of Obstetricians and Gynecologists advises "caution" in using all HRT, even though the federal trial focused only on Prempro.

From Pfizer's perspective, its FemHRT trial is safe and legitimate.

The risks highlighted in the recent major HRT study applied only to Prempro, and cannot be projected onto FemHRT or any other hormone therapy on the market, a Pfizer spokeswoman said. There are more than half a dozen combination hormone therapies commonly prescribed, including brands such as Premphase and Ortho-Prefest.

FemHRT holds a much smaller market share than Prempro, however, and Pfizer has needed to be able to claim additional benefits to increase sales. One of those benefits, it was thought, might improve skin. Other HRT research studies had shown mild skin improvements with hormone therapies including estrogen creams and skin patches, but few experiments have been conducted rigorously, with a placebo group.

The company has no plans to stop or modify the skin tone trial. But Pfizer has asked its outside researchers to inform patients about the outcome of the federal trial and update their patient consent forms, said spokeswoman Susan Yarin.

"Just as hormone therapy is known to have an effect on bones, it's known to have an effect on skin," Yarin said. "It's a natural thing to look at that." But some doctors say such research reflects an old way of thinking about HRT that is no longer valid. For decades, hormones have been regarded as a relatively benign elixir for menopausal women, routinely prescribed, taken for years and invested with near-mystical powers to forestall the ravages of age.

To some scientists' dismay, the hormones evolved into an almost permanent "replacement" for the hormones women stop producing as they age. Taking the pills became a way of life believed to prevent osteoporosis, heart disease and some cancers -- rather than short-term treatment for menopause symptoms like hot flashes and mood swings.

That world view collapsed with the shutdown of part of the federal trial, known as the Women's Health Initiative. Now, federal health officials and some menopause experts are trying to take the "replacement" out of hormone replacement therapy, emphasizing instead that it should be used only for short-term relief of symptoms.

In the medical and research communities, reaction to the FemHRT skin tone study has ranged from outrage to approval and many guarded responses in between.

Researchers agree that Pfizer did the right thing -- the required thing -- by asking its investigators to inform patients of the new data from the nationwide trial. But was updating patient consent forms enough? Some scientists are torn because they want to know whether hormones do improve the skin. But they are reluctant to give women new incentives to take hormones long term.

"So many women cite improved skin as a reason they're taking these hormones," said Dr. Marcia Stefanick, a Stanford University professor of medicine and a lead researcher with the Women's Health Initiative. "It's a claim without any scientific base, yet it has been presented over and over as another reason to take hormones." But now, she said, the study seems off-point. "What we'd really like to do at this point is work out what is a reasonably safe, short-term time frame for taking these hormones," she said.

Stefanick added that the researchers who conducted the trial noted small but elevated risks of heart attacks and blood clots in women taking Prempro as early as one year into the trial -- the same length of time as the FemHRT trial.

"The risks were small, but are they worth these unproven benefits to skin?" Stefanick said. "I wouldn't want to have beautiful skin and get a heart attack or stroke or breast cancer. It wouldn't be worth it to me." Yet Dr. Robin Kroll, director of the Menopause Center of Seattle, takes a different stance.

"To halt all investigation into different hormone replacement therapies would not make any sense medically," she said. "To say that because one study showed this with Prempro, that all other research should end would be an incredible disservice to the female population." The estrogen and synthetic progesterone in FemHRT are very different from Prempro, Kroll emphasized.

The problem, many scientists say, is that while everyone can agree the hormones are different, no one can say with any certainty whether all hormone therapies carry the same risks.

"I think it's a pretty skewed view of what's important in women's health, to continue a trial of a combination of hormones that's pretty similar to what's been proven to harm women," said Cynthia Pearson, executive director of the National Women's Health Network and a longtime critic of the routine use of HRT.

Diane Bonneau, a 52-year-old Maine woman who has taken FemHRT for two years to control her hot flashes and headaches, said she is thinking "long and hard" about stopping in light of the Women's Health Initiative study. But given how the drug helps her menopause symptoms, it's a tough choice.

"I'd be willing to risk a small health risk to feel well," she said.

Bonneau said that although she has good skin tone, she also has rosacea, or skin ruddiness, that seems to have worsened while she has been on FemHRT.

"I don't think it's a good idea," she said of the FemHRT skin study. "Women should be taking this medication primarily for their hot flashes, not cosmetic reasons. It doesn't surprise me that they'd do a study, though. They need a gimmick, right?"

If Pfizer does detect skin improvement because of FemHRT, it's difficult, in the current wave of scrutiny of hormone therapies, to know how the U.S. Food and Drug Administration will respond.

The agency's reassessment of hormone therapy labeling and marketing "is part of a basic trend at the FDA to be tougher on things that aren't going to be major medical benefits," said Jim McCamant, editor at large of the Berkeley-based Medical Technology Stock Letter. "If the trial hadn't already been started, Pfizer would never do it."