Natural Hormone Leads to Less Bleeding

Problem leads many women to stop HRT

FRIDAY, Nov. 1, 2002 (HealthDayNews) -- Women taking natural progesterone have far less bleeding than women taking a synthetic version of the same hormone, new research finds.

Not only does this vastly improve the quality of life for postmenopausal women, it may also have far-reaching implications for the future of hormone replacement therapy (HRT).

Excessive bleeding is cited as a prime reason why many women choose to discontinue hormone therapy. HRT, which protects against cancer of the uterine lining in women who have gone through menopause, has been a particularly hot issue since the U.S. government halted a large trial earlier this year. The trial was stopped after it was discovered that women on one kind of HRT had a higher incidence of breast cancer, heart attack and stroke.

What many accounts of that episode failed to mention, however, is that the progesterone used in that trial -- medroxyprogesterone acetate, or MPA -- is only one type of progesterone available.

The current research, from the Postmenopausal Estrogen/Progesterone Interventions (PEPI) study, appears in the November issue of the Journal of Obstetrics and Gynecology. In it, researchers used micronized progesterone (MP), which is chemically identical to naturally produced progesterone.

"MP is really the same hormone as that a woman makes herself before menopause," says study author Dr. Robert D. Langer, a professor of family and preventive medicine at the University of California, San Diego, School of Medicine. "It is chemically identical in all respects to the progesterone that the woman makes herself."

MPA, on the other hand, is a synthetic version of the hormone that is 35 times stronger than natural progesterone. Because the MPA was so strong, it essentially nullified the beneficial effects provided by the estrogen. So far, all indications are that MP would not have the same negative effect.

The current study looked at 875 women at seven sites around the United States over a three-year-period. The women, all 45 to 64 years of age, were divided into five groups: one that took a placebo; one that got estrogen alone; one that took estrogen plus a continuous (taken throughout the month) form of MPA; one that got estrogen plus a cyclical (taken for the first 12 days of a 28-day cycle) form of MPA; and one that took estrogen plus a cyclical form of MP.

When the results were tallied, the women taking micronized progesterone had fewer days of bleeding and less intense bleeding than women taking traditional MPA. The MP was just as good in protecting against endometrial cancer.

"MP was as effective for endometrial protection as any other of the other combinations so that was all fine across the board, but the number of bleeding problems was strikingly lower with MP," Langer says. And the MP had another benefit: Bleeding was also unexpectedly less in the crucial first six months of therapy, the time when most women decide whether or not to continue treatment. That effect carried through the next two-and-a-half years.

"It's a quality-of-life issue, and what's more important than the menstrual flow is getting caught by surprise. That's the big issue," says Dr. Philip Sarrel, professor emeritus of obstetrics and gynecology and psychiatry at Yale University School of Medicine. "If a woman is getting progesterone the first 12 days of each calendar month, she can expect that if she's going to get bleeding, it will happen on the 11th through 15th day like clockwork. It's not going to be 'unscheduled bleeding.' That's the problem we want to avoid. It really is an issue of what is going to work best in the life of a woman."

The results also add to a growing body of evidence that MP might be a good replacement for MPA, and that the halting of the trail earlier this year might not have sounded the death knell for HRT. In fact, earlier research from the PEPI study is the reason why MP was approved by the U.S. Food and Drug Administration in the first place. In that initial trial, MP was shown to have the same effect on HDL or "good" cholesterol as estrogen by itself.

"It's my contention that MP could be used more easily. I think Women's Health Initiative results said that MPA-based treatments are at best neutral and maybe in some cases have a poor benefit-to-risk ratio, whereas this treatment has greater promise and a better benefit balance," Langer says.

Sarrel first learned to use MP when he worked in London in the early 1980s. Now it's the only type of progesterone he uses in his stateside practice. "I have patients who cannot tolerate MPA. Within two to three days of starting, they get flushes or chest pains or irritability or angry outbursts, all of which are adverse affects of too much progestin," he says. "What's awful for women after menopause is to think they're all done with that. With MP, it's really minimized. It's not perfect, but it's a lot better from an everyday clinical practice point of view. It's what works best. It's the only thing I use."

What To Do

For more on postmenopausal hormone therapy, visit the National Heart, Lung, and Blood Institute or the Women's Health Initiative.

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