Progestin Singled Out As Doctors Rethink Post-Menopausal TherapiesAug 15, 2003 | Kansas City Star The problem with hormone replacement therapy is starting to look like a problem with progestin.
Progestin is one of the hormones taken by millions of women in the United States to alleviate the symptoms of menopause. The other one is estrogen.
A study published last week in The Lancet, a British medical journal, added to the evidence that hormone therapy particularly progestin increases a woman's odds of developing a serious illness. The Lancet study looked at breast cancer specifically.
The researchers surveyed about 1 million British women and concluded that for every 1,000 women who take estrogen for 10 years, an extra five develop breast cancer compared to women who don't take replacement hormones. For every 1,000 women taking estrogen plus progestin, 19 more cases of breast cancer developed than among non-users.
Because this was an observational study in which women simply reported on their hormone use, the results are considered less reliable than they would be if derived from a carefully controlled clinical study in which subjects are randomly assigned to receive either drugs or placebos.
Nonetheless, the study's outcome is helping to resolve the menopausal puzzle.
"Increasingly it looks like the problem is progestin," said Wolf Utian, a gynecologist and executive director of the North American Menopause Society. "The Lancet study shows a slight increase with estrogen, but the big increases are with estrogen plus progestin."
Progestins are similar but not identical to progesterone, the hormone made by a woman's body to counter some of the effects of estrogen. Among other things, progesterone triggers the monthly shedding of the uterine lining.
Progestins earned a black mark a year ago when the federal government stopped administering them to subjects in a large and important clinical test of hormone therapy's health effects. It's known as the Women's Health Initiative.
One group of women was receiving estrogen plus a progestin. That group is no longer being given the hormone formula because of concerns about increased rates of heart attack, stroke and breast cancer that were showing up in the group. Another group, women whose uteruses had been removed, received estrogen only. That group is still being studied. So far, no pattern of increased cardiac problems or cancer has surfaced.
Progestins have a poor track record where breast cancer and cardiac health are concerned, said Sharonne Hays, a cardiologist at the Mayo Clinic in Rochester, Minn.
Progestins tend to decrease the amount of high-density cholesterol, the "good" cholesterol that escorts the artery-clogging low-density lipoprotein out of the vascular system, she said.
Although progestins are the compounds generally tested in drug studies in the United States, Hays said Europeans favor micronized progesterone, the hormone that is identical to that made by a woman's body.
Although U.S. hormone manufacturers still make the non-identical progestins that have been raising questions, Hays said some patients and doctors are finding ways around the progestin problem. Many of them are using progesterone, which is available in a range of forms including pills, creams and suppositories.
"Certainly since the Women's Health Initiative, many women in this country have switched to progesterone in one of various forms," said Marilyn Richardson, interim director of the division of reproductive endocrinology at the University of Kansas Medical Center. Because of progestin's negative effects on cholesterol and its occasional side effects of headache, bloating and depression, Richardson said she has generally prescribed progesterone for the last 15 years.
Another increasingly popular strategy, which can be employed with progesterone or a progestin, is to take it only sporadically. Some hormone formulations include a dose of progestin every day, which is designed to prevent menstrual bleeding. Although it appeals to many women on convenience grounds, it runs counter to a woman's natural hormonal cycle, in which substantial amounts of progesterone are produced during only about one-third of the menstrual cycle.
Some people suspect that the daily dose may contribute to the problems that seem to be associated with progestin. A hormone therapy regimen can be designed with progestin or progesterone on almost any schedule that a woman desires.
Hays said the troubling research data on hormone therapy, "especially the potent negative data on progestins," has spurred some creative thinking about alternatives.
"The cyclical hormones where a woman takes progesterone only every three or four months have become exceedingly popular," Hays said. A week or two of progestin or progesterone every three or four months with a resulting period seems to be enough to keep the uterine lining from building to the point where it poses a cancer risk, she said. And a woman can plan her periods when they're least intrusive.
A few women, with their physician's consent, are starting to take estrogen without progesterone or progestin, Hays said. It has long been unquestioned medical wisdom that a woman with a uterus must take progestin or progesterone along with estrogen. That wisdom is even being questioned now, Hays said.
"I know some of our gynecologists here and elsewhere who are saying now that progestin is looking pretty bad, and that maybe offering this (estrogen alone) to women who are not at high risk (for endometrial cancer) is not a bad thing."
KU's Richardson is not one of them.
"I would not consider that a safe practice at this point," she said.
Although unopposed estrogen does increase the risk of uterine cancer, it rarely is fatal, Hays said. And regular monitoring by a physician can catch any abnormality early, she said.
As bits of research about hormone therapy continue to trickle out, Hays said, "patients are saying, `I don't like the options I've read about. What else do you have to offer me?' "
But at the same time that some women and their doctors are experimenting with new approaches, and despite hormone therapy sales having dropped about 40 percent the past year, plenty of women are still ingesting a daily dose of progestin.
"A lot of physicians are chagrined that despite data from eight years ago that showed the micronized progesterone was favorable in terms of HDL and other things, that the No. 1 prescription for post-menopausal women was Prempro," Hays said. Prempro contains both estrogen and progestin.
"The progestin question is a really a biggie."