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Doctors have known since the 1970s that taking estrogen greatly increases postmenopausal women's risk of endometrial cancer.
To counteract the effect on the uterine lining, doctors began prescribing a second hormone, progestin. Only women who have had a hysterectomy take only estrogen.
But a growing body of evidence shows that progestin, when combined with estrogen in postmenopausal women, has its own set of problems, leading some doctors to question the dogma of combination hormone therapy.
"I think unopposed estrogen is really a very low risk" in women who have not had a hysterectomy, says Yale obstetrician/gynecologist Hugh Taylor. Still, "I don't want to come out and say I'm advocating that yet without further study."
Just this week, two reports from the Women's Health Initiative, a huge government-sponsored study of postmenopausal women, point out safety differences between estrogen plus progestin and estrogen alone. "It's very likely that there's some synergistic effect here, since (estrogen and progestin) both target the same organs," says Jacques Rossouw of the National Heart, Lung, and Blood Institute, sponsor of the study.
One paper, in The Journal of the American Medical Association on Wednesday, confirmed that up to seven years of estrogen use did not raise women's risk of breast cancer. In 2002, the Women's Health Initiative reported that women's risk of breast cancer began rising between three and four years after going on estrogen plus progestin.
A second paper, out Monday in the Archives of Internal Medicine, said estrogen doesn't raise the risk of blood clots as much as estrogen plus progestin does.
"I do believe it's time to revisit the issue of combined therapy for women with a uterus," says Stanford University researcher Marcia Stefanick, lead author of the paper about estrogen and breast cancer risk. Still, "we certainly don't want to encourage women to demand that they go on only estrogen if they have a uterus."
A study published last year found that after two years there was no difference in the uterine lining between women wearing an ultra-low-dose estrogen patch and those wearing a placebo patch.
Though such a low dose helps prevent osteoporosis, it's too small to relieve menopause symptoms, says lead author Susan Johnson, a University of Iowa OB/GYN who was not involved in the Women's Health Initiative.
Women who take 0.625 milligrams of estrogen, the dose tested in the Women's Health Initiative, "have a real risk of endometrial cancer" if they don't also take progestin, Johnson says.
The initiative's estrogen-plus-progestin findings did spur the Food and Drug Administration to advise women to try as low an estrogen dose as possible for symptom relief. "When you use a lower dose of estrogen, you can also use a lower dose of progestin," Johnson notes. "That probably reduces that risk (of progestin) even further."
New York University OB/GYN Steven Goldstein advocates using transvaginal ultrasound to monitor the uterus in women who take estrogen alone. If the uterine lining stays thin, he says, women can safely forego progestin for months. Still, he says, another study is needed to confirm this.
For now, Rossouw says, probably the best bet for postmenopausal women concerned about progestin's risks is a product that can deliver the hormone right to the uterus, such as an intrauterine device.
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