The Estrogen Puzzle Do the health benefits of estrogen outweigh the risks? Lower dosages may be the key to the puzzle.
IF RESEARCHERS LIKE Donna Shoupe get their way, postmenopausal women will receive all the benefits of estrogen at much lower doses than they are taking today.
Shoupe, professor of obstetrics/gynecology and director of the USC Women’s Health Center (formerly the USC Menopause Center), is conducting research on low-dose estrogens. Today, she says, about 20 percent to 40 percent of all postmenopausal women are on estrogen replacement therapy, and 0.625 milligrams of Premarin, the most popular dose of the most prescribed estrogen, is about half the dose prescribed to women a decade ago. And, she predicts, “we’re going to get even lower.”
Shoupe is most interested in finding the optimum dose for each patient.
“I’m interested in trying to fine-tune [the dosages] so you don’t over-treat patients,” she says. “Especially because the more estrogen you give them, the more bleeding they have and the less likely they are to continue taking the medication.”
Lower doses may also help mitigate the risk of cancers – such as breast, uterine and ovarian cancer – often associated with estrogen replacement therapies.
“I do think there’s a relationship between high-dose estrogen and breast cancer,” Shoupe acknowledges. “Most of the data that links estrogen to breast cancer is high doses used for long periods of time.
“One of the big advantages of getting the dose lower, down to what we need, is so we can optimize the benefits and really get rid of the risks – or at least minimize the risks.”
Those risks have been keeping women from taking estrogen postmenopause. And those who do take it, she says, “probably take it to relieve symptoms, and they don’t realize that the real reason they should be taking it is for the long-term health benefits.”
In the future, Shoupe says, lower doses combined with greater public awareness of the health benefits will mean even more women will opt for estrogen replacement therapies.
“We’re getting a lot more options,” she says. “We’re getting a lot more estrogens, we’re getting a lot more delivery systems. There’s a ring that delivers estrogen, new patches that deliver estrogen. They’re working on patches to deliver the progestins.”
Some low doses are currently available, such as a 0.5 milligram dose of Estrace (1 milligram of Estrace is considered comparable to 0.625 of Premarin). But women haven’t been asking for the lower doses and, Shoupe says, it is an area that has not been well studied.
“Most women have been thrown into ‘menopause’ or ‘nonmenopause’ categories, which is fine if you’re trying to get a dose that can fit everybody,” she says. “But we need to refine it so that you can take all the characteristics of your patient into account and give just enough estrogen to get the benefits and substantially reduce the risks and side effects.”

For information about USC’s Women’s Health Center, call 1-800-USC-CARE.

-Monika Guttman

Estrogen and Health

RESEARCH IS SHOWING a number of long-term health benefits associated with estrogen, according to USC Women’s Health Center director Donna Shoupe. Among them:
• Improved cardiovascular health. Estrogen has been shown to cut risk of heart attack and stroke.
• Lessened osteoporosis risk. Estrogen minimizes the associated back pain, loss of height, immobility, curvature of the spine, fracture of the hips and need for surgery. • Lessened Alzheimer’s risk. After five years of estrogen replacement therapy, there’s a 70 percent reduction in the risk of Alzheimer’s.
• Better teeth. Estrogen helps patients keep their teeth longer.

Risks that may be associated with high-dose estrogen include:
• Breast cancer. Reports on the risk are conflicting. Some studies suggest a link between high-dose estrogen therapy and breast cancer, particularly for those with a family history of breast cancer. Others have found little risk.
• Endometrial cancer. Increased risk of this cancer of the lining of the uterus for estrogen users. The risk can be reduced by hysterectomy or by taking progesterone, which causes the lining of the uterus to shed monthly.

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Photograph of Donna Shoupe by Irene Fertik/Photograph of pills by Dan Logan

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