Menopausal Women Have New Options
For Safely Taking Hormone Treatments
July 13, 2004; Page D1

For nearly 30 years, women taking estrogen for menopause symptoms have been told they must also take a second hormone -- progestin -- to protect them from uterine cancer.

But now, with recent studies linking hormone therapy and progestin in particular with breast cancer and other health problems, doctors are rethinking the conventional wisdom and beginning to offer women a little-talked-about option: taking little or no progestin at all.

In a seismic shift in thinking, some doctors are now prescribing a dose of the drug just once or twice a year and sometimes opt to eliminate it entirely. (Many hormone users now take progestin daily or monthly.) Next month, Berlex plans to launch its Menostar low-dose estrogen patch -- the first estrogen product that doesn't require most women to take progestin. These new options may offer a middle ground for women who have been frightened by recent studies but still want to use hormones to cope with menopause or to prevent osteoporosis.

HEALTH MAILBOX Read Tara Parker-Pope's Health Mailbox where she answers readers' questions about medical studies, ailments and treatments.

The idea of giving estrogen alone to women who haven't had a hysterectomy would have once been unthinkable, because the hormone by itself increases the risk of endometrial cancer by causing a buildup of the uterine lining. Progestin lowers that risk by prompting the body to slough off the lining.

But during the past few years, hormone studies including the Women's Health Initiative have found that women who took the most commonly prescribed progestin -- medroxyprogesterone acetate, or MPA -- had far more health problems, including breast cancer, than women who didn't take progestin. MPA can be taken as a generic progestin and is found in Wyeth's combination therapy Prempro and in Pfizer's Provera.

Although recent research has led to controversial warnings about the risks of all menopause hormones, many doctors think the focus should instead be on the regular use of progestin, particularly MPA. "Progestin may be the thing that increases the risk of breast cancer," says Steven R. Goldstein, professor of obstetrics and gynecology at New York University School of Medicine. "So there's an added incentive to try to reduce or eliminate the progestin dose."

Dr. Goldstein says it's possible to give a woman just one or two progestin doses a year or to eventually eliminate it entirely if she is monitored with transvaginal ultrasound to detect simple hyperplasia, a benign condition that occurs when the uterine lining grows too much. Although hyperplasia can be a precursor to uterine cancer, in most women the problem is easily solved with a dose of progestin to slough off the uterine lining. In women with a uterus who take estrogen alone, only about 7% will develop simple hyperplasia.

But for some women, occasional doses of progestin and ultrasound monitoring may not be practical. Taking progestin every six or 12 months may trigger a heavy, uncomfortable bleeding episode that can last for two weeks. During the past, women have preferred daily progestin because eventually it causes little or no bleeding.

In addition, regular monitoring with transvaginal ultrasound is expensive. It can cost $250 or more and often isn't covered by insurance.

While the idea may work for wealthy women, "it's not a practical one for large numbers of women because it requires quite a bit of resources," says Bruce Ettinger, clinical professor of medicine at University of California, San Francisco. "It may not be acceptable to a lot of women to have this kind of monitoring."

One solution may be to reduce the estrogen dose so much that it no longer causes a buildup of the uterine lining, making regular monitoring or occasional progestin doses unnecessary. Last year, the Journal of the American Medical Association published a Connecticut study of 167 women, half of whom took 0.25 milligrams -- one quarter of the standard dose -- of "micronized" estradiol, which is similar to a woman's natural estrogen. Those women were given micronized progesterone just twice a year during the three-year study, and that didn't result in any increase in hyperplasia or endometrial cancer, says Karen M. Prestwood, associate professor of medicine at University of Connecticut health center.

CHANGING RISKS How the disease risks of hormone users may differ from the risks of non-users.   Estrogen alone Estrogen/ Progestin Risk Breast Cancer down 23% up 24% Heart Attack down 9% up 24% Stroke up 39% up 50% Fracture down 39% down 37% Source: Women's Health Initiative

More recently, Dr. Ettinger led a Berlex-sponsored study of the low-dose estrogen patch, which has just 0.014 milligrams of estradiol. (The standard patch has 0.05 milligrams.) Women using the low-dose patch didn't take progestin for two years, but didn't show any increased risk for endometrial problems.

But while these studies have shown that very low estrogen doses can still protect women against osteoporosis, it isn't known whether such low doses would have a meaningful impact on other menopause symptoms, such as hot flashes or vaginal atrophy, although studies on the issue are planned.

Finally, some doctors worry that the push to scale back progestins will scare women away not only from higher, more effective doses of estrogen but also from safer alternatives to MPA.

While the studies have clearly implicated MPA, many doctors believe micronized progesterone, sold under the name Prometrium, is safer because it is chemically identical to a woman's natural progesterone. In animal and lab studies on cardiovascular effects and breast cancer, natural progesterone has shown a benign effect compared with changes triggered by MPA. In addition, it's important to note that the Women's Health Initiative studied primarily older women, so many doctors say the data shouldn't apply to younger women or to other types of progestin.

Alan M. Altman, assistant professor at Harvard Medical School, says he would prefer patients move to natural progesterone rather than stopping progestin altogether. "There's enough data that natural progesterone is far less potent and has less of an impact on breast tissue," he says.