low-dose Prempro

(WOMENSENEWS)–The news rattled Marilyn Kentz even more than the hot flashes and mood swings she suffered.

“In July 2002, when the Women’s Health Initiative found the drugs I was taking for menopause could increase the risk of heart attack, I was not only shocked, but terrified,” says Kentz, 57, a writer in Los Angeles. “My father died of heart disease at the age of 42 and, determined to avoid his fate; I quit hormone therapy as soon as I heard about the study’s results.”

Without her daily doses of synthetic estrogen and progestin, hot flashes kept her up nights and mood swings left her weeping inconsolably. “My symptoms were so bad that I decided to go back on medication after a six-month break,” says Kentz.

Health advocates say one third of the former users of hormone therapy–pharmaceutical companies put that total figure at over 18 million–are likely going without treatment or trying alternative remedies.

Kentz, for instance, is now using the Femring, a vaginal ring that releases estrogen. Taken along with progestin pills, this regimen is helping her feel much better.

Hormone therapy had been offered to tens of millions of U.S. women entering menopause, the stage during which women stop menstruating and estrogen levels drop. First prescribed in the late 1960s, these drugs–either an estrogen-progestin combination or an estrogen-only version for women who had had hysterectomies–were touted as the “cure” for menopause and as protective against heart disease and breast cancer.

Then came July 9, 2002, and the publication of an article in the Journal of the American Medical Association by leaders of the federally-funded Women’s Health Initiative study, conducted by the Bethesda-based National Institutes of Health.

In that landmark article, researchers with the study (which was launched in 1991 and enrolled 161,000 women) reported that hormone therapy can lead to small increases in breast cancer, heart attacks, strokes and blood clots and that these risks outweighed the drugs’ benefits of slight protection against colorectal cancer and bone fractures.

In 2003, the year after the study, sales of synthetic hormones plummeted 38 percent and the number of women on hormone therapy plunged from 18.5 to 7.6 million.

Vaginal Ring and Non-Hormonal Drugs

Now many women, like Kentz, are using the vaginal ring. Others are taking non-hormonal drugs that prevent hot flashes and bone loss or low-dose versions of hormone therapy. Selective serotonin reuptake inhibitors (anti-depressants such as Effexor) ease hot flashes. Biophosphonates (such as Fosamax and Actonel) and selective estrogen receptor modulators (such as Evista) work to maintain bone density.

“Bioidentical” hormones are also in use, marketed under trade names such as Prometrium and TriEst.

“While regular hormone therapy uses synthetic hormones synthesized in a lab, bioidentical hormones are more natural estrogens,” says Kris Maki, a nurse practitioner in Walnut Creek, Calif., who takes bioidentical hormones for her own hot flashes. “Derived from herbal products like yam extract, these estrogens–which include estriol, estrodiol and estrone–are gentler on a woman’s system because they mirror the hormones that her own body produces.”

Remedies are also on the shelves of health food stores: phytoestrogens (found in soybeans, legumes and whole grains and mimicking human estrogen) and the herbal supplement black cohosh.

Though scientists have yet to study the long-term safety and efficacy of these alternative remedies, health advocates hold out hope for more research on all of the above.

Some Resume Hormone Therapy

In 2003, studies commissioned by two separate drug companies found that a quarter of women who had stopped using hormone therapy had since resumed it.

In the past year, Wyeth Pharmaceuticals, the Collegeville, Pa., maker of Prempro and Premarin (the two drugs used in the Women’s Health Initiative study) has released two low-dose versions of each product. “In the next few years, we hope to market several more,” says Ginger Constantine, Wyeth’s vice president of clinical development.

“Thus far, low-dose hormone therapy appears to be safe and effective and to relieve symptoms just as well as older, higher-dose versions,” says Dr. Wulf Utian, director of the North American Menopause Society in Mayfield Heights, Ohio.

Even though hormone therapy is no longer standard treatment for the indicators of menopause, some physicians continue prescribing it and controversy still surrounds the Women’s Health Initiative findings.

“The study did not investigate the safety of estrogen creams, gels and patches, which deliver estrogen through the skin instead of orally,” says Utian. “Researchers have yet to examine whether this delivery mechanism lowers the risk for heart disease and other health problems. Also, the subjects in the Women’s Health Initiative were an average age 63, more than a decade older than 51, the average age at which a woman enters menopause.”

Focus on Oral Therapy

Marcia Stefanick, a professor of Medicine at Stanford University in Stanford, Calif., and chair of the study’s steering committee, rebuts Utian’s criticisms, saying the vast majority of women on hormone therapy take pills and that only 10 percent take them through a transdermal method.

“We were investigating what most women were prescribed,” Stefanick says. “We were studying it in older women because an increasing number of hormone-therapy prescriptions were being offered to women who were well past menopause. Hormone therapy was being given to women whether they had menopausal symptoms or not, and we were trying to address the value of these hormones as a preventative health strategy.”

Follow-up studies by Women’s Health Initiative researchers have shown that oral estrogen-progestin therapy can increase the risk of dementia and blood clots and that both combination and estrogen-only oral therapy can boost the likelihood of stroke and urinary incontinence.

Since the study was published, the Food and Drug Administration has recommended that women only use hormone therapy if they are plagued by severe menopausal symptoms such as mood swings, hot flashes, disrupted sleep and vaginal dryness, itching and burning. The Rockville, Md., regulator also recommends it for women at high risk for the conditions the drugs can treat; hip fractures and cancer of the bowel or rectum.

Authorities urge menopausal woman to discuss hormone therapy with their doctors, to take the drugs in the lowest possible dose and to only take them only as long as symptoms persist.

Two major menopause studies are now underway, with results expected within the next decade.

The Bethesda-based National Institutes of Health is investigating the chronology of menopause (the timing of which has not been studied in depth) in its “Study of Women’s Health Across the Nation.” Enrolling 3,300 women, it will also examine how menopause affects the risk of heart disease and other age-related health problems.

Another study, by the Phoenix-based Kronos Longevity Research Institute, is examining hormone therapy in women ages 40-55, younger than the subjects in the Women’s Health Initiative.

Women such as Marilyn Kentz await the results. “We’re hoping for alternatives that work as well as hormone therapy,” she says. “We’re hoping for ones that can not only treat our symptoms, but also keep us in good health.”

Molly M. Ginty is a freelance writer based in New York City.

For more information:

National Institutes of Health —
Menopausal Hormone Therapy Information:

Our Bodies, Ourselves Companion Website
Midlife and Menopause: