Menopause: Hormone Replacement Therapy, Risks of Estrogen Therapy

by Food and Drug Administration (FDA)

Imagine a cocktail party conversation in 1966 turning to menopause. It would have been as unlikely as a female high school student yearning to be a soccer star.

But times have changed. Just as participating in sports has now become significant to many young women so has being open and even activist about menopause become equally important to their mothers.

The first women of the post-World War II generation known as baby boomers are reaching the age of 50, one year away from the average age of menopause among U.S. women. By the end of this century, more women than ever before will be experiencing the sometimes uncomfortable symptoms that accompany the end of menstruation and natural childbearing capacity.

For many years, U.S. doctors knew little about and paid little attention to menopause. "About 20 years ago, medical attitudes started changing," says Isaac Schiff, M.D., chief of obstetrics and gynecology, Massachusetts General Hospital. "We Ob-Gyns used to think that when women reached age 50, they weren't interested in sex anymore. But studies in retirement communities showed otherwise. We also began to see an increase in the female life expectancy. When a woman reaches age 50, she typically has another 30 years to live. As physicians, we became interested not only in the quantity of her life, but the quality of it."

The pace of medical inquiry has accelerated over the last few years, as the first of the baby boomers started experiencing menopausal symptoms. "It's not uncommon to hear it discussed at cocktail parties," says Schiff. "This is a radical turn-around from the way the mothers of these women treated it. Speak to a 50-year-old woman and she'll say, my mother never discussed it with me."

With such thinking, a new attitude toward treatment and research has emerged, says Schiff. Until recently, there were few studies on menopause. One of the largest and potentially most fruitful is the Women's Health Initiative, sponsored by the National Institutes of Health, which will study 164,500 women of various racial and ethnic backgrounds across the United States. The scientific investigation, which will not be completed until 2005, is expected to find out whether a low-fat diet, hormone replacement therapy, calcium, and vitamin D might prevent heart disease, breast and colorectal cancers, bone fractures, and memory loss.

Hormone Replacement Therapy

As many as 15 to 25 percent of postmenopausal American women take hormone replacement therapy, according to an article in the January 1995 issue of the Journal of Obstetrics and Gynecology by Diane Wysowski, Ph.D., of the Food and Drug Administration, and colleagues. Women take estrogen to alleviate menopausal symptoms, especially hot flashes (sometimes called by doctors "hot flushes"), and also to protect bones.

Since the 1940s, FDA has approved many estrogen drugs to reduce menopausal symptoms. In the 1980s, FDA also began approving specific estrogen drugs to prevent osteoporosis (literally "porous bones," a condition in which bones break easily). The agency has approved four estrogen drugs — Premarin, Estraderm, Estrace, and Ogen — for long-term use to prevent osteoporosis. Other approved uses for estrogen drugs include the treatment of symptoms of vaginal atrophy, which may include itching, burning or dryness around the vagina, certain abnormal uterine bleeding conditions due to hormonal imbalance, and the comfort-promoting treatment of certain advanced cancers.

Many scientists believe that estrogen may fight heart disease by lowering harmful cholesterol (LDL), raising beneficial cholesterol (HDL), and strengthening the lining of the blood vessels, but this has not been clearly proven. Some research also suggests that estrogen may help prevent memory loss and Alzheimer's disease, but the scientific evidence remains speculative.

Nearly all the studies on heart disease and cognitive function have been retrospective or "look back" studies. The Women's Health Initiative Study will be prospective, that is, future-oriented, says Deborah Smith, M.D., a medical adviser in FDA's Office of Women's Health. Researchers will select a group of generally healthy women to treat and observe for a number of years to see if, and at what rate, they develop symptoms. Elements of the study will be scientifically controlled and data freshly recorded. Most important, treated and untreated women will be equally healthy at the start of the study. Retrospective studies depend on information sometimes clouded by time and memory loss, and women selected by their doctors for hormone replacement have usually been healthier than the women not so prescribed.

"The other important difference about the Women's Health Initiative is that it includes a clinical trial of estrogen," says Jacques Rossouw, the lead project officer for the study. "Participants will have an equal chance of being on either estrogen or a placebo, and any differences in their health at the study's end can be ascribed to the estrogen."

Risks of Estrogen Therapy

Estrogen is most commonly prescribed in pill form. It is also available in transdermal patches, which allow the drug to be slowly absorbed into the bloodstream, in vaginal creams, which treat localized discomforts.

Estrogen replacement therapy is not risk-free. "There's been much experimental evidence and patient experience showing estrogen given alone can lead to endometrial cancer," says FDA's Smith. For that reason, a woman who still has a uterus is usually prescribed progestin in addition to estrogen. This significantly reduces the risk of abnormal changes in the uterine lining.

Endometrial cancer is not the only risk from estrogen use. Gallbladder disease is another. Women who use estrogens after menopause are more likely to develop gallbladder disease needing surgery than women who don't use estrogens.

The drug's labeling also includes warning about abnormal blood clotting. Clots can cause a stroke, heart attack, or pulmonary embolus, any of which can be fatal.

About the Author

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