HRT through the years

1920s -- The first attempt to treat menopausal symptoms in the United States, attributed to E.L. Severinghaus and J. Evans, uses a derivative from the amniotic fluid of cattle.

1942 -- Premarin, made from pregnant mares' urine, is introduced.

1952 -- A study says estrogen treatment may enhance verbal memory.

1959 -- Prolonged hormone replacement therapy, the Journal of the American Medical Association reports, protects bones, relieves menopause symptoms and poses no apparent risk of breast and cervical cancers.

1966 -- Sales of Premarin increase 170 percent in three years, and about 12 percent of postmenopausal women in the United States take the estrogen pill. Dr. Robert Wilson's book, Forever Feminine, sells a generation on estrogen.

1973 -- A clinical trial of men taking Premarin to prevent heart attacks and strokes is stopped when they have more heart attacks and blood clots.

1975 -- Almost half of all menopausal women are using HRT for a median of five years. Two studies published in the New England Journal of Medicine find that use of estrogen alone increases the risk of endometrial cancer.

1976 -- The first study showing a link between estrogen replacement and breast cancer is published in the New England Journal of Medicine.

1980 -- Dr. R. Don Gambrell reports in Obstetrics and Gynecology that adding progestin to estrogen resulted in a decline in endometrial cancer. Other reports find reductions in hip and wrist fractures.

1982 -- Cancer Research publishes several experts who say hormones are a risk factor for cancer.

1985 -- A Framingham Heart Study report shows about 1,200 women taking estrogen suffering more heart disease than women who did not. But the Nurses Health Study, based on questionnaires sent to more than 120,000 female nurses ages 30 to 55, concludes that estrogen lowers the risk of heart disease.

1990 -- Premarin, made by Wyeth Pharmaceuticals, becomes the most frequently dispensed drug in the United States. Physicians continue to tout HRT, not only for menopause's hot flashes and mood swings, but also for heart health, with the exception of women at high risk for breast cancer.

1995 -- Prempro, the first estrogen-plus-progestin HRT pill, is approved by the Food and Drug Administration. Studies suggest HRT helps protect against Alzheimer's, vision loss, colon cancer and osteoporosis.

1997 -- A reanalysis of data from 51 epidemiological studies suggests an increased risk of breast cancer with postmenopausal estrogen.

1998 -- The first major placebo-controlled trial of HRT shows it does not help women who have already had a heart attack and may increase chances of another.

2000 -- Life expectancy for women climbs to more than 80 years, almost doubling in a century and greatly increasing years lived after menopause. Women's Health Initiative researchers conducting a study of combined estrogen/progestin therapy tell participants that some are having heart attacks and strokes, offering them the option of dropping out.

2001 -- More than 13-million women are taking hormone replacement therapy.

2002 -- The Women's Health Initiative study of HRT -- more than 16,000 women to be followed for eight years -- is stopped after five years because of increasing cases of heart attack, stroke, blood clots and breast cancer. Doctors are advised to prescribe HRT only short-term (less than five years). Wyeth Pharmaceuticals' stock price plunges 25 percent, and sales plummet. 2003 -- The FDA changes labels on HRT products to reflect the results of the Women's Health Initiative, including a boxed warning about increased risks for cardiovascular disease and cancer.

SOURCES: U.S. Food and Drug Administration; the Hormone Foundation; Newsweek; Wyeth Pharmaceuticals; U.S. News & World Report.

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