Hormone Replacement Therapy (menopause) - Premature Stoppage of Women's Health Initiative

Premature Stoppage of Women's Health Initiative

Clinical medical practice changed with two parallel WHI studies of postmenopausal HRT. Prior studies were smaller, and many were of women who electively took hormonal therapy. The WHI studies were the first large, double-blind, placebo-controlled clinical trials of HRT in healthy, postmenopausal women.

The WHI estrogen-plus-progestin trial was stopped prematurely in 2002 because preliminary results suggested risks of combined conjugated equine estrogen and progestin exceeded their benefits. The estrogen-alone trial, performed on women who were post hysterectomy, due to the proliferative effect of the hormone on endometrial tissue, did not show such problems and was continued. However, in February 2004 it, too, was halted. While there was a 23% decreased incidence of breast cancer in estrogen only arm, risks of stroke and pulmonary embolism were increased, predominantly in patients who began HRT over the age of 60.

The first report on the halted WHI estrogen-plus-progestin study came out in July 2002. It followed over 16 000 women for an average of 5.2 years, half of whom took placebo, while the other half took a combination of progestin medroxyprogesterone acetate and conjugated equine estrogen.

The study reported statistically significant increases in rates of breast cancer, coronary heart disease, strokes and pulmonary emboli. The study also found statistically significant decreases in rates of hip fracture and colorectal cancer. "A year after the study was stopped in 2002, an article was published indicating that estrogen plus progestin also increases the risks of dementia." The conclusion of the study was that the HRT combination presented risks that outweighed its measured benefits. The results were almost universally reported as risks and problems associated with HRT in general, rather than with PremPro, the specific proprietary combination of conjugated equine estrogen and progestin studied.

After the increased clotting found in the first WHI results was reported in 2002, the number of Prempro prescriptions filled reduced by almost half. An unknown number of women started taking alternatives to Prempro, such as bioidentical hormones. A sharp drop in breast cancer rates was observed following these changes, and held steady in subsequent years.