a clinical comment concerning Hormone Replacement Therapy

Hormone Replacement Therapy

Concerning the Clinical Trials Report:
Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women
Principal Results From the Women’s Health Initiative Randomized Controlled Trial
Writing group for the Women’s Health Initiative Investigators
JAMA 2002, 288(3):321-333.

Comments of Kenneth A. Burry, MD :

This study was publicized in the lay media worldwide and has been sensational news. The media, as well as many physicians, have overstressed the risks and have unnecessarily frightened many postmenopausal women who still may benefit by using hormone replacement.

Since the WHI study is large, prospective and placebo controlled, the data have high validity. Clearly the primary prevention of CHD in this group was not achieved since there was an increase in risk of 1.29 (1.02-1.63). Data from the WHI support the data of the HERS study that did not show a benefit in secondary prevention of CHD, in fact there was a similar increase in risk. It should be emphasized that the women in both the HER’s trial and WHI were using MPA as the progestin. This progestin has significantly different metabolic effects than natural progesterone and other progestins.

The risk of breast cancer in the WHI study only approaches statistical significance, 1.26 (1.00-1.59) and there were no increase in deaths due to this disease. Colorectal cancer was significantly reduced and this tumor may have a lower survival rate than the women that develop breast cancer while taking hormone replacement. It is interesting that the study was stopped because of how these two cancers were “weighted” statistically. It should also be noted that quality of life was not an outcome measure of this study. This is probably an important issue since there was a high dropout rate, 42% in the hormone use group and 38% in the placebo group and there was 10.7% drop-in rate of the placebo group starting hormone therapy. A common symptom was persistent vaginal bleeding and this resulted in unblinding 3444 women in the hormone group and 548 women in the placebo group. More women in the hormone group had a hysterectomy during this study, 248 vs. 183.

There are good therapies for the prevention and treatment of CHD by the use of diet, treatment of hypertension and diabetes, and the use of statins. We also have good alternatives for the prevention and treatment of osteoporosis such as bisphosphonates and SERM’s. The take home message in my opinion is that hormone replacement (HRT) is best used in women with symptoms. Estrogen is still the best therapy for the relief of vasomotor symptoms and vaginal atrophy. The risks of HRT are not in excess when postmenopausal women’s quality of life is considered.

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