What Does the Women’s Health Initiative Tell Us About Combined Hormone Replacement Therapy?
The results of a large study of women taking hormonal therapy were recently reported & have led to a great deal of confusion concerning the use of hormonal medications. The estrogen plus progestin component of the Women’s Health Initiative, sponsored by the National Institute of Health was designed to evaluate hormonal replacement therapy as primary prevention of coronary heart disease. This study was a randomized prospective study which included 16,608 women in the combined hormonal therapy arm. However there were several significant weaknesses in the study design. The study included only one medication, “Prempro,” at one dose (0.625 mg conjugated estrogen + 2.5 mg medroxyprogesterone). The average age of the participants was 63 years and women with menopausal symptoms were excluded from the study. More than 1/3 of the women had risk factors for heart disease including hypertension, current or past smoking, or obesity and during the study 42% of the hormonal therapy group and 38% of the placebo group stopped taking their medication. When the study was halted after six years, the results showed slightly higher rates of heart disease, stroke, blood clots in the lungs, and breast cancer in the hormonal therapy group, but these outcomes were not statistically significant. The only statistically significant differences were small changes in blood clots (increased 18/10,000 person years) & osteoporotic bone fractures (decreased 5/100,000 person years).
The Women’s Health Initiative is clearly not the final word on hormonal therapy and leaves many unanswered questions. Does hormonal therapy benefit the 50-year-old healthy woman who is just entering menopause? Would different formulations and doses of hormonal therapy convey different risks?
Unfortunately with the widespread publicity this study enjoyed, the research to answer those questions probably will not be done any time soon. For now, the post-menopausal woman without symptoms probably should not be encouraged to take hormonal therapy for health benefits such preventing heart disease. However, the menopausal woman who feels that the benefit to her in terms of her quality of life is greater than the risks should be allowed to make the choice to take hormonal therapy.
What Does The Women’s Health Initiative Tell Us About Estrogen-Only Hormone Replacement Therapy?
The estrogen-only arm of the WHI which was released in spring 2004 provides reassuring news on postmenopausal ERT. Like the previously published estrogen-progesterone WHI study, the estrogen-only arm was a randomized, double-blind placebo-controlled study. This arm studied over 10,000 women status post hysterectomy for nine years.
The primary outcome of the study was the rate of CHD, which was not affected by estrogen therapy. The primary safety outcome was breast cancer which was 23% lower in the estrogen group, a surprising result which closely approached statistical significance suggesting that the increases in breast cancer shown in other hormone studies were due to progestin rather than estrogen.
The significant adverse outcomes of estrogen therapy were an increase in strokes by 12/10,000 person years, with no increase in the 50-59 year old group, and a small increase in DVT. Overall fractures were reduced by estrogen (56/10,000 person years), and there was no difference in colon cancer or total cancers. These results provide new insight into the risk and benefits of combined HRT versus ERT helping physicians make informed decisions when treating menopausal patients.