Menopause Hormone Therapy and Cardiovascular Protection

Does Age Matter? What We Know So Far About Age of Initiation of Hormone Therapy and Heart Disease in Women.

You may have thought that the dilemma over using hormone therapy for cardiovascular protection was resolved in 2002, when the Women's Health Initiative was abruptly halted. Recently however, some scientists have begun to speculate that starting hormone therapy early in menopause is the key to cardiovascular protection. Although there is insufficient scientific evidence to support these claims, many have insisted on promoting these educated guesses in the popular media and once again misleading women about hormone therapy.

In women who are at least ten years beyond the menopausal transition, scientists agree that hormone therapy does increase the risk of heart disease; if women in this stage of life choose to take hormones for menopausal symptoms, it should be for the shortest period of time at the lowest possible dose.[1] However, some scientists have recently speculated that starting prescription hormones during the menopausal transition (either before, or within a year or two after, the last menstrual period) could prevent the development of heart disease, and subsequently cardiac events such as heart attacks. This theory has been called the "Unified Hypothesis" or the "Window of Opportunity Theory" of hormone therapy.[2]

Although an interesting idea, it has not been rigorously tested in a double-blind, randomized clinical trial of menopausal women. The WHI Investigators who formalized this hypothesis actually state in a medical journal article that this theory has not been tested: "as yet there has been no clinical trial that has tested the unified hypothesis directly." [2]

Women have a right to know this critical point - that currently there is no good scientific evidence to support this theory as a clinical recommendation for women. In media reports, many practitioners and scientists have presented the scientific controversy surrounding hormone therapy and heart disease as resolved by this hypothesis, which it is not. In fact, the current recommendations for hormone therapy issued by the American Heart Association expressly contradict this hypothesis.[3]

To date, the most reliable evidence on hormone therapy use by women in the early stages of menopause is from the Women's Health Initiative. Although critics often state that the WHI was a clinical trial of "older" women in their 60's & 70's, over 12% of WHI participants were aged 50 to 54 at baseline (n = 2,029), making it the largest randomized clinical trial of hormone therapy ever conducted in this age group. Statistical analyses of the WHI data did not indicate significant differences by age in the effect of estrogen and progesterone (E+P) on the risk of heart disease; in other words, younger WHI participants who took E+P were at no less risk nor were they more protected from heart disease compared to older participants. Another recent analysis of the WHI data on women who had undergone hysterectomy also found that estrogen alone did not provide significant cardiovascular protection in women aged 50-59. [4]

The American Heart Association and a National Institutes of Health Consensus Panel have both clearly stated that hormone therapy should NOT be used as a protective agent against cardiovascular disease.[1,2] A health care practitioner who prescribes hormones as a protective measure against heart disease for younger women in their forties or fifties is making irresponsible clinical recommendations without sufficient scientific evidence, and may actually be endangering the health of the patient.

Currently, there are two ongoing clinical trials of hormone therapy in younger menopausal women: the KEEPS trial at the Kronos Longevity Institute and the ELITE trial at the University of Southern California. Both of these studies began enrolling participants in 2005; study results are expected in 2008 at the earliest. However, neither of these clinical trials will provide enough scientific evidence to support or refute the hypothesis that use of hormone therapy at mid-life is a critical factor for cardiovascular protection. Nor will the evidence from either of these studies be sufficient to warrant a change in clinical recommendations.

References

1. National Institutes of Health State of the Science Conference Statement: Management of Menopause-Related Symptoms. Annals of Internal Medicine, June 21, 2005; 142:1003-1013.

2. Phillips, LS & Langer, RD. Postmenopausal hormone therapy: critical reappraisal and a unified hypothesis. Fertility & Sterility, March, 2005; 83:558-566.

3. American Heart Association. Postmenopausal Hormone Therapy & Cardiovascular Disease in Women. Accessed November 15, 2005 at: www.american presenter.jhtml?identifier=4536

4. Hsia, J. et al. (2006). Conjugated Equine Estrogens and Coronary Heart Disease. Archives of Internal Medicine, v. 166, pg. 357-365.

Updated: 2/06