Does the Timing of Menopause Hormone Therapy Really Matter When it Comes to Heart Disease?

By Jonathan Raymond and Cindy Pearson

If you’ve read women’s health news lately, there’s a good chance you’ve noticed two diametrically opposed articles about menopause hormone therapy (HT) – one saying it is not a viable long term option because its risks are too great; the other saying that it may benefit your heart, provided the therapy is started immediately after a woman passes through menopause. The latter argument is highly controversial, both in its logic and for women who are considering using this therapy. We at the NWHN are concerned that the proven risks of HT are being downplayed and that the effort to reinstate it as an all-purpose health potion, based solely on this newfound timing theory, has dangerous implications for women’s health.

By the 1990s, after more than two decades of observational studies and animal-modeled lab data, HT had garnered a reputation as one of the best things aging women could use to protect themselves from cardiovascular disease. Physicians maintained this near-religious belief in HT’s benefits until results from randomized trials started to call it into question.

The first clinical trial to address the connection between HT hormone use and heart health was the Heart and Estrogen/Progestin Replacement Study (HERS), which looked at whether the estrogen/progestin combination Prempro would reduce second heart attacks or cardiac death in women with established coronary artery disease. This study of over 2,700 women found no reduction in second heart attacks among women using the drug. In fact, HERS found an initial increase in second heart attacks within the first two years of using Prempro. The trial actually did very little to overturn the belief that hormones were good for the heart, however; rather, certain scientists (many of whom received hefty grants from hormone manufacturer Wyeth) started to amend their reasoning: estrogens were “good” for women’s hearts -- women simply needed to be healthy in order for the drugs to work.

In 2002 and 2004, investigators for the Women’s Health Initiative (WHI), the first primary prevention trial of hormone use, halted the estrogen/progestin (Prempro) and the estrogen alone (Premarin) arms of the trial when the drugs’ risks were found to exceed the benefits in healthy women ages 50--79. Specifically, just like in HERS, Prempro lead to an increase in heart attacks, as well as in strokes, blood clots, and breast cancer. Premarin was found to raise women’s risk of stroke and blood clots, while not reducing the risk of heart disease. With these shocking results, it seemed that HT proponents would not have a leg to stand on as far as the drug’s cardiovascular protection was concerned.

Rather than abandoning the notion that hormones helped women’s hearts, however, these proponents revved up yet another amendment to the hormone-heart health theory. The proponents of menopause HT started claiming that healthy older women weren’t actually healthy. In their view, women who are a few years past menopause most likely have undiagnosed, subclinical heart disease (atherosclerosis) that has not yet manifested itself in the form of a first heart attack. The HT proponents proclaimed that women needed to be started on HT as soon as they became menopausal. As “evidence,” hormone proponents point to estrogen’s known positive effects, such as lowered cholesterol and arterial dilatation, which they maintain reduces the risk of heart disease.

Unfortunately, estrogens do not have just positive effects on risk factors. Estrogens have been known for a long time to adversely affect blood clotting, blood pressure, triglyceride levels, and C-reactive protein (a marker of inflammation). These effects were recently re-confirmed in an analysis of the Study of Women’s Health Across the Nation (SWAN), a community-based five-year longitudinal study of 3,302 women going through natural menopause. The SWAN results reinforced the various positive and negative effects that HT has on various markers of cardiovascular disease in recently menopausal women.

Which brings us back to the “timing is everything” theory. Whether timing truly matters is highly questionable. This idea only arose when the negative trial results of both HERS and WHI contradicted the observational, laboratory and animal data that showed a benefit to heart health. When you look at the overall results of the trials -- as well as the troublesome negative effects of estrogen, which were recently reemphasized in SWAN -- you have to wonder if these ever-evolving theories about the benefits of taking estrogen after menopause have a true scientific basis, or if they’re just an attempt to re-crown hormone therapy as the #1 selling drug in America.

Jonathan Raymond is a long-time NWHN supporter and hormone skeptic. Cindy Pearson is NWHN's executive director.