Lown Cardiovascular Research Foundation

Harvard Heart Letter | March 2008

Focus on hormones

Estrogen therapy — benefits in the timing?

New findings suggest safety in short-term use of estrogen to ease the symptoms of menopause.

Is estrogen good for a woman’s heart, or bad for it? That’s a simple question with a complex and as-yet incomplete answer. It almost certainly depends on a woman’s age and where the estrogen, the main female sex hormone, is coming from.

The estrogen a woman’s body naturally makes is good for the heart. The reputation of estrogen supplements, however, has ping-ponged between fountain of youth and health scourge.

Ping: In the 1960s, a best-selling book called Feminine Forever promised that taking estrogen would not only ease hot flashes and other symptoms of menopause but would also help women retain the bloom of youth and fend off chronic diseases. Sales of estrogen shot up.

Pong: In the 1970s, evidence that taking estrogen alone increased the chances of developing endometrial cancer prompted many women and their doctors to turn away from estrogen therapy.

Ping: In the 1980s and 1990s, a number of large studies showed that women who chose to take estrogen after menopause were less likely to have heart attacks than those who didn’t take the hormone. Doctors began to enthusiastically recommend estrogen therapy (plus progesterone, as needed, to prevent endometrial cancer) as one way for older women to protect their hearts.

Pong: In 2002, findings from the Women’s Health Initiative (WHI) stunned the medical community. In this large, randomized trial, thousands of women were blindly assigned to take estrogen (or estrogen plus progesterone) or a placebo. After four years, the hazards of hormone therapy (heart attacks, strokes, and blood clots) overshadowed the benefits (stronger bones and a possible protection against colorectal cancer). These results shook many women who had been taking estrogen to protect their hearts.

Ping? New research since then suggests that taking estrogen may be good for women in their 50s, but not for older women.

The change

At some point in a woman’s life, her ovaries start to shut down in response to a host of genetic and environmental signals. The monthly cycle of egg development and estrogen production begins to fade, then stops altogether. Most American women experience this transition, called menopause, between 48 and 55 years of age, though it can begin earlier or later.

Many women keenly feel the fluctuations and fall in estrogen production as hot flashes and skin flushing, night sweats, vaginal dryness, mood swings, skipped periods or spotting in between periods, lack of interest in sex, or urinary or vaginal infections. Estrogen has proved to be more effective at easing these symptoms than soy, black cohosh, and other alternative therapies.

Estrogen and the heart

Laboratory studies, animal studies, and clinical studies in women all suggest the same thing: that estrogen, at least early in life, is good for the heart and blood vessels. It can improve a woman’s cholesterol profile by lowering harmful LDL and boosting protective HDL. Estrogen helps arteries stay flexible and makes blood less likely to clot. In animal experiments, estrogen slowed or even halted the progression of atherosclerosis when given early in life. Given all these favorable effects, the negative results from the WHI came as something of a surprise.

One drawback of the trial is that the average age of the women in it was 63, which means they started taking estrogen a decade or so after menopause. Later analyses of data from the WHI, along with results of other studies, suggest that taking estrogen might — strong emphasis on “might” — have cardiovascular benefits for younger women and pose hazards for older women. How? It’s possible that estrogen stirs up inflammation inside cholesterol-laden plaque, which is more abundant in older women than younger women. This could cause plaque to rupture, creating blood clots that can lead to heart attack and stroke.

Benefits in the timing?

This so-called timing hypothesis has attracted attention and gained some support. While it doesn’t revive the idea of using estrogen to fight heart disease, it does suggest that short-term use of estrogen around the time of menopause poses little cardiovascular risk.

At first glance, the decision to take estrogen during menopause may seem more complicated than it should be. In an editorial in 2007 in the BMJ, two leading hormone therapy experts, Drs. Deborah Grady and Elizabeth Barrett-Connor, succinctly summed up the rules that should guide decision-making: “While some details are unclear or complex, the basic approach to using postmenopausal hormone therapy is clear and simple: treat bothersome menopausal symptoms with the lowest effective dose of hormone therapy for the shortest time possible and do not use it to prevent disease.”