About five years ago, Sally Shepard, a 52-year-old human resources consultant from Santa Cruz, California, began experiencing hot flashes and especially heavy and irregular periods as part of perimenopause, the few years leading up to menopause. Shepard, who surfs, skis, golfs, and runs 20 miles a week, felt less motivated to stay active. But when Shepard asked about hormone therapy, her doctor discouraged her.
Throughout the ’90s, the pills and patches that delivered a combination of estrogen and progestin (a synthetic form of progesterone) were prescribed freely to menopausal women. By the end of that decade, an astounding 22 percent of women over 40 were being prescribed hormone therapy. It was considered a godsend, not just to ease the discomfort, but to ward off the risk of heart disease and brittle bones associated with menopause, not to mention the gloom and misery that sometimes accompanies “the change.”
But problems with hormone therapy arose in 2002 when a large clinical trial (the Women’s Health Initiative) sponsored by the National Institutes of Health was shut down after it became clear that taking the medication resulted in higher rates of stroke, heart disease, and breast and ovarian cancers. In a hastily assembled press conference in July 2002, the researchers shocked the world by announcing that the risks of taking the popular drugs outweighed the benefits. The news also came as a surprise to doctors, who had expected the trial to show hormone therapy protected women’s hearts. Droves of frightened menopausal women threw out their pills and hormone patches, leaving those with severe symptoms to endure the embarrassing hot flashes and sheet-drenching night sweats that disrupted their sleep and left them weary, dazed, and cranky.
“The pendulum had swung from hormone therapy is good for all women, to hormone therapy is bad for all women,” says Dr. JoAnn Manson, a WHI investigator and chief of preventive medicine at Brigham and Women’s Hospital in Boston, an affiliate of Harvard University. But it appears the pendulum is swinging again. Today, more than a decade after the WHI trial, a new consensus is emerging that, at least for younger women with moderate to severe menopausal symptoms, the benefits of short-term hormone therapy may outweigh the risks.
Shepard discovered the shift by doing some exploration of her own: “It didn’t seem those studies that had been so hyped in the news [back in 2002] were relevant to my circumstance.” She went back to her doctor, intent on reopening the discussion. To her surprise, this time her doctor was on board. “I don’t know if she had a change of heart … or if it took me being aggressive about it,” Shepard says. But, since she began hormone therapy, the hot flashes and abnormal bleeding are gone, and she has a lot more energy and what she can only describe as a “happiness factor.”
No one had predicted the outcome of the Women’s Health Initiative hormone studies. When they were first planned in 1992, they were designed as large, scientifically rigorous randomized trials to test whether hormone therapy could protect women from heart disease — something that had already been seen in smaller, less rigorous scientific studies.
So confident were scientists about the benefits of hormone therapy that the drugs were already widely prescribed not just to relieve symptoms of menopause, but to prevent heart disease. “Cardiologists were even starting women on the drugs in their 70s and 80s,” says Dr. Wulf Utian, founder of the North American Menopause Society and author of the 2011 book, Change Your Menopause: Why One Size Does Not Fit All. “There was a lot of wild use of hormones.”
The combination study was huge, involving more than 16,000 women aged 50 to 79, with most study volunteers at least a decade past menopause. (Significantly, the average age of study participants was 63.) The trial started in 1997 and was meant to be completed in 2005, but on May 31, 2002, a safety monitoring board found the number of breast cancers in women taking hormones exceeded a pre-specified limit and halted the study.
How bad was it? An initial analysis published in July 2002 in the Journal of the American Medical Association (JAMA)found women taking combination hormone therapy had a 41 percent higher risk of strokes, a 29 percent higher risk of heart attacks, and twice as many blood clots as women in the placebo group. (They also had a 37 percent lower risk of colon cancer and a 33 percent lower risk of having a hip fracture, but that information didn’t make the headlines.)
As frightening as these results sound when expressed as percentages, the actual risk to any individual woman was still quite low. In a press release about the results, WHI Acting Director Dr. Jacques Rossouw explained that over the course of a year, only 8 more out of 10,000 postmenopausal women with a uterus who took combination therapy would have an invasive breast cancer; 7 more would have a heart attack; 8 more would have a stroke; and 18 more would have blood clots compared with women not taking hormone therapy.
Still, WHI investigators took an all-or-nothing approach, and for the once hormone-happy medical community, the result was a major about-face. Sales of Prempro, the drug used in the combination estrogen and progestin study, fell nearly 50 percent in the first two years following the study.
Manson credits the WHI study with stopping the gross overuse of hormone therapy, especially in high-risk women long past menopause. But Utian argues that many younger women, who may have benefited from hormone treatments for menopausal symptoms, suffered. “What happened unfortunately is we went from gross overuse to gross under use,” he says. He believes the net effect of the WHI study may have been to harm more women than it helped. “Even now, it’s very difficult to get an internist to prescribe hormones.”