Over its long history, hormone replacement therapy for women in menopause has been the Jekyll and Hyde of medications. It has careened from savior to villain, from cure-all for every female complaint to poison. And when in 2002, the National Institutes of Health-funded, $1-billion Women’s Health Initiative loudly announced that women taking HRT had an increased risk of breast cancer, its role as “savior” all but disappeared. Other dire alleged consequences included heart disease, stroke, dementia and even “all-cause mortality.”
Understandably, millions of women panicked, along with much of the medical establishment, and dropped the option of hormone therapy altogether. (Estrogen is given by itself to women who have had hysterectomies and, as HRT, in combination with progesterone to those who still have a uterus.)
The good news about estrogen has been lost: namely that more than 70 years of findings from animal studies, human studies, observational studies and randomized controlled studies demonstrate the benefits of estrogen. Most remarkably, the research shows the failure of the accepted hypothesis that estrogen causes breast cancer. In fact, estrogen has been successfully used as a treatment for women with the disease, and, remarkably, it can often be safely administered to most women who have had breast cancer.
Heart disease, not cancer, is the leading cause of death for women in every decade of their lives (it is even the leading cause of death for breast cancer survivors). Hormone replacement therapy can decrease that risk by 30% to 50%. It can also cut in half the risk of osteoporotic hip fracture — a crucial benefit because as many older women die annually after breaking a hip as die of breast cancer. And numerous animal and human studies indicate that estrogen is the only intervention that prevents or reduces the risk of Alzheimer’s disease and other forms of dementia in women.
HRT is the most effective treatment for familiar menopausal symptoms, including hot flashes, night sweats, insomnia, vaginal dryness and loss of sexual desire, and for the less familiar symptoms: heart palpitations, joint and muscle aches, headaches, bladder problems and depression. Forget the black cohosh and chaste tree; they are no better than placebos.
Finally, because of estrogen’s benefits for heart, brain and bones, women on hormone replacement therapy live, on average, several years longer than those not taking it. This is one reason that the North American Menopause Society and 30 other international groups concluded that “there are no data to support routine discontinuation [of HRT] in women age 65 years.”
These findings, long replicated, emerge from a wide variety of studies; taken together, they create a persuasive mosaic. Some investigators, nonetheless, believe it doesn’t matter how many studies we can cite if they are observational studies —- those in which participants are not randomly assigned to an intervention group and placebo group. They argue that such “unscientific” research should almost never be relied on for clinical guidance, at least not if there is a randomized controlled trial to call upon. That is why many physicians and some medical groups, such as the U.S. Preventive Services Task Force, have based their HRT guidelines almost exclusively on the randomized, controlled Women’s Health Initiative.
To this argument there are two responses: Observational studies are not always bad, and randomized controlled trials are not always good or unbiased.
Consider first that the increased risk of breast cancer supposedly discovered by the WHI — which caused the study to be halted prematurely — was not statistically significant. In subsequent reanalyses, it had completely vanished. This news did not make headlines.
The study’s sample wasn’t even representative of healthy women in menopause. The average age of women in the study was 63, yet the researchers generalized their conclusions to include women entering menopause in their 50s. (That’s how they could claim that estrogen doesn’t even alleviate menopausal symptoms — most of the women in their sample were way beyond having menopausal symptoms! ) Nearly half the participants were current or past smokers, more than a third had been treated for high blood pressure and 70% were seriously overweight or obese.
The WHI claimed that hormone replacement increased the risk of heart problems, but the fine print revealed that the risk occurred only among women who were in their 70s and older. The investigators revised their findings five years after they were initially published and concluded that women who started HRT in the first 10 years following menopause reduced their risk of coronary artery disease. This news did not make headlines either.
We don’t suggest that all women should take hormones, or will benefit if they do. We are well aware that every medication carries risks. Neither of us has financial ties to the pharmaceutical industry. We simply are persuaded that the minor risks of HRT for some women are far outweighed by the major benefits for most women.
Each woman’s decision and each physician’s counsel should be made with the best scientific evidence in hand, and the way the results of the Women’s Health Initiative were misread and miscommunicated did not provide it. On the contrary, its investigators primarily generated fears where they were not warranted — indeed, where they were flat wrong. Unfortunately, their misbegotten 17-year-old claims continue to reverberate. Our own conclusion is not that hormones will make women “feminine forever” — just healthier longer.