It was the summer of 2002 when the news about hormone replacement therapy (HRT) shook us to the core.
In what felt like a bomb dropped on all womankind, the U.S. federal government halted the hormone trial of the Women's Health Initiative early – a study designed to evaluate the risks and benefits of hormone replacement therapy on disease prevention.
The reason: Not only had HRT failed to be the protective fountain of youth doctors and women had long since believed, evidence was mounting that taking it may be harmful.
"It was like an abrupt hit in the solar plexus -- with a message that was loud and clear: If you value your life, don't even be in the same room as a bottle of hormones," says Steven Goldstein, MD, professor of medicine at NYU Medical Center and board member of the North American Menopause Society.
And while the study also found hormone therapy reduced the risk of fractures and possibly colon cancer, on a cultural as well as a medical level that didn't seem to matter. The moment the estrogen hit the fan, women began rejecting hormone use in droves.
At the time, certainly the WHI findings seemed to be the final word on HRT. But fast-forward five years and we find the picture of hormone replacement therapy is changing yet again.
"We have had time and resources to carefully tease out the data and perhaps collect a little bit more, and what we have found at least reassures us that for some women who have menopausal symptoms, HRT is not the ominous prescription we thought when the data first came out," says Cynthia Stuenkel, MD, professor of medicine at the University of California at San Diego.
Clearly, at least some of the problems with HRT brought to light in 2002 are still in place today.
The WISDOM (Women's International Study of Long Duration Oestrogen after Menopause) study recently published in the BMJ duplicated many of the same findings detailed by the WHI, particularly concerning the increased risk of heart disease in older women who began or restarted hormone therapy long after menopause.
At the same time, however, in the five years since the WHI, another, equally important fact has emerged: The seemingly huge difference a few birthday candles can make when it comes to the impact of HRT on a woman's heart.
Why Age Matters
Because the WHI study included women from ages 50 to 79, the initial results were a combined tabulation of all age groups together. But Goldstein says that when data was re-analyzed to focus on the youngest members alone, an entirely different risk-to-benefit ratio of HRT began to emerge.
"What we discovered is that if a woman is between the ages of 50 and 55 when she starts taking hormones, or if she begins HRT less than 10 years after she started menopause, she has less heart disease and less death from any cause, compared to the placebo group," says Goldstein.
Those results were published in April 2007 in the Journal of the American Medical Association – and then again reinforced by similar research published in The New England Journal of Medicine the following June.
Here researchers focused on younger women who had a hysterectomy, and took estrogen alone. These results suggested that in these women HRT may also have protective effects on the heart.
"Women who were in their 50s in the estrogen-alone trial tended to have less coronary artery calcium if they received estrogen compared to placebo. And coronary artery calcium is ... a strong predictor of future risk of coronary heart disease, so these results lend support to the theory that estrogen may slow early stages of arteriosclerosis," says researcher JoAnn Manson, MD, DrPH, chief of preventive medicine, Brigham and Women's Hospital, and professor of medicine and women's health, Harvard Medical School, Boston.
Unfortunately, Goldstein says neither message seems to have been relayed to women or even their doctors, and as a result many women are suffering unnecessarily, afraid to use hormones to quell menopause symptoms in order to protect their heart.
"We have strong evidence to show that if it is less than 10 years since you started menopause, using HRT on a short-term basis is not likely to harm you, and it can help you; you shouldn't be afraid," he says.
Cardiologist Nieca Goldberg, MD, agrees. "Women can sort of relax a little -- that when they’re younger and need to go on hormone therapy because of their symptoms, that this may not be detrimental to their heart," she says.
Those at risk for stroke, however, may not share this same sense of relief. In the same April 2007 JAMA study, researchers found the risk of stroke increased in HRT users by some 32% -- and that age or years since menopause didn't matter.
HRT and Breast Cancer
While the impact of HRT on the heart may seem less ominous today than in 2002, links to breast cancer are less clear -- and some say less encouraging.
Many experts say that more than coincidence was at work when, in the years following the WHI announcement, women stopped taking hormones en masse -- and the incidence of breast cancer subsequently declined.
"A drop in hormone use may not have been the sole reason we saw fewer breast cancers, but I am certainly convinced it played a significant role," says Julia Smith, MD, director of the Lynne Cohen Breast Cancer Preventive Care Program at the NYU Medical Center in New York City.
But Smith says the back-story linking hormone use and breast cancer goes far beyond just connecting a few incriminating dots. It's a complex relationship, she says, that is still not fully explained – or explainable.
"What we have learned since the WHI is that for most women taking hormones short term -- for two or three years for symptom relief -- there won't be an increase in breast cancer in the short term, but this doesn't necessarily mean these women won't see an increase in breast cancer in the long term," says Smith.
Stuenkel tells WebMD even Mother Nature validates this line of thinking.
"Population studies for a women who go into menopause at age 55 instead of 50, there is an overall increased risk of breast cancer, so the duration of hormone stimulation definitely matters," says Stuenkel. Indeed, the WHI showed breast cancer risks clearly increased the longer a woman remained on HRT.
At the same time, however, Goldstein notes that at least one reanalysis of the WHI findings published in JAMA in 2006 found that women who had a hysterectomy and used estrogen-only therapy for an average of seven years had no increase in breast cancer rates.
"In fact, risks of at least one type of breast cancer were reduced in these women," says Goldstein.
But again, Stuenkel reminds us that the duration of hormone use might change that picture, too. She points to results from the Harvard Nurses' Health Study published in the Archives of Internal Medicine in 2006, which reported that those women who took estrogen only experienced an increase in breast cancer after 20 years of use.
"I have not bought into the idea that estrogen alone reduces breast cancer, and for me the duration of exposure is still a key issue – when it comes to HRT, I just don't believe there's going to be a free lunch for any woman," says Stuenkel.
Where We Are Today
While studies are still ongoing, and reanalysis of the original data continues to shape our opinions, experts say there are a few lessons learned thus far that are not likely to change.
Among them: That hormone replacement therapy is not a panacea for disease prevention -- even in situations where it was found to be helpful, such as reduction in hip fractures.
Moreover, if hormone replacement therapy must be used to quell menopause symptoms, the lowest possible dose for the shortest possible duration is now the standard of care.
Today the emphasis rests on the importance of treating every woman individually, with decisions about hormone use made strictly on a case-by-case basis.
"Gone forever are the days when every doctor routinely prescribed HRT for every woman over 50; today, the decision to go on hormone therapy, even short term, must take into consideration a host of individual health and lifestyle factors," says Smith.
Among the most important things to discuss with your doctor, says Smith, is your personal and family history of heart disease, stroke, blood clots, breast cancer and breast disease, and your reproductive history. Also important: personal lifestyle choices such as smoking, alcohol use, diet, and your current weight and blood pressure.
"I think one of the most valuable lessons to come out WHI is that every woman needs -- and deserves to have -- individualized care, not just for menopause symptoms, but for all health concerns," Stuenkel notes.
And that, she says, is a lesson we should not soon forget.
- Have you made a decision about HRT? Tell us about it on the Menopause Support Group message board.