Miriam E Tucker
March 07, 2015

SAN DIEGO, California — Menopausal hormone-replacement therapy does not appear to affect mortality either positively or negatively, according to a new systematic review and meta-analysis.


The findings, from 43 randomized clinical trials, were presented March 6 here at the Endocrine Society’s annual meeting, ENDO 2015, by Khalid Benkhadra, MD, a postdoctoral research fellow in the Evidence-Based Practice Research Program–Knowledge and Evaluation Research Unit, Mayo Clinic, in Rochester, Minnesota.
This is the first investigation specifically aimed at answering the question, Dr Benkhadra told Medscape Medical News.


"Women shouldn’t be fearful of long-term events, but each case is an individual....Clinicians should engage postmenopausal women and share decision-making so they can reach an agreement," he said.


For Cynthia A Stuenkel, MD, clinical professor of medicine at the University of California, San Diego, School of Medicine, the lack of benefit found in the meta-analysis was the more notable finding.


"I think there are still questions about the potential mortality benefit in younger women, but I would say this is reassuring about no increase in mortality," she told Medscape Medical News.


Meta-analysis Included WHI


Dr Benkhadra and colleagues identified the 43 randomized controlled trials with several online database searches dating back to their inceptions and continuing through August 2013. All compared menopausal hormone therapy with either placebo or no treatment and reported an effect size for outcomes. The landmark Women's Health Initiative was among the 43 studies, Dr Benkhadra told Medscape Medical News.


The study population totalled more than 52,000 women with a mean age of 62 years and an average 5 years of follow-up.


There were no significant associations between use of menopausal hormone-replacement therapy and all-cause mortality (risk ratio [RR], 0.99), and no associations related to hormone type or preexisting heart disease.


No significant associations were found between hormone use and mortality due to myocardial infarction (RR, 1.04), breast cancer (RR, 0.93), or stroke (RR, 1.49). In all those cases, the 95% confidence interval crossed 1.0.


When analyzed separately, there were also no associations with risks for death from cancers of the lung, ovary, or colon/rectum. Results were similar for estrogen-only therapy and for combined estrogen-progesterone therapy.


However, Dr Benkhadra cautioned that the certainty of these results is "low to moderate" and that the length of follow-up was limited to 5 years.


Most recently, hormone-replacement therapy was reported to be significantly associated with a small but increased risk for ovarian cancer in postmenopausal women in an article published in the Lancet.


No Stratification by Age Is a Limiting Factor


Dr Stuenkel told Medscape Medical News that some of the estrogen-alone data from the Women's Health Initiative and other studies had suggested a decrease in mortality with menopausal hormone replacement, and one problem with the current meta-analysis is that there was no stratification by age at initiation of treatment. It is thought that there is a timing factor, or critical window of opportunity, for hormone therapy.


"I think we're very clear that hormone-replacement therapy is a very reasonable option for treating the symptoms of menopause. But we dance around the question related to prevention....If a healthy 50-year-old woman going through menopause starts hormone therapy, might her outcome be different from a 70-year-old woman, who...might have greater risk for cardiovascular disease? It's a tricky question."


However, she noted, most symptomatic women do not wait that long to seek treatment.


"The Women’s Health Initiative...has altered the way we practice in that we're really very cautious about initiating therapy even in women over age 60 because we know that our vasculature ages. But some women remain symptomatic, so that's the tricky part, although most women...will come in closer to the time of menopause, so even if they're at the far end of the bell curve going through their menopause at age 55, chances are they're not going to wait 5 years."

Dr Benkhadra and coauthors as well as Dr Stuenkel have disclosed no relevant financial relationships.


ENDO 2015: The Endocrine Society Annual Meeting. Abstract FRI-125, presented March 6, 2015.

Source: http://www.medscape.com/viewarticle/...p&uac=180112PN