The story of post-menopausal hormone therapy took yet another turn for the complex.
Last week, the New England Journal of Medicine published a trial suggesting that the cardiovascular effects of post-menopausal oral estrogen replacement -- and that they may even be beneficial.
Before we jump into the new study, let's do a quick recap of the post-menopausal hormone therapy saga.
Nonrandomized from the 1990s indicated that post-menopausal hormone therapy might -- particularly heart disease -- and was something of a "fountain of youth."
With some not-so-gentle encouragement from the pharmaceutical industry, including , many clinicians began encouraging post-menopausal women to consider hormone therapy for its disease prevention benefits.
In 2002, results of the (WHI) -- a randomized trial of post-menopausal hormone therapy -- rocked the medical community by demonstrating that hormone therapy increased the risk of both breast cancer and cardiovascular disease, and that the overall risks with respect to disease prevention outweighed the benefits.
In response to the WHI, use of post-menopausal hormone therapy rapidly declined, though some began to wonder whether the benefits and risks of post-menopausal hormone therapy might be more favorable in younger women compared with those studied in the WHI, who had a mean age of 63 years.
Enter the , the randomized controlled trial published last week in NEJM involving 643 women. ELITE compared the vascular effects of hormone therapy in younger women who entered menopause within the previous 6 years compared with older women who entered menopause at least 10 years earlier.
Women in both age cohorts were randomized to receive either oral estrogen along with vaginal progesterone or placebo (of note, in the WHI women received both hormones orally), and were followed for 5 years.
ELITE found that for women who began treatment within 6 years of entering menopause, hormone therapy seemed to decrease cardiovascular risk as assessed by the surrogate measure carotid artery intima-media thickness (CIMT).
Among women at least 10 years post-menopause, hormone therapy had no impact on CIMT. Hormone therapy also did not affect coronary artery calcium scores on CT scans in either the younger or older cohorts.
While the CIMT findings are mildly reassuring for younger women, we agree with the who points out: "The relevance of these results to clinical coronary heart disease events remains questionable. The trial assessed only surrogate measures of coronary heart disease and was not designed or powered to assess clinical events."
Moreover, we are skeptical that CIMT is a valuable surrogate marker to begin with.
In the WHI -- a well-designed randomized controlled trial -- hormone therapy increased cardiovascular events in older post-menopausal women. If CIMT was a reliable marker for cardiovascular risk, we'd expect to see increased CIMT among the older women studied in the ELITE who were treated with hormones. But this wasn't the case, raising important questions about the validity of CIMT as a surrogate marker. (One caveat is that, as noted above, in the WHI progestin was given orally while in ELITE it was given topically.)
Though the ELITE trial will get plenty of media attention, it changes nothing in our opinion. On the balance, post-menopausal hormone therapy should not be used to prevent chronic disease. Even if the cardiovascular effects of hormone therapy are relatively less harmful in younger women, hormones have other deleterious effects such as increasing the incidence and aggressiveness of breast cancer.
In order to convince us that hormones are safe in younger post-menopausal women, we would need high-quality randomized trials examining clinically relevant outcomes in this population. ELITE was not this.
Still, we do see an important place for post-menopausal hormone therapy. The symptoms of menopause can be very troublesome to some women, including hot flashes, sleep disturbances, urinary symptoms. When conservative measures fail, hormones can be very effective for short-term management of these symptoms. Most of the risks -- which are modest in absolute terms -- arise when hormones are used for several years or longer.
So although hormone therapy for the treatment of bothersome menopausal symptoms is perfectly appropriate, both clinicians and patients who use hormones for this indication should realize that, from a chronic disease standpoint, hormones cause more harm than good. The sooner women are able to taper off these medications, the better.
"Updates in Slow Medicine" applies the latest medical research to support a thoughtful approach to clinical care. It is produced by , of Harvard Medical School, and , of AltaMed Health System in Los Angeles. , is a palliative care fellow at the Mount Sinai Hospital in New York. To learn more, .