October 10th, 2012

Danish Study Gives a Boost to Hormone Replacement Therapy ‘Timing Hypothesis’

Hormone replacement therapy (HRT) suffered a sharp blow a decade ago when the Women’s Health Initiative failed to show any cardiovascular benefit in women taking HRT. Despite the setback, many researchers theorized that HRT might still be beneficial in women who start HRT close to menopause. Now a study from Denmark published in BMJ lends strong support to the “timing hypothesis.”

Louise Lind Schierbeck and colleagues analyzed data from 1006 recently postmenopausal or perimenopausal women who were randomized to HRT or no treatment.

After 10 years, there were 16 primary endpoint events (the composite of death, admission to the hospital for heart failure, or MI) in the HRT group compared with 33 in the control group (hazard ratio 0.48, CI 0.26-0.87, p=0.015).

  • Mortality: 15 versus 26, HR 0.57, 0.30-1.08, p=0.084
  • Heart failure: 1 versus 7, HR 0.14, 0.02-1.16, p=0.07
  • MI: 1 versus 4, HR 0.25, 0.03-2.21, p=0.21.

There was no significant difference between the groups in the rate of any cancer or of breast cancer. Women who were under 50 years of age at the start of the trial appeared to enjoy the greatest benefit from HRT.

The authors concluded:

Our findings suggest that initiation of hormone replacement therapy in women early after menopause significantly reduces the risk of the combined endpoint of mortality, myocardial infarction, or heart failure. Importantly, early initiation and prolonged hormone replacement therapy did not result in an increased risk of breast cancer or stroke.

Andrew Kaunitz told Physician’s First Watch that, when “taken together with findings from a subanalysis of younger women from the WHI, these data should reassure clinicians and women that use of hormone therapy in recently menopausal women is safe.”

3 Responses to “Danish Study Gives a Boost to Hormone Replacement Therapy ‘Timing Hypothesis’”

  1. Jose Gros-Aymerich, MD says:

    Sorry, too few patients in this study for my taste, HRT should probably be still considered with caution and never as an standard routine therapy for all menopausal women, and its Rx carefully assessed in a case by case, individualized way, with an important participation of the woman in the decisions regarding her health in this field. Or not? Salut +

  2. Dan Hackam, MD PhD says:

    Very interesting paper – and a good read to boot. Agree that N was small, as were the numbers of events. Composite endpoint statistically significant but none of the components of the composite are statistically significant, although positive trends seen. Worrisome that they used administrative databases to determine follow-up rather than direct patient contact. I don’t think one can draw any conclusion about the post-trial follow-up period (years 10 through 16), as most patients stopped therapy during that time, based on the WHI results which were released Summer 2002. I agree with Jose that these results should be viewed with caution.

  3. Judith Andersen, AB, MD says:

    Couldn’t agree more with Dr. Grose-Aymerich: Clinical trial data address the general; physicians treating individual patients treat (or should) the individual. Still the Women’s Health Initiative initial reporting did a major disservice to women and the physicians treating them by misassessing the impact of the message from this clinical trial that regarded ingested fixed-dose estradiol +/- progesterone as equivalent to endogenously produced or cutaneously supplied estrogen +/- progesterone. It is, I think, now clear, that women without a uterus benefit, both in cardiovascular as well as general health, from estrogen replacement. The risk of endometrial carcinoma in women who with a uterus who receive post-menopausal estrogen is still being reassessed, but should not be underestimated. There are few data that address the individual risk of a woman with no family history of cancer and an intact, albeit, non-functioning uterus, of developing endometrial cancer with transdermal estrogen replacement. A tough decision for many women, a difficult recommendation for physicians. As always, well-designed clinical trials that include the potential for subgroup analysis in their initial incarnation are important. The WHI, purporting to help women and their primary caregivers make decisions about HRT, came to many erroneous conclusions that have been incorporated into general medicine practice recommendations, to the detriment of many women eligible for HRT.