Women’s Health Initiative Publishes New Comprehensive Results from Hormone Therapy Trials

 The study presents information on a wide range of diseases and quality-of-life outcomes, comparisons of the two hormone therapy trials side-by-side and a full breakdown of results by age and time since menopause onset and is published in the October 2, 2013 edition of JAMA.

“Our main goal was to provide as much information as possible from the WHI hormone therapy trials to help women and their clinicians make the most informed decisions about hormone therapy use,” said JoAnn Manson, MD, who is first author of the report, chief of Preventive Medicine at Brigham and Women’s Hospital (BWH), and one of the principal investigators of the WHI.  “The WHI findings, presented in this new detail, provide the strongest evidence base available to guide clinical decision making and individualized care.”

The researchers conclude that the findings from the two WHI trials do not support use of hormone therapy for prevention of chronic disease; however, researchers note that treatment is appropriate for symptom management in some women.  The results indicate that hormone therapy has a complex pattern of health risks and benefits and demonstrate that younger women (defined as ages 50-59) tend to have a more favorable risk-to-benefit profile than older women.  Other key findings include:

  • Combination estrogen plus progestin (in women with an intact uterus) had more risks than estrogen alone (used in women with hysterectomy), primarily due to an increased risk of breast cancer with the former but not the latter.
  • Both forms of hormone therapy increased the risk of stroke, blood clots in the legs, gallstones and urinary incontinence.
  • Benefits of hormone therapy include decreased risk of hip fractures, other fractures, diabetes and hot flashes/night sweats.
  • Estrogen plus progestin increased dementia in women ages 65 years and older, but neither treatment affected cognition in younger women.
  • For estrogen alone, younger women had more favorable results for all-cause mortality, heart attacks, colorectal cancer, and combined chronic disease. Younger women’s overall risk-to-benefit profile on estrogen alone was more favorable than for older women.
  • Effects on quality-of-life outcomes with hormone therapy were mixed, with improvement in sleep and joint pain but increases in breast tenderness.

After stopping hormone therapy, most risks and benefits dissipated.  However, over the 13 year cumulative follow-up period, breast cancer risk remained slightly elevated for estrogen plus progestin but became significantly reduced for estrogen alone.  For estrogen plus progestin, a significant reduction in uterine (endometrial) cancer emerged during follow up and the risk of hip fracture remained significantly (but modestly) reduced.  For both forms of hormone therapy, there was no increase or decrease in the rate of total cancer (all types combined), cancer mortality, cardiovascular mortality, or all-cause mortality in the overall study population.

These findings indicate that the absolute risks of adverse events in younger women are much lower than in older women and, because menopausal symptoms are more common in younger age groups, the quality-of-life benefits are likely to outweigh the risks for many women who seek treatment for symptoms during the menopause transition. However, the study’s findings do not support long-term use for disease prevention.

“It is important to distinguish between the use of hormone therapy for symptom management and its use for the purpose of chronic disease prevention.  Short-term use of hormone therapy to manage moderate-to-severe hot flashes or other symptoms in early menopause remains appropriate, and the WHI findings should not be used as a basis for denying women such treatment”, said Manson.   Among women in the 50 to 59 year age group, fewer than 1 out of 100 had adverse events during five years of hormone therapy use, while the risks were four to five times higher among the older women.

“Although studies of other hormone therapy formulations, doses and routes of delivery are needed to find treatments with fewer risks, these medications are now among the best studied treatments in medical history. Clinicians can share information from the WHI trials with their patients and help them make more informed choices,” Manson said.

In an accompanying editorial, Betsy Nabel, MD, president of Brigham and Women’s Hospital and former director of the National Heart Lung and Blood Institute (NHLBI), reflects on the legacy of the WHI, saying, “Twenty-two years following its inception, the WHI is a model for publicly-funded, rigorous, thorough and objective clinical trials that broadly affect human health.”

The WHI enrolled 27,347 women nationwide in the two hormone therapy trials and is sponsored by the National Institutes of Health’s NHLBI.  For more information about the WHI, please visit the Women’s Health Initiative website.

Brigham and Women’s Hospital