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Lengthened WHI Follow-Up: Postmenopausal Estrogen Therapy

Women's Health Initiative follow-up of postintervention phase showed estrogen had no substantial adverse effects on most health outcomes; reduction in relative risk for breast cancer persisted.

In the Women's Health Initiative (WHI) Estrogen-Alone Trial, 11,000 postmenopausal women with hysterectomies (age range at baseline, 50–79) received conjugated equine estrogen or placebo for a median of 5.9 years; the trial was stopped at mean follow-up of 7.1 years when initial findings showed excess risk for stroke in the estrogen group. Subsequent analysis showed that, in younger WHI participants (age range at baseline, 50–59), estrogen use was associated with lower risk for coronary heart disease (CHD) and overall mortality during the intervention period. Now, investigators have assessed postintervention health outcomes in 7645 WHI participants.

Overall, at a mean 10.7 years after baseline, estrogen use was not associated with excess risk for stroke or other adverse outcomes (CHD, deep venous thrombosis, hip fracture, colorectal cancer, and mortality during follow-up). As had been noted in previous WHI analyses of the intervention phase, risk for invasive breast cancer was lower in the estrogen group than in the placebo group (hazard ratio, 0.77; 95% confidence interval, 0.62–0.95); moreover, among younger women, estrogen use was associated with lower risk for CHD (HR, 0.59; 95% CI, 0.38–0.90) and marginally lower risk for mortality during follow-up (HR, 0.73; 95% CI, 0.53–1.00).

Comment: Although these new findings from the WHI are intriguing, they do not imply that estrogen-only therapy should be recommended at this time for cardioprotection or breast cancer chemoprophylaxis. What these results do provide is reassurance to young menopausal women who are posthysterectomy and who present with bothersome vasomotor symptoms that use of estrogen therapy for as long as 6 years is safe.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health April 5, 2011

Citation(s):

LaCroix AZ et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: A randomized controlled trial. JAMA 2011 Apr 6; 305:1305.(http://dx.doi.org/10.1001/jama.2011.382)

• Medline abstract (Free)

Jungheim ES and Colditz GA. Short-term use of unopposed estrogen: A balance of inferred risks and benefits. JAMA 2011 Apr 6; 305:1354.(http://dx.doi.org/10.1001/jama.2011.405)

• Medline abstract (Free)

Reader Remarks:

Review and add to remarks on this article

• A questionable analysis...
  JW R, 9 May 2011 9:16 AM EST
  Specialty: Unspecified
  I have always been skpetical of subgroup analyses in clinical trials, especially when they clash with the overall findings. The... [more]
• Abrupt End of Original WHI trial
  Levonne K Kelly, retired, 31 May 2011 12:44 PM EST
  Specialty: Unspecified
  I question the validity of the above followup study since my abrupt termination of the WHI study pills was followed... [more]

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