BACKGROUND AND PURPOSE:

• Manson et al. (Ann Intern Med., 2019) compared estrogen therapy outcomes in women with and without bilateral salpingo-oophorectomy (BSO)

METHODS:

• Subgroup analyses of the randomized Women’s Health Initiative (WHI) Estrogen-Alone Trial
• Participants
  • Women aged 50 to 79 years with prior hysterectomy and known oophorectomy status
  • Treatment length median: 7.2 years
  • 18-year follow-up
• Intervention groups
  • Conjugated equine estrogens (CEE) | 0.625 mg/d
  • Placebo
• Primary outcomes: Measured during the intervention and follow-up
  • Coronary heart disease | Invasive breast cancer | All-cause mortality
  • A “global index”: Above endpoints with inclusion of
    • Stroke | Pulmonary embolism | Colorectal cancer | Hip fracture
• Outcomes stratified by time of CEE initiation (by 10-year age groups)

RESULTS:

• 9,939 women were included in this subgroup analysis
• Overall, outcomes in the CEE arm did not differ significantly according to BSO status

Intervention Phase

• Outcomes in CEE arm did differ by age during the intervention phase based on BSO status
  • ≥70 years and previous BSO: CEE was significantly associated with adverse effects
    • Global index hazard ratio (HR): 1.42 (95% CI, 1.09 to 1.86)
  • 50 to 59 years and 60 to 69 year brackets: Treatment effects were in the nonadverse direction
    • Global index: P trend by age = 0.016
    • Breast cancer: P trend by age = 0.010
  • Age did not impact outcomes in the non-BSO group

Cumulative Follow-Up (intervention and post-intervention phase)

• Outcomes in CEE arm did differ during the intervention phase based on BSO status
  • 50 to 59 years with BSO
    • Treatment-associated reduction in all-cause mortality
    • Hazard ratio, 0.68 (95% CI, 0.48 to 0.96)
    • Most pronounced in women who had procedure <45 years
  • No BSO effect in older women (P trend by age = 0.034)
  • Age did not impact outcomes in the non-BSO group

CONCLUSION:

• Overall, there was no effect of BSO on outcomes but when stratified by age, differing outcomes were seen in women with previous BSO
  • Women ≥70 had a greater risk for adverse effects during the treatment period

The authors state

This provides some reassurance to clinicians and their younger patients with BSO that, in the absence of contraindications, the use of estrogen beyond the average age of natural menopause to manage menopausal symptoms or—in women at high risk for fracture who cannot tolerate alternative osteoporosis therapies—to lower osteoporosis risk  should not have net adverse effects.

Learn More – Primary Sources: 

Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy: A Randomized Trial

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