PURPOSE:

• Low estrogen levels in menopause may affect sexual function in two ways
  • Symptoms of vulvovaginal atrophy
  • Estradiol modulates serotonergic function that regulates mood and desire
• Recent meta-analysis suggests that estrogen is associated with small to moderate improvement in sexual function
• Taylor et al. (JAMA Internal Medicine) sought to address the relationship between estrogen and sexual function in recently menopausal women based on route of administration

METHODS:

• Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS)
  • Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017
• 4 year prospective, randomized, double-blinded, placebo-controlled trial
• Menopausal hormone therapy in healthy, recently menopausal women (within 6 months to 3 years of LMP )
• Randomized to the following groups
  • 0.45 mg/d oral conjugated equine estrogens (o-CEE)
  • 50 µg/d transdermal 17β-estradiol (t-E2)
  • Placebo
  • 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month
• Main Outcomes
  • Sexual function: Assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points; higher scores indicate better sexual function)
    • Low sexual function: Defined as an FSFI overall score of less than 26.55

RESULTS:

• 670 women agreed to participate in this sexual function study
• t-E2 treatment compared with placebo was associated with improvement in the FSFI overall score across all time points (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002)
• o-CEE treatment compared to placebo demonstrated no significant difference in FSFI overall score
• There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22)
• t-E2 treatment compared with placebo was associated with
  • Significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001
  • Significant decrease in pain (0.67; 95% CI, 0.25-1.09; P = .002)
• 67% of those on t-E2 treatment had low sexual function compared with 76% on placebo (P = .04)
• For o-CEE there was no significant reduction in the odds of low sexual function

CONCLUSION:

• T-E2 provides modest improvement in sexual function in healthy, recently menopausal women
• Limitations include
  • KEEPS demographic (white, higher educated women) may not be generalizable
  • Distress associated with sexual function was not addressed/diagnosed using clinical interviews
  • Hormonal symptoms of vulvovaginal atrophy not assessed

Learn More – Primary Sources:

Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS)

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