Am Fam Physician. 2024;109(4):310-311
Author disclosure: No relevant financial relationships.
Details for This Review
Study Population: 36 studies with 23,299 women in two main groups: early menopausal women (fewer than 5 years since amenorrhea or menopause) with or without menopausal symptoms and “unselected” postmenopausal women (last menstrual period more than 5 years earlier, regardless of menopausal symptoms)
Efficacy End Points: Primary: sexual-function composite score; secondary: domains of sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain
Harm End Points: Not evaluated in this review
| Benefits |
| Slight improvement in sexual-function composite score for estrogen alone compared with placebo or no intervention (standardized mean difference = 0.50; 95% CI, 0.04 to 0.96) in women experiencing early postmenopause (< 5 years since amenorrhea) or experiencing other symptoms due to menopause |
| Slight improvement in sexual-function composite score for selective estrogen-receptor modulators compared with placebo or no intervention (mean difference = 2.24; 95% CI, 1.37 to 3.11) in unselected postmenopausal women |
| Harms |
| Not evaluated |
Narrative: Perimenopausal or menopausal women may experience many symptoms due to fluctuating or declining hormone levels, especially as estrogen levels change. Symptoms may include hot flashes, night sweats, and mood changes. As circulating estrogen levels decrease, vaginal mucosa can atrophy, leading to dyspareunia and decreased sexual function, including decreased interest, arousal, vaginal lubrication, or ability to achieve orgasm.
Hormone therapy has some benefit in treating hot flashes and genitourinary syndrome of menopause (e.g., vaginal dryness, painful intercourse, urinary urgency), but the overall specific effect on sexual function is unclear.1
The Cochrane review and meta-analysis discussed here included 36 trials (23,299 women in aggregate) and assessed the effect of hormone therapy on sexual function in periand postmenopausal women.2 Patients were divided into two main groups: early menopausal women (fewer than 5 years since amenorrhea or menopause) with or without menopausal symptoms and “unselected” postmenopausal women (last menstrual period more than 5 years earlier, regardless of menopausal symptoms). The main outcome was a sexual-function composite score measured by any validated tool. Secondary outcomes included the domains of sexual function—desire, arousal, lubrication, orgasm, satisfaction, and pain.
For women experiencing early menopause, with or without menopausal symptoms, the review showed moderate-quality evidence that compared with placebo or no intervention, treatment with estrogen therapy (oral, transdermal, and vaginal formulations) alone may slightly improve the sexual-function composite score (standardized mean difference = 0.50; 95% CI, 0.04 to 0.96). The standardized mean difference is used to compare the average differences in symptom scales when different scales are used in the included studies. When considering standardized mean difference values, 0.20 to 0.49 is considered a small effect, 0.50 to 0.79 is considered moderate, and greater than 0.8 is considered large.3 Regarding the secondary outcomes of the domains of sexual function in this same group of women, low- to moderate-quality evidence demonstrated that compared with placebo or no intervention, treatment with estrogen therapy alone may slightly improve pain with intercourse (standardized mean difference = 0.35; 95% CI, 0.14 to 0.56), vaginal lubrication (standardized mean difference = 0.47; 95% CI, 0.21 to 0.73), and sexual satisfaction (standardized mean difference = 0.29; 95% CI, 0.08 to 0.51). The effect of estrogen therapy alone on orgasm was uncertain, and the effect on sexual desire and arousal was not studied in this population.
This Cochrane review showed very low-certainty evidence that the effect on the sexual-function composite score was uncertain for the use of synthetic steroids, selective estrogen receptor modulators (SERMs), and SERMs plus estrogen compared with placebo or no intervention in early menopausal women, with or without menopausal symptoms. The benefit of estrogen plus progesterone for this population was not reported in any of the included studies.
For unselected postmenopausal women, low-quality evidence in the review demonstrated that compared with placebo or no intervention, treatment with SERMs may slightly improve the sexual-function composite score (mean difference = 2.24; 95% CI, 1.37 to 3.11). The mean difference is the average difference between the same symptom scales used in the assessed studies. For this same population, low-quality evidence demonstrated that compared with placebo or no intervention, treatment with SERMs probably slightly improved secondary outcomes, including sexual desire (mean difference = 0.25; 95% CI, 0.14 to 0.36), arousal (mean difference = 0.28; 95% CI, 0.11 to 0.46), vaginal lubrication (mean difference = 0.62; 95% CI, 0.42 to 0.82), satisfaction (mean difference = 0.23; 95% CI, 0.07 to 0.39), and pain (mean difference = 0.53; 95% CI, 0.33 to 0.74). Additionally, very low-quality evidence demonstrated an improvement in orgasm (mean difference = 0.35; 95% CI, 0.15 to 0.55) in this population.
Moderate-quality evidence in the review demonstrated that compared with placebo or no intervention, estrogen alone probably slightly improved lubrication (standardized mean difference = 0.47; 95% CI, −0.09 to 1.02) but had little or no effect on sexual-function composite scores in unselected postmenopausal women. The effect of estrogen alone on other secondary outcomes in this population is uncertain.
Additionally, for unselected postmenopausal women, low-quality evidence showed that estrogen plus progesterone compared with placebo or no intervention may slightly improve lubrication (mean difference = 0.45; 95% CI, 0.13 to 0.77).
The evidence was uncertain for the use of SERMs plus estrogen or estrogen plus progesterone on the sexual-function composite score in unselected postmenopausal women. The evidence was also uncertain for the use of synthetic steroids on the primary and secondary outcomes. No studies reported secondary outcomes for SERMs plus estrogen.
Caveats: No studies included in this review focused only on women with sexual dysfunction. Importantly, out of the 36 included studies, 25 were funded by the pharmaceutical industry, and 20 were considered at high risk of bias. Studies were also grouped according to hormone or medication (e.g., estrogen, SERMs) regardless of route (e.g., oral, transdermal, vaginal), which limits the clinical applicability of the outcomes. Additionally, some studies compared estrogen with no intervention rather than placebo. This review also did not assess the harms of hormone therapy for the treatment of sexual function.
It is recommended that when treating patients who have a uterus with oral or transdermal (but not necessarily vaginal) estrogen for hormone therapy, progesterone treatment also be prescribed to prevent estrogen-related endometrial hyperplasia.4
Conclusion: This review demonstrated some benefits. However, intervention heterogeneity and lack of reporting of potential harms lead to some uncertainty of the evidence. Given this information, we have assigned a color recommendation of yellow for the use of hormone therapy to treat sexual dysfunction in peri- and postmenopausal women.
