Hormonal therapy for sexual function in menopausal women

We aimed to assess the effect of hormonal therapy (HT), specifically estrogens alone, estrogens in combination with progestogens, synthetic steroids, and SERMs, on sexual function in perimenopausal and postmenopausal women. The time around and after the last menstrual period (menopause) is associated with many symptoms, including a decline of sexual function. HT is a generic term that refers to any type of hormone therapy used during menopause for alleviation of menopause-related symptoms. We carried out an electronic search of medical literature databases, searching for randomised controlled trials (RCTs) comparing hormone therapy (HT) to either no treatment or a placebo treatment. No other type of study was included. The last search was performed in December 2012.

Twenty-seven studies were included; they were conducted in more than 30 countries. Sexual function was assessed in 8802 women in the treatment groups and in 7591 women in the control groups. A single study was responsible for the inclusion of 8462 women, 51.2% of the total number. We grouped the studies by participant characteristics with regard to menopausal symptoms. The symptomatic or early menopausal group was from nine studies in which women were perimenopausal (one study), up to 36 months postmenopause (one study), up to five years postmenopause (one study), experiencing vasomotor or other menopausal symptoms (five studies), or experiencing hot flushes and sexual dysfunction (one study). The unselected postmenopausal women group came from 18 studies. The group included women regardless of menopausal symptoms and allowed inclusion of women with more than five years since their final menstrual period. No studies were restricted to women with sexual dysfunction and only five studies evaluated sexual function as a primary outcome. Eighteen studies were deemed at high risk of bias, and the other nine studies were at unclear risk of bias. Twenty studies received commercial funding.

Findings for sexual function (measured by overall score) were as follows:

In the comparison of estrogens alone versus control, for symptomatic or early postmenopausal women the observed effect was compatible with a small to moderate benefit for sexual function in the HT group (high-quality evidence). For unselected postmenopausal women the observed effect was compatible with no effect to a small benefit, provided by low-quality evidence.

In the comparison of estrogens combined with progestogens versus control, for symptomatic or early postmenopausal women, the observed effect was compatible with a small to moderate benefit for sexual function in the HT group (moderate-quality evidence). For  unselected postmenopausal women, the observed effect was compatible with no effect to a small benefit (moderate-quality evidence).

In the comparison of tibolone versus control, for symptomatic or early postmenopausal women the observed effect was compatible with no effect to a small benefit for sexual function in the HT group (low-quality evidence). For unselected postmenopausal women, the observed effect was compatible with no effect to a moderate benefit (low-quality evidence).

In the comparison of SERMs (raloxifene and bazedoxifene) versus control, for symptomatic or early postmenopausal women the observed effect was compatible with no effect to a moderate benefit for sexual function in the HT group (low-quality evidence). For unselected postmenopausal women, the observed effect was compatible with a small harm to small benefit (low-quality evidence).

Comparing bazedoxifene combined with estrogens to control, for symptomatic or early postmenopausal women the observed effect was compatible with no effect to a small benefit, with moderate-quality evidence. No study was included in the subgroup of unselected postmenopausal women.

The included studies did not allow a comprehensive assessment of harms from these therapies; other systematic reviews must be taken into account to understand the possible harms of HT.

We concluded that HT treatment with estrogens alone or in combination with progestogens is associated with a small to moderate improvement in sexual function when used specifically in women with menopausal symptoms or who were in early postmenopause (within five years after onset of menopause), but not when used for any postmenopausal woman. Evidence regarding other HTs (tibolone, raloxifene, and bazedoxifene) is of low quality. The current evidence does not suggest an important effect of tibolone, raloxifene and bazedoxifene, alone or combined with estrogens, on sexual function.

Authors' conclusions: 

HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function, particularly in pain, when used in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), but not in unselected postmenopausal women. Evidence regarding other HTs (synthetic steroids and SERMs) is of low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function. More studies evaluating the effect of synthetic steroids, SERMS and the association of SERM + estrogens would improve the quality of the evidence for the effect of these treatments on sexual function in peri and postmenopausal women. Future studies should also evaluate the effect of HT solely among women with sexual complaints.

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Background: 

The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints.

Objectives: 

To assess the effect of hormone therapy (HT) on sexual function in perimenopausal and postmenopausal women.

Search strategy: 

We searched for articles in the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, ISI Web of Knowledge and OpenGrey. The last search was performed in December 2012.

Selection criteria: 

We included randomised controlled trials comparing HT to either placebo or no intervention (control). We considered as HT estrogens alone; estrogens in combination with progestogens; synthetic steroids (for example tibolone); or selective estrogen receptor modulators (SERMs) (for example raloxifene, bazedoxifene). Studies of other drugs possibly used in the relief of menopausal symptoms were excluded. We included studies that evaluated sexual function using any validated assessment tool. The primary outcome was a composite score for sexual function and the scores for individual domains (arousal and sexual interest, orgasm, and pain) were secondary outcomes. Studies were selected by two authors independently.

Data collection and analysis: 

Data were independently extracted by two authors and checked by a third. Risk of bias assessment was performed independently by two authors. We contacted study investigators as required. Data were analysed using standardized mean difference (SMD) and relative risk (RR). We stratified the analysis by participant characteristics with regard to menopausal symptoms. The overall quality of the evidence for the primary outcome was evaluated using the GRADE criteria.

Main results: 

The search retrieved 2351 records from which 27 studies (16,393 women) were included. The 'symptomatic or early post-menopausal' subgroup included nine studies: perimenopausal women (one study), up to 36 months postmenopause (one study), up to five years postmenopause (one study), experiencing vasomotor or other menopausal symptoms (five studies), or experiencing hot flushes and sexual dysfunction (one study). The 'unselected postmenopausal women' subgroup included 18 studies, which included women regardless of menopausal symptoms and permitted the inclusion of women with more than five years since the final menstrual period. No studies were restricted to women with sexual dysfunction. Only five studies evaluated sexual function as a primary outcome. Eighteen studies were deemed at high risk of bias, and the other nine studies were at unclear risk of bias. Twenty studies received commercial funding.

Findings for sexual function (measured by composite score):

For estrogens alone versus control, in symptomatic or early postmenopausal women the SMD and 95% CI were compatible with a small to moderate benefit in sexual function for the HT group (SMD 0.38, 95% CI 0.23 to 0.54, P < 0.00001, 3 studies, 699 women, I² = 55%, high-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.16, 95% CI -0.02 to 0.34, P = 0.08, 2 studies, 478 women, I² = 44%, low-quality evidence). The subgroups were not pooled because of considerable heterogeneity.

For estrogens combined with progestogens versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with a small to moderate benefit for sexual function in the HT group (SMD 0.42, 95% CI 0.19 to 0.64, P = 0.0003, 1 study, 335 women, moderate-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.09, 95% CI -0.02 to 0.20, P = 0.10, 3 studies, 1314 women, I² = 0%, moderate-quality evidence). The subgroups were not pooled because of considerable heterogeneity.

For tibolone versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.13, 95% CI 0.00 to 0.26, P = 0.05, 1 study, 883 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a moderate benefit (SMD 0.38, 95% CI 0.04 to 0.71, P = 0.03, 2 studies, 142 women, I² = 0%, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.17, 95% CI 0.04 to 0.29, P = 0.008, 3 studies, 1025 women, I² = 20%).

For SERMs versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a moderate benefit for sexual function in the HT group (SMD 0.23, 95% CI -0.04 to 0.50, P = 0.09, 1 study, 215 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with small harm to a small benefit (SMD 0.04, 95% CI -0.20 to 0.29, P = 0.72, 1 study, 283 women, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.13, 95% CI -0.05 to 0.31, P = 0.16, 2 studies, 498 women, I² = 2%).

A comparison of SERMs combined with estrogens versus control was only evaluated in symptomatic or early postmenopausal women. The 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.21, 95% CI 0.00 to 0.43, P = 0.05, 1 study, 542 women, moderate-quality evidence).

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