Key messages
• Estrogen (the hormone associated with sexual and reproductive development in women) alone probably improves sexual function scores compared to placebo.
• We are unsure of the effect of estrogen plus progestogens (another female hormone), synthetic steroids (such as tibolone), selective estrogen receptor modulators (that affect how estrogen works) or selective estrogen receptor modulators plus estrogen on sexual function compared to placebo or no treatment.
• Different hormone treatments and doses, and questionnaires used for assessment, may have caused the variation seen in results.
What is menopause and its effects on women?
Menopause is when women's periods stop, usually at around the age of 45 to 55 years. During menopause the ovaries gradually stop producing estrogen, the hormone that regulates periods. The reduction in estrogen can cause unwanted symptoms before periods stop (perimenopausal), during menopause and after menopause (postmenopausal). Symptoms include mood changes, hot flushes, and night sweats. Sexual complaints such as painful intercourse, lack of interest in sex, and problems related to arousal or orgasm are common after menopause and can affect women's self-esteem, self-confidence, and sexual health.
What is hormone therapy, and how might it help women’s sexual function?
Hormone therapy consists of various hormones or combinations of hormones that can help reduce menopausal symptoms. It can be given as skin patches, sprays or gels, tablets, or implants, and is used to treat a wide range of perimenopausal and postmenopausal symptoms. Hormone therapy might improve symptoms affecting sexual function such as dryness, itching, and painful intercourse by increasing lubrication, blood flow, and sensation in vaginal tissues.
What did we want to find out?
We wanted to find out if hormone therapy improves women's sexual functioning and whether effects are different in different stages of menopause. We were also interested in which types of hormone therapy were most effective: estrogen alone, estrogen combined with other hormones, or synthetic (manufactured) steroids or hormones.
What did we do?
We searched for studies that looked at the different types of hormone therapy compared to placebo (a dummy drug) or no treatment and its effect on sexual function in perimenopausal or postmenopausal women. We searched for studies that used estrogen alone; estrogen in combination with progestogens; synthetic steroids, (such as tibolone); selective estrogen receptor modulators (SERMs, that affect how estrogen works by blocking or activating different parts of the body, such as raloxifene or bazedoxifene); and selective estrogen receptor modulators combined with estrogen.
We were most interested in the effect of hormone therapy on the global sexual function score, which measures the effect of hormone therapy on all the areas of sexual function combined: desire, arousal, lubrication, orgasm, satisfaction and pain. We also wanted to know the effect of hormone therapy on the individual areas that make up the global sexual function score. Scores had to be evaluated using a recognised and validated questionnaire.
We divided women by length of time since their last period:
• within 5 years of their last period with or without menopausal symptoms; and
• more than 5 years since their last menstrual period, regardless of menopausal symptoms.
We compared and summarized the results of the studies and assessed our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 36 studies including 23,299 women. All but one study involved women after menopause; the other included women during menopause. Some but not all women had bothersome symptoms such as hot flushes, night sweats, and vaginal dryness.
• For women within 5 years of their last period, treatment with estrogen alone probably slightly improves sexual function based on the sexual function composite score compared to placebo.
• For women whose last period was more than 5 years earlier, estrogen alone probably makes little or no difference to sexual function based on sexual function scores compared to a placebo.
• For both groups of women, we are unsure of the effect of estrogen plus progestogens, synthetic steroids, selective estrogen receptor modulators alone, or selective estrogen receptor modulators plus estrogen on sexual function compared to placebo or no treatment.
What are the limitations of the evidence?
Our confidence in the evidence is moderate to very low due to variation in the results. This was probably because studies used different drugs and doses, and different questionnaires for assessment.
How up-to-date is the evidence?
The evidence is current to December 2022.
Hormone therapy treatment with estrogen alone probably slightly improves the sexual function composite score in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), and in unselected postmenopausal women, especially in the lubrication, pain, and satisfaction domains. We are uncertain whether estrogen combined with progestogens improves the sexual function composite score in unselected postmenopausal women. Evidence regarding other hormone therapies (synthetic steroids and SERMs) is of very low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest the beneficial effects of synthetic steroids (for example tibolone) or SERMs alone or combined with estrogen on sexual function. More studies that evaluate the effect of estrogen combined with progestogens, synthetic steroids, SERMs, and SERMs combined with estrogen would improve the quality of the evidence for the effect of these treatments on sexual function in perimenopausal and postmenopausal women.
The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in 2013.
We aimed to assess the effect of hormone therapy on sexual function in perimenopausal and postmenopausal women.
On 19 December 2022 we searched the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Science, two trials registries, and OpenGrey, together with reference checking and contact with experts in the field for any additional studies.
We included randomized controlled trials that compared hormone therapy to either placebo or no intervention (control) using any validated assessment tool to evaluate sexual function. We considered hormone therapy: estrogen alone; estrogen in combination with progestogens; synthetic steroids, for example, tibolone; selective estrogen receptor modulators (SERMs), for example, raloxifene, bazedoxifene; and SERMs in combination with estrogen.
We used standard methodological procedures recommended by Cochrane. We analyzed data using mean differences (MDs) and standardized mean differences (SMDs). The primary outcome was the sexual function score. Secondary outcomes were the domains of sexual response: desire; arousal; lubrication; orgasm; satisfaction; and pain. We assessed the certainty of the evidence using the GRADE approach.
We included 36 studies (23,299 women; 12,225 intervention group; 11,074 control group), of which 35 evaluated postmenopausal women; only one study evaluated perimenopausal women. The 'symptomatic or early postmenopausal women' subgroup included 10 studies, which included women experiencing menopausal symptoms (symptoms such as hot flushes, night sweats, sleep disturbance, vaginal atrophy, and dyspareunia) or early postmenopausal women (within five years after menopause). The 'unselected postmenopausal women’ subgroup included 26 studies, which included women regardless of menopausal symptoms and women whose last menstrual period was more than five years earlier. No study included only women with sexual dysfunction and only seven studies evaluated sexual function as a primary outcome. We deemed 20 studies at high risk of bias, two studies at low risk, and the other 14 studies at unclear risk of bias. Nineteen studies received commercial funding.
Estrogen alone versus control probably slightly improves the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.50, 95% confidence interval (CI) (0.04 to 0.96; I² = 88%; 3 studies, 699 women; moderate-quality evidence), and probably makes little or no difference to the sexual function composite score in unselected postmenopausal women (SMD 0.64, 95% CI −0.12 to 1.41; I² = 94%; 6 studies, 608 women; moderate-quality evidence). The pooled result suggests that estrogen alone versus placebo or no intervention probably slightly improves sexual function composite score (SMD 0.60, 95% CI 0.16 to 1.04; I² = 92%; 9 studies, 1307 women, moderate-quality evidence).
We are uncertain of the effect of estrogen combined with progestogens versus placebo or no intervention on the sexual function composite score in unselected postmenopausal women (MD 0.08 95% CI −1.52 to 1.68; 1 study, 104 women; very low-quality evidence).
We are uncertain of the effect of synthetic steroids versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 1.32, 95% CI 1.18 to 1.47; 1 study, 883 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 0.46, 95% CI 0.07 to 0.85; 1 study, 105 women; very low-quality evidence).
We are uncertain of the effect of SERMs versus control on the sexual function composite score in symptomatic or early postmenopausal women (MD −1.00, 95% CI −2.00 to -0.00; 1 study, 215 women; very low-quality evidence) and of their effect in unselected postmenopausal women (MD 2.24, 95% 1.37 to 3.11 2 studies, 1525 women, I² = 1%, low-quality evidence).
We are uncertain of the effect of SERMs combined with estrogen versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.22, 95% CI 0.00 to 0.43; 1 study, 542 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 2.79, 95% CI 2.41 to 3.18; 1 study, 272 women; very low-quality evidence).
The observed heterogeneity in many analyses may be caused by variations in the interventions and doses used, and by different tools used for assessment.