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To systematically review and synthesize evidence evaluating the comparative effectiveness of treatments for menopausal symptoms, along with potential long-term benefits and harms of those treatments.
The following electronic databases were searched through January 2014: MEDLINE®, Embase®, Cochrane Controlled Trials Register, and AMED Allied and Complementary Medicine. Gray literature searches included clinicaltrials.gov, the Food and Drug Administration Web site, and relevant conference abstracts.
Menopausal symptom outcomes included: vasomotor, quality of life, psychological, sexual function, urogenital, and sleep disturbance. Randomized controlled trials provided the evidence base for symptom relief. Standardized mean differences were calculated to allow pooling of outcomes from varied measures. Network meta-analyses were performed when possible, along with pairwise comparisons. Systematic reviews, cohort studies, and case-control studies provided evidence for the following long-term benefits and harms: breast, colon, endometrial, and ovarian cancer; coronary heart disease and venous thromboembolic events; gallbladder disease; and osteoporotic fractures.
Evidence from 283 trials provided results for vasomotor symptoms (211 trials), quality of life (125 trials), psychological symptoms (108 trials), sexual function (94 trials), urogenital atrophy (71 trials), and sleep disturbance (56 trials). The most commonly studied agents were estrogens, isoflavones, and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs). Estrogens appeared to be the most effective treatment in relieving vasomotor symptoms and were accompanied by better quality-of-life scores. SSRIs/SNRIs relieve vasomotor symptoms less effectively than estrogens but were accompanied by the largest improvement in global measures of psychological well-being. Estrogens administered vaginally diminished pain during sex and testosterone increased sexual activity. Measures of urogenital atrophy were improved with ospemifene and vaginal or oral estrogens. Estrogens also improved sleep, but the effect appeared to be modest. Over the long term, estrogen combined with progestogen has both beneficial effects (fewer osteoporotic fractures) and harmful effects (increased risk of breast cancer, gallbladder disease, venous thromboembolic events, and stroke). Estrogens given alone do not appear to increase breast cancer risk, although endometrial cancer risk is increased. There is limited evidence on the long-term effects of most nonhormone treatments. No studies were identified that examined the efficacy or safety of compounding practices for hormone therapies.
Women experiencing symptoms of menopause can consider a number of potential treatments of varying efficacy. From a large body of evidence, there is considerable certainty that estrogens are the most effective treatment for relieving vasomotor symptoms and are accompanied by the greatest improvement in quality-of-life measures. For other common symptoms--psychological, urogenital, and sleep disturbance--although estrogens are effective, some nonhormonal agents compare favorably. Estrogens are accompanied by potential long-term harms that require consideration. There is limited evidence on the potential consequences of long-term use of nonhormonal agents when those agents are used to treat menopausal symptoms.