Drugs for the treatment of menopausal symptoms. Original paper

What was reviewed?

This review article comprehensively evaluates the current pharmacological treatments for menopausal symptoms, focusing on hormone replacement therapy (HRT), non-hormonal options, and emerging therapies. It addresses the efficacy, safety, and mechanisms of various estrogen, progestogen, androgen, selective estrogen receptor modulators (SERMs), and alternative compounds used to manage vasomotor symptoms, urogenital atrophy, bone loss, mood disorders, and sexual dysfunction in perimenopausal and postmenopausal women.

Who was reviewed?

The review synthesizes evidence from randomized controlled trials, observational studies, and meta-analyses involving diverse populations of menopausal women across clinical settings globally. It includes women experiencing a spectrum of menopausal symptoms such as hot flushes, night sweats, sleep disturbance, mood changes, urogenital atrophy, and metabolic complications. The review integrates findings on standard populations as well as subgroups with comorbidities affecting treatment decisions and outcomes.

Most important findings

The review confirms that estrogen therapy remains the most effective treatment for vasomotor and urogenital symptoms associated with menopause. It emphasizes the differential pharmacokinetics and safety profiles of oral versus transdermal estrogen, highlighting that non-oral routes tend to have fewer thromboembolic risks and more physiological hormone metabolism. Progestogens are necessary alongside estrogen in women with an intact uterus to prevent endometrial hyperplasia, though choice of progestogen influences side effects and tolerability. Non-hormonal agents such as gabapentin, clonidine, and selective serotonin reuptake inhibitors (SSRIs) provide moderate relief for vasomotor symptoms, especially in women who cannot undergo HRT. Phytoestrogens and black cohosh lack consistent evidence for efficacy, and safety concerns remain, particularly hepatotoxicity with black cohosh. Newer therapies include tibolone, a synthetic steroid with tissue-selective effects, showing benefit for sexual function and bone health but with some cardiovascular risks in older women.

The review also touches on androgen therapy, particularly testosterone, which shows promise in treating hypoactive sexual desire disorder in surgically menopausal women, though concerns regarding breast cancer risk and cardiovascular effects necessitate cautious use. Emerging selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene offer fracture prevention and reduced breast cancer risk but may worsen vasomotor symptoms.

Key implications

Clinicians should tailor menopausal symptom management based on individual risk profiles, symptom severity, and patient preferences. Estrogen therapy remains first-line for significant symptoms but must be balanced against risks of thromboembolism and cancer, emphasizing the benefits of transdermal over oral routes when feasible. Non-hormonal alternatives offer options for those contraindicated for HRT but generally provide less symptom relief. The heterogeneity of menopause symptoms and comorbidities calls for personalized approaches, including consideration of novel SERMs and androgens. Further research into the interaction between menopausal therapies and the microbiome may enhance understanding of systemic effects and optimize treatment strategies. Safety monitoring, especially for long-term hormone use, remains paramount.