A Randomized Double-Blind Placebo-Controlled Trial of a Botanical Formulation for Symptom Management in Male...

Background/Objectives: Male climacteric syndrome (MCS) affects quality of life through psychological, somatic, sexual, and endocrine-related symptoms. This study evaluated whether a botanical formulation containing Elaeagnus multiflora fruit and Cynanchum wilfordii extracts (EMF_CWW) improved MCS-related symptoms compared with placebo. Methods: We conducted a 12-week, randomized, double-blind, placebo-controlled trial (Clinical Research Information Service registration: KCT0010695) in 70 men aged 45-75 years with MCS. Participants received EMF_CWW (1500 mg/day) or placebo. The primary outcome was the change in Aging Males' Symptoms (AMS) total score from baseline to Week 12. Secondary outcomes included AMS subdomains, Androgen Deficiency in Aging Males (ADAM) positivity, hormonal parameters, lipid profile, and safety. Efficacy analyses were conducted in the per-protocol population (n = 64), and safety analyses were conducted in the safety population (n = 70). Results: EMF_CWW did not demonstrate superiority over placebo for the primary outcome. AMS total score decreased in both groups (treatment: -14.2 ± 12.5; placebo: -15.5 ± 12.3), with no significant between-group difference (p = 0.6726). AMS subdomains and ADAM positivity also improved in both groups without significant between-group differences. Free testosterone increased non-significantly in the treatment group (+0.8 ± 2.4 pg/mL; p = 0.0727) and significantly in the placebo group (+1.3 ± 2.6 pg/mL; p = 0.0076), with no between-group difference (p = 0.8720). No treatment-related serious adverse events were observed. Conclusions: EMF_CWW did not demonstrate efficacy superior to placebo for improving MCS-related symptoms or hormonal outcomes. The improvements observed in both groups highlight placebo responsiveness, regression to the mean, and symptom variability in MCS trials. No apparent short-term safety signal was observed; however, long-term safety cannot be concluded. Larger trials with standardized repeated morning testosterone measurements are required.