Paroxetine versus placebo for the management of vasomotor symptoms in surgical menopause: A pilot double-blind randomized clinical trial.

OBJECTIVE

To evaluate the efficacy and safety of low-dose paroxetine (20 mg/day) compared with placebo for managing vasomotor symptoms (VMS) in women with surgical menopause.

METHODS

This was a pilot randomized, double-blind, placebo-controlled trial conducted at the Instituto Hondureño de Seguridad Social (IHSS), Tegucigalpa, Honduras, from January 30 to July 31, 2025. Women aged <48 years, within 6 months of total hysterectomy with bilateral salpingo-oophorectomy, and experiencing moderate-to-severe VMS (≥ 7 episodes/week) were eligible. Participants were randomized 1:1 to receive paroxetine 20 mg/day or matching placebo (folic acid 5 mg) for 12 weeks. The primary outcome was change in total Menopause Rating Scale (MRS) score. Secondary outcomes included quality of life (SF-36) and adverse events. Analysis followed the per-protocol approach, with intention-to-treat sensitivity analysis.

RESULTS

Of 150 women assessed, 90 were randomized. A total of 47 women in the paroxetine group and 43 in the placebo group completed follow-up and were analyzed. At 12 weeks, the paroxetine group showed greater reduction in total MRS score compared with placebo (mean 16.9 ± 7.7 vs. 22.6 ± 6.1; mean difference -5.7, 95% CI -8.6 to -2.8; P < 0.001). SF-36 scores also improved more with paroxetine (91.0 ± 6.4 vs. 86.9 ± 4.8; mean difference 4.1, 95% CI 1.7 to 6.5; P = 0.001). Adverse events (headache, fatigue, drowsiness) were more frequent with paroxetine but mild and transient; no serious events occurred. The dropout rate was 14.4% (13/90), and intention-to-treat analysis showed consistent findings with slightly attenuated effect sizes.

CONCLUSION

In this pilot study, paroxetine 20 mg/day showed promise in reducing VMS and improving quality of life in Honduran women with surgical menopause, with acceptable tolerability. The high attrition rate underscores the need for larger trials to confirm these findings.