Could melatonin help with hot flushes in prostate cancer patients on ADT?

A randomized, double-blind, placebo-controlled trial from Iran reports a significant reduction in frequency of mild hot flushes with use of melatonin in patients with prostate cancer (PC) undergoing androgen deprivation therapy (ADT).

ADT, a cornerstone of advanced PC management, acts through suppressing circulating testosterone levels with the aim of reducing proliferation and hampering survival of PC cells. While effective at slowing tumour progression, ADT disrupts the hypothalamic–pituitary–gonadal axis, leading to hypogonadism and a range of side effects, including hot flushes, reduced libido, erectile dysfunction, and gynaecomastia. [World J Mens Health 2021;39:429-443]

Earlier researched demonstrated that melatonin supplementation significantly improved sleep quality in men receiving ADT. Although the primary focus of that study was on mood and sleep disturbances, these improvements may have been mediated through the alleviation of vasomotor symptoms such as night sweats and hot flushes. [Iran J Pharm Res 2022;21:e128817]

“Our study aimed to determine whether melatonin could improve vasomotor symptoms and sexual health outcomes, thereby enhancing overall quality of life in men receiving ADT,” wrote the researchers from Isfahan University of Medical Sciences in Iran. [Asian Pac J Cancer Prev 2026;27:453-462]

The study included 41 men with advanced metastatic or nonmetastatic PC who self-reported sexual dysfunction or were experiencing ≥4 episodes of hot flushes per week during the past month while receiving ADT. In the intervention group, 19 men (mean age, 71 years) received melatonin 3 mg BID for 4 weeks, while the placebo group consisted of 22 men (men age, 68 years) receiving matched placebo. All participants completed an initial assessment using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and International Index of Erectile Function (IIEF) questionnaires, which showed no statistically significant differences at baseline between the two groups.

Post-intervention results indicated an increase in average FACT-P scores for both groups, with a statistically significant difference (p=0.01) noted only in the intervention group. The average IIEF scores increased slightly in both the intervention and placebo groups following the 4-week intervention. However, these changes were not statistically significant for either group, indicating that the intervention did not lead to meaningful improvements in erectile function.

Repeated-measures analysis of variance revealed a statistically significant reduction in the mean total frequency of hot flushes in the melatonin group over the 4-week follow-up period (p=0.00). This reduction was particularly prominent among patients reporting mild episodes of hot flushes, with significant within-group improvements across the first 3 weeks. In contrast, there were no statistically significant changes in the frequency of moderate hot flushes in either group. Notably, while the intervention group demonstrated a consistent downward trend in total and mild hot flush episodes, this frequency increased slightly in the placebo group over time.

“Independent t-test analyses further confirmed significant differences between the intervention and placebo groups at each weekly time point, favouring melatonin [p<0.05]. Moreover, patients receiving melatonin were more likely to experience a reduction or stabilization in hot flush frequency vs baseline, indicating a higher likelihood of therapeutic response relative to placebo,” reported the researchers.

Administration of melatonin at a daily dose of 6 mg over a 4-week period was not associated with any clinically significant adverse events or treatment discontinuation. Nonetheless, three cases of excessive daytime sleepiness were reported in the intervention group. However, this finding did not reach statistical significance when compared with placebo group.