The Effect of Circadian-Aligned Melatonin Supplementation on Pain and Hormonal Fluctuations in Women with Luteal Phase Dysfunction

Background & Objective: Luteal Phase Dysfunction (LPD) is characterized by inadequate progesterone secretion or action, often leading to infertility, early pregnancy loss, and cyclical symptoms. Melatonin, a circadian regulator with antioxidant properties, may enhance corpus luteum function when administered in a timing-specific manner. The present study was conducted with aim to evaluate the effect of circadian-aligned melatonin supplementation on luteal progesterone levels, ovulatory outcomes, pain, and symptom burden in women with LPD.Materials & Methods: This randomized, double-blind, placebo-controlled trial was conducted on ۱۰۰ women aged ۲۲-۳۵ years with confirmed LPD who were allocated to receive either melatonin (۳ mg) or placebo daily at ۹:۰۰ PM from cycle day ۱۴-۲۵ for three cycles. Primary outcomes included mid- (day ۲۱) and late-luteal (day ۲۴) serum progesterone concentrations; secondary outcomes comprised ovulation confirmation, pain (Visual Analogue Scale, VAS), and symptom burden (Daily Record of Severity of Problems, DRSP).Results: Baseline demographic and cycle characteristics were comparable between the two groups. By cycle ۳, the melatonin group demonstrated significantly higher day ۲۱ progesterone (median ۹.۸۵ ng/mL [IQR ۹.۶۶-۱۳.۴۰] vs. ۸.۷۸ [۶.۷۳–۹.۸۱], P<۰.۰۰۰۱) and day ۲۴ progesterone (mean±SD ۱۱.۱۵±۳.۴۷ ng/mL vs. ۹.۰۵±۳.۱۴ ng/mL, P=۰.۰۰۲۱). A greater proportion exceeded the ≥۱۰ ng/mL threshold on day ۲۱ (۳۲.۰% vs. ۱۰.۰%, P=۰.۰۱۴۱). DRSP luteal mean scores were significantly lower with melatonin (۴۵.۱۴±۱۴.۸۴ vs. ۵۲.۱۶±۱۰.۱۷, P=۰.۰۰۷۱), indicating reduced symptom burden. No significant between-group differences were found in VAS pain scores or ≥۳۰% pain reduction rates. Ovulation confirmation rates were similar in the two groups.Conclusion: Circadian-aligned melatonin supplementation significantly improved luteal progesterone profiles and reduced overall luteal-phase symptom severity in women with LPD, without a statistically significant effect on mean pain scores. These findings support melatonin’s potential as a low-risk, non-hormonal adjunct targeting both endocrine and symptomatic dimensions of LPD, meriting further investigation in fertility-focused trials.

کلیدواژه ها:

Melatonin ، LPD&lrm ، ، Progesterone ، Infertility ، DRSP