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

Background 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 3, the melatonin group demonstrated significantly higher day 21 progesterone (median 9.85 ng/mL IQR 9.66-13.40 vs. 8.78 6.73–9.81, P<0.0001) and day 24 progesterone (mean±SD 11.15±3.47 ng/mL vs. 9.05±3.14 ng/mL, P=0.0021). A greater proportion exceeded the ≥10 ng/mL threshold on day 21 (32.0% vs. 10.0%, P=0.0141). DRSP luteal mean scores were significantly lower with melatonin (45.14±14.84 vs. 52.16±10.17, P=0.0071), indicating reduced symptom burden. No significant between-group differences were found in VAS pain scores or ≥30% 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.