Oral L-ergothioneine supplementation in women with suboptimal ovarian reserve: a single-center, open-label, self-controlled pilot study of ovarian reserve markers, endocrine profiles, and reproductive aging-related symptoms

PURPOSE: To evaluate the efficacy and safety of oral L-ergothioneine (EGT) in improving ovarian reserve and clinical symptoms in women with suboptimal ovarian function. As a proof-of-concept study, we explored correlations between hormonal shifts and symptom amelioration. METHODS: This single-center, open-label trial enrolled 40 women (aged 35-45 years) experiencing age-related reproductive decline (baseline AMH: 1.0-3.0 ng/mL) and menstrual disorders. Participants received oral EGT (120 mg/day) for three consecutive menstrual cycles. The primary outcome was the change in serum AMH. Secondary outcomes included sex hormones (FSH, E2), antral follicle count, and validated questionnaires (KI, PSQI, SF-36) and an exploratory Menstrual Symptom Score. RESULTS: Thirty-six participants completed the intervention without product-related adverse events. EGT supplementation was associated with increases in core ovarian markers: mean AMH increased from 1.81 ± 0.72 to 2.46 ± 1.54 ng/mL (mean change + 0.65 ng/mL, 95% CI [0.14, 1.17], p = 0.018). Concurrently, basal FSH decreased (8.38 ± 2.83 to 7.05 ± 2.51 mIU/mL, mean change - 1.33, 95% CI [- 2.50, - 0.17]; p = 0.032, FDR-adjusted p = 0.048) and E2 increased (43.78 ± 18.87 to 63.46 ± 50.81 pg/mL; mean change + 19.69, 95% CI [3.99, 35.38]; p = 0.019, FDR-adjusted p = 0.048). Clinical assessments showed progressive reductions in KI (5.42 ± 3.66 to 1.90 ± 2.16, p < 0.0001) and PSQI scores (6.89 ± 1.82 to 5.50 ± 1.40, p < 0.0001), alongside improved menstrual and SF-36 scores (p < 0.001). Subgroup analysis stratified by baseline ovarian reserve showed a significant AMH increase in the low-reserve subgroup (p = 0.017) but not the high-reserve subgroup. Exploratory correlation analysis showed that ΔFSH was associated with improvements in sleep quality (ΔPSQI, r = 0.43, p < 0.05) and E2 increases (r = -0.46, p < 0.05), linking hormonal stabilization directly to systemic relief. CONCLUSION: In this open-label, single-arm pilot study, oral EGT supplementation was associated with increases in serum AMH and favorable shifts in the basal FSH/E2 profile, alongside improvements in reproductive aging-related and sleep symptoms. Because the design lacks a control group, these changes cannot be attributed to EGT alone and may partly reflect natural variation, regression to the mean, or placebo effects. These hypothesis-generating findings warrant confirmation in adequately powered, placebo-controlled trials. TRIAL REGISTRATION: ChiCTR2500104484; Prospectively registered on 2025-06-18.