L-ergothioneine may improve ovarian reserve markers and symptoms in women with diminished ovarian reserve
Photo by Cht Gsml / Unsplash
Key Takeaway
Interpret preliminary L-ergothioneine findings for DOR with caution due to study design limitations.
In a single-center, open-label, self-controlled clinical trial, 40 women aged 35-45 with diminished ovarian reserve (baseline AMH 1.0-3.0 ng/mL) and menstrual disorders received oral L-ergothioneine 120 mg/day for three consecutive menstrual cycles. The primary comparison was pre- versus post-treatment within the same participants, with 36 women completing the study.
After treatment, serum AMH increased from a mean of 1.79 to 2.47 ng/mL (p=0.029). Basal FSH decreased from 8.22 to 7.05 mIU/mL (p=0.032), and E2 increased from 46.00 to 63.46 pg/mL (p=0.030). Patient-reported outcomes also improved: the modified Kupperman Index (measuring menopausal symptoms) decreased from 5.42 to 1.90 (p<0.0001), and PSQI sleep scores decreased from 6.89 to 5.50 (p<0.0001). Menstrual and SF-36 quality-of-life scores also showed significant improvement (p<0.001). A correlation was observed between the decrease in FSH and improvement in PSQI scores (r=0.43, p<0.05).
The study reported no safety or tolerability data. Key limitations include the small sample size, lack of a parallel control group, and open-label design, which introduces significant potential for bias. The short, three-cycle follow-up period limits understanding of long-term effects. As a preliminary, single-center study, these findings are hypothesis-generating and cannot establish efficacy. Clinical relevance for practice is currently very limited.
View Original Abstract ↓
Purpose: To evaluate the efficacy and safety of oral L-ergothioneine (EGT) in improving ovarian reserve and clinical symptoms in women with diminished ovarian reserve (DOR). As a proof-ofconcept study, we explored correlations between hormonal shifts and symptom amelioration. Methods: This single-center, open-label trial enrolled 40 women (aged 35-45 years) with DOR (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 clinical questionnaires (modified Kupperman Index [KI], PSQI, SF-36, and Menstrual Symptom Score). Results: Thirty-six participants completed the intervention without product-related adverse events. EGT significantly improved core ovarian markers: mean AMH increased from 1.79 {+/-} 0.71 to 2.47 {+/-} 1.52 ng/mL (p = 0.029). Concurrently, basal FSH decreased (8.22 {+/-} 2.93 to 7.05 {+/-} 2.47 mIU/mL, p = 0.032) and E2 increased (46.00 {+/-} 22.70 to 63.46 {+/-} 50.10 pg/mL, p = 0.030). 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 revealed upward AMH trends across both the 35-39 and 40-45 age cohorts. Crucially, endocrine restoration ({Delta}FSH) significantly correlated with improvements in sleep quality ({Delta}PSQI, r = 0.43, p < 0.05) and E2 increases (r = -0.46, p < 0.05), linking hormonal stabilization directly to systemic relief. Conclusion: Oral EGT safely enhances serum AMH and optimizes the FSH/E2 balance in women with DOR, yielding substantial relief from peri-menopausal and sleep disturbances. This pilot proofof- concept study provides the first clinical evidence supporting EGT's systemic benefits in reproductive aging, laying the groundwork for future placebo-controlled trials. Trial Registration: ChiCTR2500104484; Prospectively registered on 2025-06-18. Keywords: L-Ergothioneine, diminished ovarian reserve, anti-Mullerian hormone (AMH), oxidative stress, clinical trial
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