Modified gengnianchun formula outperforms androgens in treating chronic stress-induced diminished ovarian reserve

Background and objectives

Chronic stress-induced hypercortisolism causes diminished ovarian reserve (DOR), contributing to infertility and miscarriage. Androgen supplementation is an emerging therapeutic approach for DOR. The traditional Chinese herbal decoction modified Gengnianchun formula (MGNC) has shown clinical efficacy in treating DOR. This study aimed to compare the effectiveness of MGNC with that of androgens in a stress-induced DOR mouse model.

Methods

Sexually mature female C57 mice aged six weeks were randomly assigned to six groups (n = 10 per group, with 3 independent replicates per group), including the control, model, low-dose testosterone (LT), medium-dose testosterone (MT), high-dose testosterone (HT), and MGNC groups. This sample size and study design were determined based on preliminary experimental data. Chronic stress was induced in mice, except for the control group, by daily glucocorticoid injection, and the mice in the LT, MT, HT, and MGNC groups were treated at the same time with testosterone (low, medium, or high dose) or MGNC for six weeks. Body weight, estrous cycles, ovarian follicle counts, hormone profiles, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and testosterone, and in vitro preantral follicle growth rates (via MGNC-enriched or androgen-treated serum) were assessed.

Results

All groups presented stable body weights. MGNC ameliorated estrous cycle irregularities caused by stress, while testosterone exacerbated the abnormality. Moreover, MGNC outperformed LT in improving primordial/primary/antral follicle counts and corpus luteum formation, while MT and HT did not improve ovarian follicle reserve. LT was associated with the highest serum estradiol level, but none of the testosterone doses reduced FSH levels or the FSH/LH ratio, whereas MGNC lowered FSH and the FSH/LH ratio. Additionally, MGNC-enriched serum significantly enhanced the in vitro follicular growth rate in corticosterone-supplemented culture medium, and this effect was superior to that observed with testosterone-pretreated serum.

Conclusions

Our findings demonstrate that MGNC and appropriately dosed androgens (LT) ameliorate CORTN-mediated chronic stress–induced DOR phenotypes; however, androgen effects were strongly dose-dependent, with MT and HT exacerbating abnormalities. In contrast, MGNC showed consistent efficacy across all outcomes and outperformed all androgen regimens, underscoring its translational potential for DOR treatment, particularly in patients with contraindications to hormone therapy. Nevertheless, the underlying molecular mechanism of MGNC and clinical efficacy validation through randomized clinical trials require further study.

Full text:

https://www.xiahepublishing.com/2835-6357/FIM-2025-00047

The study was recently published in the Future Integrative Medicine.

Future Integrative Medicine (FIM) is the official scientific journal of the Capital Medical University. It is a prominent new journal that promotes future innovation in medicine.It publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.

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