Premature ovarian insufficiency (POI) is a complex endocrine disorder characterized by the loss of ovarian function before the age of 40, leading to hypoestrogenism, infertility, and various metabolic complications. Recent studies have suggested that the gut microbiota, particularly the estrobolome—the collection of microbial genes involved in estrogen metabolism—plays a crucial role in maintaining hormonal balance. This study aimed to assess the relationship between the activity of the gut microbiota estrobolome and estrogen metabolites in women with POI.

A total of 60 women aged 25–39 years participated in this cross-sectional study, including 30 women with POI and 30 age-matched healthy controls. Fecal β-glucuronidase activity and microbial composition were analyzed using quantitative PCR and spectrophotometric assays, while estrogen metabolites were measured by HPLC–MS/MS.

Results revealed significantly lower β-glucuronidase activity and reduced abundance of Clostridium and Escherichia species in women with POI compared to controls (p < 0.001). Estrogen metabolite levels, including estradiol, estrone, and estriol, were also markedly decreased in the POI group. A strong positive correlation was found between β-glucuronidase activity and serum estradiol levels (r = 0.71, p < 0.001).

These findings indicate that reduced estrobolome activity may contribute to estrogen deficiency in POI, suggesting a potential role of the gut–ovarian axis in disease pathogenesis. Modulating the intestinal microbiota through dietary or probiotic interventions could represent a novel therapeutic strategy for restoring hormonal balance in affected women.

Premature ovarian insufficiency; Gut microbiota; Estrobolome; β-glucuronidase; Estrogen metabolism; Hormonal imbalance; Reproductive endocrinology.

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