Probiotics ameliorates hypothalamic amenorrhea in a rat model of PCOS

Polycystic ovary syndrome (PCOS) is a common endocrinometabolic disorder affecting women of reproductive age, characterized by hormonal imbalances, irregular menstrual cycles, and often, infertility. Hypothalamic amenorrhea, a condition marked by the cessation of menstruation due to disruptions in the hypothalamic-pituitary-gonadal axis, is a frequent manifestation in PCOS. Probiotics, beneficial microorganisms known for improving metabolic health, have shown promise in restoring hormonal balance and enhancing fertility. In this study, we hypothesize that probiotics would ameliorate hypothalamic amenorrhea by modulating hypothalamic kisspeptin and reducing inflammation in a rat model of PCOS.

Eight (8)-week-old female Wistar rats were grouped into four with n = 5. Letrozole administration (1 mg/kg, p.o.) for 21 days induced PCOS, thereafter the animals were treated with probiotics (3 × 10⁹ CFU, p.o.), while control animals received distilled water. The treatment lasted for six weeks.

Reduced insulin sensitivity, hyperinsulinemia, ovarian dysfunction with evidence of disrupted steroid hormone levels (testosterone/17β-Estradiol) and cystic follicles as well as hypothalamic lipid accumulation, elevated inflammatory markers (NF-kB/TNF-α) and antioxidant depletion (GSH/NrF2), which are accompanied by decreased level of kisspeptin. Nonetheless, administration of probiotics reversed these pathological alterations by enhancement of hypothalamic kisspeptin and suppression of inflammatory response.

Altogether, the present results demonstrate that probiotics significantly ameliorated hypothalamic amenorrhea by mitigating hypothalamic lipid accumulation, suppressed inflammation, and replenished antioxidants. Crucially, probiotics enhanced hypothalamic kisspeptin levels, a key regulator of reproductive function, highlighting their potential as a therapeutic strategy for restoring ovarian function in PCOS.