Therapeutic Effects of Marjoram (Origanum majorana L.) Extract and Nano-Formulation on Hormonal Parameters and Ovarian Histology in Letrozole-Induced Polycystic Ovary Syndrome in Rats

Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder characterized by hyperandrogenism, hormonal imbalances, and ovarian dysfunction, affecting approximately 30% of female infertility cases globally. This study evaluated the therapeutic efficacy of marjoram (Origanum majorana L.) aqueous extract and zinc oxide nano-loaded marjoram formulation on letrozole-induced PCOS in female Wistar rats. Fifty rats (150-250 g) were randomly assigned to five groups (n=10): negative control (physiological saline), carboxymethylcellulose (CMC) control, PCOS induction (1 mg/kg letrozole for 58 days), marjoram extract treatment (45 mg/kg for 30 days post-induction), and nano-marjoram treatment (45 mg/kg for 30 days post-induction). Serum hormonal parameters and ovarian histology were assessed. Letrozole induction produced characteristic PCOS features with significant hormonal alterations: 44% FSH decrease (5.78 vs. 10.30 mIU/mL, p<0.05), 46% LH increase (20.07 vs. 13.71 mIU/mL, p<0.05), 43% progesterone decrease (6.87 vs. 12.07 mIU/mL, p<0.05), 32% estradiol decrease (72.91 vs. 106.66 pg/mL, p<0.05), 125% testosterone increase (0.45 vs. 0.20 pg/mL, p<0.05), and 158% inhibin-B increase (378.59 vs. 146.58 pg/mL, p<0.05) compared to controls. Nano-marjoram treatment demonstrated superior therapeutic effects, restoring FSH by 51% (8.73 mIU/mL), reducing LH by 18% (16.44 mIU/mL), increasing progesterone by 36% (9.33 mIU/mL), increasing estradiol by 24% (90.64 pg/mL), reducing testosterone by 42% (0.26 pg/mL), and reducing inhibin-B by 53% (179.35 pg/mL) relative to PCOS group. Histological examination revealed that nano-marjoram treatment significantly improved ovarian architecture, increasing the number of corpora lutea, restoring Graafian follicles, and reducing cystic follicles and inflammatory infiltration compared with the PCOS group. These findings demonstrate that marjoram, particularly in nano-formulation, effectively ameliorates PCOS-associated hormonal dysregulation and ovarian pathology through antioxidant and anti-androgenic mechanisms, suggesting potential clinical applications for PCOS management.