Stanozolol, an anabolic-androgenic steroid, modulates expression of receptors and disrupts uterine histoarchitecture in Mus musculus.

Abuse of Anabolic-Androgenic Steroids (AAS) by professional and recreational athletes for endurance performance and physique is increasing globally, consequently resulting in secondary pathophysiological effects. The present investigation

Aims: to determine the effect of one of the AAS, stanozolol (ST), on uterine physiology and histology. A total of 15 female mice were assigned to three experimental groups (n = 5). ST was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/kg bwt or 1% alcohol-baseline control) for 30 days, and treatment was withdrawn on the 31st day. In this study, we evaluated histomorphometry of the uterus, immunoexpression of the estrogen receptor α (ERα), the androgen receptor (AR), and the prolactin receptor (PRLR), after ST treatment. In addition, we measured serum levels of testosterone (T), estradiol (E 2 ), and prolactin (PRL). Morphometric evaluation of uterus demonstrated aberrant endometrial luminal epithelial proliferation, marked by irregular branching with papillary formations. Prolonged administration of ST resulted in disruption of uterine organization, reflecting its deleterious impact on uterine histoarchitecture. In the high-dose treated group, divergent ERα immunoexpression-characterized by endometrial downregulation and myometrial upregulation-correlated with increased myometrial thickness and subsequent hyperplasia. ST, being a derivative of Dihydrotestosterone (DHT), an anabolic steroid, may exert its androgenic-to-enhanced anabolic efficacy through non-genomic actions in the myometrium, while inducing distinct pathologic changes in the endometrium, suggesting a compartment-specific effect in the murine uterus. Prolonged treatment of ST augmented stromal immunoexpression of AR in the endometrium, suggesting AR-dependent mechanisms in this compartment. Substantial hyperexpression of prolactin receptor (PRLR) in both endometrium and myometrium suggests a potential stimulatory effect of ST on PRLR. High-dose ST administration significantly elevated circulating T and PRL levels while suppressing E 2 concentrations, indicating interference with the hypothalamic-pituitary-gonadal (HPG) axis, reflecting an altered hormonal milieu. It is inferred that prolonged treatment of ST resulted in aberrant endometrial proliferation, histoarchitectural anomalies, compartment-specific differential immunoexpression of hormone receptors in the endometrium and myometrium, and altered serum hormonal milieu.