Impact of Morphine on Female Rat Reproductive Function and Its Pharmacological Modulation

Abstract

In recent years, the number of patients seeking medical care with reproductive dysfunction resulting from previous long-term use of opiate narcotic analgesics (ONA) has increased significantly. Chronic exposure to opioid receptor agonists leads to profound disruptions in the neuroendocrine regulation of the reproductive system, causing hypogonadotropic hypogonadism and structural disorganization of the ovaries. The aim of this experimental study was to evaluate the nature of reproductive function impairment in female rats following long-term morphine administration and to provide a pathogenetic rationale for pharmacological correction strategies. The experiment was conducted on adult female Wistar rats with regular estrous cycles, which received morphine hydrochloride according to an escalating-dose regimen. To correct the resulting disturbances, the opioid antagonist naltrexone was administered concurrently, alongside a combination of agents with antioxidant and neuroprotective properties. The methodology included daily cytological analysis of vaginal smears to monitor the estrous cycle stage, radioimmunoassay of serum gonadotropins (FSH, LH) and sex hormones (estradiol, progesterone), histological examination of ovarian and uterine tissues with morphometric assessment of the follicular reserve, and evaluation of oxidative stress in ovarian tissue. The study revealed that chronic morphine intoxication leads to persistent disruption of cyclic activity—progressing to complete anestrus—as well as suppression of LH and estradiol secretion, atresia of mature follicles, and a reduction in the number of corpora lutea. Morphological analysis documented atrophic changes in the endometrium and a decrease in ovarian mass. Administration of pharmacological modulators facilitated the partial restoration of pulsatile gonadotropin secretion, normalization of the estrous cycle, and preservation of the follicular reserve. In conclusion, it is determined that the toxic effect of morphine is mediated both by central suppression of the hypothalamic-pituitary axis and by direct peripheral mechanisms of ovarian dysfunction. These findings support the rationale for using combination therapy to restore fertility in cases of opioid dependence.