Picralima nitida is traditionally used in African medicine as an aphrodisiac and contraceptive agent. Previous investigations demonstrated acute enhancement of sexual behavior but chronic suppression of fertility. However, the endocrine and molecular mechanisms underlying these biphasic reproductive effects remain unclear. This study aimed to evaluate hormonal modulation, oxidative stress parameters, apoptotic markers, and receptor expression profiles following acute and chronic administration of ethanolic seed extract of P. nitida in rodents. Male and female rodents were treated with graded doses (30–300 mg/kg) for acute (1 day) and chronic (14–28 days) durations. Serum reproductive hormones were quantified using ELISA. Testicular and ovarian tissues were analyzed for oxidative stress markers, apoptosis-related proteins, and androgen/estrogen receptor expression. Acute administration significantly elevated testosterone levels and enhanced sexual orientation behaviors. Chronic exposure reduced testosterone, increased estradiol levels, decreased sperm count, prolonged estrous cycle, and induced seminiferous degeneration. Increased malondialdehyde and caspase-3 expression suggested oxidative stress-mediated apoptosis. These findings indicate that P. nitida exerts biphasic endocrine modulation via hypothalamic–pituitary–gonadal axis interference. The extract may have potential as a reversible herbal contraceptive but requires careful dosing consideration.
