Odetayo_2025_Psychopharmacology.(Berl)__

INTRODUCTION: Tamoxifen (TAM) is an off-label treatment option for men with breast cancer, infertility, and gynecomastia. Unfortunately, one of the undesirable effects of TAM is sexual dysfunction. Therefore, this study was designed to investigate the possible associated mechanisms with TAM-induced sexual dysfunction and the possible ameliorative effect of omega-3 fatty acids (O3FA). METHODOLOGY: Animals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days. RESULTS: TAM exposure impaired sperm qualities (count, motility, viability, and normal morphology) and led to a decline in serum testosterone and an increase in luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol. Furthermore, TAM led to an increase in mount, intromission, and ejaculation latencies and a decrease in their corresponding frequencies. It also led to a decrease in motivation to mate and an increase in post-ejaculatory interval. These events were associated with impaired pregnancy outcomes, hormonal imbalance, a decrease in nitric oxide/cyclic cyclic guanosine monophosphate and dopamine and an increase in acetylcholine esterase and serotonin activities. These observed TAM-induced sexual dysfunction markers were ameliorated in animals that received O3FA and TAM co-treatment. CONCLUSIONS: O3FA ameliorates TAM-induced sexual dysfunction.