Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats

Many obese patients are exposed to hypolipidemic and serotonin‐norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin‐treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co‐exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs. Obese patients can be exposed to rosuvastatin and sibutramine, which have adverse effects on rat reproduction. This study investigated the effects of combined exposure to rosuvastatin and sibutramine on the adult male rat reproductive tract. Sibutramine alone or combined with rosuvastatin affected sperm quality and reserves, androgen levels, and reproductive organ weights. Rosuvastatin reduced ejaculation frequency and, when administered alone or combined with sibutramine, impaired epididymal morphology. Sexual behavior and fertility were altered after co‐exposure, suggesting a small synergistic effect.