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Several theories have been hypothesized regarding the mechanisms by which smoking lowers testosterone levels owing to Leydig cell dysfunction by various mechanisms such as chronic hypoxia, smoke-induced oxidative stress (ROS), neuroendocrinal effect of nicotine on hypothalamo-pituitary-gonadal axis, direct cytotoxic effect on Leydig cells either causing downregulation of key enzymes of steroidogenesis (NR5A1, CYP11A1, and 3b-HSD1) or by inducing apoptosis (by increase in Bax (proapoptotic protein) and caspase-3 expression, and a decrease in Bcl-2 (an antiapoptotic protein) expression[]