Table 1.

Effects of each substance/drug on testosterone levels and sperm production, and main evidences of the pathophysiological mechanisms.↑: increase in testosterone/sperm concentration; ↓: decrease in testosterone/sperm concentration; ↔: no effects on testosterone/sperm concentration; FSH: follicle-stimulating hormone; GABA: gamma-aminobutyric acid; GnRH: gonadotropin-releasing hormone, LH: luteinizing hormone; ROS: reactive oxygen species; StAR: steroidogenic acute regulatory protein

Substance	Effect on Testosterone	Hypothesized Mechanisms	Effect on Sperm Concentration	Hypothesized Mechanisms
Alcohol	↓	Suppression of β-LH gene expression [14] Prolactin increase after acute ingestion [9] Inhibition of 3β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase [9] Suppressed expression of StAR via ROS [10] Induction of the enzyme aromatase [11]	↓	Induction of apoptosis [10] Pro-oxidant effect [29]
Cigarette smoking	↑	Enhanced GnRH or LH release [38,41] Inhibition of prolactin release [38] Competitive inhibition of testosterone glucuronidation [43]	↓	Induction of apoptosis [52,53] Pro-oxidant effect [56,57,58]
Caffeine	↑	Induction of a stress-like hormonal pattern [64]	↔	Pro-oxidant effect at very high doses [69]
Cannabis	↔	Inhibition of GnRH and LH in animal models [81,83] Reduced expression of LH receptor on testis in animal models [86] Reduced activity of testicular 3β-hydroxysteroid dehydrogenase in animal models [86]	↓	Induction of apoptosis [71]
Cocaine	↔	Panhypopituitarism for pituitary infarction or inflammation (case reports) [96,97]	↓	Testicular vasoconstriction and ischemia [99] Induction of apoptosis [102] Pro-oxidant effect (reperfusion injury) [103]
Amphetamines	↓	Decreased expression of GnRH mRNA [112] Activation of adenylate cyclase [106] Inhibition of 3b-hydroxysteroid dehydrogenase, P450c17, and 17-ketosteroid reductase [107] Reduced Ca2+ influx [107] Increased testicular GABA concentration [111]	↓	Induction of apoptosis [114,115,116] Pro-oxidant effect [110] Testicular thermic damage [119] Increased testicular serotonin concentration [115] Increased testicular GABA concentration [111] Reduced testicular expression of progesterone and estrogen receptors [116]
Opioids	↓	Inhibition of GnRH secretion [120,134] Hyperprolactinemia [120]	↓	Induction of apoptosis [128,140] Pro-oxidant effect [128,129,130,131,132,133,134,135,136,137,138,139,140]
Anabolic-androgenic steroids (AAS)	↓	Inhibition of GnRH secretion [143] Inhibition of LH and FSH secretion [145] Depletion of Leydig cells [149]	↓	Reduction of intra-testicular testosterone levels [150,151] Induction of apoptosis [151]