Alcohol, Tobacco, Recreational Drugs and Steroids: Alterations in Testicular Function and Semen Quality

Anabolic Steroids: Since its isolation and characterization in۱۹۳۵, testosterone has been further studied, leading to the synthesisof numerous derivatives with different properties fromthe original molecule. These derivatives are called “anabolicandrogenicsteroids” (AAS), or more commonly, “anabolic steroids”.Initially, these substances were restricted to professionalathletes and bodybuilders, becoming gradually more popularamong recreational and non-professional power athletes. Currentestimates indicate as many as over ۵۰ million AAS usersin the world. Interestingly, two thirds are noncompetitive bodybuilders,or even non-athletes, using these substances with aestheticalor performance purposes only. In addition to it, steroidsmay also be found in “dietary supplements”, which were supposedto be AAS-free. International surveys recently reportedan overall steroid contamination rate of ۱۵-۲۵%, depending onthe country. AAS abuse is, therefore, an issue of major publichealth concern, considering its increasing prevalence. Infertilityis defined as the inability to achieve natural pregnancyafter ۱۲ months of regular unprotected intercourse, with themale partner being solely responsible or in combination withthe female in ۵۰% of all infertile couples. Environmental andlifestyle issues are of increasing concern and specially relatedto male infertility, besides the traditional causes like varicocele,obstructive and non-obstructive azoospermia, infection, genetics,etc. Some reversible some not, being hypogonadotropic hypogonadisma typical example of a known reversible condition,while primary testicular impairment is often related to a lessreversible one. Structural modifications have been introducedinto the testosterone molecule in an attempt to maximize theanabolic effect and minimize the androgenic ones. However, allAASs are virializing if administered for long enough, at highenough dosages. Therefore, they are synthetic derivatives oftestosterone, and not only testosterone itself. The AAS structuralbase is the “steran nucleus”, consisted of three condensedcyclohexan rings in nonlinear junction, and a cyclopentanering. The anabolic effects are dose dependent, and usually occurwhen supra physiological testosterone levels (higher than۱۰۰۰ng/dL) are found, which generally requires weekly dosesof ۳۰۰mg or more. Besides, AAS may also be classified consideringtheir main activity: ۱. “Testosterone-like” effect, verypotent, with great muscle strength gains. They usually show ananabolic/androgenic rate close to ۱:۱, similar to testosteroneitself. The high aromatization rates are also comparable to testosterone’s.They include all testosterone esters, methyltestosteroneand others. ۲. “Dihydrotestosterone-like” (DHT-like) effect,potent but highly androgenic. Since they resemble a ۵DHTmolecule, they basically cannot be aromatized to estrogens. Italso explains the low water and salt retention of drugs of thisgroup. They include stanozolol and oxandrolone. ۳. “Nandrolone-like” effect, the less potent of all, with the highest anabolic/androgenic rate. They have some progesterone-like activity,inhibiting the hypothalamic axis. These are the mostly useddrugs in the clinical setting, when anabolic effects are desired(reversing catabolic states, such as AIDS associated cachexia,severe burns, and chronic obstructive pulmonary disease). Theyinclude the nandrolone esters and trembolone.Crack-cocaine: Cocaine consumption and addiction has becomea global, unresolved, and increasingly legal and healthissue in Western countries, reaching alarming epidemic proportions(Withers et al., ۱۹۹۵). Within its borders, Brazil hasexperienced increased cocaine consumption in an affordableand smokable freebase form that is six-fold more powerful andmore addictive than the cocaine powder, i.e. “crack-cocaine”.The crack-cocaine processing starts by pressing the leaves ofthe Erythroxylun coca together with sulfuric acid (H۲SO۴) toproduce the cocaine powder. The crack-cocaine is produced bydissolving powdered cocaine in a mixture of water and sodiumbicarbonate (NaHCO۳, baking soda), in a ۱:۱ ratio to reducethe costs of cocaine production. The mixture is boiled until asolid substance form. The solid is removed from the liquid,dried, and then broken into the chunks (rocks) that are illegallysold as crack. In ۲۰۱۰, the government of Brazil launchedan integrated plan to combat the trafficking and consumptionof crack-cocaine and other drugs (INCB, ۲۰۱۰). The use ofcrack-cocaine is widespread in large cities, and crack-cocainehas become popular among young adults, particularly teenagers,because of the “advantage”. Demand for crack-cocaineappears to be emerging in South American countries; in ۲۰۰۸,seizures of crack-cocaine were reported in Argentina, Brazil,Chile, Paraguay and Venezuela (INCB, ۲۰۱۰). The human testisis a known target organ for injury resulting from exposureto pharmaceutical and environmental agents. Today there areover ۷ million crack addicts in Brazil alone, being the largestnumber of addicted in the world. This is a public health crisis ofenormous proportions. Risks for other countries are tremendousand actions should be fearless taken to avoid its disseminationparticularly in adolescents and young adults.The known central and peripheral pharmacological effects andsystemic intoxication by intravenously injected cocaine mayhave gender-related differences, with more deleterious effectsin male mammals (in which lower levels are sufficient to causetesticular toxicity. Additionally, there are deleterious effects ontesticular function in rats of different ages, which is serious forperipubertal male rats.Marijuana: Marijuana, the popular name for dried Cannabissativa, is the most consumed drug worldwide. The main compoundand most potent psychoactive agent, delta-۹-tetrahydrocannabinol(THC), acts as a negative competitor to the endogenouscannabinoid anandamide, by interacting with specificreceptors. These receptors are expressed mostly in the centralnervous system (CNR۱) and sperm (CNR۱ and CNR۲) affectingsperm motility and acrosome reaction. In particular for themarijuana study. Background: To examine the effects of Marijuana consumptionon seminal parameters and hormonal levels in men.Materials and Methods: Individuals were evaluated withphysical examination (testicular volume) using an orchidometer,a pachymeter, Doppler-stethoscope, ultrasound byDoppler-color, complete semen analysis. Seminal analysiswas performed according to the WHO’s guidelines and morphologyalso according to the Kruger´s criteria biochemicalmarkers of sperm function and functional tests, including:creatine-kinase (CK), anti-sperm antibodies, reactive oxygenspecies (ROS), DNA fragmentation (SCSA). The study includedmarijuana users (study group) aged ۲۱ to ۵۸ years-old,and pre-vasectomy patients (control group) from both the privatelaboratory Androscience and university-based andrologyevaluation for the controls. Data analysis was performed usingthe Wilcoxon test and a linear model of gamma distributionto extract the age effects on each parameter; p value of <۰.۰۵was adopted.Results: Significant effect of Marijuana was observed in hormonelevels, seminal pH, total sperm count, total progressivemotility and both WHO and Kruger morphology (P<۰.۰۰۱).Conclusion: The consumption of C. sativa has a significantnegative effect on male reproductive health, reflected in a significantdisturbance in some hormone levels and a significantreduction in sperm quality.Alcohol: Alcohol is a psychoactive substance that may createdependence and affects the overall health of man by differentmechanisms, which can be fatal in excessive chronic use. Thepossible association between alcohol consumption and reducedmale fertility has been the subject of several studies and stillremains unclear.Background: To demonstrate the effects of alcohol consumptionin fertile men of reproductive age, evaluating semen parametersand hormonal profile.Materials and Methods: For this study, were included data ofsemen analysis, hormone profile and testicular volume of prevasectomycandidates with no risk factors for sperm/testiculardysfunction from Univesity-based public hospital and from aprivate setting - Androscience, High complex Clinical and ResearchAndrology Laboratories. The study was approved byEthics Committee (۱۲۳۳۱/۱۴). We conducted T-Test for independentsamples and adopted P<۰.۰۵.Results: Subjects who reported not being drinkers constitutedthe control group, mean age of the patients ۳۴.۷ ± ۵.۴۳.Who declared themselves consumers was included in alcoholgroup, mean age ۳۷.۳۵ ± ۶.۵۵. Statistical differences wereseen in following seminal parameters: pH (۷.۶۵ vs. ۷.۹۷;P<۰.۰۷), motility grade A (۸.۵۹ vs. ۴.۶۱%; P<۰.۰۰۳), strictcriteria (۶.۴۶ vs ۴.۱۱%; P<۰.۰۱) and WHO (۲۱.۴۴ vs. ۱۵.۲۲%;P<۰.۰۰۴) normal morphology and total number of round cells(۱۴.۷۵ vs. ۵.۶۶ million; P<۰.۰۰۱). In hormonal parameters,there was an increase of ۱۷-OH progesterone in alcohol consumptions(۱.۰۵ vs. ۱:۵۴ng/mL; P<۰.۰۱۱), as well LH levelsin wine consumption.Conclusion: In view of results, we suggest that alcohol intakeaffects adversely the production of ۱۷-OH progesterone andspermatogenesis, resulting in reduced mobile and morphologicalquality of sperm. Thus, the intake of alcohol appears to beassociated with reduced male reproductive potential and shouldbe advised to be ingested in limited amounts.