Public Enemy #1 for Male Fertility: Anabolic SteroidsFor several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3, anabolic-androgenic steroids AAS users have been reported in can anabolic steroids cause permanent infertility United States can anabolic steroids cause permanent infertility an increasing prevalence, making AAS consumption a major public health growing concern. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent tren enanthate cycle length on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened.
Drugs & Male Fertility | Cleveland Clinic
For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes.
Up to date, 3,, anabolic-androgenic steroids AAS users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways.
Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism ASIH , and the more recent experimental reports on structural and genetic sperm damage.
Initially, these substances were restricted to professional bodybuilders, becoming gradually more popular among recreational power athletes. Up to date, 3,, Anabolic-Androgenic Steroids AAS users have been reported in the United States [ 1 , 2 ], and considering its increasing prevalence, AAS consumption has become an issue of major concern.
When combined with a proper diet and an intense training program, anabolic steroids are able to increase strength and muscle mass in some people. They have many side effects which can be permanent or potentially fatal.
Most side effects are mild and reversible like the alteration of the male reproductive system, discussed in this article. The abuse of anabolic steroids, is often associated with transient or persistent alterations of male reproductive function by different routes. Since testosterone isolation and characterization in , many derivatives have been synthetized, which properties differ from those of testosterone. These derivatives are called anabolic-androgenic steroids AAS , or more commonly, anabolic steroids.
Initially, these substances were restrictly used by professional athletes and bodybuilders. Nowadays, non-professional and recreational use become more and more popular. This increasing prevalence of AAS consumption in become a major public health issue in these countries. The authors reported an average consumption of 3. According to Article L of the Code of Sport in France [ 9 ], it is forbidden for any athlete to hold or use, without duly justified medical reason, dopants or restricted products at sporting competitions or events.
Concerning Prohibition of this practice, the World Anti-Doping Code [ 10 ] has proven to be a very powerful and effective tool in the harmonization of anti-doping efforts worldwide, but not enough to fight against this illegal phenomenon. Testosterone is the most important androgen in the human body. Effects of androgens are most evident during puberty, when they induce deep physiological changes in the male body: Testosterone has several possible metabolic fates [ 11 ].
First, it binds to the androgen receptor AR in target tissues to exert its effects. Following a different path, testosterone may be aromatized to estradiol to exert estrogenic effects, typically water retention, breast tissue growth and an increase in body fat deposition.
It includes growth promotion, protein and collagen synthesis and an increase in muscle size and bone metabolism. Androgenism is defined as physiological changes in the male body, including the onset of secondary male characteristics, hair growth pattern, sebaceous gland activity, maturation of sperm and libido. Characteristically, more anabolic steroids present weaker AR bindings, and more androgenic steroids strongly bind the AR, exerting a more potent effect.
Structural changes have been made to the testosterone molecule in order to maximize the anabolic effects and minimize the androgenic ones. However, all AASs are virilizing if administered for long time enough, at high enough dosages [ 13 ]. Traditionally, AASs are classified into two categories according to the route of administration and their carrier solvent [ 2 , 14 , 15 ]:.
Anabolic-androgenic steroids may also be classified according to their main effects as follows [ 2 , 14 , 15 ]:. This may also facilitate the administration of multiple AASs necessary to achieve supraphysiological doses for longer periods, and so minimizing the plateauing effect.
Drugs used by AAS consumers are not confined to anabolic steroids. Some of these accessory drugs are potentially more dangerous than AAS; the unsupervised use of insulin, diuretics, and thyroxin can precipitate a number of medical emergencies [ 17 ].
Accessory Drugs and Dietary Supplements [ 17 ]. Concerning the muscle fiber hypertrophy, a study showed that increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number [ 18 ].
However, the indirect effects should also be considered. These include antiglucocorticoid effects, which are mediated by testosterone occupation of cortisol receptors which have a remarkable affinity with testosterone and create an anti-catabolic effect [ 19 ].
Their incidence is unclear, as the denominator of AAS use is not clear. Erectile dysfunction and libido loss may also occur, especially after discontinuation, when endogenous testosterone levels are usually low [ 13 ]. Hepatic effects are most often related to oral alkylated agents.
They include the uncommon hepatic peliosis, cholestatic jaundice and hepatic neoplasms, such as focal nodular hyperplasia, which are all closely related to dose and duration of usage [ 20 ]. The most severe consequences of long-term AAS use are associated with the cardiovascular system. Hypertension, arrhythmia, erythrocytosis and ventricular dysfunctions have been reported. Mortality risk among chronic users is estimated to be 4.
Cases of renal failure secondary to rhabdomyolysis and diffuse membranoproliferative glomerulonephritis in heavy users have been reported. Aggressive behaviour, depression, mood swings, altered libido, euphoria and even psychosis are some of the psychiatric patterns related to AAS [ 21 ]. Overpharmacy may increase the risk of violent criminality. Withdrawal syndrome and dependency were also described, and the likelihood of psychiatric effects is greater where there is previous psychiatric history, or alcohol or drug abuse [ 22 ].
Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicles, prostate and penis. In addition, androgens are necessary for puberty, male fertility and male sexual function. High levels of intratesticular testosterone secreted by Leydig cells, are required for spermatogenesis. The AR is in all male reproductive organs and can be stimulated either by testosterone or its potential metabolite: Exogenous administration of testosterone synthesis derivatives induces negative feedback on the hypothalamic-pituitary axis and therefore inhibiting the secretion of both FSH and LH.
Infertility after AAS abuse commonly presents as oligozoospermia or azoospermia, associated with abnormalities in sperm motility and morphology [ 25 ]. Experiments in animal models mainly report AAS-induced Leydig cell alterations, but cellular morphology anomalies have also been reported [ 26 ].
Nethertheless, specific end-stage spermatogenesis impairment, with a lack of advanced forms of spermatids, has been described [ 27 ]. After AAS discontinuation, Leydig cells tend to proliferate but remain below the regular counts, even after longer periods [ 28 ]. Apoptosis has been reported to play an important role in the regulation of germ cell populations in the adult testis. Recently, the correlation between apoptosis and high AAS doses and exercises has been experimentally assessed in animal models.
The innovative use of both transmission electron microscopy and fluorescence in situ hybridization FISH has recently been reported in an AAS user sperm sample, searching for genetic and ultrastructural consequences of steroid abuse. Immaturity, necrosis and apoptosis were assessed, and a high percentage of structurally normal spermatozoa were found, which showed the absence of a correlation between AAS and ultrastructural sperm changes.
In contrast to these findings, FISH sperm analysis revealed XY and chromosomes 1 and 9 disomies, suggesting anomalies in the meiotic process and genetic damage among AAS users [ 30 ].
The aim is to avoid the impact of the negative feedback on LH after long term AAS administration, which may lead to a persistent state of hypogonadism and poor sperm quality. In a study of colts, the long-term effects of the anabolic steroid norandrostenololylaurate on sperm characteristics were studied in three experiments [ 31 ]. It was concluded that the adverse effects of corticosteroids on semen characteristics were reversible, at least in the treated groups at the age of 7—25 months.
In another study on sperm parameters, it was concluded that according to the duration of use of anabolic steroids and the period since the last drug administration prior to the survey, the percentages of motile sperm and whose form is normal were significantly reduced among bodybuilders compared to healthy volunteers [ 32 ].
The infertility treatment with testosterone does not improve spermatogenesis; the administered exogenous testosterone and its metabolite, estrogen, suppresses the production of Gonadotropin-releasing hormone GnRH by the hypothalamus and the production of luteinizing hormone LH by the pituitary gland, and therefore the production of testicular testosterone.
According to most reports, the quality of sperm tends to normalize spontaneously within 4—12 months after cessation of anabolic steroid abuse [ 32 ]. However, the negative effect on sperm quality may persist for long periods. Simply stopping the use of ASA may lead to the resumption of fertility in a certain proportion of male users [ 33 , 34 ]. Patients may also be treated by induction of spermatogenesis with gonadotropins or gonadoliberin analogues, including hCG IM injections, human menopausal gonadotropin hMG or even recombinant FSH.
The use of hCG alone or in combination with hMG was reported as an effective treatment for this group of patients [ 35 ]. Stopping the use of large doses of anabolic steroids in the long term can lead to the development of withdrawal symptoms.
Drugs that are targeted to relieve these symptoms include antidepressants, non-steroidal anti-inflammatory and clonidine. Comparisons between patients and control case series are difficult because of the concealing of the practice, but also due to various changes in consumption practices and doses employed [ 37 ]. However, male infertility related to the abuse of AAS is underdiagnosed and yet it is a potentially curable form.
In the absence of spontaneous recovery of spermatogenesis following the cessation of the AAS and after exclusion of other causes of infertility, hormonal therapy should be initiated as a therapeutic alternative [ 25 ].
Anabolic steroids are able to increase strength and muscle mass in some people when combined with a proper diet and an intense training program. All anabolic steroids are also androgenic. Anabolic steroids are marked with numerous side effects, some of which are potentially fatal, and some of which are permanent. However, most side effects are mild and reversible. Education alone is probably not the miracle strategy inciting stopping the abuse of anabolic steroids, but is an essential first step in the fight against this problem.
The common factor in the medical literature available on the misuse of AAS is very heterogeneous. This limits objective comparisons between the different drugs and diets. The AAS abuse can disrupt the health of the person at multiple levels. The impact on male fertility is one of the least reported, but certainly one that clinicians should know better. The infertility evaluation of a AAS consumer should include a physical examination, a seminal analysis, a study of hormonal profile and genetic analysis.
Immediate cessation of the use of AAS should be encouraged. We are lead to the conclusion that the impact of steroids on male fertility is not just a purely transitory state. In short, the best policy is to strongly discourage the use of steroids and, for consumers who persist in their abuse, to offer them an appropriate ethics and clinical uro-andrologic support.
REO was involved in review proposal, execution, manuscript drafting, table design and critical discussion. TA was involved in manuscript drafting, figure and table design and critical discussion. CD was involved in analysis and interpretation of data. NH was involved in manuscript drafting. PE was involved in critical discussion.