madman
Super Moderator
Abstract
The anabolic-androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analyzed 179 cases of AAS users. Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery. In conclusion, this review presents evidence that AASinduced hypogonadism is a seriously underestimated problem, and in the majority of cases, full recovery is very difficult to succeed.
1 | SUMMARY
Testosterone, a sex hormone, along with other androgens, has a major role in the development of sexual characteristics (masculinizing or androgenic effect) and stimulation of muscle protein synthesis, thus promoting hypertrophy (anabolic effect). Due to the effects provided by testosterone, synthetic derivatives of steroid hormones have been developed and used for decades in diverse circumstances. These drugs are used for the treatment of diseases, but also, indiscriminately used without any medical indication for the improvement of performance in sports and particularly for aesthetic reasons (Evans, 2004; Pope et al., 2014; Sagoe et al., 2014).
AAS abuse may cause a severe disarrangement on the HPG axis and consequently, generating negative feedback, which occurs a significant decrease in testosterone synthesis and secretion by the testes. This situation usually results in clinical symptoms such as sexual impotence, decreased libido decreased physical capacity, and even depressive symptoms in a condition medically known as secondary hypogonadism or anabolic steroid-induced hypogonadism (ASIH; Hartgens & Kuipers, 2004; Wu et al., 2010).
Usually, hypogonadism related to AAS abuse is not commonly reported and discussed in medical and academic circles. However, the scientific data indicate that this kind of hypogonadism can be much more common and more problematic than it is usually pointed (Kanayama et al., 2015). A retrospective database analysis of all 6,033 men evaluated for hypogonadism from 2005 to 2010, identified AAS abuse as the main cause for hypogonadism incidence where 97 men were diagnosed with profound hypogonadism, defined as testosterone 50 ng/dl or less, and among these 97, 42 men (43%) had the AAS abuse as the origin of hypogonadism (Coward et al., 2013).
*Thus, considering the AAS abuse a public health problem, due to the fact that hypogonadism caused by AAS abuse is a side effect often underestimated the aim of this systematic review was to identify and to review different studies with a focus on AAS abuse-related Hypogonadism and, then, bring some light about the reversibility of this condition in men.
8 | DISCUSSION
The administration of AAS increases the serum androgens levels to a supraphysiological state, which implies an important derangement on the HPG axis and suppression of GnRH, LH, FSH, and testosterone (Evans, 2004; Vilar Neto et al., 2018). This disorder results in a reduction of serum testosterone levels and illustrates secondary hypogonadism, in this case, more specifically known as anabolic steroid-induced hypogonadism (ASIH), which is characterized by the functional incompetence of the testes with subnormal or impaired testosterone synthesis and/or spermatozoa resulting from the exogenous administration of AAS (Hartgens & Kuipers, 2004).
Nevertheless, AAS abuse is commonly associated with secondary hypogonadism (ASIH); there are real possibilities of this condition to evolve to primary hypogonadism (testicular failure).
*In truth, the pathophysiology of ASIH is certainly much more complex than a simple effect from the negative feedback caused by the excess of androgens. That is because AAS abusers are usually using a blend of high-dose synthetic androgens. In addition to the endocrine disruption, the AAS abuse can also contribute to a primary testicular failure through a direct toxic effect, as suggested by animal studies by Boetcher et al. and Chainy et al. (Boettcher et al., 2011; Chainy et al., 1997; Karavolos et al., 2015; Karila et al., 2004).
Diverging from common sense, the analyzed studies in this review clearly show that the deleterious effects of AAS abuse on the HPG axis are not occasional and not necessarily transient. Instead, the recent findings lead us to consider the AAS impact on the HPG axis as an unpredictable and permanent event.
9 | CONCLUSION
The present review shows that AAS abuse-induced hypogonadism is still a poorly studied health issue. Even searching among 13 scientific databases, only 14 related studies could be selected for this review
Our data analyses showed that deleterious effects of AAS abuse on endogenous testosterone synthesis are not occasional and not necessarily transient. Therefore, hypogonadism is an expected event for AAS users and it is a serious and underrated problem. In addition, this condition may be the cause of fertility problems, depression, low libido, and sexual impotence in men.
The ASIH does not seem to have its origin and problem exclusively related to negative feedback and HPG axis disorder. The simultaneous use of different types of AAS, in high doses and for a prolonged period of time may also be associated with primary testicular failure, which could contribute to explain the cases in which recovery was not possible.
The analyzed cases in this review suggest that the ASIH is a reversible condition; however, the time required and the success rate are uncertain and essentially depend on the patient age and how long he was exposed to supraphysiological androgens levels, and certain medical and pharmacological intervention is a key factor to achieve recovery.
The anabolic-androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analyzed 179 cases of AAS users. Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery. In conclusion, this review presents evidence that AASinduced hypogonadism is a seriously underestimated problem, and in the majority of cases, full recovery is very difficult to succeed.
1 | SUMMARY
Testosterone, a sex hormone, along with other androgens, has a major role in the development of sexual characteristics (masculinizing or androgenic effect) and stimulation of muscle protein synthesis, thus promoting hypertrophy (anabolic effect). Due to the effects provided by testosterone, synthetic derivatives of steroid hormones have been developed and used for decades in diverse circumstances. These drugs are used for the treatment of diseases, but also, indiscriminately used without any medical indication for the improvement of performance in sports and particularly for aesthetic reasons (Evans, 2004; Pope et al., 2014; Sagoe et al., 2014).
AAS abuse may cause a severe disarrangement on the HPG axis and consequently, generating negative feedback, which occurs a significant decrease in testosterone synthesis and secretion by the testes. This situation usually results in clinical symptoms such as sexual impotence, decreased libido decreased physical capacity, and even depressive symptoms in a condition medically known as secondary hypogonadism or anabolic steroid-induced hypogonadism (ASIH; Hartgens & Kuipers, 2004; Wu et al., 2010).
Usually, hypogonadism related to AAS abuse is not commonly reported and discussed in medical and academic circles. However, the scientific data indicate that this kind of hypogonadism can be much more common and more problematic than it is usually pointed (Kanayama et al., 2015). A retrospective database analysis of all 6,033 men evaluated for hypogonadism from 2005 to 2010, identified AAS abuse as the main cause for hypogonadism incidence where 97 men were diagnosed with profound hypogonadism, defined as testosterone 50 ng/dl or less, and among these 97, 42 men (43%) had the AAS abuse as the origin of hypogonadism (Coward et al., 2013).
*Thus, considering the AAS abuse a public health problem, due to the fact that hypogonadism caused by AAS abuse is a side effect often underestimated the aim of this systematic review was to identify and to review different studies with a focus on AAS abuse-related Hypogonadism and, then, bring some light about the reversibility of this condition in men.
8 | DISCUSSION
The administration of AAS increases the serum androgens levels to a supraphysiological state, which implies an important derangement on the HPG axis and suppression of GnRH, LH, FSH, and testosterone (Evans, 2004; Vilar Neto et al., 2018). This disorder results in a reduction of serum testosterone levels and illustrates secondary hypogonadism, in this case, more specifically known as anabolic steroid-induced hypogonadism (ASIH), which is characterized by the functional incompetence of the testes with subnormal or impaired testosterone synthesis and/or spermatozoa resulting from the exogenous administration of AAS (Hartgens & Kuipers, 2004).
Nevertheless, AAS abuse is commonly associated with secondary hypogonadism (ASIH); there are real possibilities of this condition to evolve to primary hypogonadism (testicular failure).
*In truth, the pathophysiology of ASIH is certainly much more complex than a simple effect from the negative feedback caused by the excess of androgens. That is because AAS abusers are usually using a blend of high-dose synthetic androgens. In addition to the endocrine disruption, the AAS abuse can also contribute to a primary testicular failure through a direct toxic effect, as suggested by animal studies by Boetcher et al. and Chainy et al. (Boettcher et al., 2011; Chainy et al., 1997; Karavolos et al., 2015; Karila et al., 2004).
Diverging from common sense, the analyzed studies in this review clearly show that the deleterious effects of AAS abuse on the HPG axis are not occasional and not necessarily transient. Instead, the recent findings lead us to consider the AAS impact on the HPG axis as an unpredictable and permanent event.
9 | CONCLUSION
The present review shows that AAS abuse-induced hypogonadism is still a poorly studied health issue. Even searching among 13 scientific databases, only 14 related studies could be selected for this review
Our data analyses showed that deleterious effects of AAS abuse on endogenous testosterone synthesis are not occasional and not necessarily transient. Therefore, hypogonadism is an expected event for AAS users and it is a serious and underrated problem. In addition, this condition may be the cause of fertility problems, depression, low libido, and sexual impotence in men.
The ASIH does not seem to have its origin and problem exclusively related to negative feedback and HPG axis disorder. The simultaneous use of different types of AAS, in high doses and for a prolonged period of time may also be associated with primary testicular failure, which could contribute to explain the cases in which recovery was not possible.
The analyzed cases in this review suggest that the ASIH is a reversible condition; however, the time required and the success rate are uncertain and essentially depend on the patient age and how long he was exposed to supraphysiological androgens levels, and certain medical and pharmacological intervention is a key factor to achieve recovery.
