AAS misuse and male infertility

madman

Super Moderator
Anabolic steroid misuse and male infertility: management and strategies to improve patient awareness (2021)


ABSTRACT

Introduction:
Anabolic-androgenic steroid use is an uncommon but important cause of male infertility. As paternal age and anabolic steroid use increase, providers are more likely than ever to encounter men with infertility and prior or concurrent anabolic steroid use. In this review, we outline the background, epidemiology, and pathophysiology of anabolic steroid-induced male infertility and provide recommendations regarding the diagnosis, management, and future prevention of this condition.

Areas covered:
Male reproductive physiology is a tightly regulated process that can be influenced by exogenous sources such as anabolic steroids and selective androgen receptor modulators (SARMs). Data suggest that a combination of selective estrogen receptor modulators (SERMs), human chorionic gonadotropin (hCG), aromatase inhibitors (AIs), and recombinant follicle-stimulating hormone (rFSH) may lead to spermatogenesis recovery.

Expert opinion: Anabolic steroids and SARM users continue to exhibit a lack of understanding regarding the potential side effects of their use on male fertility. Current literature suggests that spermatogenesis can be safely recovered using a combination of SERMs, hCG, AIs, and rFSH although additional studies are necessary. While anabolic steroid prevention strategies have largely been focused on the individual level, further investigation is necessary and should be approached in a socioecological manner.




1. Introduction

Functional male testes and an intact hypothalamic-pituitary-gonadal (HPG) axis are essential for normal male fertility and adequate testosterone production. This process is maintained through precise coordination of stimulatory hormones and negative feedback mechanisms. Any disruption in this pathway can lead to male hypogonadism and dysfunction of spermatogenesis. Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone that were initially researched in the 1930s and are approved for a variety of conditions such as testosterone deficiency, osteoporosis, breast cancer, delayed puberty, and cachexia [1]. Despite having a therapeutic role in medicine, AAS are commonly abused by men to achieve supraphysiologic androgen levels and increase muscle mass. In fact, AAS use is currently on the rise with a worldwide prevalence as high as 6.4% [2]. This is concerning and likely related to a growing preoccupation and obsession among men with obtaining a muscular physique, commonly referred to as the ‘Adonis complex’ and ‘bigorexia’ [3,4].
While AAS has desired effects on muscle growth, strength gains, and fat loss, their use is not without risk. AAS use can lead to acne, hair loss, gynecomastia, hepatic dysfunction, hypogonadism, male infertility and has been linked with cardiovascular disorders and even premature death [5–8]. AAS use is known to cause male infertility via suppression of the natural HPG axis, but there appears to be limited data regarding the management of AAS-induced infertility. In this review, we outline the background and epidemiology of AAS and patient motivations for AAS use, summarize the pathophysiology of AAS induced male hypogonadism and provide treatment recommendations and strategies for AAS induced male infertility.




2. Male reproductive physiology

3. Anabolic androgenic steroids

3.1. Background and epidemiology
3.2. Patient motivations and bigorexia
3.3. The good, the bad, and the ugly


4. Selective androgen receptor modulators: the new kid on the block
4.1. Cardarine and MK-677

5. Effects of anabolic steroid use on spermatogenesis

6. Treatment strategies for anabolic steroid-induced infertility

6.1. hCG and FSH
6.2. Selective estrogen receptor modulators (SERMs)
6.3. Aromatase inhibitors (AIs)


7. Clinical recommendations

8. Future prevention




9. Conclusions

As both the prevalence of AAS use and age of paternity continues to increase, clinicians are more likely than ever to encounter men with AAS-induced infertility. It is important for physicians to understand this disease process and fully outline the risks associated with AAS use, including the effects on male reproductive health. Physicians must counsel patients in a healthy and non-judgmental fashion to discontinue AAS and offer a supplemental TRT taper for those with severe hypogonadal symptoms following AAS cessation. Although studies are limited, it appears that AAS-induced infertility (prior or concurrent use) can be safely managed with the aforementioned regimen. CC and hCG appear to play crucial roles in the recovery of spermatogenesis. Despite increased interest and research examining AAS use, it appears that studies outlining successful AAS prevention tactics are lacking. Further research examining the effectiveness of socioecological-based AAS prevention strategies may be of particular interest.




10. Expert opinion


Anabolic steroid use is on the rise and users continue to exhibit a lack of understanding regarding the potential effects on male fertility. In addition, it appears that SARMs are becoming increasingly popular among men and can have similar adverse effects on male fertility and testosterone production. The available literature, although limited, suggests that spermatogenesis can be safely recovered using a combination of SERMs, hCG, AIs, and rFSH, although additional studies are needed to further establish these findings. The lack of clinical evidence regarding the management of AAS-induced infertility is a large barrier to the implementation of the aforementioned regimens into clinical practice. The large majority of AAS use is illicit and banned in most countries. AAS users infrequently seek care from medical providers due to the perceived lack of knowledge regarding AAS use and physician distrust in addition to fears of discrimination. In fact, most of these men self-regulate their usage and tend to be relatively disciplined and precise. Physicians may not come in contact with AAS users until problems arise, which may be years after their first usage and once dependence has set in. The variability and number of anabolic steroids used are also barriers to further research.

There are over 20 different types of common anabolic compounds utilized by AAS users. These substances have varying levels of potency and differing mechanisms of action. AAS users will often combine multiple compounds at variable dosages which can pose a challenge to researchers. These obstacles, in addition to the shroud of secrecy surrounding AAS use makes it difficult to conduct extensive, large-scale clinical studies which will be a necessity over the next five to ten years.


More importantly, despite increased interest and research in the field of AAS over the last few decades, there appears to be a lack of evidence regarding effective prevention tactics. While anabolic steroid prevention strategies have largely been focused on the individual level, further investigation is necessary and should be approached in a socioecological manner, targeting not just individuals but multiple ecological levels including social network, institutional, community, and societal. The lack of regulation and quality control regarding illegal AAS manufacturing is another barrier to studying AAS prevention. Furthermore, it is difficult to launch prevention campaigns as there is no single product to target and no central organization that has the interest to increase public awareness unlike other substance abuse prevention campaigns (opioid epidemic, pharmaceutical companies, and the Food and Drug Administration). Increased FDA and governmental regulation of illegal AAS manufacturers will be necessary to prevent future AAS use, especially as AAS use is likely to worsen with the aging population and the increasingly hypercompetitive nature of sports. Continued prevention strategies from athletic organizations such as the World Anti-Doping Agency will also be crucial. It is prudent to continue to publish articles such as these to increase physician awareness regarding AAS and their consequences. Finally, it appears that a large proportion of young adult men obtain most of their AAS information via online social media platforms such as Facebook, YouTube, Instagram, TikTok, and online bodybuilding forums. As social media use increases and platforms continue to rapidly evolve, it will be prudent to examine prevention strategies targeting the different realms of the social network in the coming years.
 

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madman

Super Moderator
Figure 1. The HPG axis including the mechanism of action of inhibitors and stimulators. AAS: anabolic androgenic steroids, GnRH: gonadotropin-releasing hormone, SERMs: selective estrogen receptor modulators, LH; luteinizing hormone, FSH: follicle-stimulating hormone, hCG: human chorionic gonadotropin, AI: aromatase inhibitors.
Screenshot (4601).png
 

madman

Super Moderator
Figure 2. Commonly used anabolic-androgenic steroids grouped according to effect. DHT: dihydrotestosterone.
Screenshot (4602).png

Screenshot (4603).png
 

madman

Super Moderator
Figure 3. Management strategies for AAS-induced infertility. TRT: testosterone replacement therapy, AAS: anabolic androgenic steroid, SA: semen analysis, T: testosterone, LH: luteinizing hormone, FSH: follicle-stimulating hormone, ART: assisted reproductive technology, hCG: human chorionic gonadotropin, QOD: every other day, CC: clomiphene citrate, QD: every day, rFSH: recombinant follicle-stimulating hormone.
Screenshot (4604).png
 

madman

Super Moderator
Article highlights

● Anabolic-androgenic steroid use is an important cause of male infertility that physicians should be aware of.

● The hypothalamic-pituitary-gonadal axis is a finely tuned process that is easily influenced by exogenous anabolic steroid use which leads to impaired spermatogenesis and male infertility.

● The majority of anabolic steroid users are unaware of the fertility side effects associated with its use.

● Chronic anabolic steroid use has been linked with myocardial infarction, cardiomyopathy, accelerated atherosclerosis, stroke, and premature death.

● Anabolic steroid users can be categorized into four separate groups: the YOLO (You Only Live Once) type, the Athlete type, the Well-Being type, and the Expert type.

● A growing preoccupation with male body image and increasing social media use among men may contribute to the rising prevalence of anabolic steroid use.

● Selective androgen receptor modulators are a new class of performance and image-enhancing compounds being misused by men and can have similar side effects of hypogonadism and male infertility.


● While data regarding the management of anabolic steroid-induced infertility is limited, studies suggest that the use of SERMs (clomiphene citrate), hCG, anastrozole, and rFSH may have success with spermatogenesis recovery although some patients may experience permanent dysfunction of the HPG axis following steroid use.


Although anabolic steroid prevention tactics have been enacted, the prevalence of steroid use appears to be on the rise. Future prevention efforts may be more successful if a socioecological approach is utilized, targeting not just individuals but multiple ecological levels including social network, institutional, community, and societal.
 

madman

Super Moderator
* While data regarding the management of anabolic steroid-induced infertility is limited, studies suggest that the use of SERMs (clomiphene citrate), hCG, anastrozole, and rFSH may have success with spermatogenesis recovery although some patients may experience permanent dysfunction of the HPG axis following steroid use.
 

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