madman
Super Moderator
Common symptoms associated with usage and cessation of anabolic androgenic steroids in men (2022)
Aditi Sharma, Clinical Research Fellow, Bonnie Grant, Specialist Trainee, Department of Endocrinology and Metabolism, Heraa Islam, Visiting Researcher, Aditi Kapoor, Visiting Researcher, Anjali Pradeep, Medical Student, Channa N. Jayasena, NIHR Post-Doctoral Fellow and Reader in Reproductive Endocrinology
Anabolic-androgenic steroids (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to stop AAS are prone to distressing withdrawal symptoms which may trigger relapse in use. It is important to develop therapies to support AAS withdrawal. The illicit nature of AAS use has impeded the robust characterization of its clinical withdrawal syndrome within any single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use and AAS withdrawal. Reported clinical features of AAS withdrawal include headache, fatigue, myalgia, restlessness, insomnia, low mood and libido, anorexia, suicidal ideation, body image dissatisfaction, and steroid cravings; novel therapies for AAS withdrawal would need evaluation against these symptoms.
Introduction
Anabolic-androgenic steroids (AAS) are an umbrella term for drugs designed to increase the bodily effects of testosterone directly or indirectly. AAS include testosterone (T) itself, its metabolite dihydrotestosterone (DHT), and synthetic derivatives such as 19-nortestosterone (nandrolone), methyltestosterone (MT), ehtyltestosterone, ethynyltestosterone (ethisterone) and vinyltestosterone [1]. However, drugs increasing endogenous T secretion such as human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERM) may also be considered AAS. T is used therapeutically for the treatment of male hypogonadism, and other AAS have been used to treat cachexia associated with chronic diseases such as human immunodeficiency syndrome, cancer, burns, renal and hepatic failure, and anaemia associated with leukaemia or kidney failure [2]. However, AAS now have widespread illegal use as image and performance enhancing drugs (IPED), predominantly in young men [3]; this has been fueled by a large ‘black-market’ of online availability, and online message boards and websites promoting and advising on AAS use [4]. AAS have damaging health consequences. Men who try stopping AAS experience distressing withdrawal which often triggers relapse in use [5]. There are currently no treatments proven to alleviate AAS withdrawal symptoms to support long-term cessation in users. To test future AAS withdrawal therapies, it is important to design and validate symptom scores of AAS withdrawal. The illicit nature of AAS use has impeded the robust description of its clinical withdrawal syndrome within a single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use and AAS withdrawal.
Results
Endocrine symptoms of AAS use
It is well-known that long-term AAS suppresses testicular function by suppressing hypothalamic gonadotrophin-releasing hormone (GnRH) and pituitary gonadotropins. AAS use is therefore an iatrogenic cause of hypogonadotropic hypogonadism. Former AAS users commonly present to endocrine clinics with features of hypogonadism such as low libido and erectile dysfunction [6]. However, it is unclear whether symptoms of hypogonadism during AAS withdrawal differ from symptoms associated with other forms of hypogonadism.
*There is currently no consensus approach or clinical guideline for managing hypogonadism following AAS cessation. Many clinicians make the logical assumption that recovery from hypogonadism is inevitable, so provide reassurance while recommending monitoring for biochemical recovery (of serum testosterone); unfortunately, some former AAS users do not engage with this approach, since it does not directly address the hypogonadal symptoms they are experiencing, which may be accompanied by any other troubling symptoms discussed later in this article. Further studies are needed to investigate the effectiveness and acceptability of ‘watchful waiting’ monitoring approaches to past AAS users and determine when/if there exists a threshold of time beyond which former AAS users should be treated simply as men with long-term hypogonadism (prescribed therapeutic testosterone). Such decisions are clearly controversial, so would benefit from a multidisciplinary, evidence-based approach engaging both clinicians, (past) AAS users, and policymakers.
Neuropsychiatric symptoms of AAS use
AAS have powerful effects on the limbic system of the brain [12].
*Further studies are needed to clarify the precise relationships among exogenous testosterone exposure, pre-morbid psychological burden, and adverse behavioural changes during AAS use in men
Effects of AAS on musculature and strength
AAS increases muscle mass with associated reductions in fat mass.
*In conclusion, AAS have dramatic effects on physical appearance. There is limited evidence suggesting that AAS may increase muscle strength, but the results are surprisingly equivocal. One possible explanation is that AAS may shorten the recovery time from hard exercise, allowing more strenuous exercise in users to increase muscle bulk
Other symptoms of AAS use
AAS have well-described adverse effects on the cardiovascular system including dyslipidaemia, hypertension, and cardiac dysfunction which may lead to adverse cardiovascular events [10,26]. However, it is rare for men to experience cardiovascular symptoms related to AAS use.
AAS may cause various forms of short-term hepatic injury including cholestasis and peliosis hepatis, and hepatocyte proliferation on liver biopsy [28].
*There is a lack of large-scale data on the delayed effects of AAS in men. However hepatocellular, renal cell and prostate carcinoma have also been described in AAS users [30-32], although causality cannot be inferred. Truncal acne is a common side effect of AAS [10]. The clinical effects of AAS exposure are summarised in Fig. 2.
Symptoms associated with AAS withdrawal
The clinical features of AAS withdrawal are understudied, and most studies lack objective validation of self-reported drug cessation using toxicology screening. Nevertheless, Brower KJ [33] classified withdrawal from AAS in two distinctive phases, acute and chronic. The acute phase includes sympathetic activation leading to somatic symptoms of headache, tremors, palpitations, and nausea. This phase manifests within 1-2 days of AAS withdrawal, following which the chronic phase develops which comprises of symptomologies including, hypogonadism with fatigue, myalgia, and lower libido because of testosterone deficiency. Furthermore, psychiatric symptoms involving intense fear, depressive disorder, cravings, dysmorphia, and insomnia can also develop [33]. AAS withdrawal symptoms are summarised in Fig. 3.
*However, it is important to consider that AAS cessation may also ameliorate some distressing psychiatric features of AAS use. This is illustrated by observing that mood disorders have been reported to be more common in current AAS users when compared to those who had recently stopped AAS (within 3 months post-cessation) [7]. Studies are required to elucidate the predictors of withdrawal symptoms; however, likely risk factors are prior psychiatric illness, the potency of androgen exposure, duration of AAS, and doses of AAS use.
Conclusion
Our review reveals growing but limited clinical evidence exploring the clinical features of AAS withdrawal. Acute features of sympathetic overactivation (headache, tremors, palpitations, and nausea) are followed by chronic symptoms which may be broadly classified into neuropsychiatric and reproductive-endocrine. Low mood, suicidal thoughts and body image dissatisfaction are described during AAS withdrawal. Furthermore, hypogonadism during AAS withdrawal is associated with low libido, erectile dysfunction, and fatigue. However, a much broader evidence base is required, exploring the effects of specific AAS drug classes on different user demographics. In particular, there exists a paucity of data on female AAS use. Endocrinologists are currently restricted to treating frustrated past AAS users with biochemical monitoring for expectant reproductive recovery while psychiatrists are faced with the devasting presentations of illness provoked by AAS in users. Further studies are needed to provide evidence for novel interventions which may encourage cessation, reduce the distressing features of withdrawal, and discourage relapse in AAS users.
Aditi Sharma, Clinical Research Fellow, Bonnie Grant, Specialist Trainee, Department of Endocrinology and Metabolism, Heraa Islam, Visiting Researcher, Aditi Kapoor, Visiting Researcher, Anjali Pradeep, Medical Student, Channa N. Jayasena, NIHR Post-Doctoral Fellow and Reader in Reproductive Endocrinology
Anabolic-androgenic steroids (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to stop AAS are prone to distressing withdrawal symptoms which may trigger relapse in use. It is important to develop therapies to support AAS withdrawal. The illicit nature of AAS use has impeded the robust characterization of its clinical withdrawal syndrome within any single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use and AAS withdrawal. Reported clinical features of AAS withdrawal include headache, fatigue, myalgia, restlessness, insomnia, low mood and libido, anorexia, suicidal ideation, body image dissatisfaction, and steroid cravings; novel therapies for AAS withdrawal would need evaluation against these symptoms.
Introduction
Anabolic-androgenic steroids (AAS) are an umbrella term for drugs designed to increase the bodily effects of testosterone directly or indirectly. AAS include testosterone (T) itself, its metabolite dihydrotestosterone (DHT), and synthetic derivatives such as 19-nortestosterone (nandrolone), methyltestosterone (MT), ehtyltestosterone, ethynyltestosterone (ethisterone) and vinyltestosterone [1]. However, drugs increasing endogenous T secretion such as human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERM) may also be considered AAS. T is used therapeutically for the treatment of male hypogonadism, and other AAS have been used to treat cachexia associated with chronic diseases such as human immunodeficiency syndrome, cancer, burns, renal and hepatic failure, and anaemia associated with leukaemia or kidney failure [2]. However, AAS now have widespread illegal use as image and performance enhancing drugs (IPED), predominantly in young men [3]; this has been fueled by a large ‘black-market’ of online availability, and online message boards and websites promoting and advising on AAS use [4]. AAS have damaging health consequences. Men who try stopping AAS experience distressing withdrawal which often triggers relapse in use [5]. There are currently no treatments proven to alleviate AAS withdrawal symptoms to support long-term cessation in users. To test future AAS withdrawal therapies, it is important to design and validate symptom scores of AAS withdrawal. The illicit nature of AAS use has impeded the robust description of its clinical withdrawal syndrome within a single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use and AAS withdrawal.
Results
Endocrine symptoms of AAS use
It is well-known that long-term AAS suppresses testicular function by suppressing hypothalamic gonadotrophin-releasing hormone (GnRH) and pituitary gonadotropins. AAS use is therefore an iatrogenic cause of hypogonadotropic hypogonadism. Former AAS users commonly present to endocrine clinics with features of hypogonadism such as low libido and erectile dysfunction [6]. However, it is unclear whether symptoms of hypogonadism during AAS withdrawal differ from symptoms associated with other forms of hypogonadism.
*There is currently no consensus approach or clinical guideline for managing hypogonadism following AAS cessation. Many clinicians make the logical assumption that recovery from hypogonadism is inevitable, so provide reassurance while recommending monitoring for biochemical recovery (of serum testosterone); unfortunately, some former AAS users do not engage with this approach, since it does not directly address the hypogonadal symptoms they are experiencing, which may be accompanied by any other troubling symptoms discussed later in this article. Further studies are needed to investigate the effectiveness and acceptability of ‘watchful waiting’ monitoring approaches to past AAS users and determine when/if there exists a threshold of time beyond which former AAS users should be treated simply as men with long-term hypogonadism (prescribed therapeutic testosterone). Such decisions are clearly controversial, so would benefit from a multidisciplinary, evidence-based approach engaging both clinicians, (past) AAS users, and policymakers.
Neuropsychiatric symptoms of AAS use
AAS have powerful effects on the limbic system of the brain [12].
*Further studies are needed to clarify the precise relationships among exogenous testosterone exposure, pre-morbid psychological burden, and adverse behavioural changes during AAS use in men
Effects of AAS on musculature and strength
AAS increases muscle mass with associated reductions in fat mass.
*In conclusion, AAS have dramatic effects on physical appearance. There is limited evidence suggesting that AAS may increase muscle strength, but the results are surprisingly equivocal. One possible explanation is that AAS may shorten the recovery time from hard exercise, allowing more strenuous exercise in users to increase muscle bulk
Other symptoms of AAS use
AAS have well-described adverse effects on the cardiovascular system including dyslipidaemia, hypertension, and cardiac dysfunction which may lead to adverse cardiovascular events [10,26]. However, it is rare for men to experience cardiovascular symptoms related to AAS use.
AAS may cause various forms of short-term hepatic injury including cholestasis and peliosis hepatis, and hepatocyte proliferation on liver biopsy [28].
*There is a lack of large-scale data on the delayed effects of AAS in men. However hepatocellular, renal cell and prostate carcinoma have also been described in AAS users [30-32], although causality cannot be inferred. Truncal acne is a common side effect of AAS [10]. The clinical effects of AAS exposure are summarised in Fig. 2.
Symptoms associated with AAS withdrawal
The clinical features of AAS withdrawal are understudied, and most studies lack objective validation of self-reported drug cessation using toxicology screening. Nevertheless, Brower KJ [33] classified withdrawal from AAS in two distinctive phases, acute and chronic. The acute phase includes sympathetic activation leading to somatic symptoms of headache, tremors, palpitations, and nausea. This phase manifests within 1-2 days of AAS withdrawal, following which the chronic phase develops which comprises of symptomologies including, hypogonadism with fatigue, myalgia, and lower libido because of testosterone deficiency. Furthermore, psychiatric symptoms involving intense fear, depressive disorder, cravings, dysmorphia, and insomnia can also develop [33]. AAS withdrawal symptoms are summarised in Fig. 3.
*However, it is important to consider that AAS cessation may also ameliorate some distressing psychiatric features of AAS use. This is illustrated by observing that mood disorders have been reported to be more common in current AAS users when compared to those who had recently stopped AAS (within 3 months post-cessation) [7]. Studies are required to elucidate the predictors of withdrawal symptoms; however, likely risk factors are prior psychiatric illness, the potency of androgen exposure, duration of AAS, and doses of AAS use.
Conclusion
Our review reveals growing but limited clinical evidence exploring the clinical features of AAS withdrawal. Acute features of sympathetic overactivation (headache, tremors, palpitations, and nausea) are followed by chronic symptoms which may be broadly classified into neuropsychiatric and reproductive-endocrine. Low mood, suicidal thoughts and body image dissatisfaction are described during AAS withdrawal. Furthermore, hypogonadism during AAS withdrawal is associated with low libido, erectile dysfunction, and fatigue. However, a much broader evidence base is required, exploring the effects of specific AAS drug classes on different user demographics. In particular, there exists a paucity of data on female AAS use. Endocrinologists are currently restricted to treating frustrated past AAS users with biochemical monitoring for expectant reproductive recovery while psychiatrists are faced with the devasting presentations of illness provoked by AAS in users. Further studies are needed to provide evidence for novel interventions which may encourage cessation, reduce the distressing features of withdrawal, and discourage relapse in AAS users.
