Continuing Education Activity

Androgen use has become a major public health concern due to the transition of use of androgens from strictly sports to a much wider spectrum of the population. Anabolic-androgenic steroids (AAS) are steroidal androgens which include natural androgens such as male sex hormone testosterone or could be synthetic to mimic the action of the endogenous male hormone. Some people misuse anabolic steroids for various reasons. For example, athletes abuse anabolic steroids to enhance performance and prolong endurance. Non-athletic people misuse anabolic steroids to increase body weight and lean muscle mass without increasing fat mass in the body. The potential side effects of anabolic steroid abuse are significant, and health care providers should be aware of patients at risk of anabolic-androgenic steroid misuse. This activity describes the evaluation and management of anabolic steroid use disorder and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

• Identify the at-risk patient populations for anabolic steroid use disorder.
• Review the legitimate medical uses for anabolic steroid therapy.
• Outline the treatment and management options available for patients exhibiting signs of anabolic steroid misuse disorder.
• Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients presenting with anabolic steroid misuse disorder.

Introduction

The term "anabolic" means the use of body energy to promote growth and regulate constructive metabolism. Anabolic-androgenic steroids (AAS) are steroidal androgens, which include natural androgens such as male sex hormone testosterone or could be synthetic to mimic the action of the endogenous male hormone. Androgen use has become a major public health concern due to the transition of the use of androgens from strictly sports to a much wider spectrum of the population. The lifetime prevalence of anabolic-androgenic steroid (AAS) use worldwide is estimated to be 1% to 5%[1]. Due to their abuse potential, the Anabolic Steroid Control Act of 2004 amended the Controlled Substances Act to redefine anabolic steroids to "any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone) sets forth a list of substances included as anabolic steroids, including tetrahydrogestrinone (THG), androstenedione, and specified related chemicals". Testosterone and its analogs are placed in DEA Schedule III. 

Androgens stimulate and precipitate the development of male sex characteristics. Anabolic steroids and androgens are medically prescribed (orally or injectable) to treat hormonal imbalance for hypogonadism, impotence in men, delayed puberty in adolescent boys. For women, they can be used to treat breast cancer, endometriosis, osteoporosis, and muscle loss in patients with cancer or HIV. Misuse or abuse is commonly seen in athletes to enhance performance and prolong endurance. Non-athletes misuse anabolic steroids to increase their body weight and lean muscle mass without increasing the body's fat mass.[2][3][4][5] 

Etiology

Approximately 3 to 4 million Americans used anabolic-androgenic steroids to increase muscle mass, whether for sports to increase their performance or cosmetic purposes, such as enhancing their appearance. People who have misused steroids may be suffering from muscle dysmorphia, which is a behavioral syndrome. AAS are frequently used by fighters, bouncers, and security personnel to enhance their appearance and job performance. The popular term used for the anabolic steroids is “steroids,” and other common names are "roids," "juice," "andro," "gear," and "stackers." 

Epidemiology

The prevalence of AAS abuse has steadily increased over the last two decades.[6] Due to the increasing prevalence, the potential health hazards of anabolic steroids are also rising. A meta-analysis of 187 studies demonstrated that being athletic and/or male were significant predictors of AAS abuse[7]. The prevalence in males is 6.4%, compared to 1.6% in females.[7] According to NIDA(2018), anabolic steroid misuse is predominately seen in male weightlifters in their 20s or 30s. According to the 2019 NIDA-funded Monitoring the Future study, steroid use continues to be a concern among high school students. A study in Germany showed that 48.1% of AAS abusers, who frequented fitness centers, received their supply from healthcare providers.[8][9] In a 2006 survey of 500 AAS users, 78.4% were nonathletic and non-competitive bodybuilders.[10][11]  The method of choice for administration for the majority of AAS users (99.2%) was self-administrable injections.[7] Of concern was that as high as 13% reported unsafe practices for injecting the steroids, such as sharing needles, reusing needles, and sharing vials.[12]

Pathophysiology

Among AAS users, about 30% develop dependence, which is characterized by chronic AAS use despite negative consequences and adverse effects on physical, psychosocial, or occupational functioning.[13] According to a model on AAS dependence, in stage 1, which is referred to as "myoactive" phase, high-dose AAS are used with dietary and rigorous weight training. Stage 2 is characterized by the chronic and high amounts of AAS use leading to the brain reward development, contributing to abuse and dependence.[14] Internet and social media have thrown enormous challenges to the day to day lives and practices of the modern world.  The dissemination of misinformation via these mediums, combined with the lack of restrictions on AAS lead to dangerous practices by young athletes.[15]  

Hypogonadism is a hallmark of AAS abuse, which may have profound effects on the reproductive system. The majority of AAS users found to have low gonadotropin and testosterone levels even after the discontinuation of AAS.[16] Administration of exogenous AAS results in down-regulation of the HPA axis leading to reduced endogenous production of testosterone by suppressing the normal testicular function (reduced testicular volume, sperm, and testosterone production)[1].  In a retrospective study, 21% of 382 men with hypogonadism receiving testosterone treatment reported taking exogenous androgens. For men who have a history of taking androgens and then stopping them, the sperm count returns to normal after approximately four months to a year. Older men would take a longer time to recover than younger men after discontinuation. Androgen intake may lead to low sperm count, small testes, high hemoglobin and hematocrit values, low serum to non-detectable serum LH, and low sex hormone-binding globulin. These findings should raise the suspicion of exogenous androgen intake in men competing in sports.[7] 

Cardiovascular risk of AAS includes myocardial dysfunction, coronary atherosclerosis[17]; hypercoagulopathy and hepatic dysfunction[18], hypertension, life-threatening arrhythmia, and sudden death.[19] Concentric Left ventricular hypertrophy is commonly seen in long term steroid users even after discontinuation of AAS.[20] Prolonged use of AAS will also lead to elevation of LDL and reduction of HDL, conferring an increased risk of the cardiac event.[19] AAS abuse may also lead to psychiatric and behavioral disturbances.[18] According to an observational study by Christoffersen et al, there is increased aggression, violent behaviors, and a 9 fold increased risk of crime and imprisonment in people with AAS abuse.[21] The long term complications of AAS intake by females include hirsutism, acne, temporal male-pattern hair recession, deepening of the voice, and clitoromegaly.[1] Some women will experience oligomenorrhea or even amenorrhea, as well as breast atrophy.  

History and Physical

A comprehensive history and physical examination are needed to diagnose AAS abuse. The clinician may suspect AAS abuse in the following situations:

• Child or adolescent who is experiencing early development of secondary sexual characteristics, decrease in height, and premature closure of epiphyses
• Females experiencing temporal hair recession, hirsutism, acne, irregular menses, breast atrophy, deepening of the voice (irreversible), clitoromegaly, decrease in total body fat and increase in muscle mass[16].
• Males exhibiting rapid increased in muscle mass and strength and experiencing changes such as gynecomastia, small testes, low sperm count, impotence, and acne[1][16]

Evaluation

Exogenous administration of androgens should be suspected in a patient who is in a competitive sport or activity, who demonstrates behavioral changes such as aggression, depression, or irritability, or with blood work changes such as deficient luteinizing hormone (LH) concentration, high hematocrit, and low sex hormone-binding globulin (SHBG).[22] Gynecomastia in males and Hirsutism in females may be further investigated to rule out AAS use[1].

Treatment / Management

According to the current evidence, the most effective treatment for AAS is the discontinuation of AAS use, treatment of withdrawal symptoms, a combination of behavioral therapy, and symptomatic treatments. Treatment of AAS is based on the duration of use, the likelihood of withdrawal symptoms, treatment goals of the patient, and risk-benefit analysis of the treatments. Anawalt(2019) discusses four management strategies for AAS;1. Cessation with no medical therapy; 2. Cessation and initiation of clomiphene therapy; 3. Cessation and initiation of hCG therapy; 4. Conversion of nonprescription AASs to prescription testosterone[1].

In AAS users with less than one year of use, testosterone levels normalize to baseline within 6 months of discontinuation[1]. However, in chronic users, prolonged duration of hypogonadism and low testosterone is observed[23][24][23]. Restoration of hormonal balance is important to prevent hypogonadism. In athletes, androgen use must be discontinued immediately, even though withdrawal symptoms are expected. If initiating testosterone replacement therapy for the treatment of hypogonadism, therapeutic use exemptions from appropriate agencies should be sought before initiation of replacement therapies.[1]. Clomiphene or hCG therapy may be considered for men with chronic high dose AAS use[1]. Providers should also address other behavioral and mental health comorbidities concurrently.  Anxiety and depression should be treated with antidepressants and cognitive-behavioral therapies. In patients with conduct disorder and other substance use disorders, appropriate behavioral interventions along with appropriate referrals are warranted[1][25]. 

Differential Diagnosis

Clinicians should investigate the use of anabolic-androgenic steroids in middle-aged males and young men who present with gynecomastia, hirsutism, coronary artery disease (CAD) and left ventricular dysfunction.[26][1][26] Additionally, healthcare providers should investigate comorbid mental health issues or substance use disorders.

Toxicity and Side Effect Management

The common side effects of androgens include gynecomastia, shrinking of testicles, azoospermia, and infertility in men[16]; and mood changes and aggression (“roid rage”), stunted height, and early puberty. Females with AAS abuse may have severe acne, menstrual irregularities, hirsutism, and clitoromegaly.[16] All groups can experience high blood pressure, changes in cholesterol, liver diseases such as cysts, heart diseases such as coronary artery disease, kidney diseases, and the risk of infections due to unsterile injections.[11] In observational studies on males who used anabolic steroids, there was also higher coronary plaque formation volume when compared to non-users. Moreover, approximately 71% of the anabolic steroid users had impaired ability to pump blood efficiently, leading to lower-than-normal left ventricle ejection fraction.[27][28]

Prognosis

Like with any substance with addictive potential, abrupt cessation of the AAS use leads to withdrawal symptoms including anxiety and depression.[1] Other withdrawal symptoms include fatigue, sleep problems, loss of appetite, decreased libido, and steroid cravings. Among the most serious withdrawal symptoms is depression, which could lead to suicidal ideation and suicide attempts. Studies have shown that patients who misuse steroids may use other illicit drugs to help reduce side effects such as depression, anxiety, irritability, and lack of sleep.[29][30][31]

Complications

• Androgen use complications include cardiac hypertrophy, decreased serum HDL cholesterol, hypogonadism after discontinuing exogenous androgens, and neuropsychiatric concerns.[24] Many studies show an association between the nonmedical use of androgens and increases in risky and criminal behavior among the androgen intake abusers.[21]
• In a survey of 10000 to 15000 college students, the use of androgens correlated highly with drinking and driving, cigarette smoking, illicit drug use, and alcohol misuse.[32][33]
• Anabolic steroids are completely prohibited in sports, whether in- or out-of-competition. The following organizations prohibit anabolic steroids intake: National Collegiate Athletic Association (NCAA), International Olympic Committee (IOC), U.S. Anti-Doping Agency (USADA), and World Anti-Doping Agency (WAD). 

Deterrence and Patient Education

The potential side effects of anabolic steroid misuse are significant and chronic. Health care providers should be aware of patients at risk of anabolic-androgenic steroid misuse. Ongoing patient education about the potential side effects should be provided for patients who take androgens for therapeutic use. Timely identification of the anabolic steroid abuse and appropriate referral for treatment is highly warranted. 

Enhancing Healthcare Team Outcomes

Clinicians should target treating depression, body-image, and dysmorphia and associated detrimental behavioral patterns in groups at risk of anabolic-androgenic steroid misuse.