A 31-year-old man presents to clinic for evaluation of a 3-year history of infertility. He has no significant medical history and takes no medications. He exercises twice a day, often with heavy weightlifting, and eats a high-protein diet. He reports occasional alcohol use and remote marijuana use. His temperature is 99.5°F (37.5°C), blood pressure is 148/90 mmHg, pulse is 84/min, and respirations are 15/min. He is sexually active with his wife and has no history of sexually transmitted infections. Physical exam reveals small testes and a receding hairline. He also has palpable tissue underneath his nipples bilaterally. His muscle tone is normal in his upper and lower extremities bilaterally. His laboratory values are below:

Serum:
Creatinine: 1.3 mg/dL
Glucose: 110 mg/dL
Total bilirubin: 0.8 mg/dL
Aspartate aminotransferase (AST, GOT): 410 U/L
Alanine aminotransferase (ALT, GPT): 275 U/L

Hemoglobin: 12 g/dL
Leukocyte count: 5,300/mm^3
Platelet count: 250,000/mm^3

Which of the following is the most likely cause of this patient’s infertility?
Klinefelter syndrome
Cryptorchidism
Anabolic steroid use
Excess growth hormone use
Anabolic steroid use
This patient with infertility is presenting with decreased testicular size, receding hairline, gynecomastia (palpable breast tissue), and transaminitis. This is most likely due to exogenous testosterone from anabolic (androgenic) steroid use.

Young people (especially athletes and heavy weightlifters) looking to improve their physical performance may rely on the use of anabolic steroids (testosterone, boldenone, and stanozolol). These steroids adversely impair endogenous testicular function, causing infertility secondary to decreased testicular size and sperm count. Furthermore, hepatic dysfunction and cardiac dysfunction can occur at high doses. Excess testosterone is converted to estradiol, leading to breast enlargement and signs of gynecomastia. Aggression and mood disturbances may also occur in patients with excessive anabolic steroid use. Finally, skin findings of anabolic steroid use include accelerated male pattern baldness and acne. Patients should be counseled on avoiding these agents.

Van Wagoner et al. study the chemical composition of products marketed as selective androgen receptor modulators (SARMs). The authors find that less than half of the analyzed products contained compounds in the amount listed on the label. The authors recommend that clinicians counsel athletes and bodybuilders that these products are often mislabeled, are not regulated, and have not been shown to be safe or effective.

Incorrect Answers:
Answer B: Cryptorchidism is the failure of testicular descent into the scrotum and typically manifests in infancy. While uncorrected cryptorchidism can be a cause of infertility, this is an unlikely diagnosis in a man with palpable testes. Furthermore, cryptorchidism would not explain this patient’s receding hairline or gynecomastia.

Answer C: Excess growth hormone use should be suspected because growth hormone can be taken exogenously to improve athletic performance and can present with hypertension. This typically also presents with hyperglycemia and enlarged hands and feet.

Answer D: Klinefelter syndrome is an inherited disorder that also presents with infertility, gynecomastia, and decreased testicular size. This disorder also causes mental impairment and would not explain the patient’s elevated aminotransferases.

Answer E: Myotonic dystrophy is a multi-system disorder that can also present with testicular atrophy, reduced fertility, and hair loss. Patients with myotonic dystrophy also have widespread muscular atrophy and weakness, as well as clinical features of myotonia (e.g., difficulty releasing a handshake).

Bullet Summary:
Anabolic steroid use in men can cause reduced fertility by suppressing endogenous testosterone activity, and presents with gynecomastia, testicular atrophy, accelerated male balding patterns, and hepatotoxicity.