Description

• FDA definition: Testosterone <300 ng/dL (in men)
• Testosterone is essential for normal sexual development and function.
• Testosterone levels may decline with aging and in certain disease states.
• Low androgen levels increase the risk of low-trauma fractures and are associated with a decline in sexual function, sense of well-being, muscle mass, and strength.
• System(s) affected: Body composition and strength; Bone; Cardiovascular; Reproductive; Mood; Central Nervous System; Hematologic
• Synonym(s): Hypogonadism; Hypoandrogenism; androgen deficiency in the aging male syndrome

Epidemiology

• 12.3/1,000 person-years in the US
• Late-onset hypogonadism: 481,000 new cases in the US men 40–69 years old

• 2–4 million men in US; because of problems of definition, the prevalence in women is undetermined.
• 12% of men in their 50s; 28% between 70 and 79; 49% in men ≥80

Risk Factors

• Obesity, type 2 diabetes, COPD
• Medications that affect testosterone production or metabolism
• Stress
• Undescended testicles
• Trauma; infection; radiation or tumors of testis, pituitary, hypothalamus; chemotherapy
• Exposure to environmental endocrine modulators
• Chronic infections or inflammatory disease

Some chromosomal disorders are inherited:

• Klinefelter: XXY karyotype (small testis, eunuchoid body habitus, gynecomastia)
• Kallmann: Abnormal gonadotropin-releasing hormone (GnRH) secretion due to abnormal hypothalamus development (micropenis, anosmia)

General Prevention

General health maintenance, such as prevention and treatment of obesity

Pathophysiology

• Normal hypothalamic–pituitary–testis axis:
  • Hypothalamus produces GnRH, which stimulates pituitary to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
  • LH stimulates the testis to produce testosterone.
  • Testosterone inhibits production of LH through negative feedback.
• Primary testosterone deficiency: Testes produces insufficient amount of testosterone; FSH/LH levels are elevated.
• Secondary testosterone deficiency (also known as hypogonadotropic hypogonadism): Low testosterone from inadequate production of LH

Etiology

• Congenital syndromes: Undescended testicles
• Orchiectomy; testicular trauma
• Infectious: Mumps orchitis, HIV/AIDS, tuberculosis
• Systemic:
  • Cushing syndrome
  • Hemochromatosis
  • Autoimmune
  • Granulomatous
  • Severe illness (e.g., renal disease, cirrhosis)
  • Sickle-cell disease
• Obesity; obstructive sleep apnea
• Drugs that decrease production: Corticosteroids, ethanol, ketoconazole, spironolactone, marijuana, opioids, cimetidine
• Elevated prolactin:
  • Prolactinoma
  • Dopamine antagonists block inhibitory dopamine effects on prolactin secretion: Neuroleptics, metoclopramide, etc.
• Idiopathic hypogonadotropic hypogonadism
• Chemotherapy
• Radiation to the testis

Commonly Associated Conditions

• Infertility, low sperm count, erectile dysfunction
• Osteopenia/Osteoporosis
• Diabetes, dyslipidemia, depression: Increased incidence and shorter time to diagnosis (1)
• Increased ratio of fat to lean body mass
• Free testosterone levels are lower in those with Alzheimer disease (2).