Determining when men need testosterone

Klinefelter syndrome is a genetic disorder and cause of primary hypogonadism.
Klinefelter syndrome is a genetic disorder and cause of primary hypogonadism.

Testosterone deficiency, or hypogonadism, is the most common type of hormonal deficiency in men. In middle-aged men, testosterone levels decrease 1%-2% yearly with advancing age. Studies suggest that approximately 20% of men in their 60s and 50% of those in their 80s have low serum testosterone levels.1 Obesity, metabolic syndrome, type 2 diabetes mellitus, and hypertension may increase the risk of hypogonadism.2

Men with testosterone deficiency have symptoms that are often underrecognized, underreported, or denied by the patient and the clinician alike. Some of the symptoms overlap with those of other chronic conditions, especially depression and fatigue. Key complaints that should lead to the suspicion of testosterone deficiency are changes in sexual function (especially a decline in erectile quality), libido, and ejaculate volume.3 Other symptoms include:

  • Infertility 
  • Decrease in beard and body hair growth 
  • Increase in body fat 
  • Decrease in size or firmness of testicles 
  • Decrease in muscle mass 
  • Development of breast tissue (gynecomastia) 
  • Loss of bone mass (osteoporosis )

Testosterone deficiency can also contribute to mental and emotional changes. As testosterone levels decrease, some men may experience symptoms similar to those of menopause in women but without the certain cessation of reproductive function. Besides depression, these symptoms may include irritability, fatigue, and decreased sex drive.

Other than aging, there are several other causes of testosterone deficiency in an adult male, and these are categorized as primary, secondary, or combined. Causes of primary hypogonadism include Klinefelter syndrome (a chromosome abnormality), undescended testes, injury to the testes, or testicular damage attributable to radiation or chemotherapy.

Secondary hypogonadism results from failure of the pituitary to produce enough follicle-stimulating hormone and luteinizing hormone to stimulate the testes. Common causes include obesity, stress, aging, recreational drug use, and pituitary lesions or other endocrine causes.

Combined hypogonadism exhibits characteristics of both primary and secondary causes and is commonly seen with cirrhosis, aging, and sickle cell disease.

Clinical exam

The clinician should first investigate possible causes of acquired testicular failure (e.g., mumps orchitis, trauma, radiation exposure, surgery, and chemotherapy). Inquire about both prescription and recreational drug use, since certain agents (e.g., spironolactone, marijuana, heroin, and methadone) may interfere with testosterone synthesis. Establish whether there is a history of paternity—an indicator that at some point in the past, the testosterone level likely was normal.

The diagnosis of testosterone deficiency is based on examination findings and a test of the serum testosterone levels. Specific issues to consider in the physical exam include developmental anomalies in the genital system. Examine the genitalia for hypospadias (a congenital opening of the urethra on the undersurface of the penis), and check the scrotum for signs of cryptorchidism (undescended testes). Determine whether both testes are palpable, their position in the scrotum, and their consistency and size. Examine for signs of Klinefelter syndrome, such as tall stature (especially if the legs are disproportionately long), small or soft testes, and a eunuchoid body status, although many patients will not demonstrate a “typical” Klinefelter habitus. Finally, evaluate the extent of body virilization. Inquire about the rate of beard growth, libido and sexual function, muscle strength, and energy levels. Check for gynecomastia. The physical examination is typically unhelpful in making the diagnosis of testosterone deficiency, except in cases of profound and long-term hypogonadism.

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