IMPORTANT NOTE: JAAPA CME activities consist of 2 articles. To obtain credit, you must also read
Juvenile idiopathic arthritis: Can you
recognize this complex diagnosis?; the post-test will include questions related to both articles. AAPA Fellow members should complete and submit the post-test on the AAPA Web site by going to
www.aapa.org and searching for keyword
JAAPA post-tests. All others may complete and submit the post-test online at no charge at
www.mycme.com. To obtain 1 hour of AAPA Category I CME credit, PAs must receive a score of 70% or better on each test taken.
KEY POINTS
■ The Endocrine Society advises against screening for hypogonadism in the general population and recommends taking a conservative approach to testosterone replacement therapy (TRT) in older men.
■ TRT is FDA-approved for the treatment of hypogonadism.
■ No large-scale, placebo-controlled studies on the long-term effects of TRT have been completed.
■ Patients receiving TRT should be monitored regularly for symptom response and potential side effects.
As the American population ages,1 physician assistants will likely encounter more older patients seeking medical therapies to improve quality of life. Short-term studies on the effects of testosterone replacement therapy (TRT) suggest that testosterone may be one such treatment. Testosterone also has the potential to benefit certain younger patients, and its use is becoming increasingly popular. As of 2008, prescriptions for testosterone numbered more than 3.3 million.2 Growing use of testosterone replacement may be attributable, at least in part, to pharmaceutical marketing. Patients watching television or searching online may encounter the term low T, a reference to low testosterone levels,3 and be enticed by promises of improved sexual function, muscle mass, and mood.
The use of testosterone replacement therapy is controversial. To date, no large-scale, placebo-controlled studies on the long-term effects of testosterone replacement have been completed. However, patients exposed to marketing efforts and armed with Internet-acquired medical information may expect health care providers to be knowledgeable about testosterone replacement, even as the research evolves. The FDA has approved testosterone to treat hypogonadism, a condition that can result from low testosterone levels, and more patients are using TRT. Therefore, PAs need to familiarize themselves with the indications, risks, and management guidelines associated with testosterone replacement.
HYPOGONADISM
The terms androgen deficiency and hypogonadism are used interchangeably and refer to a clinical syndrome in which a patient with low testosterone levels manifests one or more consistent signs or symptoms.4,5 The signs and symptoms associated with hypogonadism include diminished energy, depressed mood and impaired cognition, diminished muscle mass and strength, decreased bone density, anemia, and sexual symptoms such as erectile dysfunction (ED) and diminished libido.
More specific signs and symptoms include incomplete sexual development, eunuchoidism; reduced sexual desire (libido) and activity, decreased spontaneous erections; breast discomfort, gynecomastia; loss of body (axillary and pubic) hair, reduced shaving; small or shrinking testes (especially <5 mL); inability to father children, low sperm counts; height loss, low-trauma fracture, low bone mineral density; and hot flushes, or sweats.4
Less specific symptoms and signs include decreased energy, motivation, initiative, aggressiveness, self-confidence; feeling sad, depressed mood, dysthymia; poor concentration; sleep disturbance, increased sleepiness; mild anemia (normochromic, normocytic, in the female range); reduced muscle bulk and strength; increased body fat, increased body mass index; and diminished physical or work performance.4
Hypogonadism affects as many as 4 million men in the United States5 and is considered common in aging men6 and in those with HIV4,7 or type 2 diabetes mellitus.8 Hypogonadism may also occur in association with other diseases or result from the use of certain medications (Table 1). Forms of hypogonadism include primary hypogonadism, which occurs when the testicles fail to produce adequate levels of testosterone; and secondary hypogonadism, which results from a failure of the hypothalamus or pituitary to produce sufficient levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Both forms may be congenital or acquired. Combined primary and secondary hypogonadism occurs when both testicular and hypothalamic-pituitary function are diminished.
MEASURING TESTOSTERONE LEVELS
Total serum testosterone is the measurement generally used to guide testosterone replacement therapy. The total testosterone level includes free testosterone, testosterone bound to sex hormone-binding globulin (SHBG), and testosterone bound to albumin. SHBG, a glycoprotein that is produced in the liver and transports testosterone in the blood, binds 60% to 70% of testosterone.9 This SHBG-bound testosterone is biologically inactive. Free (1%-3%) and albumin-bound (20%-30%) testosterone are available to tissues and are therefore termed the biologically active or bioavailable fraction.9
A total serum testosterone level between 300 and 1,000 ng/dL is considered normal, although testosterone assays are not currently standardized and slight variations between laboratories may exist. An absolute level to define hypogonadism has not been established; however, testosterone levels higher than 200 to 300 ng/dL are generally accepted as normal.4,10 Testosterone levels vary throughout the day. The most accurate measurements are drawn before 10:00 am.11
Measurement of both total and free testosterone levels may help identify the etiology of testosterone deficiency. For example, obesity is associated with a decrease in the serum concentration of SHBG. A lower SHBG concentration results in a subsequent decrease in total testosterone level, while the level of free testosterone remains unaffected.
Select groups, such as men with HIV disease, may benefit from testing for testosterone deficiency regardless of symptoms. However, The Endocrine Society guidelines advise against screening for androgen deficiency in the general population.4