Testosterone treatment is controversial for men and even more so for women. Prescriptions for testosterone are becoming more common. Testosterone is used primarily to treat symptoms of sexual dysfunction in men and women and hot flashes in women.
Potential benefits include improved libido, increased bone mass, and an increased sense of well-being. In individuals with human immunodeficiency virus infection or other chronic diseases, testosterone has been shown to improve mood and energy levels, even in patients with normal testosterone levels.
Testosterone can be administered by injection, patch, topical gel, pill, or implant. Side effects in men include polycythemia and acne. Side effects in women include acne, hepatotoxicity, and virilization and usually, only occur when testosterone is used in supraphysiologic doses.
Long-term studies of the effects of testosterone on prostate cancer, breast cancer, and heart disease have not been completed. Mammograms and monitoring of prostate-specific antigen, hematocrit, and lipid levels are recommended for patients taking testosterone.
In the United States, approximately 43 percent of women and 31 percent of men experience sexual dysfunction. It is not surprising that testosterone, primarily used to treat sexual problems, is being prescribed more often than in the past; a 500 percent increase in sales has been documented from 1993 to 2001. However, testosterone therapy is controversial, particularly for use in women.
The safety and effectiveness of testosterone supplementation have not been clearly defined, although there is an extensive review by the Institute of Medicine outlining what is known about testosterone therapy in older men.
Testosterone in Men
Testosterone levels in adult men decline at an average rate of 1 to 2 percent per year. This change can be caused by the normal physiologic changes of aging, testicular dysfunction, or hypothalamic-pituitary dysfunction. By 80 years of age, more than 50 percent of men have testosterone levels in the hypogonadal range. Hypogonadism is defined as a low serum testosterone level coupled with any of the signs and symptoms outlined below. The presentation varies from person to person.
Signs and Symptoms of Hypogonadism in Men
- anemia;
- depressed mood;
- diminished bone density;
- diminished energy, sense of vitality, or sense of well-being;
- diminished muscle mass and strength;
- impaired cognition;
- increased fatigue.
Sexual symptoms include decreased libido, erectile dysfunction, difficulty achieving orgasm, the diminished intensity of the experience of orgasm, diminished sexual penile sensation.
Testosterone Measurement
Laboratory measures of testosterone include total testosterone, free testosterone, and steroid hormone-binding globulin. In addition, luteinizing hormone and follicle-stimulating hormone levels can be used to differentiate primary from secondary hypogonadism.
Approximately 98 percent of the circulating testosterone is bound to steroid hormone–binding globulin or albumin. The amount of bioavailable testosterone is the sum of the free testosterone and a portion of the bound testosterone. Total testosterone (normal range, 300 to 1,000 ng per dL [10.4 to 34.7 nmol per L]) is the most commonly used measure of testosterone in research studies and in clinical practice.
Changes in steroid hormone–binding globulin can affect the bioavailable testosterone. Because measures of bioavailable testosterone are not standardized, they are not used routinely. There are no consistent guidelines for the level of total testosterone that defines hypogonadism; however, many studies use the American Association of Clinical Endocrinologists (AACE) definition of a total testosterone level of less than 200 ng per dL (6.9 nmol per L).
Causes of Hypogonadism in Men
Primary (decreased testosterone, increased luteinizing hormone, and follicle-stimulating hormone):
- Klinefelter syndrome;
- androgen receptor defects;
- 5–alpha-reductase deficiency;
- myotonic dystrophy;
- cryptorchidism;
- hemochromatosis;
- mumps orchitis;
- aging;
- HIV; AIDS; other chronic diseases.
Secondary (decreased testosterone, normal or decreased luteinizing hormone, and follicle-stimulating hormone):
- Kallmann syndrome;
- fertile eunuch syndrome;
- pituitary disorders;
- HIV; AIDS; other chronic diseases.
Possible Benefits of Testosterone Therapy for Men
Possible benefits of testosterone replacement therapy in men are as follows:
- increased libido;
- Increased lean muscle mass;
- Improved cognition;
- Improved mood;
- Increased sense of well-being;
- Decreased erectile dysfunction;
- Increased bone density;
- Increased muscle strength;
- Increased muscle mass.
Which disorders can be treated with testosterone?
Sexual Dysfunction
Men with low testosterone levels commonly complain of decreased sex drive or erectile dysfunction. Treatment with testosterone gel, transdermal patch, or intramuscular injection is indicated for men with low total testosterone levels who have these symptoms.
Regardless of the route of administration, studies have shown improvement in libido and sexual function in hypogonadal men. Other small, short-term trials of sexual function in men, including some with men who have normal testosterone levels, show mixed results. The optimal delivery method has not been determined.
Bone Density, Body Composition, and Muscle Strength
The bone mineral density of hypogonadal men decreases as testosterone levels decrease, potentially increasing the risk of fractures. Bioavailable testosterone and estrogen levels are more correlated with density changes than total testosterone.
Testosterone replacement may stop bone loss and increase bone density; however, many studies demonstrate equivocal results, and none have shown a decreased rate of fractures with testosterone therapy. Lean body mass increases consistently occur with testosterone treatment in healthy men; however, muscle strength does not significantly increase.
Depression, Mood, Cognition, and Well-Being
The indications for the use of testosterone in cognitive and psychological impairment are still unclear; however, studies of healthy older men with testosterone deficiency have yielded interesting results. Neuropsychological testing has revealed improvements in spatial cognition and spatial and verbal memory with testosterone replacement.
Little positive effect on mood or depression has been clearly demonstrated for hypogonadal men. Two trials (not placebo-controlled) have demonstrated improvements in quality of life.
HIV and AIDS
Most men with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) have decreased androgen levels, although the levels may remain in the low-normal range.
Testosterone replacement has been shown to increase mood and sense of well-being in this population. Improvements in libido, energy, and muscle strength also have been demonstrated.
Safety
Most studies of testosterone therapy in hypogonadal men have been on men younger than 65 years, but the Institute of Medicine examined the effectiveness and safety of testosterone treatment in older men. The committee found no compelling evidence of major adverse side effects resulting from testosterone therapy.
However, because of the lack of well-done, long-term studies, the report states that its use is appropriate only for those conditions approved by the U.S. Food and Drug Administration (FDA) and that it is inappropriate for wide-scale use of testosterone therapy to prevent possible future disease or to enhance strength or mood in otherwise healthy older men.
Because of safety concerns, the Institute of Medicine recommended that well-constructed, short-term studies of testosterone in older men be conducted for conditions that do not already have effective therapies. If effective, they recommended that long-term studies be conducted to determine safety.
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