Androgen Deficiency in the Aging Male
A 69-year-old male is seen for an annual examination. He reports to his physician that he has a decrease in his libido, a decrease in the rigidity of the penis during sexual intimacy as well as rapid detumescence, a loss of energy, and is falling asleep after meals. The physical exam reveals a 3/4” loss of height since that recorded at his last examination, and decreased hair on his arms and legs. He has a minimally enlarged benign prostate gland. The serum testosterone was 220 ng/dL. The luteinizing hormone (LH) and prolactin levels were normal. Prostate-specific antigen (PSA) was 2.0 ng/mL. His hematocrit was 42%. A bone mineral density measurement using dual x-ray absorptiometry was suggestive of osteopenia.
With the aging of the baby boomers and their keen interest in wellness and sexuality, we can expect to see older male patients experiencing the clinical signs and symptoms of androgen deficiency. This deficiency seen in aging men has been compared to the hormone deficiency seen in menopausal women. However, menopause describes an absolute gonadal failure and the effects of abrupt withdrawal of estrogens. Older men experience a gradual decline of androgen production. This has been referred to as the syndrome of male hypogonadism, androgen deficiency in the aging male (ADAM), or partial androgen deficiency in the aging male (PADAM).1 The decline of serum testosterone appears to be age-related and gradual, estimated at about 1% decline per year after the age of 30 years. The prevalence of testosterone deficiency is estimated to be 20% in men age 60-69 and up to 50% in men older than age 80.2
It is estimated that there are 2-4 million men in the United States suffering from androgen deficiency, and only 5% of the men are receiving treatment.3 The cause of androgen deficiency is most commonly a result of decrease in production of testosterone in the Leydig cells within the testes. Other causes include a decreased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus resulting in inadequate production of LH from the anterior pituitary gland, and an increased production of sex hormone–binding globulin (SHBG) that binds the circulating testosterone, leaving less hormone available to target tissues. Medications known to decrease testosterone levels include GnRH agonists and antagonists, estrogens, glucocorticoids, thiazides, opiates, and some psychotropic drugs such as the selective serotonin reuptake inhibitors.2 Last, lifestyle factors such as obesity, tobacco abuse, and chronic alcohol ingestion will alter circulating androgen levels and affect target tissues.4
Clinical signs of androgen deficiency can be elusive. The most common clinical manifestations are shown in the Table. The laboratory evaluation consists of a total serum testosterone level. Normal values are 300-1000 ng/dL. The blood should be drawn in the morning, as serum testosterone has a diurnal variation and peaks between 8:00 and 10:00 am. Blood levels that are below 400 ng/dL are suspect for androgen deficiency. Low testosterone levels should have an LH level to differentiate primary from secondary hypogonadism and a serum prolactin level. Low levels of LH and/or prolactin should have an additional work-up to rule out tumors of the pituitary gland. Treatment for documented androgen deficiency with testosterone replacement therapy includes intramuscular injections, topical gels, and patches containing testosterone. Oral preparations should be avoided because of their associated hepatoxicity. Testosterone injections (200 mg of testosterone proprionate or testosterone enanthanate given every 2 weeks) are the least expensive. However, the injections are associated with supraphysiologic peaks immediately after the injections and troughs at the end of the 2-week period, with the attendant increase in symptoms.
Currently, the gels and patches that are applied every day provide the normal physiologic diurnal variation. As a result, the blood levels of testosterone are close to normal physiologic levels. All men who receive testosterone replacement therapy should have a PSA test and digital rectal exam to rule out prostate cancer. Patients need to be followed every 4-6 months, monitoring the hemoglobin and hematocrit and checking the serum testosterone level if there is no improvement in the clinical symptoms. Once the adequate dosage has been determined, follow-up exams every 6 months and an annual digital rectal exam and PSA test are required. Contraindications to testosterone replacement therapy include patients with known prostate cancer, breast cancer, or hematocrit levels about 55%. Relative contraindications include men with untreated obstructive sleep apnea, severe lower urinary tract obstructive symptoms, and congestive heart failure, because of the risk of fluid retention with testosterone replacement therapy.
OUTCOME OF THE CASE PATIENT
The patient received testosterone gel, one 5-g packet per day. He was seen in follow-up 3 months after initiating therapy, and he reported improvement in his energy level and libido, and a resolution of his erectile dysfunction. A follow-up PSA and hemoglobin were normal.
Androgen deficiency in the male is a common disorder affecting millions of American men. The symptoms are insidious and consist of decline in sexual function, decrease in cognitive abilities, decrease in muscle mass and strength, and decrease in bone mineral density. It is important for physicians caring for older men to query them about these signs and symptoms and, if present, to obtain a serum testosterone level. Patients with low or lower limits of normal serum testosterone should be considered as candidates for testosterone replacement therapy if there are no contraindications to its use.
The author reports no relevant financial relationships.