Male hormone replacement including testosterone
The average age of men in the U.S. is projected to rise significantly over the next 25 years. As this happens, there will be a dramatic increase in age-related health problems too, including cancer, strokes, heart disease and hormone deficiency. Although the health risks associated with age-related hormonal decline in women, termed menopause, have been thoroughly addressed, it has now been shown that hormonal changes in the aging male are associated with significant health problems.
Male testosterone and age
There is a progressive decline in testosterone production in men with age. A general rule of thumb is that testosterone levels decrease about 1% yearly after age 30. Despite the fact that it is not as rapid a drop in hormones as women get with menopause, it certainly is just as real. This has been termed male menopause, male climacteric, andropause, or more appropriately, partial androgen deficiency in the aging male (PADAM). Serum testosterone levels in men fall progressively from the third decade to the end of life, mainly due to a decline in the cells in the testis that make the hormone (Leydig cells). This decline may also be due to changes in hormones (GnRH, LH) and proteins (SHBG, albumin) that regulate testosterone production.
The role of testosterone in men
Testosterone affects the function of many organs in the body (Table 1). In the brain, it influences libido or sex drive, male aggression, mood and thinking. Testosterone can improve verbal memory and visual-spatial skills. It as also been shown to decrease fatigue and depression in men with low levels. It is responsible for muscle strength and growth, and stimulates stem cells and blood cells in bones and kidneys. Penile growth, erections, sperm production, and prostatic growth and function all depend on testosterone. It also causes body hair growth, balding, and drives beard growth. Thus, testosterone makes us who we are, and influences how we look.
TABLE 1. TESTOSTERONE EFFECTS IN THE NORMAL MALE
Suppression of clotting factors (II, V, VII), low HDL-cholesterol
Stimulates erythropoietin production which increases blood counts
Linear growth, closure of the epiophyses, increases bone mineral density
Advantages of testosterone replacement therapy
- Better bones: In men with low testosterone levels, testosterone can improve bone mineral density and reduce bone fractures, an effect similar to that found in postmenopausal women on estrogen replacement. Importantly, hip fractures are 2-3 times as likely to kill an older man as a woman of the same age, and 40% of older male patients with hip fractures die within 1 year of the injury.
- Leaner body: Testosterone results in increases in lean body mass, possibly strength and can decrease fat mass. By stimulating erythropoietin, testosterone increases blood counts. It appears to improve lipid profiles and dilates blood vessels in the heart but no data has yet shown that it reduces heart attacks or strokes. It appears not to alter LDL or total cholesterol levels. In recent work, it has been shown that men with chronically low testosterone levels have 2-3 fold higher risk of developing metabolic syndrome and have up to a 40% greater risk of death than men with normal testosterone levels.
- Better sexual health: Sexual function also improves with testosterone. Most studies agree that sexual drive is improved by testosterone. Penile erections may be improved with testosterone, but only in men with low testosterone levels. Important, isolated low testosterone is an unusual (6%) cause of erectile problems in older men as lower sex drive and age-related changes to the penis are far more common.
Low testosterone symptoms and diagnosis
To make an accurate diagnosis of low testosterone, symptoms or findings must accompany a blood draw showing a low testosterone level. This combination makes treatment worthwhile to pursue. Symptoms include decreased sexual desire and erectile dysfunction, changes in mood associated with fatigue, depression and anger, and decreases in memory and spatial orientation ability. On examination, there may be decreased lean body mass with reduced muscle volume and strength, and increases in abdominal girth. Decreased or thinning of facial and chest hair and skin alterations such as increases in facial wrinkling and pale-appearing skin suggestive of anemia may also be noted. Testicles that have become smaller or softer may also be present. Finally, low bone mineral density with osteopenia or osteoporosis may also suggest a problem.
Not all of these findings need to be present at the same time to diagnose the problem. In fact, many of these symptoms can be attributed simply to the natural and unavoidable consequence of aging. For example, frailty may be due to many causes, some of which include loss of muscle strength, bone fractures, decreased mood, and impaired cognition, symptoms typical of testosterone deficiency. However, the association of such symptoms along with a low testosterone certainly implicates this as a problem. By these criteria, it is estimated that only 10% of men with low testosterone levels are currently being diagnosed.
Monitoring of testosterone therapy
Testosterone replacement is generally considered a long term therapy and patients need to be monitored regularly as outlined in Table 3. Prior to starting treatment, a digital rectal examination and serum PSA are important. Within a month or two after treatment is started, symptoms and testosterone levels should be assessed. During the first year of therapy, patients should be followed regularly to assess clinical response. After the first year, patients who are stable may be followed annually. Annual evaluations should include testosterone, hemoglobin, liver function tests, lipid profile and PSA tests. Bone density and psychological evaluations can be done depending on the original reasons for treatment.
TABLE 3. TESTOSTERONE EFFECTS IN THE NORMAL MALE
|Time Period||Indicated Assessment|
|Baseline (Pre-treatment)||Blood counts (hematocrit), Full Testosterone pannel, PSA. Estrodial, liver and lipid profile to create baseline|
|2-3 months of treatment||Assess efficacy: testosterone level and symptoms. Adjust dose for either variable. Add estrogen receptor lockers if needed.|
|3-6 month intervals during 1st year||Assess symptomatic response, voiding symptoms and sleep apnea. Testosterone, liver and lipid profile, PSA, and hematocrit (depending on formulation).|
|Annually after 1st year||Assess symptomatic response to treatment, voiding symptoms and sleep apnea. Testosterone, liver and lipid profile, PSA, and hematocrit (depending on formulation).|
Risks and side effects of testosterone therapy
The general risks of testosterone replacement are:
- Water retention: This may lead to hypertension, leg swelling, or worsening heart failure. Weight and blood pressure monitoring are important for at-risk patients on therapy.
- Infertility: Testosterone therapy of any type generally leads reduced sperm production. In fact, zero sperm counts occur in 90% of patients within 10 weeks of starting therapy. Sperm counts usually rebound within 6-12 months after therapy is stopped. Patients on testosterone should be informed that fertility will be impaired during treatment. However in most cases it will rebound if therapy is stopped.
- Excessive red blood cell count: Excessive red blood cell count (polycythemia) was a commonly observed side effect in a meta-analysis of clinical trials of testosterone therapy. Blood counts (hematocrit) levels above 50 have been associated with an increased risk of stroke. Polycythemia is most commonly seen with injectable testosterone. Monitoring blood counts is important for patients on testosterone replacement. In addition, testosterone may suppress clotting factors II, V, and VII, and worsen bleeding in patients on anticoagulation.
- Liver damage: Liver damage has been reported with oral treatments. However, it is very rarely observed with injectable formulations.
- Sleep apnea: Although it does not cause sleep apnea, testosterone therapy can worsen existing sleep apnea. Men at risk of sleep apnea include elderly and obese men, and those with chronic obstructive pulmonary disease.
- Breast tenderness: Painful breast enlargement (gynecomastia) due to high levels of estrogen (which comes from testosterone) can develop during therapy. Medications call estrogen receptor blockers can treat this side effect. These blockers are included in the Nextgen protocol.
- Altered cholesterol balance: Testosterone therapy is not thought to affect total cholesterol or LDL cholesterol, but the affect on high-density lipoprotein (HDL) levels remains unclear. It is reasonable to follow lipid levels during treatment.
- Prostate health: One of the most concerning risks of androgen replacement is the potential to worsen detected or undetected prostate cancer. However, no link has been made to testosterone replacement and the development of prostate cancer. Careful follow-up of patients at risk for prostate cancer while on testosterone therapy is important. The FDA recommends that testosterone therapy not be given to men with prostate or breast cancer. A second concern is whether testosterone treatment worsens urinary symptoms in men with enlarged prostates. For this reason, voiding symptoms should be monitored in treated patients.