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.

DIHYDROTESTOSTERONE (DHT)

The natural androgen DHT is a metabolite of testosterone. It is a selective androgen because, unlike testosterone, it cannot be converted to estrogens. It is also a potent androgen, binding to receptors more avidly than testosterone. DHT has an effect on several target tissues, including external genitalia, prostate and skin. DHT deficient men have normal muscle mass and are not osteoporotic. In normal men, DHT supplements suppress pituitary FSH and LH secretion, likely causing infertility. As an androgen, DHT is relatively “prostate sparing.” Because of its potency and potential, significant research is being conducted with DHT supplements for androgen replacement.

DEHYDROEPIANDROSTERONE (DHEA)

DHEA is available in over-the-counter formulations in the US. It is a steroid hormone made by the adrenal gland and its level progressively declines beginning the third decade of life and beyond. As a consequence of this, studies have attempted to correlate levels of DHEA and DHEA-sulfate with many health conditions. Clinical trials looking at DHEA for multiple conditions have been inconsistent. Placebo-controlled studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels. In men with poor adrenal function, 50mg of oral DHEA can increase serum androgen levels to within the physiologic range for young adults, improve sexual function, mood and self-esteem, and decrease fatigue/exhaustion. However, its value in older men is not well established.

GROWTH HORMONE

There are decreases in growth hormone and insulin-like growth factor-I with age in both men and women. In addition, treatment of young GH-deficient adults with growth hormone improves body composition, muscle strength, physical function, and bone density, and reduces blood cholesterol and cardiovascular disease risk. Some of these improvements are in health domains similar to those affected by testosterone. However, growth hormone treatment is often accompanied by carpal tunnel syndrome, peripheral swelling, joint pain and swelling, breast tenderness, glucose intolerance, and possibly increased cancer risk. In older individuals, growth hormone treatment improves lean body mass and reduces body fat. However, clinically significant functional benefits, prolongation of youth, and life extension have not been demonstrated. Until more research better defines these risk/benefit relationships, treatment of elderly individuals with growth hormone is not recommended.

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.

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, transdermal and transbuccal 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.

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.

Contact Dr. Turek about Male Hormone Replacement

References:

• Turek PJ. Smith’s Urology, 17th ed. Edited by EA Tanagho and JC McAninch. Appleton and Lange, Stamford, 2003. Chapter 46.