Benefits and Possible Risks of Testosterone Replacement Therapy

Hypogonadism, or reduced testicular function, can have serious health consequences for men if left untreated. Low testosterone can lead to infertility, impotence, weight gain, cardiovascular disease, osteoporosis and depression. Testosterone replacement therapy (TRT) is indicated for men with proven low testosterone levels to maintain secondary sex characteristics and control symptoms of hypogonadism.

 There are several methods of testosterone administration: intramuscular, transdermal, sublingual and buccal. What all these methods have in common is the avoidance of the gastrointestinal tract, since taking testosterone in pill form causes it to be rapidly deactivated in the liver, rendering it ineffective.

 In Bulgaria, the most available intramuscular testosterone is in the form of testosterone esters or testosterone undecanoate. In the first case, it is applied once every 14 to 21 days, and in the second - every 3 months.

 Contraindications for starting testosterone therapy include:

 1. Immediate reproductive desires – testosterone suppresses normal sperm production.

 2. High hematocrit levels.

 3. Men with breast or prostate cancer.

 4. Men with a palpable prostate nodule.

 5. Prostate-specific antigen (PSA) levels > 4 ng/ml or > 3 ng/ml and high risk for prostate cancer (eg, family history).

 6. Severe untreated sleep apnea.

 7. Severe heart failure.

 8. Experienced myocardial infarction or stroke in the previous 6 months.

 9. Thrombophilia.

Before starting testosterone replacement therapy, especially in men over the age of 50, PSA should be tested and a urologist should be consulted to rule out a prostate mass. After initiation of therapy, PSA should be monitored every 3 to 12 months. Re-consultation with a urologist is necessary if within the first 12 months there is an increase in PSA of more than 1.4 ng/ml compared to the baseline or if the value reaches more than 4 ng/ml.

 Symptoms of hypogonadism were assessed 3 to 12 months after initiation of therapy and annually thereafter. Treatment with testosterone esters may have more labile symptom control due to large variations in serum testosterone levels, whereas testosterone undecanoate has a more stable action profile.

 Testosterone levels are monitored for the first 3 to 6 months, then once a year, with the goal of being in the middle of the normal range.

The hematocrit is examined 3 to 6 months after the start of therapy and then once a year. If it rises above 54%, therapy should be suspended until it normalizes, after which it can be resumed at a lower dose.

 In men with osteoporosis, bone density monitoring of the lumbar spine and/or femoral neck is recommended for 1 to 2 years after initiation of therapy.

 Benefits of testosterone replacement therapy

 1. Secondary sexual characteristics:

     - In young men who have not reached puberty, testosterone therapy leads to the development of secondary sex characteristics such as facial hair, voice loss, bone and muscle mass gain, and penis enlargement.

 2. Improving libido and sexual function:

     - In men with proven low testosterone levels, an improvement in libido and sexual function is observed. Testosterone has no effect in men with normal levels of the hormone. In these cases, 5-alpha reductase inhibitors (eg sildenafil) are recommended.

 3. Increasing self-esteem and reducing depressive symptoms:

     - Testosterone replacement therapy can improve self-esteem and reduce depressive symptoms. It also increases physical potential and the accumulation of muscle mass, significantly improves the ratio of muscle to fat tissue and, accordingly, the metabolic profile.

 4. Improvement of bone density:

     - In men with hypogonadism and osteoporosis, an improvement in bone density may be observed. At high fracture risk, additional treatment specific to osteoporosis may be necessary.

 Adverse effects of testosterone replacement therapy

 1. Acne and oily skin.

 2. Erythrocytosis (increased number of red blood cells).

 3. Detection of subclinical prostate carcinoma and growth of metastatic tumors.

 4. Decreased spermatogenesis and fertility.

 5. Gynecomastia or development of mammary gland carcinoma.

 6. Balding.

 7. Provoking or worsening sleep apnea.

References

- Shalender Bhasin, Juan P Brito, Glenn R Cunningham, Frances J Hayes, Howard N Hodis, Alvin M Matsumoto, Peter J Snyder, Ronald S Swerdloff, Frederick C Wu, Maria A Yialamas, Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 5, May 2018, Pages 1715–1744, [https://doi.org/10.1210/jc.2018-00229](https://doi.org/10.1210/jc.2018-00229)