Clinical Hypogonadism and Androgen Replacement Therapy: An Overview

Side Effects of Testosterone Replacement

Coronary Artery Disease Risk

Because men have a higher incidence of cardiovascular risk, it is proposed that they are at higher risk for heart disease. In reality this relationship is poorly defined. Published studies of testosterone replacement have not shown an increase of adverse cardiac events (Rhoden & Morgentaler, 2004) but patients with established risk factors must be carefully assessed.

Fluid Retention

This side effect may be most pronounced in the frail or ill elderly male, and generally resolves after the first few months of treatment.

Alteration of Serum Lipid Profile

While many of the existing studies are inconsistent in their reporting of the effects of testosterone replacement therapy on serum lipid levels (Rhoden & Morgentaler, 2004), evidence suggests that testosterone replacement does not affect the lipid profile. Nonetheless, some data seems to indicate that supraphysiologic doses of testosterone will raise low-density lipoproteins, lower high-density lipoprotein, and raise triglycerides (Morales et al., 2000). However, as the goal of testosterone treatment is restoration to the normal range, the risk seems to be modest.

Liver Toxicity

All prescribing information for available forms of exogenous testosterone in cludes some mention of risk for liver toxicity. The risk for liver toxicity is highest with oral preparations, modest with injections, and exceedingly low with the topical preparations. No incidence of liver toxicity has been reported in any clinical trial, but this continues to influence how caregivers follow patients on testosterone replacement.

Polycythemia

Some men exhibit a marked increase in red blood cell production that requires testosterone therapy be stopped, be significantly titrated, or can even require phlebotomy (Vermeulen, 2001). The risk appears to be higher with IM preparations (Rhoden & Morgentaler, 2004) and may be due to the supraphysiologic levels that are seen. This risk is also higher in men who have co-morbidities known to increase hematocrit levels, such as chronic obstructive lung disease.

Prostate Disease

This is the most troublesome potential side effect. Tumors of the prostate are androgen sensitive, and the growth of the prostate itself is influenced by the presence of testosterone and its metabolite DHT. Rhoden and Morgentaler (2004) reported that several studies failed to show an acceleration of voiding symptoms after androgen replacement therapy. These authors also reported that there has been a low frequency of prostate cancer in men treated for hypogonadism, although the available data extends only 36 months. They concluded that there are no data to support the claim that treatment with exogenous testosterone increases the risk for prostate cancer.

Sleep Apnea

Androgen replacement appears to have some poorly understood influence centrally on the control of breathing (Rhoden & Mor gentaler 2004) and may worsen sleep apnea in patients who have been previously diagnosed. This correlation has not been conclusively established.

Impairment of Spermatogenesis

Administration of exogenous testosterone interrupts the normal signaling of the HPA, and will result in oligospermia or azoospermia that may not be reversible. While this may be of little concern to the patient with ADAM, it can significantly alter the management of hypogonadism in men who wish to preserve their fertility.

Cite this: Clinical Hypogonadism and Androgen Replacement Therapy: An Overview - Medscape - Aug 01, 2006.

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