Weighing the Risks and Benefits of Testosterone Treatment in Male Hypogonadism

Failing to produce physiologically appropriate concentrations of testosterone and/or normal amounts of sperm can affect men in profound ways, depending on the causes and scope of their condition.

In a comprehensive review of the topic published in Lancet, Shehzad Basaria, MD, MBBS, of Brigham and Women’s Hospital and Harvard Medical School, noted that male hypogonadism may develop pursuant to either testicular disease or dysfunction of the hypothalamic-pituitary unit. Generally, affected patients present with signs and symptoms of androgen deficiency, which can be confirmed by testing for low serum testosterone (T) concentrations on multiple occasions.

Currently, very rough estimates indicate approximately 6% of American men have hypogonadism, although some surveys have reported rates up to 40%. Men with obesity, diabetes, and HIV infection are at increased risk, while systemic illness, eating disorders, drug misuse, and excessive exercise can cause transient hypogonadism.

Though the US Food and Drug Administration (FDA) has approved several T-replacement therapies to treat hypogonadism, the ideal drug and delivery vehicle depends on patient preference, insurance coverage, cost, availability, and formulation-specific properties. For instance, patients who have or have had prostate or breast cancers, uncontrolled congestive heart failure (CHF), severe lower-urinary-tract symptoms, or erythrocytosis are poor candidates for T replacement, and men who have prostate-specific antigen (PSA) levels >4 mcg/L, obstructive sleep apnea (OSA), or uncontrolled heart failure (HF) should not receive T treatment.

In the review, Basaria weighed the benefits and risks of injectable, oral, transdermal, and transbuccal T therapies, in addition to covering the end-organ effects of T supplementation and providing a concise treatment-monitoring plan.

Although Basaria said the benefits of T-replacement therapy typically outweigh the risks in young men with organic hypogonadism, he cautioned clinicians to be wary of potential long-term risks to the prostate and cardiovascular systems of men aged older than 60 years with pathological hypogonadism.