Alternatives to Testosterone Replacement Therapy

Adult male hypogonadism (HG) is the most common form of diminished gonadal activity in men. Most clinicians prescribe testosterone replacement therapy (TRT) to treat primary HG, but other therapeutic options are available. Researchers from the University of Florence in Florence, Italy, have published an expert opinion piece in the December 2014 issue of Expert Opinion in Pharmacotherapy.

These researchers stress that clinicians need to respect patients’ needs and expectations, especially as they relate to fertility. They note that TRT leads to a paradoxical effect: it shuts down gonadotropin production which suppresses any residual testicular activity (i.e., spermatogenesis) and can further atrophy the testes.

The authors review several alternatives with an eye to effectiveness and cost.

Men with secondary HG (sHG) who have concerns about fertility can be treated with gonadotropin therapy, the treatment of choice. Gonadotropin-releasing hormone therapy is an alternative but it is quite costly and plagued with adherence issues. Approximately 75% of men respond to these treatments with improved sperm counts.

Obese men with HG often experience significant improvement with lifestyle modifications and especially weight loss.

Antiestrogens have been used to treat sHG and restore fertility. An investigational drug, enclomiphene has been shown to improve hormonal levels, sexual activity, and sperm production.

Stimulating hypothalamic activity with kisspeptin or neurokinin-B agonists can also address HG.

These experts recommend using TRT for primary HG when fertility is not a concern. They address the pros and cons of each alternative in this well-written review.