Testosterone replacement therapy: The focus is shifting

February 1, 2009

Hypogonadism, or low serum testosterone, is associated with the unpleasant sequelæ of fatigue, low sex drive, diminished erections, and an increased tendency for fractures due to decreased bone mineral density.

The incidence of hypogonadism increases with age, as does the occurrence of prostate cancer, and many men with this malignancy will exhibit the symptoms of hypogonadism. In the past, these men were denied TRT, as it was thought that replacing testosterone would exacerbate their disease-an inference based on the finding that removing male hormone halts the progression of advanced prostate cancer in most men.

Supporting this theory were studies from the 1960s in which men with advanced disease who had undergone bilateral orchiectomy were given TRT. A large number of these men soon expired of their cancer.

In men with advanced prostate cancer whose disease has been stabilized by LHRH agonists, some urologists are administering intermittent hormone ablation, in which patients are given a holiday from the unpleasant symptoms of hypogonadism by temporarily stopping the LHRH agonist until testosterone levels rise. Many of these men have gone without hypogondal symptoms for prolonged periods, and are able to lead more enjoyable and productive lives.

It seems that the androgen receptor in the prostate cell has a limited ability to bind testosterone derivatives and is saturated at a low level. At this level, additional testosterone cannot influence prostate growth. In castrate men, the level may be so low that additional testosterone can bind to the receptor and accelerate multiplication of prostate cells. This theory may explain the different response to testosterone replacement in castrated and non-castrated prostate cancer patients.

There is an increasing trend to treat hypogonadism in the presence of prostate cancer (see, "TRT may be viable Tx option in men with prostate Ca," page 1). Numerous recent manuscripts reinforce the safety of this approach. If one is to embrace this trend, careful follow-up on PSA levels is prudent at least twice a year initially and yearly thereafter.

The focus seems to be shifting from flaming the fire of prostate cancer with testosterone replacement to not denying the hypogonadal patient with prostate cancer his rightful due and equal quality of life with his eugonadal peers.

Dr. Mulcahy, a member of the Urology Times Editorial Council, is in private practice in Phoenix.