Table of Contents

Chapter 6: Using Hormone Therapy

i. Blocking Testosterone Release

The hypothalamus is a small structure in the brain that helps to regulate many of the normal metabolic functions such as body temperature and water balance. Part of the way that it does this is by releasing chemicals that trigger other parts of the body to release hormones. The first step in testosterone release occurs when the hypothalamus releases luteinlzing-hormone releasing hormone (LHRH), which causes the pituitary gland at the base of the brain to release luteinizing hormone (LH). LH, in turn, stimulates the testicles, or testes, to secrete testosterone. (Note that LHRH is sometimes called GnRH, or gonadotropin-releasing hormone.)

Because LHRH release is the first step in this process, one common therapeutic strategy to block the secretion of testosterone is the use of LHRH agonists or analogues. These drugs mimic the action of LHRH, and effectively force the system to shut down because of LHRH overload. Upon shut-down, the testicles receive no signal to produce or secrete testosterone, so the factory production lines are halted. Drugs in this class include leuprolide (Eligard, Lupron, and Viadur), goserelin (Zoladex), and triptorelin (Trelstar).

The LHRH antagonist abarelix (Plenaxis) directly prevents the release of LHRH by the hypothalamus. As of this writing, this drug has been discontinued by the manufacturer and is now only available to men who had already been receiving it from their doctors. No other LHRH antagonists are as yet available.

As an alternative to drug therapy, the surgical removal of the testicles, known as orchiectomy or surgical castration, will shut down the testosterone factory in the testicles permanently. This approach has been used successfully since the 1940s, but because it’s a permanent and irreversible surgical solution, most men opt for drug therapy instead.

Some advantages to orchiectomy include its low cost and simplicity compared to multiple years’ worth of LHRH agonists: the procedure is performed on an outpatient basis in your urologists’s office and regular LHRH injections are not needed.

A final option in this setting is the use of estrogens, hormones that inhibit LHRH release from the hypothalamus. Like orchiectomy, the estrogens were used early in prostate cancer research studies, and have proven effective in many men. But it has also been linked to an increase in cardiovascular side effects and, because it is one of the main hormones that affect female characteristics, signs of demasculinization such as increased breast size and tenderness, are commonly seen. Typically, doctors will save this option for men whose PSA levels are rising after they start to lose their sensitivity to hormone therapy.