Review ArticleTestosterone Surge: Rationale for Gonadotropin-Releasing Hormone Blockers?
Section snippets
Characteristics of Testosterone Surge and Clinical Flare
The initial response to treatment with a GnRH agonist is a transient increase in the LH and testosterone levels. The LH levels can increase by up to 10-fold, and the testosterone levels can increase by approximately twofold. These increases are evident 2 to 3 days after the initial injection and can last up to 10 to 20 days from administration.8, 9 In turn, the increase in testosterone levels induces an increase in prostate-specific antigen, a marker of tumor growth (Fig. 3).10 Additional
Clinical Effect of Testosterone Surge
Accumulating evidence has suggested that, as well as inducing a worsening of clinical symptoms in many patients with metastatic disease, the testosterone surge associated with GnRH agonist therapy might also affect survival. As reviewed by Thompson et al.,15 sudden deaths during the flare associated with GnRH agonist therapy have been reported in seven series of patients. In these series involving approximately 300 patients (the exact number of patients involved was not given for three of the
GnRH Antagonists
GnRH antagonists are a new class of ADT that could have significant clinical benefits. These agents bind to the GnRH receptor in the pituitary to produce immediate blockade of LH and follicle-stimulating hormone secretion. This in turn results in fast suppression of serum testosterone levels, free of the testosterone surge and its clinical consequences (Fig. 2B). Thus, GnRH antagonists are, physiologically, a more logical approach to suppressing the growth of prostate cancer cells. A number of
Conclusions
ADT plays a key role in the treatment of patients with advanced or metastatic prostate cancer. Currently, GnRH agonists are the mainstay of management of metastatic disease and have been shown to achieve long-term suppression of serum testosterone levels. However, GnRH agonists induce an initial surge in testosterone, which results in worsening symptoms in approximately 10% of patients with metastatic disease. Of particular concern is the risk of ureteral obstruction and spinal cord
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H. Van Poppel is an investigator in the degarelix clinical trials.