Failure to Maintain a Suppressed Level of Serum Testosterone during Long-Acting Depot Luteinizing Hormone-Releasing Hormone Agonist Therapy in Patients with Advanced Prostate Cancer

Abstract

Objectives: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. Methods:Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. Results: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. Conclusions: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

Obesity and Sex Steroids during Gonadotropin-Releasing Hormone Agonist Treatment for Prostate Cancer

“…Other investigators have reported failure to maintain castrate testosterone levels during GnRH agonist therapy (18,19). In a prospective study of 37 men receiving leuprolide 3-month depot for prostate cancer, for example, 4 (11%) men failed to achieve testosterone levels <20 ng/dL (18).…”

Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

“…Even using the standard definition for castration testosterone level of 1.7 nmol/L, a significant proportion of patients on LHRH agonists (2-12.5%) do not achieve this level, [19][20][21][22] and an even greater proportion (13-37.5%) fail to achieve the more stringent testosterone level of 0.7 nmol/L. 19,20,22,23 In a population-based series of 1442 men in Quebec undergoing LHRH agonist therapy with curative radiation therapy, the risk of any breakthrough during 2334 person-years of followup was 4.5% when using a cutoff of 1.7 nmol/L and 25% when using a cutoff of 0.7 nmol/L.…”

“…19,20,22,23 In a population-based series of 1442 men in Quebec undergoing LHRH agonist therapy with curative radiation therapy, the risk of any breakthrough during 2334 person-years of followup was 4.5% when using a cutoff of 1.7 nmol/L and 25% when using a cutoff of 0.7 nmol/L. 24 Using clinical data from chart reviews or existing databases, Pickles et al analyzed breakthrough rates above castrate levels of testosterone in men undergoing adjuvant LHRH agonist therapy with curative radiation therapy in British Columbia.…”

Current Medical and Surgical Options for Androgen Deprivation in Prostate Cancer Patients

“…For example, in one study [18] in which patients received leuprolide acetate, measurement of serum testosterone at 29 days after administration showed that 34% of patients had testosterone levels of 20 ng/dL. Similarly, Morote et al [19] assessed serum testosterone levels in patients treated with 3-monthly GnRH-A injections and found that 37.5% of patients had testosterone levels of 20 ng/dL.…”