No Significant Changes in Lipid and Glucose Metabolism with Degarelix and Leuprolide Treatment in Prostate Cancer

Table of Content

Introduction

A recent meta-analysis demonstrated a positive correlation between androgen deprivation therapy (ADT) and the risk of developing metabolic syndrome (MetS) in patients with prostate cancer (PCa). The current modalities used in ADT include degarelix, leuprolide and orchiectomy. In a mouse model, the fewest characteristics of MetS were seen with degarelix as compared to orchiectomy and leuprolide after 4 months of ADT. The effects of gonadotropin releasing hormone (GnRH) agonists or orchiectomy on lipid and glucose metabolism in PCa has been elucidated. However, the effects of GnRH antagonists on MetS has not been assessed.

Aim

This prospective study evaluated the effects of degarelix and leuprolide on the development of MetS in patients with PCa.

Method

Study Design

  • Prospective, randomized, parallel-arm, open-label, single-center trial
  • Patients aged>20 years with histologically confirmed PCa and life expectancy of atleast 12 months were included
  • The cohort was randomized to receive monthly degarelix or monthly leuprolide for 6 months
  • Degarelix group received a starting dose of 240 mg followed by a maintenance dose of 80 mg every 28 days
  • Leuprolide group received 3.75 mg every 28 days and prophylactic 80 mg of bicalutamide once daily during the initial dosing period of 14 days

Endpoints

Primary Endpoints

  • Changes in fasting blood sugar (FBS)

Secondary Endpoints

  • Changes in body weight
  • Abdominal circumference
  • Lipid profiles
  • Hemoglobin A1c (HbA1c)
  • Follicle-stimulating hormone (FSH)
  • Subcutaneous and visceral fat areas before and after 6 months of ADT measured using computed tomography

Results

  • Out of the enrolled 100 patients, 85 completed the trial comprising of 40 and 45 patients in the degarelix and leuprolide groups respectively
  • The prevalence of MetS was similar in degarelix and leuprolide groups after 6 months of ADT (7.5% vs 4.4% respectively)
  • The mean increases in the endpoints in both the groups are shown in table 1.
Table 1. Mean increases in endpoints

 

Degarelix group

Leuprolide group

P value

FBS

2.5%

2.5%

0.46

HbA1c

1.8%

3.5%

0.87

Subcutaneous fat areas

24.8%

25%

 

Visceral fat areas

32.7%

23.2%

 

  • Similarly, there were no significant changes in body weight, abdominal circumference, cholesterol and triglycerides between the groups
  • After 6 months, the total testosterone levels decreased at castration level in degarelix group (8.1+6.4 ng/dL) and leuprolide group (6.5+4.6 ng/dL)
  • The degarelix group had significantly lower FSH levels than leuprolide group (p<0.05)  

Conclusion

  • There were no significant differences in the lipid and glucose metabolism in the patients of prostate cancer treated with degarelix and leuprolide after 6 months of androgen deprivation therapy.
  • The patients treated with degarelix had significantly lower follicle-stimulating hormone levels.

World J Urol 2019. Doi:10.1007/s00345-019-02937-x.