Premium
Metabolic consequences of gonadotropin‐releasing hormone agonists vs orchiectomy: a randomized clinical study
Author(s) -
Østergren Peter B.,
Kistorp Caroline,
Fode Mikkel,
Bennedbæk Finn N.,
Faber Jens,
Sønksen Jens
Publication year - 2019
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.14609
Subject(s) - triptorelin , medicine , orchiectomy , endocrinology , insulin resistance , adipose tissue , prostate cancer , confidence interval , gonadotropin releasing hormone agonist , androgen deprivation therapy , urology , lean body mass , odds ratio , hormone , insulin , cancer , gonadotropin releasing hormone , body weight , luteinizing hormone
Objectives To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin‐releasing hormone (Gn RH ) agonist and those treated with orchiectomy. Patients and Methods Fifty‐eight hormone‐naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks. The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [ VAT ], subcutaneous adipose tissue [ SAT ], lean body mass [ LBM ] and android/gynoid fat [AG] ratio) assessed with dual X‐ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between‐group differences. Results No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [ CI ] −0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm 3 , 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance ( P < 0.001). No differences in changed VAT , LBM or AG ratio were observed between the groups. The pooled analyses, combining data from both groups, showed androgen deprivation therapy ( ADT ) to significantly increase fat mass, SAT , VAT , serum cholesterols (total, high‐density lipoprotein and low‐density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12–24 weeks of ADT . Conclusions Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12–24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with Gn RH agonists and that these increases are associated with an increase in insulin resistance.