Variations in circulating sex steroid levels in metastatic prostate cancer patients with combined androgen blockade: observation and implication

Abstract

Testosterone is the major precursor of estradiol (E2) in men. We hypothesized that, in metastatic prostate cancer, androgen deprivation therapy suppression of serum androgen to the castration level may also disrupt serum E2 level, and variation in serum E2 level might play a role in the development of castration-resistant prostate cancer. Our investigation was designed to observe the variation in circulating oestrogen and androgen levels in metastatic prostate cancer patients after combined androgen blockade, and to explore the possible clinical significance. We recruited 105 consecutive metastatic prostate cancer patients who were treated with combined androgen blockade from June to August 2011, and divided them into three groups according to different hormone-sensitivity status, including 58 hormone-sensitive prostate cancers, 27 after failure of first-line hormone therapy (androgen-independent prostate cancer) and 20 castration-resistant prostate cancers. Another 36 consecutive patients with treatment-naive metastatic prostate cancer during the same period were used as controls. Serum testosterone, E2 and E2/testosterone (E2/T) ratio were analysed and compared between the groups. After combined androgen blockade, testosterone was suppressed to a low level, regardless of different hormone sensitivity (p > 0.05). Mean serum testosterone was 4.07, 0.15, 0.11 and 0.09 ng/mL in treatment-naive, hormone-sensitive, androgen-independent and castration-resistant prostate cancer respectively. For each group, mean E2 was 33.06, 9.23, 9.13 and 15.05 pg/mL respectively. Mean E2/T was 9.58, 269.29, 292.06 and 996.67 respectively. Recovery of E2 and increased E2/T ratio were more significantly associated with combined androgen blockade failure, especially in castration-resistant prostate cancer (p < 0.001). This study indicated that metabolism of oestrogen might change during combined androgen blockade in metastatic prostate cancer patients, and oestrogen-related pathways might play a role in the development of castration-resistant prostate cancer.