Neoadjuvant
androgen deprivation
therapy (NADT) is one strategy for the treatment of early-stage
prostate cancer; however, the long-term outcomes of NADT with radical
prostatectomy including biochemical failure-free survival are not promising. One proposed mechanism is incomplete
androgen ablation. In this study, we aimed to evaluate the efficiency of serum hydroxy-
androgen suppression in patients with localized high-risk
prostate cancer under NADT (
leuprolide acetate plus
abiraterone acetate and
prednisone) and interrogate the primary sources of circulating hydroxy-
androgens using our recently described stable
isotope dilution liquid chromatography mass spectrometric method. For the first time, three
androgen diols including 5-androstene-3β,17β-diol (5-adiol), 5α-androstane-3α,17β-diol (3α-adiol), 5α-androstane-3β,17β-diol (3β-adiol), the
glucuronide or
sulfate conjugate of 5-adiol and 3α-adiol were measured and observed to be dramatically reduced after NADT. By comparing patients that took
leuprolide acetate alone vs
leuprolide acetate plus
abiraterone acetate and
prednisone, we were able to distinguish the primary sources of these
androgens and their conjugates as being of either testicular or adrenal in origin. We find that
testosterone, 5α-dihydrotestosterone (DHT), 3α-adiol and 3β-adiol were predominately of testicular origin. By contrast,
dehydroepiandrosterone (
DHEA), epi-
androsterone (epi-AST) and their conjugates, 5-adiol
sulfate and
glucuronide were predominately of adrenal origin. Our findings also show that NADT failed to completely suppress
DHEA-sulfate levels and that two unappreciated sources of intratumoral
androgens that were not suppressed by
leuprolide acetate alone were 5-adiol-sulfate and epi-AST-
sulfate of adrenal origin.