Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease

Abstract

Objectives To evaluate the effect of finasteride on serum Androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial (PCPT). Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men beside testosterone and also a substrate for 5α-reductase enzyme. Results We observed 22% increase in andostenedione levels compared to baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted OR and 95% CI for the 3rd tertile of absolute change of androstenedione levels compared to the 1st tertile was 0.42 (95% CI 0.19–0.94) for low-grade (Gleason <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and risk of high-grade disease. Conclusions The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to DHT and of androstenedione to 5α-androstanedione-3, 17-dione, which also leads to reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.

DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence

“…Deregulation of ABP‐related genes is known to play an important role in PCa progression . These genes encode for enzymes involved in the production of testosterone and dihydrotestosterone (DHT) for activation of androgen receptor‐mediated oncogenic signaling . Though many ABP‐related genes like SRD5A2 , FASN , CYP17A1 , HSD3B1 , HSD17B3 , and CYP19A1 are up‐regulated in advanced PCa, on the contrary, CYP11A1 and SRD5A2 are concurrently down‐regulated .…”

Predictive Clinicopathologic Features and Prognostic assessment of pT0 prostate cancer: a case control study

“…Finally, it is worth noting that half of the patients in the pT0 group were taking nasteride for a long period of time before surgery. Although studies have suggested that nasteride has a chemoprevention effect on low-grade prostate cancer, the association with the presence of stage pT0 prostate cancer is unknown [22].…”

Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial

“…Total testosterone, 3a-dG, androstenedione, and SHBG levels were quantified in serum by highly specific immunoassays as previously described. 4,6…”

“…We have previously demonstrated that there were no statistically significant associations of baseline serum testosterone, 5α-androstane-3α,17β-diol glucuronide (3α-androstanediol glucuronide, 3α-dG), androstenedione, or sex hormone-binding globulin (SHBG) concentrations with risk of total, low- or high-grade prostate cancer in the placebo 4, 5 or finasteride 4, 6 treatment arm of the Prostate Cancer Prevention Trial (PCPT), consistent with most results in the literature. 7-9 Serum 3α-dG, a distal metabolite of DHT, was used as a surrogate measure of intraprostatic DHT and marker for SRD5A activity 10 and serum SHBG as a carrier protein for androgens.…”