Effects of 12-Month Treatment with Transdermal Testosterone Gel or an Aromatase Inhibitor on Prostate Volume and PSA Levels in Older Men with Low Testosterone

Presentation Number: THR-137
Date of Presentation: March 5th, 2015

Jenny Pena Dias*1, Denise Melvin2, Chee W. Chia3, Josephine Mary Egan3 and Shehzad Basaria4
1NIH/NIA, Brooklyn, MD, 2NIH/NIA, Baltimore, MD, 3National Institute on Aging, Baltimore, MD, 4Brigham and Women's Hospital - Harvard Medical School, Boston, MA


Background:  Testosterone (T) therapy is being increasingly prescribed to older men with age-related decline in circulating T levels. The prostate is an androgen-responsive organ. Randomized trials of T replacement in older men have demonstrated a greater increase in prostate- specific antigen (PSA) levels in the T group compared with placebo while some studies have reported an increase in prostate volume (PV) in response to T therapy. Testosterone is metabolized to dihydrotestosterone (DHT) and estradiol (E2)(1). Although some studies have investigated the role of DHT on PV and PSA levels, the relative contribution of E2 on these parameters remain unclear. Furthermore, the differential effects of T or E2 on lower urinary tract symptoms (LUTS) are understudied.

Objective: To investigate the relative contribution of T or E2 on PV, PSA levels and LUTS in older men with age-related low T levels.

Methods: In a 12-month randomized, double-blind, placebo-controlled, proof-of-concept study, we randomized men age 65 years and older (range: 65-82) with serum T levels <350 ng/dl to transdermal T gel (5gm daily, n=10), anastrazole (1mg daily, n=10) or placebo (n=11). Serum PSA and LUTS [using International Prostate Symptom Score (IPSS) questionnaire] were measured at baseline, 3, 6 and 12 months. PV was measured using a transrectal ultrasound at baseline and 12 months.

Results: The change in serum PSA was significantly higher than baseline at 3 and 6 months in T-group (ΔPSA at 3 month=0.2±0.1 (p-value<0.05), ΔPSA at 6 month=0.3±0.2 (p-value<0.01), ΔPSA at 12 month=0.04±0.10 (p-value:0.47)) and AI-group (ΔPSA at 3 month =0.3±0.1 (p-value<0.05), ΔPSA at 6 month =0.4±0.1 (p-value<0.001), ΔPSA at 12 month=0.02±0.08 (p-value:0.58)).  There was no significant change in PSA levels in the placebo arm. At 12 months, PV significantly increased by 4.5±1.7 cc (p-value: 0.03) in the T-group while no significant change was observed in the AI-group (PV= -1.7±3.5 cc) or Placebo group (PV= -1.1±1.5 cc). At 12-month, the total IPSS score was higher in the T-group compared with the Placebo group (p-value: 0.04) while no change was seen in the AI-group.

Conclusion: In this proof-of-concept study, we show that the increase in PSA level is primarily an androgen-driven process. However, the trophic effects of T on PV are mediated via its aromatization to E2. Further studies are needed to confirm this observation.


Disclosure: SB: Consultant, Eli Lilly & Company, Principal Investigator, Abbott Laboratories, Consultant, Endo Pharmaceuticals. Nothing to Disclose: JP, DM, CWC, JME