Testosterone deficiency (TD) affects 18-38% of men undergoing radical prostatectomy (RP) for localised prostate cancer and may impair postoperative sexual rehabilitation. Testosterone replacement therapy (TRT) may improve sexual function and is assumed to be oncologically safe following RP, though evidence is based on nonrandomised, retrospective studies. The ENFORCE study evaluates the effects of TRT on sexual function recovery and on biochemical recurrence (BCR) following RP in men with TD.
The ENFORCE study is a phase 3, multicentre, randomised, single-blind, placebo-controlled trial being conducted at ten Dutch centres. Eligible patients with TD (total testosterone <8 nmol/l, or total testosterone 8-12 nmol/l with free testosterone <225 pmol/l) and minimal preserved erectile function (Expanded Prostate Cancer Index Composite 26 [EPIC-26] sexual domain ≥40) undergoing RP are randomised to receive TRT or placebo from 6-12 wk after RP until 1 yr after RP.
The primary endpoint is sexual function at 12 mo (EPIC-26 sexual domain). The secondary endpoints include sexual function at 6 and 24 mo, and quality of life, and hormonal and urinary function at 12 and 24 mo, assessed by the EPIC-26 and Aging Males' Symptoms questionnaires. BCR is evaluated at 12, 24, and 60 mo.
Outcomes include patient-reported outcomes and laboratory results. Linear regression will assess the effect of TRT on sexual function, adjusting for baseline variability.
Strengths include the randomised design and long-term follow-up. Limitations include potential recruitment challenges due to specific inclusion criteria, limited to men with TD and minimal preserved sexual function.
This work was supported by KWF Dutch Cancer Society, Besins Healthcare, and Canisius Wilhelmina Hospital Research Fund.
This trial was approved by the Medical Research Ethics Committee Oost-Nederland (ClinicalTrials.gov, NCT04833426).
For men with low testosterone undergoing surgery for prostate cancer (radical prostatectomy), testosterone replacement therapy (TRT) may improve recovery of sexual function and general well-being. The ENFORCE trial investigates whether TRT indeed improves sexual recovery after prostate cancer surgery and whether it can be administered safely. Although TRT is generally believed to be safe, this is based on small or potentially biased studies, and has never been investigated in a large clinical trial. Some concerns remain that TRT increases the risk of prostate cancer recurrence. The results of this trial may provide answers about the benefits and safety of TRT after prostate cancer surgery.
European urology oncology. 2025 Jun 12 [Epub ahead of print]
Diederik Baas, Joost van Drumpt, Lambertus Kiemeney, Jack Beck, Peter Busch Østergren, Michiel Sedelaar, Robert Hoekstra, Alexander Bellaar Spruyt, Harm van Melick, Max Bruins, Pim van Leeuwen, André Vis, Carl Wijburg, Luc Roelofs, Roderick van den Bergh, Robert van Soest, Jean-Paul van Basten, Diederik Somford
Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands; Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands., Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands; Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands. Electronic address: ., Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands; IQ Health Science Department, Radboud University Medical Centre, Nijmegen, The Netherlands., Department of Urology, St. Antonius Hospital, Nieuwegein, The Netherlands., Department of Urology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands., Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands; Department of Urology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands., Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands; Department of Urology, Máxima Medical Centre, Veldhoven, The Netherlands., Department of Urology, Zuyderland Medical Centre, Heerlen, The Netherlands., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands., Department of Urology, Rijnstate, Arnhem, The Netherlands., Department of Urology, Treant Group, Emmen, The Netherlands., Anser Prostate Operation Clinic, Rotterdam, The Netherlands; Department of Urology, Erasmus MC, Rotterdam, The Netherlands; Department of Urology, Franciscus Gasthuis & Vlietland, Rotterdam/Schiedam, The Netherlands., Anser Prostate Operation Clinic, Rotterdam, The Netherlands; Department of Urology, Franciscus Gasthuis & Vlietland, Rotterdam/Schiedam, The Netherlands., Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands; Prosper Prostate Cancer Clinics, Nijmegen/Eindhoven, The Netherlands.