Table 1. Serum testosterone (continuous 5 nmol/L increments) in observational studies (prospective, retrospective) and its effects on PCa events (stage and grade). Only included studies that conducted multivariable analyses and reported magnitude of association (odds ratio, relative risk, etc.).
| Study author and year | Study design | Number of participants for independent studies | Follow-up (years or months) | Total or free testosterone (continuous increment 5 nmol/L, low levels vs. high levels) | Prostate cancer: total, grade and/or stage (n) | Results: only adjusted multivariable models | Statistically significant (SS: P<0.05) or not significant (NS) |
|---|---|---|---|---|---|---|---|
| Mearini et al. 2013 (27) | Prospective | 206 (103 PCa cases and 103 BPH) | Not applicable | Total testosterone, ng/mL | Total prostate cancer, n=103 | Continuous: OR =0.706; 95% CI =0.556–0.897 | SS (P=0.004) |
| Lane et al. 2008 (28) | Prospective study, radical prostatectomy | 455 | Median 14 (range 2–29 months) | Total testosterone, ng/dL | Gleason score pattern 4–5 at prostatectomy | Continuous: OR =0.998; 95% CI =0.997–1.000 | SS (P=0.048) |
| Massengill et al. 2003 (29) | Retrospective, radical prostatectomy | 879 | Mean 37.7 (months) | Total testosterone, ng/dL | Extraprostatic disease (pT3–T4)- cancer on any inked margin, any capsular penetration, or pelvic lymph node or seminal vesicle involvement, n=343 | Continuous: OR =0.999; 95% CI =0.998–1.000 | SS (P=0.0464) |
| Salonia et al. 2011 (30) | Prospective, radical prostatectomy | 673 | Not applicable | Total testosterone, ng/mL | Extracapsular extension (ECE), n=96 | Continuous: OR =1.06; 95% CI (not provided) | NS (P=0.26) |
| Seminal vesicle invasion (SVI), n=88 | Continuous: OR =0.96; 95% CI (not provided) | NS (P=0.47) | |||||
| High-grade prostate cancer (HGPCa) [defined with ECE, SVI, or Gleason grades (≥4+3)], n=153 | Continuous: OR =0.96; 95% CI (not provided) | NS (P=0.48) | |||||
| Karamanolakis et al. 2006 (31) | Prospective | 85 | Not applicable | Total testosterone, ng/mL | Incident prostate cancer, n=22 | Continuous: OR =0.13; 95% CI =0.05–0.35 | SS (P=0.0001) |
| Imamoto et al. 2005 (32) | Prospective, radical prostatectomy | 82 | Mean 20 (months) | Total testosterone, ng/mL | Extraprostatic disease (PT3-T4, N1), n= 24 | Continuous: HR =2.167; 95% CI =1.291–3.637) | SS (P=0.0034) |
| Muller et al. 2012 (25) | Prospective | 3,255 | Prostate biopsy at 24 and 48 (months) | Total testosterone, nmol/L | Gleason 2–6, n=819 | Continuous (untransformed): OR =1.0; 95% CI =0.99–1.03) | NS (P=0.59) |
| Gleason 7–10, n=228 | Continuous (untransformed): OR =1.00; 95% CI =0.98–1.03) | NS (P=0.72) | |||||
| Yano et al. 2007 (33) | Retrospective | 420 | Not applicable | Total testosterone, ng/mL | Positive prostate biopsy | Continuous: HR =1.31; 95% CI =1.03–1.65 | SS (0.02) |
| Muller et al. 2012† (25) | Prospective | 3,255 | 4 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=679) | Continuous (for 5 nmol/L): RR =1.02; 95% CI =0.97–1.07 | NS |
| Daniels et al. 2010† (34) | Prospective | 2,025 | 4.7 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=275) | Continuous (for 5 nmol/L): RR =1.02; 95% CI =0.91–1.15 | NS |
| Gill et al. 2010† (35) | Prospective | 1,388 | 1.9 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=452) | Continuous (for 5 nmol/L): RR =0.95; 95% CI =0.86–1.05 | NS |
| Weiss et al. 2008†(36) | Prospective | 1,614 | 13 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=727) | Continuous (for 5 nmol/L): RR =1.07; 95% CI =0.97–1.20 | NS |
| Travis et al. 2007† (37) | Prospective | 1,066 | 3.4 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=533) | Continuous (for 5 nmol/L): RR =1.00; 95% CI =0.85–1.18 | NS |
| Severi et al. 2006† (38) | Prospective | 2,377 | 8.7 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=518) | Continuous (for 5 nmol/L): RR =1.00; 95% CI =0.88–1.14 | NS |
| Parsons et al. 2005† (39) | Prospective | 794 | 18.5 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=88) | Continuous (for 5 nmol/L): RR =1.07; 95% CI =0.71–1.63 | NS |
| Platz et al. 2005† (26) | Prospective | 896 | 5 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=448) | Continuous (for 5 nmol/L): RR = 0.97; 95% CI =0.80–1.17 | NS |
| Ozasa et al. 2004† (40) | Prospective | 141 | 10 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=40) | Continuous (for 5 nmol/L): RR =1.11; 95% CI =0.63–1.96 | NS |
| Stattin (Finland) et al. 2004† (41) | Prospective | 375 | 10.8 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=84) | Continuous (for 5 nmol/L): RR =1.06; 95% CI =0.85–1.32 | NS |
| Stattin (Norway) et al. 2004† (41) | Prospective | 2,133 | 16.4 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=534) | Continuous (for 5 nmol/L): RR =0.93; 95% CI =0.86–1.00 | NS |
| Stattin (Sweden) et al. 2004† (41) | Prospective | 423 | 3.5 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=86) | Continuous (for 5 nmol/L): RR =0.96; 95% CI =0.89–1.04 | NS |
| Chen et al. 2003† (42) | Prospective | 600 | 3 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=300) | Continuous (for 5 nmol/L): RR =0.96; 95% CI =0.86–1.07 | NS |
| Heikkilä et al. 1999† (43) | Prospective | 466 | 24 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=166) | Continuous (for 5 nmol/L): RR =1.02; 95% CI =0.86–1.20 | NS |
| Dorgan et al. 1998† (44) | Prospective | 344 | 4.1 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=166) | Continuous (for 5 nmol/L): RR =0.87; 95% CI =0.68–1.12 | NS |
| Vatten et al. 1997† (45) | Prospective | 239 | 10 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=59) | Continuous (for 5 nmol/L): RR =0.95; 95% CI =0.70–1.28 | NS |
| Gann et al. 1996† (46) | Prospective | 612 | 6.3 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=222) | Continuous (for 5 nmol/L): RR =1.08; 95% CI =0.91–1.28 | NS |
| Nomura et al. 1996† (47) | Prospective | 282 | 22 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=141) | Continuous (for 5 nmol/L): RR =1.00; 95% CI =0.80–1.26 | NS |
| Hsing et al. 1993† (48) | Prospective | 196 | 13 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=98) | Continuous (for 5 nmol/L): RR =1.09; 95% CI =0.87–1.37 | NS |
| Barrett-Connor et al. 1990† (49) | Prospective | 1,001 | 14 (years) | Total testosterone, nmol/L (increase of 5 nmol/L) | Incident prostate cancer (n=57) | Continuous (for 5 nmol/L): RR =1.00; 95% CI =0.74–1.35 | NS |
†, previously meta-analyzed in Boyle et al. 2016 (50).