Factors influencing prostate-specific antigen response among men treated with testosterone therapy for 6 months

J Sex Med. 2014 Nov;11(11):2818-25. doi: 10.1111/jsm.12657. Epub 2014 Aug 18.


Introduction: Factors influencing prostate-specific antigen (PSA) changes in men undergoing testosterone (T) therapy have not been well studied.

Aim: The aim of this study was to assess the influence of selected variables on PSA changes in hypogonadal men administered with 1.62% testosterone gel (T-gel) for 6 months.

Methods: A double-blind, placebo-controlled study of 274 (234 T-gel, 40 placebo) hypogonadal men >18 years of age, with baseline T concentrations <300 ng/dL, PSA ≤2.5 ng/mL, and negative digital rectal examination. Subjects received once-daily T-gel for T therapy.

Main outcome measures: Changes in mean serum PSA, percentage of free PSA (%fPSA), and T from baseline to 6 months (182 days).

Results: Mean age was 53.5 years and baseline mean values were total T 247 ng/dL, PSA 0.9 ng/mL, and %fPSA 24.6%. Among men treated with T-gel, T increased to 499 ng/dL and PSA increased by 0.1 ng/mL (P = 0.0012). PSA increased ≥0.3 ng/mL in 26.3%, <0.3 ng/mL in 73.7%, including a decline from baseline in 33.0%. In the placebo group, T increased 29 ng/dL to 274 ng/dL, and PSA decreased 0.1 ng/mL, compared with baseline. A greater increase in PSA was noted in men ≥60 years old than in men <60 years old (0.4 vs. 0.05 ng/mL, respectively; P = 0.0006). Mean PSA did not change in men with baseline serum T >250 ng/dL, whereas it increased by 0.2 ng/mL in men with T ≤250 ng/dL (P = 0.0031). PSA increased 0.3 ng/mL in men with baseline %fPSA <20% and 0.1 ng/mL in men with %fPSA ≥20%.

Conclusions: Overall, T-gel treatment was associated with a minor increase in PSA, of questionable clinical significance. Factors predicting greater PSA increases included age ≥60 years, baseline T ≤250 ng/dL, and %fPSA <20%. Men with T >250 ng/dL and age <60 years demonstrated minimal or no PSA change.

Keywords: Androgens; Hormone Replacement Therapy; Prostate-Specific Antigen; Testosterone.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Hormone Replacement Therapy* / adverse effects
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / drug therapy*
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Testosterone / adverse effects
  • Testosterone / therapeutic use*
  • Young Adult


  • Testosterone
  • Prostate-Specific Antigen