Sexual Function After Prostatectomy Improved By TRT

Testosterone replacement therapy significantly improved sexual activity, sexual desire, body composition, physical function, and peak aerobic performance in men with hypogonadism who had undergone radical prostatectomy for low-grade prostate cancer, according to results from the SPIRIT trial published in JAMA Internal Medicine.¹

Results from SPIRIT, which is the first randomized, placebo-controlled trial to evaluate TRT in this population, also showed that there was no biochemical recurrence observed in either the treatment or placebo arm.

“A history of prostate cancer has been generally viewed as a contraindication for testosterone treatment, but our study found that over three months, TRT was safe and improved sexual and physical function,” lead study author Shalender Bhasin, MBBS, of the division of Endocrinology, Diabetes, and Hypertension in the Mass General Brigham department of Medicine, stated in a news release.² “While longer and larger studies are needed, our findings provide an important rationale for continuing to evaluate TRT as a treatment for men who have received radical prostatectomy,” added Bhasin.

SPIRIT Study: Efficacy of TRT for Sexual Desire, Function

The primary efficacy end point for the SPIRIT study was change in sexual activity as measured by the Psychosexual Daily Diary Questionnaire question 4, which captures any form of sexual activity over a 7-day diary period. Outcomes for this metric showed a statistically significant and clinically meaningful advantage for TRT over placebo. The between-group difference in sexual activity over the 12-week treatment period was 0.91 daily events (95% CI, 0.56-1.26; P <.001), exceeding the prespecified minimally clinically important difference of 0.5 units.¹

Sexual desire, assessed using the DeRogatis Inventory of Sexual Function–Sexual Desire score, also improved significantly with TRT compared with placebo (between-group difference, 2.96 units; 95% CI, 1.46-4.45; P <.001). The EPIC-26 prostate cancer quality-of-life sexual domain score, which captures erectile ability, frequency, quality, and sexual bother, improved significantly more with TRT than placebo (between-group difference, 5.35; 95% CI, 1.63-9.07; P =.005).

While erectile function scores increased from baseline in both the testosterone and placebo groups at weeks 6 and 12, the between-group difference in erectile function score did not reach statistical significance (between-group difference, 0.93; 95% CI, −0.43 to 2.29; P =.18). Negative affect as measured by the PANAS negative affect score decreased significantly more in testosterone-treated men than placebo-treated men (between-group difference, −1.39; 95% CI, −2.53 to −0.25; P =.02). Changes in positive affect, energy levels, and PANAS positive affect score did not differ significantly between groups.

TRT produced significant improvements in body composition compared with placebo. Whole-body lean mass increased by a between-group difference of 2.56 kg (95% CI, 1.88-3.24 kg), appendicular lean mass by 1.50 kg (95% CI, 1.10-1.90 kg), and trunk lean mass by 1.06 kg (95% CI, 0.70-1.41 kg). Whole-body fat mass decreased significantly more in the testosterone group (−1.52 kg; 95% CI, −2.21 to −0.84 kg), as did appendicular fat mass (−0.58 kg; 95% CI, −0.88 to −0.28 kg) and trunk fat mass (−0.97 kg; 95% CI, −1.40 to −0.55 kg). Changes in leg press strength did not differ significantly between arms.

Physical function and aerobic performance also favored TRT. Loaded stair-climbing power and peak aerobic capacity (VO2 peak) improved significantly more with testosterone than with placebo, though these assessments were limited to the Boston trial site among participants without contraindications to performance testing.

Across the trial, PSA levels remained undetectable throughout treatment in all but three participants: one in each group with baseline PSA below 0.04 ng/mL had at least one detectable PSA value during treatment that remained below 0.1 ng/mL, and one testosterone-treated participant with a baseline PSA of 0.1 ng/mL had PSA values above 0.1 ng/mL but below 0.2 ng/mL during treatment. No clinical recurrences were observed.

Safety of TRT in SPIRIT Study

Erythrocytosis occurred in 3 participants in the TRT group and none in the placebo group. Compared with placebo, TRT was associated with greater increases in serum creatinine, hemoglobin, hematocrit, and total white blood cell, neutrophil, and monocyte counts, as well as greater decreases in alkaline phosphatase, total cholesterol, HDL cholesterol, non-HDL cholesterol, and LDL cholesterol. Urinary symptoms as measured by the International Prostate Symptom Score and EPIC-26 urinary domain score did not change in either group.¹

The overall frequency of adverse events and serious adverse events was comparable between arms. Forty-nine participants in the TRT group and 47 in the placebo group experienced at least one adverse event. Three serious adverse events occurred in the testosterone arm and one in the placebo arm. No major adverse cardiovascular events, venous thromboembolic events, or pulmonary emboli were recorded in either group.

SPIRIT Trial Design and Patient Characteristics

The SPIRIT trial enrolled 136 men aged 40 years or older with organ-confined, low-grade prostate cancer — Gleason score 6 (3+3) or 7 (3+4) — who had undergone radical prostatectomy, had maintained undetectable PSA for at least two years post-surgery, had two fasting morning testosterone levels below 275 ng/dL and/or free testosterone of 70 pg/mL or less, and reported at least one hypogonadal symptom: low libido, erectile dysfunction, or fatigue. Men treated with radiation therapy or androgen deprivation therapy were excluded.¹

Participants were randomized 1:1 to weekly intramuscular injections of testosterone cypionate 100 mg or placebo for 12 weeks, with stratification by age (40 to 60 years or >60 years), site, and PDE5 inhibitor use. The trial was conducted at Brigham and Women's Hospital in Boston and Johns Hopkins Hospital in Baltimore. Enrollment ran from May 13, 2019, to May 16, 2025, with 125 of 136 randomized participants completing the study.

The 2 arms were well matched at baseline. Mean age across the full cohort was 68.6 years. Race was predominantly White (86.0%), with 11.8% Black or African American participants. BMI averaged 29.5 (SD, 4.5). Gleason score distribution was 38.2% at 3+3 and 61.8% at 3+4. The majority (87.5%) had stage pT2N0M0 disease. Mean preoperative PSA was 6.3 ng/mL (SD, 5.7). Baseline total testosterone averaged 396.5 nmol/L (SD, 135.7) and free testosterone 50.6 pmol/L (SD, 11.5). Twenty-seven percent of participants in each group reported PDE5 inhibitor use at baseline. Adherence with injections was 95% in the TRT group and 94% in the placebo group.

References

1. Bhasin S, Burnett AL, Gagliano-Jucá T, et al. Testosterone treatment in prostate cancer survivors with hypogonadism: a randomized clinical trial. JAMA Intern Med. Published online May 11, 2026. doi:10.1001/jamainternmed.2026.1343

2. Mass General Brigham. Testosterone improved function after prostate surgery. Newsroom press release. Published May 8, 2026. Accessed May 13, 2026. https://tinyurl.com/yc854r49