No Significant Differences in Sexual Function: Hypofractionated and Conventional Radiotherapy

Sexual Function After Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Cancer: Results From the Randomized Phase III HYPRO Trial

Ruud C. Wortel, MD; Floris J. Pos, MD, PhD; Wilma D. Heemsbergen, PhD; Luca Incrocci, MD, PhD

ONLINE: September 2016 – The Journal of Sexual Medicine


Introduction and Goal

Dose-escalated external beam radiotherapy (EBRT) up to 78 Gy has been an effective, relatively relapse-free treatment for men with localized prostate cancer. However, the conventional method to EBRT can raise gastrointestinal and genitourinary toxicity rates.

Hypofractionated radiotherapy, another approach, delivers fewer high-dose fractions of radiation to improve tumor control. This method allows for increased tumor dose, but provides greater convenience for the patient.

Past trials on the effects of hypofractionation on sexual function have had mixed results. This study, part of the HYpofractionated irradiation for PROstate cancer (HYPRO) trial in the Netherlands, addressed this concern.


Eight hundred twenty men with intermediate- or high-risk stage T1b-T4NX-0MX-0 prostate cancer participated in the study. They were randomly assigned to receive either conventional fractionation (39 x 2 Gy) or hypofractionation (19 x 3.4 Gy). The average age for both groups was 71 years.

At baseline – and again 6-, 12-, 24-, and 36-months after treatment – the men completed the International Index of Erectile Function (IIEF), a 15-item self-report questionnaire designed to evaluate five domains of sexual function: erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction.


Three hundred twenty-two men (166 in the hypofractionation group and 156 in the conventional group) were included in the final analysis. The median length of follow-up was 37 months.

There were no significant differences in IIEF scores between the two groups. Erectile function domain scores tended to decrease over time, but sexual desire scores remained steady. Orgasmic function, intercourse satisfaction, and overall satisfaction declined during the first 12 months.

About 39% of the men in the hypofractionation group and 39% in the conventional group underwent short-term androgen deprivation therapy (ADT) lasting 6 months or less. (Because ADT can lower men’s testosterone levels and result in sexual dysfunction, ADT for longer than 6 months was an exclusion criterion for the study.)

Men in the hypofractionation group who did not undergo ADT (hormone-naïve”) had significantly higher IIEF scores in the orgasmic function domain at the 36-month follow-up point.


The authors noted that many factors can contribute to ED in men who have had radiation therapy. Neural, vascular, endothelial, and smooth muscle damage are all possible during treatment.

They added that more trials on hypofractionation are needed to learn more about the sexual implications of this approach.

Certain limitations were acknowledged:

• It was unclear to what extent ADT affected the men’s testosterone levels and, in turn, their baseline IIEF scores.
• The IIEF addresses sexual function for the previous 4 weeks. Men who were sexually inactive during that time period, but had good erectile function beforehand, might have been classified as having ED.

“The HYPRO trial showed no clinically meaningful differences in sexual function between conventionally fractionated and hypofractionated radiotherapy,” the authors concluded. “However, orgasmic function scores in hormone-naïve patients were statistically significantly higher at 3-year follow-up in the hypofractionation arm.”