Elsevier

European Urology

Volume 70, Issue 6, December 2016, Pages 974-982
European Urology

Platinum Priority – Prostate Cancer
Editorial by Sarah K. Holt, George R. Schade and John L. Gore on pp. 983–984 of this issue
Ejaculation Frequency and Risk of Prostate Cancer: Updated Results with an Additional Decade of Follow-up

https://doi.org/10.1016/j.eururo.2016.03.027Get rights and content

Abstract

Background

Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.

Objective

To incorporate an additional 10 yr of follow-up into an original analysis and to comprehensively evaluate the association between ejaculation frequency and PCa, accounting for screening, clinically relevant disease subgroups, and the impact of mortality from other causes.

Design, setting, and participants

A prospective cohort study of participants in the Health Professionals Follow-up Study utilizing self-reported data on average monthly ejaculation frequency. The study includes 31 925 men who answered questions on ejaculation frequency on a 1992 questionnaire and followed through to 2010. The average monthly ejaculation frequency was assessed at three time points: age 20–29 yr, age 40–49 yr, and the year before questionnaire distribution.

Outcome measurements and statistical analysis

Incidence of total PCa and clinically relevant disease subgroups. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results and limitations

During 480 831 person-years, 3839 men were diagnosed with PCa. Ejaculation frequency at age 40–49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ≥21 compared to 4–7 ejaculations per month was 0.81 (95% confidence interval [CI] 0.72–0.92; p < 0.0001 for trend) for frequency at age 20–29 yr and 0.78 (95% CI 0.69–0.89; p < 0.0001 for trend) for frequency at age 40–49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death.

Conclusions

These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease.

Patient summary

We evaluated whether ejaculation frequency throughout adulthood is related to prostate cancer risk in a large US-based study. We found that men reporting higher compared to lower ejaculatory frequency in adulthood were less likely to be subsequently diagnosed with prostate cancer.

Introduction

Prostate cancer (PCa) accounts for approximately 15% of all new cancer diagnoses among men worldwide, and the burden of disease continues to increase globally [1]. While diet and physical activity may provide some promise for secondary prevention [2], [3], [4], [5], there are no evidence-based recommendations to offer healthy adult men to reduce PCa risk. The few established disease risk factors—age, race, family history, and germline polymorphisms—are not modifiable [6].

Sexual behaviors represent potential modifiable risk factors and may influence PCa development through a variety of specific mechanisms. One biological mechanism involves prostatic accumulation of potentially carcinogenic secretions, which may create more opportunity for PCa development, sometimes referred to as the prostate stagnation hypothesis [7], [8]. On the basis of this premise, a prospective report from the Health Professionals Follow-up Study (HPFS) cohort published in 2004 found a statistically significant inverse association between monthly ejaculation frequency and PCa risk based on 8 yr of follow-up [8]. Compared to men reporting an average of 4–7 ejaculations per month (EPM), the risk of PCa among men reporting ≥21 EPM in middle age was 50% lower. Although these initial findings were intriguing, the strongest reduction in risk was noted for ejaculation frequency in the time period immediately before questionnaire administration, raising concerns about the potential influence of undiagnosed PCa on the results.

To confirm and build on these results [8], we conducted an updated study within the HPFS cohort with an additional 10 yr of follow-up and 3839 PCa cases, more than double the number included in the original report. This updated analysis allows us to address possible reverse causation, investigate the potential impact of PSA screening, and determine whether the association between ejaculation frequency and PCa differed according to the clinical disease characteristics, as has been observed for other PCa risk factors [9]. Finally, because ejaculation frequency may be an indicator of health status and could be related to mortality from multiple causes, the current analysis considers the impact of competing causes of death on our findings. Thus, this updated analysis represents a comprehensive evaluation of the association between ejaculation frequency and PCa in a large US-based prospective cohort.

Section snippets

Study population

The HPFS is an ongoing prospective cohort study among 51 529 US male health professionals [8]. In brief, cancer-free, predominantly Caucasian (>91%) health professionals aged 40–75 yr were recruited in 1986 and have been followed with biennial questionnaires on medical history and lifestyle, including known or suspected cancer and chronic disease risk factors, diet, use of supplements, and preventive behaviors. Ejaculation frequency was assessed in the 1992 questionnaire, which was completed by

Baseline characteristics

Ejaculation frequency declined with age. The proportion of men reporting average frequency of ≥13 EPM was 57% at age 20–29 yr but dropped to 32% at age 40–49 yr. The Spearman correlation between ejaculation frequency as an ordinal variable and ages 20–29 and 40–49 yr was 0.66. Some 40% of men were in the same frequency category for ages 20–29 and 40–49 yr, and 47% of men moved down a single category from age 20–29 yr to age 40–49 yr.

The baseline age-standardized characteristics of the study

Discussion

The results of this prospective cohort study involving 31 925 men, 18 yr of follow-up, and 3839 PCa cases offer additional evidence of a role for ejaculation frequency in the etiology of PCa, particularly for low-risk disease. The absolute difference in PCa rate between ≥21 and 4–7 EPM was 2.39 cases/1000 person-years for frequency at age 20–29 yr, 2.20 cases/1000 person-years for frequency at age 40–49 yr, and 3.89 cases/1000 person-years for frequency in the year before questionnaire

Conclusions

This large prospective study provides the strongest evidence to date of a beneficial role of ejaculation in prevention of PCa, a disease for which relatively little is understood about etiology generally and knowledge of modifiable risk factors is particularly scant. The results are robust to adjustment for many dietary, lifestyle, and screening behaviors, but additional work on the underlying biological mechanisms should be undertaken to corroborate these findings given the potential for

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    These authors contributed equally to this work.

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