Ejaculatory frequency and the risk of aggressive prostate cancer: Findings from a case-control study

doi:10.1016/j.urolonc.2017.03.007

Urologic Oncology: Seminars and Original Investigations

Volume 35, Issue 8, August 2017, Pages 530.e7-530.e13

https://doi.org/10.1016/j.urolonc.2017.03.007 Get rights and content

Highlights

•
We investigated if ejaculatory frequency is associated with advanced prostate cancer.
•
Higher frequency in a man’s 30s is protective for advanced prostate cancer.
•
This association was present only for men with new sexual partners after age 30.

Abstract

Objectives

Recent literature reports inverse associations with ejaculator frequency and prostate cancer (PC). We sought to explore the relationship between ejaculatory frequency from ages 20 to 50 and subsequent development of aggressive PC.

Material and methods

We conducted a case-control study sampling 2,141 men from private urology practices in Victoria, Australia. Cases were defined as men with high grade or high stage PC and controls being biopsy negative men. Ejaculation frequency recalled at age decades 20, 30, and 40 second was assessed by questionnaire. Unconditional multivariable logistic regression models were used to generate odds ratios (ORs).

Results

An inverse association with ejaculatory frequency at age 30 to 39 was observed (OR per 5-unit increase per week = 0.83, 95% CI: 0.72–0.96) but not at ages 20 to 29 (OR = 1.01, 95% CI: 0.89–1.14) or ages 40 to 49 (OR = 0.95, 95% CI: 0.81–1.12). This result differed between men with new sexual partners after age 30 (OR = 0.77, P = 0.009) and those with no new partners (OR = 0.97, P = 0.8) though the test for a difference between these estimates was not significant (P = 0.11).

Conclusion

We found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced PC, which was not significantly modified by number of new sexual partners. No relationship was found for ejaculatory frequency in the third and fifth decades of life.

Introduction

Prostate cancer (PC) has some established nonmodifiable risk factors such as family history and ethnicity but modifiable risk factors of similar strength are lacking [1]. This lack might be linked to the phenotypic heterogeneity of PC, which has been exaggerated in past decades by widespread prostate specific antigen (PSA) testing, which increased the diagnosis of prostatic tumors with low metastatic potential [2].

The function of the prostate is to add proteins and other molecules to the ejaculate. These exert an effect on semen liquefaction though the precise role this plays in reproduction is not defined [3]. It is plausible that greater frequency of ejaculation and thus repeated demands on the functional role of the prostate may alter the risk of subsequent PC. A recently published cohort study [4] reported an inverse association between increased ejaculation in the third and fifth decades of life and organ confined PC mirroring findings from our earlier case-control study [5]. Both studies used the same instrument to measure ejaculatory frequency, a questionnaire that we had developed to capture all ejaculations, not only those occurring during episodes of sexual intercourse. These findings may be due to a differential in sex hormone levels or the accumulation of intraluminal secretions in the prostate, both being correlated to PC incidence in different ways [6], [7]. We present the outcomes from a case-control study aiming to assess the relationship with aggressive/advanced PC (APC). We assessed exposure by asking for a numerical estimate of ejaculatory frequency at different ages regardless of whether these occurred from intercourse or masturbation. This permitted a direct evaluation of the exposure effect rather than using surrogates such as age at first intercourse, number of partners or marital status, which have been described more commonly in the literature [8], [9], [10], [11], [12].

Section snippets

Study design

The design was a case-control study based on a sampling frame of urology practices in the State of Victoria, Australia, following identification through the Victorian Cancer Registry (VCR). To minimize information biases to which case-control designs are prone, controls were sought that had experienced similar levels of clinical investigation, in particular an elevated PSA test, but who proved to be biopsy negative for PC. Ethical approval was received from the Cancer Council Victoria ethics

Results

The total study sample comprised 2,141 participants, 1,236 cases from a total of 3,763 defined as eligible (33%) and 905 controls from 1,310 asked to participate (69%) (Fig. 1). The median time interval between the diagnosis of APC and date of questionnaire completion was 324 days (interquartile range: 249–429). The time interval for controls was not recorded.

Cases were older, more likely to have a positive first-degree family history, reside in a lower socioeconomic area, be current or former

Discussion

Ejaculatory frequency has been postulated as one of the few modifiable risk factors for the development of PC. This case-control study sheds further light on this association as it relates to the aggressive phenotype of the disease. We detected slight decreases in the odds of aggressive PC (APC) for increasing ejaculatory frequency in the fourth decade of life (i.e., age in the 30 second) but only for men with new sexual partners and those with very high reported frequency. This secondary

Conclusion

The significant inverse association found only for ages 30 to 39 years is unusual given that at other ages there was no evidence of any relationship. It is probable that this finding, being isolated, is spurious. As is the result that the association is stronger for men who have multiple sexual partners after age 30, given the test for interaction was not significant. We encourage further studies that numerically measure ejaculatory frequency at different ages and which focus on aggressive PC

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Cited by (14)

Ejaculation Frequency and Prostate Cancer Risk: A Narrative Review of Current Evidence
2024, Clinical Genitourinary Cancer
Prostate cancer, constituting a substantial portion of global cancer incidence and mortality, prompts a critical examination of potential modifiers, notably ejaculation frequency. This narrative review explores the complex relationship between ejaculation frequency and prostate cancer risk, addressing the paucity of consensus and the intricate interplay of factors. The evidence drawn from eleven studies with diverse methodologies reveals a complex understanding of this association. While some studies suggest an inverse correlation between ejaculation frequency and prostate cancer risk, signifying a potential protective effect, others present conflicting findings, necessitating a comprehensive exploration. Evidence synthesis underscores the importance of considering age, urinary health, and lifestyle factors in elucidating the ejaculation frequency-prostate cancer relationship. Notably, technological advancements, including machine learning models and genetic markers, enhance the precision of patient counselling and individualized care. In a clinical context, the findings emphasize the clinical relevance of incorporating sexual behavior into preventive strategies. Public health campaigns emerge as influential tools, breaking taboos, raising awareness, and empowering men to prioritize their well-being. The paradigm shift in prostate cancer understanding, fueled by technology and personalized medicine, holds promise for more accurate risk assessments. Liquid biopsies, multiparametric MRI, and considerations of the gut microbiome present avenues for tailored preventive strategies. However, methodological challenges and study variations necessitate further research, emphasizing consistency, exploring underlying mechanisms, and a life course perspective.
Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults
2020, Journal of Sexual Medicine
Citation Excerpt :
The authors also described a negative trend in the third decade, independent of those in the fourth or fifth.42 Other studies have found similar findings.43,44 Potential explanations are given by the hormone-dependency of both sexual activity, including libido and prostate cancer or the concept of prostatic carcinogenesis involving the luminal fluid, prostatic tissue interaction.45
Sexual activity can be referred to as a health behavior and may also act as an indicator of health status.
To evaluate temporal trends in sexual activity and to examine associations of sexual activity with all-cause and cause-specific mortality risk.
We examined the trends and prevalence of sexual activity and association of sexual activity with all-cause and cause-specific mortality in a nationally representative sample using data from the US National Health and Nutrition Examination Survey from 2005 to 2016 and the National Health and Nutrition Examination Survey 2005-2014 Linked Mortality File (through December 31, 2015).
All-cause, cardiovascular disease, and cancer mortality.
A total of 15,269 US adults (mean age, 39.1 years [standard error, 0.18 years]) were included in the trend analysis. In the 2015-2016 cycle, while 71.7% (95% CI, 67.7–75.7%) US adults aged 20-59 years engaged in sexual activity ≥ 12 times/year (monthly), only 36.1% (95% CI, 31.6–40.7%) of them engaged in sexual activity ≥ 52 times/year (weekly). Since the 2005–2006 cycle, the estimated prevalence of sexual activity, ≥52 times/year and ≥12 times/year, were both stable over time among overall and each age group (all P for trend >0.1). During a median follow-up of 5.7 years (range, 1–11 years) and 71,960 person-years of observation, among 12,598 participants with eligible information on mortality status, 228 deaths occurred, including 29 associated with cardiovascular disease and 62 associated with cancer. Overall, participants with higher sexual activity frequency were at a lower risk of all-cause death in a dose-response manner (P for trend = 0.020) during the follow-up period. In addition, the multivariable-adjusted hazard ratios for all-cause mortality, CVD mortality, cancer mortality, and other cause mortality among participants who had sex ≥52 times/year compared with those having sex 0–1 time/year were 0.51 (95% CI, 0.34 to 0.76), 0.79 (95% CI, 0.19 to 3.21), 0.31 (95% CI, 0.11 to 0.84), and 0.52 (95% CI, 0.28 to 0.96), respectively.
Sexual activity appears to be a health indicator of all-cause and cancer mortality in US middle-aged adults.
Clear strengths of the present study include the large representative sample of the noninstitutionalized US population as well as the identification of precise estimates in relation to sexual activity and mortality. However, because of the observational nature of the study design, causality could not be determined.
Sexual activity was found to be associated with a lower risk of mortality from all cause and cancer.
Cao C, Yang L, Xu T, et al. Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults. J Sex Med 2020;17:1903–1913.
Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and Progression: A Systematic Review of the Literature by the European Association of Urology Section of Oncological Urology (ESOU)
2019, European Urology Focus
Citation Excerpt :
Nonetheless, it has not been proved that EF is increasing with a higher number of female partners. EF has been proposed as a modifiable risk factor for PCa; this association has been studied recently by two research groups [91,92]. In a prospective cohort study, Rider et al [91] showed a decreased risk of low-grade PCa in patients with an EF of ≥21/mo at ages 20–29 and 40–49 yr.
Smoking, sexual activity, and physical activity (PA) are discussed as modifiable lifestyle factors associated with prostate cancer (PCa) development and progression.
To evaluate the available evidence concerning the association of smoking, sexual activity, and sports and exercise on PCa risk, treatment outcome, progression, and cancer-specific mortality.
A systematic review of studies published between 2007 and 2017 using MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement criteria was conducted.
While data concerning the impact of smoking on PCa development remain conflicting, there is robust evidence that smoking is associated with aggressive tumor features and worse cancer-related outcome, which seems to be maintained for 10 yr after smoking cessation. Less convincing and limited evidence exists for the association of sexual activity with PCa risk. The findings related to PA and PCa support the inference that exercise might be a useful factor in the prevention of PCa and tumor progression, while it is not finally proved under which specific conditions PA might be protective against disease development.
Smoking is associated with aggressive tumor features and worse cancer-related prognosis; as this negative impact seems to be maintained for 10 yr after smoking cessation, urologists should advise men to quit smoking latest at PCa diagnosis to improve their prognosis. As several studies indicate a positive impact of exercise on tumor development, progression, and treatment outcome, it is certainly reasonable to advocate an active lifestyle. Least convincing evidence is available for the interaction of sexual activity and PCa, and well-conducted and longitudinal studies are clearly necessary to evaluate whether the suggested associations between PCa risk and sexual behavior are real or spurious.
In this systematic review, we looked at the impact of smoking, sexual activity, and sports and exercise on prostate cancer risk and outcome after treatment. While the evidence for sexual activity is not overall clear, we found that smoking might lead to more aggressive cancers and result in worse treatment outcome. Physical activity might prevent prostate cancer and improve cancer-related outcomes as well. Hence, it is certainly reasonable to advocate an active lifestyle and advise men to quit smoking.
New Insights into Ejaculatory Frequency and Prostate Cancer Risk: Association, Causation, or What Do We Have to Lose?
2018, European Urology
Sexual Activity and Risk of Prostate Cancer: A Dose–Response Meta-Analysis
2018, Journal of Sexual Medicine
Citation Excerpt :
In the subgroup analyses by age stratification, significant inverse association was observed in the 40s group (OR 0.82, 95% CI 0.76–0.89; P < .001; I2 = 0%; P = .909) (Figure S2). A dose-response meta-analysis was applied by age stratification in 20s,22,25,27,31,36 30s,22,25,27,31,36 40s,22,25,27,31,35,36 and a total group22,25,27,29–31,36,37 that included available data of all age stratifications data. As shown in Figure 4, there was no linear association between EF and PCa risk in the 40s group (Pnon linearity = .003) (Figure 4D) and the total group (Pnon linearity < .001) (Figure 4A).
The role of sexual activity (SA) on prostate cancer (PCa) risk is still controversial.
To determine the associations among number of female sexual partners, age at first intercourse, ejaculation frequency (EF), and the risk of PCa.
A systematic literature search on MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify the relevant studies published before April 2018. We calculated the summary odds ratio (OR) and 95% CI to determine the association between SA and PCa risk. A 2-stage dose-response meta-analysis was performed to explore the trend from the correlated log OR estimates.
Outcome measures included characteristics of included studies, associations among number of female sexual partners, age at first intercourse, as well as EF and PCa risk.
A total of 21 case-control studies and 1 cohort study with 55,490 participants (14,976 patients and 40,514 controls) were included in this meta-analysis. Linear and significant dose–response associations were found among number of female sexual partner as well as age at first intercourse and PCa risk, an increment of 10 female sexual partners associated with a 1.10-fold increase of PCa risk (OR 1.10, 95% CI 1.01–1.21), and the risk of PCa was decreased by 4% for every 5-year delay in age at first intercourse (OR 0.96, 95% CI 0.92–0.99). Although no linear association was observed between EF and the risk of PCa, moderate EF (2–4 times per week) was significantly associated with a lower risk of PCa (OR 0.91, 95% CI 0.87–0.96).
Modification of SA factors would appear to be a useful low-risk approach to decreasing the risk of PCa.
This is the first dose–response meta-analysis performed to describe the association between SA and PCa risk. However, the direction of causality between SA and risk of PCa should be interpreted with caution because most included studies used case-control design.
Meta-analysis of the included studies indicated that men with fewer sexual partner numbers, older age at first intercourse, and moderate frequent ejaculation were associated with a significantly decreased risk of PCa.
Jian Z, Ye D, Chen Y, et al. Sexual Activity and Risk of Prostate Cancer: A Dose–Response Meta-Analysis. J Sex Med 2018;15:1300–1309.
Australian genome-wide association study confirms higher female risk for adult glioma associated with variants in the region of CCDC26
2023, Neuro-Oncology

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^☆: This project is funded in part by NHMRC, Australia project Grant #623204.

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Original articleEjaculatory frequency and the risk of aggressive prostate cancer: Findings from a case-control study☆

Highlights

Abstract

Objectives

Material and methods

Results

Conclusion

Introduction

Section snippets

Study design

Results

Discussion

Conclusion

Lancet

Eur Urol

Eur Urol

Mod Pathol

Cancer Epidemiol

J Urol

J Sex Med

J Sex Med

J Urol

Development, molecular biology, and physiology of the prostate

Sexual factors and prostate cancer

BJU Int

Circulating steroid hormones and the risk of prostate cancer

Cancer Epidemiol Biomarkers Prev

Sexual behaviour, history of sexually transmitted diseases, and the risk of prostate cancer: a case-control study in Cuba

Int J Epidemiol

Sexual factors and the risk of prostate cancer

Am J Epidemiol

Sexual behaviour, STDs and risks for prostate cancer

Br J Cancer

Original article
Ejaculatory frequency and the risk of aggressive prostate cancer: Findings from a case-control study☆