Is Sexual Activity an Effective Way to Expel Distal and Intramural Ureteral Stones? An Updated Systematic Review and Meta-analysis

Is Sexual Activity an Effective Way to Expel Distal and Intramural Ureteral Stones? 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An Updated Systematic Review and Meta-analysis Edgar Paulo da Silva Neto, Rafael Morriello, David Romeiro Victor, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4414149/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose: Ureterolithiasis is a prevalent condition with a high morbidity, typically causing incapacitating pain and, if not treated correctly, can lead to renal failure. This research has sought to investigate the link between sexual activity, including masturbation, and a higher rate of spontaneous expulsion of ureteral stones. Material and Methods: We searched PubMed, Embase, and Cochrane for randomized clinical trials (RCT) assessing the effectiveness of sexual activity or masturbation in the elimination of distal or intramural ureteral stones. Heterogeneity was assessed with I². Values of p < 0.05 were considered statistically significant. Statistical analysis was performed using Review Manager 5.4.1 (Cochrane Center, The Cochrane Collaboration). Results: We included 8 RCTs, totaling 755 patients, of which 383 (50.7%) engaged in sexual activity or masturbation 3-4 times per week for an average duration of 4 weeks. The expulsion rate at 2 weeks (OR: 3.48; [95% CI: 2.37 to 5.11]; p < 0.00001) and at 4 weeks (OR: 3.28; [95% CI: 2.23 to 4.83]; p < 0.00001) was higher in the sexual activity or masturbation group. The average time for stone expulsion (MD: -3.27; [95% CI: -5.38 to -1.17]; p < 0.002) was shorter in the experimental group, as well as the average number of analgesic injections (MD: -0.6; [95% CI: -0.91 to -0.29]; p < 0.0001). Conclusion: Our findings suggest that sexual activity or masturbation appears to be effective as an expulsive medical therapy for patients with distal or intramural ureteral stones. Ureterolithiasis Ureteral Calculi Sexual Behavior Masturbation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Urolithiasis stands as one of the most common urological conditions, with ureteral stones compromising 20% of all diagnosed cases. [ 1 ] Indeed, an estimated 11% of the United States population has experienced stone disease at least once. [ 2 ] This high prevalence has continued to grow in the last decades, owing to factors such as population aging, improved detection of asymptomatic stones, dietary shifts, and higher rates of metabolic syndrome. [ 3 – 5 ] Moreover, as urolithiasis is sensible to the climate’s temperature, this trend will likely be further aggravated by the effects of global warming. [ 6 ] In this scenario, there is a growing need for accessible therapeutic modalities to help in its management. Currently, a range of these strategies, both invasive and non-invasive, are available. Thus, for ureteral stones requiring active removal, European Association of Urology (EAU) guidelines outline ureteroscopic lithotripsy (URS) and extracorporeal shock wave lithotripsy (ESWL) as potential treatment options. [ 7 ] However, in cases where active removal is unnecessary, the guidelines suggest watchful waiting due to the high likelihood of spontaneous stone passage. [ 7 ] This conservative approach should then be supplemented with medical expulsive therapy (MET) using α-blockers when stones larger than 5 mm are located in the distal ureter. [ 7 ] The efficacy of MET has spurred researchers to explore other alternative methods for facilitating the conservative expulsion of distally located stones. Among these methods, sexual activity or masturbation has garnered attention in the medical literature due to its apparent safety and availability. To date, two meta-analyses have been conducted to pool the results of the different trials conducted on this intervention. [ 8 , 9 ] Yet, the small number of studies included in each may have imposed limitations, possibly constraining their conclusions. Therefore, this systematic review and meta-analysis aim to update and reassess the current evidence through the inclusion of the most recent randomized controlled trials (RCTs). Material and Methods This systematic review and meta-analysis were performed and reported following the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement guidelines ( Supplemental Methods 1 ). [ 10 ][ 11 ] The prospective protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID CRD42024506063). Data source and search Strategy We systematically searched PubMed (MEDLINE), Embase, and Cochrane Central Register of Controlled Trials in January 2024 for RCTs involving patients with distal or intramural ureteral stones who engaged in sexual activity or masturbation. The search terms included “ureterolithiasis” and “sexual behavior”. The complete search strategy is provided in Supplemental Methods 2. After removing duplicates, two authors (E.P.S.N. and B.V.L.A.M.) screened titles and abstracts and independently assessed full-text articles to identify relevant works to be included according to prespecified criteria. Eligibility Criteria Inclusion in this meta-analysis was restricted to studies that met the following eligibility criteria: (1) randomized clinical trials (RCTs); (2) adult patients (> 18 years) with distal or intramural ureteral stones; (3) data availability of any outcome of interest; (4) patients without prior use of alpha-blocker agents. Exclusion criteria: (1) non-randomized studies; (2) studies involving pediatric or pregnant patients; (3) studies including patients with proximal or intermediate ureteral stones; (4) current use of alpha-blockers. Data extraction Two authors (E.P.S.N. and R.M.) independently extracted the data using a standardized document to collect the following characteristics: inclusion and exclusion criteria, study design, follow-up period, population characteristics, stone size, stone site, endpoint data, and definitions. The senior author resolved discrepancies between the authors. Outcomes The prespecified outcomes of interest included: (1) expulsion rate up to 2 weeks; (2) expulsion rate up to 4 weeks; (3) average quantity of analgesic injections; (4) average expulsion time; and (5) need for URS. Quality Assessment We assessed the risk of bias in randomized studies using version 2 of the Cochrane Collaboration’s Risk of Bias tool (RoB-2) [ 12 ], according to the recommendations from the Cochrane Handbook for Systematic Reviews of Interventions. [ 10 ] Each trial underwent a risk of bias score assignment, indicating whether there was a high risk, low risk, or uncertain risk of bias across five domains: randomization process, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results. Two authors (E.P.S.N. and B.V.L.A.M.) independently conducted the assessment and discrepancies were resolved by consensus. Statistical Analysis We estimated combined treatment effects using Odds Ratios (OR) for categorical outcomes with a 95% confidence interval (CI). Continuous endpoints were assessed using standardized mean differences (MD). Heterogeneity was examined using the Cochrane Q test and I 2 statistics; I 2 values > 25% were considered significant for heterogeneity. We employed a random-effects model for all endpoints as we assumed that different studies are measuring different, but still related, treatment effects. Values of p < 0.05 were considered statistically significant. Review Manager 5.4.1 software (Cochrane Center, The Cochrane Collaboration) was used for statistical analysis. Results Study selection and characteristics We identified 80 results in the initial search, and after removing duplicate records and excluding ineligible studies based on title and abstract, 10 studies remained and were reviewed in full based on inclusion criteria. After a full review, a total of 8 studies were included in this meta-analysis, all comprising RCTs (Fig. 1 ). [ 13 – 20 ] A total of 755 participants with distal or intramural ureteral stones were included, of which 685 (90.7%) were male. Approximately 383 patients (50.7%) engaged in sexual activity or masturbation varying from 2 to 4 times per week among the studies, while 372 (49.2%) patients in the control group maintained only symptomatic control with analgesics or antispasmodics and were instructed to abstain from any sexual activity during the follow-up period. Study characteristics are reported in Table 1 . The studies did not show major discrepancies regarding patient follow-up time, but the average size of the stones varied considerably among them, ranging from 4.7 to 11.1cm and from 4.9 to 11.9 in the intervention and the control group, respectively. Table 1 Main characteristics of the included studies. Study Design Recruiting period Stones Stone detection Exclusion criteria Intervention - Sexual intercourse frequency Stone site Distal (%) I/C Intramural (%) I/C Abdel-Kader , 2017 RCT, single-center April 2015 -March 2016 Distal ureteral or intramural stones US, plain X-ray film or CT Unmarried; ED; stones > 10mm, irregular or spiky; hydronephrosis; fever; impaired renal function; previous ureteric surgery 3–4 times a week 57 / 54 43 / 46 Bayractar , 2017 RCT, single center December 2015 - May 2017 Radiopaque distal ureteral stones 5-10mm X-ray, CT Unmarried; ED; those who reported more than one sexual activity/ masturbation per week; stones < 5mm or ≥10mm or multiple;18 years; not married; severe hydronephrosis; fever; renal insufficient; previous ureteric surgery; urinary infection; pregnancy; ureteral stenosis; VUR; neurogenic bladder 3 times a week NA NA Bhatti , 2023 RCT, single center November 2021 - February 2023 Radiopaque distal or intramural ureteral stones 4-8mm US, plain X-ray film or CT Unmarried; ED or loss of libido; stones < 4mm or multiple or spiky; hydronephrosis; impaired renal function urinary infection; neurogenic bladder; VUR; fever; skeletal deformity; renal insufficient; previous ureteric surgery 2–3 times a week 60 / 52 20 / 28 Doluoglo , 2015 RCT, single center September 2013 - October 2014 Radiopaque distal ureteral stones US, plain X-ray film and CT Who did not have an active sexual partner; ED; DM; stones > 6mm or nonopaque or multiple; urinary infection; severe hydronephrosis; previous ureteric surgery; high creatinine; previously use of α-1 adrenergic receptor or calcium canal blockers At least 3 times a week NA NA Khan , 2022 RCT, multi-center October 2021 - March 2022 Distal ureteral stones 5-10mm US, plain X-ray film and CT DM; arterial hypertension At least 3–4 times a week NA NA Li , 2019* RCT, single center March 2016 - January 2017 Distal or intramural ureteral stones 7-15mm Plain X-ray film and CT Abnormal kidney anatomy and function; weigh > 100kg; previous administration of drugs that may induce stones; previous urologic surgery; hydronephrosis; coagulation dysfunction, urinary infection; tamsulosin allergy; creatinine > 2 mg/dL; multiple stones; fever; hypotension; refractory pain; VUR; meurogenic bladder; DE At least 3 times a week NA NA Turgut , 2021 (a) RCT, Single center September 2018 – June 2020 Distal or intramural ureteral stones < 10mm US, DUSG and CT Unmarried females; pregnancies; breast feeding; ≤ 18 years; sexual dysfunction; urinary infection; renal insufficienc; high creatinine level; severe hydroureteronephrosis; open or endoscopic ureteral surgery history; vesicoureteral reflux; neurogenic bladder; intermediate (stones on the ureter–iliac artery cross) or proximal ureter stones; stones ≥ 10 mm in size; multiple ureter stones 3–4 times a week 60 / 57.2 40 / 42.8 Turgut , 2021 (b) RCT, Single center February 2018 - March 2020 Distal ureteral stones ≥ 5 mm and < 10 mm Plain X-ray, US film and CT Age < 18 years; stones < 5 mm or ≥ 10 mm; intermediate (stones on the ureter–iliac artery cross) or proximal ureteral; multiple ureteral stones; urinary infection; renal insufficiency; high creatinine level; severe hydroureteronephrosis; previous ureteral surgery; vesicoureteral reflux; neurogenic bladder; erectile dysfunction; inability or refusal to masturbate for any reason At least 3–4 times a week NA NA Abbreviations : RCT: Randomized Controlled Trial; US: ultrasound; CT: computed tomography; DUSG: direct urinary system graphy; ED: erectile dysfunction; VUR: vesicoureteral reflux; DM: diabetes mellitus. I: intervention; C: control. *All patients underwent shock wave lithotripsy within 24 hours after diagnosis. Pooled analysis of all studies All 8 included studies were included in the assessment of the expulsion rate of ureteral stones up to 2 weeks, demonstrating that sexual activity or masturbation group significantly increased the stone elimination rate ([73.8%] 283 out of 383) compared to the control group ([46.5%] 173 out of 372) (OR: 3.48; [95% CI: 2.37 to 5.11]; I 2 = 29%; p < 0.00001) (Fig. 2 A). In comparison with the control group ([61.5%] 187 out of 304), the sexual activity or masturbation group ([84%] 263 out of 313) also maintained a significantly higher expulsion rate at 4 weeks (OR: 3.28; [95% CI: 2.23 to 4.83]; I 2 : 0%; p < 0.00001) (Fig. 2 B). The pooled analysis of 6 studies demonstrated a significantly shorter average expulsion time of the stones in the sexual activity or masturbation group compared to the control group (MD: -3.27; [95% CI: -5.38 to -1.17]; I 2 = 77%; p < 0.002) (Fig. 3 ). Pain control in participants was measured by the average number of analgesic injections used at clinical discretion. Non-steroidal anti-inflammatory drugs or antispasmodics were administered whenever participants experienced ureteral colic. Thus, the average daily frequency of analgesic injections used by the sexual activity or masturbation group was significantly lower compared to the control group (MD: -0.6; [95% CI: -0.91 to -0.29]; I 2 = 87%; p < 0.0001) (Fig. 4 ). Participants who did not eliminate the stones by the end of 4 weeks underwent URS. When compared to the control group ([39.1%] 108 out of 276), the need for the mentioned procedure was significantly lower in the sexual activity or masturbation group ([16.4%] 47 out of 285) (OR: 0.31; [95% CI: 0.21 to 0.46]; I 2 = 0%; p < 0.00001) (Fig. 5 ). Quality assessment The risk of bias in individual studies was assessed using the Cochrane Collaboration’s RoB-2 tool to evaluate the bias risk in randomized studies (9), summarized in Supplementary Fig. 2 . Two studies were classified as high risk for not reporting relevant outcome data. [ 17 , 18 ]. The other randomized clinical trials presented a low risk of bias (Supplementary Fig. 1). Sensitivity Analysis The number of analgesic injections and the mean stone clearance time were the primary outcomes that showed high heterogeneity between studies (I²=87% and I 2 = 77%, respectively). The leave-one-out sensitivity analysis for these two outcomes revealed that no single study significantly influenced heterogeneity so that the analyses remained consistent with the overall results. In the sensitivity analysis, the OR for the number of analgesic injections and the mean stone clearance time ranged from − 0.71 to -0.49 and − 3.96 to -2.36, respectively. Discussion This meta-analysis included a total of 8 RCTs yielding 755 patients. The key findings of this systematic review and meta-analysis include: (1) the stone expulsion rate at 2 weeks, as well as at 4 weeks, was significantly higher in the sexual activity or masturbation group; (2) the average time for stone elimination was shorter in the experimental group; (3) the average number of analgesic injections used for pain control during crises was lower in the sexual activity or masturbation group; and (4) the need for URS was significantly lower in participants in the sexual activity or masturbation group. The peristalsis of the distal ureter and the ureterovesical junction, as well the erection, are controlled by myogenic and neurogenic mechanisms. The neurogenic mechanisms are modulated by the autonomic nervous system through noradrenergic nerves, cholinergic nerves, and non-cholinergic non-adrenergic nerves (NANC). During erection and sexual activity, there is an increase in the release of nitric oxide, an inhibitory neurotransmitter that blocks the action of NANC, promoting relaxation of the smooth muscles in the ureteral and ureterovesical regions. This could potentially explain the contribution of sexual activity to the elimination of distal ureteral stones. [ 21 , 22 ] The physiological mechanisms attempting to elucidate the contribution of sexual activity or masturbation in the elimination of distal ureteral stones are well described in men. Although these mechanisms are not well-known in women, it is possible that similar mechanisms can also occur in this group of patients, which could explain similar positive results in studies that recruited women. The size and location of ureteral stones are two important predictors of spontaneous elimination. It is reported that up to 98% of stones ≤ 5 mm are eliminated spontaneously. Furthermore, the more distal the stone, the higher the likelihood of spontaneous elimination, reaching a 75% chance for distal stones and a 79% chance for stones at the ureterovesical junction. [ 23 – 25 ] In our study, the size of ureteral stones ranged from 4 to 15 mm, and their location were limited to distal or intramural, encompassing patients with modest chances of spontaneous elimination. The EAU guidelines advocate the use of alpha-blockers as MET for patients with stones smaller than 10 mm. A previous meta-analysis demonstrated comparable results between male sexual activity and the use of alpha-blockers. Although the expulsion rate was higher in the sexual activity group at 2 weeks (70.7% vs. 63.9%) and at 4 weeks (84.3% vs. 81.1%), the difference between the groups was not statistically significant. The average time of expulsion and the need for analgesia or additional interventions also did not differ significantly between the groups. Therefore, these results from Juman et al. suggest that sexual activity may be an alternative to pharmacological MET with alpha-blockers. [ 26 ] The results of our meta-analysis are consistent with the conclusions of previous meta-analyses, except for the average time of stone expulsion reported by Xu et al., that concluded that there was no statistically significant difference between the groups. In addition, none of the previous studies assessed the need for URS. [ 8 , 9 ] Our findings support the consideration of sexual intercourse as an alternative to the conservative treatment of distal or intramural ureteral stones, especially when alpha-blockers are contra-indicated or are associated with adverse effects and aiming to reduce costs associated with drug use and hospital procedures. It could also be a behavioral measure to be recommended in association with drug treatment and, in this case, the synergy effects must be better evaluated in further studies. Moreover, more controlled, multicenter studies with larger and more diverse population samples are needed, particularly including the female population, to minimize the impact of type I statistical errors in future assessments. This systematic review and meta-analysis had several limitations. Firstly, most of the included clinical trials were single-center and had a small and less diverse population, which could have impacted the statistical power of this study. Furthermore, the study population was predominantly male, limiting the extrapolation of results to the female population, demonstrating the need of further studies involving this subgroup. While the number of sexual activities maintained by the experimental group was nearly standardized in individual studies, the ideal number of sexual activities or masturbation for stone elimination remains uncertain. Lastly, it was not possible to assess the long-term effectiveness of sexual intercourse, beyond 4 weeks, as the included studies followed recommendations describing higher risks of hydronephrosis or even irreversible renal dysfunction in patients undergoing medical expulsive therapy for more than 4 weeks. [ 27 ] Conclusion The results of this meta-analysis suggest that sexual activity or masturbation contributes to expulsive treatment for distal or intramural ureteral stones, with higher expulsion rates, lower expulsion time, improved pain control, and less need for interventions. It demonstrated to be a viable alternative to conservative management of distal ureterolithiasis and patients should, therefore, be informed of its benefits; despite further studies are wanted to better select patients for this strategy. Abbreviations CI – Confidence interval MET – Medical expulsive therapy OR – Odds ratio PRISMA – Preferred Reporting Items for Systematic Reviews and Meta-Analysis PROSPERO – International Prospective Register of Systematic Reviews RCT – Randomized controlled trial(s) RoB-2 – Cochrane risk-of-bias tool for randomized trials URS – Ureteroscopic lithotripsy Declarations Acknowledgments Author contributions E.P.S.Neto: conception and design, acquisition of data, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript. R.Morrielo: conception and design, acquisition of data, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript. D.R.Victor: conception and design, statistical analyses, drafting of the manuscript, critical revision of the manuscript. C.M.P.Reis: conception and design, acquisition of data, analysis and interpretation of data. G.E.Lech: conception and design, acquisition of data, analysis and interpretation of data. R.O.S.Silva: conception and design, acquisition of data, analysis and interpretation of data. P.Viana: conception and design, acquisition of data, analysis and interpretation of data. B.V.L.A.Melão: conception and design, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript. Data availability All data generated or analysed during this study are included in this published article and its supporting information files. Funding No funds, grants, or other support was received for conducting this study. Conflict of interest All authors declare no relationships that could be construed as a conflict of interest. Ethical approval Ethical approval was not required for a meta-analysis of previously published randomised controlled trials. Research involving human participants and/or animals The study did not involve human participants and/or animals. Informed consent No individual participants were included in the study. References Ahmed AA, Al-sayed AS. Tamsulosin versus Alfuzosin in the Treatment of Patients with Distal Ureteral Stones: Prospective, Randomized, Comparative Study. Korean J Urol 2010;51:193–7. https://doi.org/10.4111/kju.2010.51.3.193. Hill AJ, Basourakos SP, Lewicki P, Wu X, Arenas-Gallo C, Chuang D, et al. Incidence of Kidney Stones in the United States: The Continuous National Health and Nutrition Examination Survey. J Urol 2022;207:851–6. https://doi.org/10.1097/JU.0000000000002331. 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Supplementary Files SUPPLEMENTARYMATERIALIUN.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 29 Jul, 2024 Reviews received at journal 06 Jul, 2024 Reviewers agreed at journal 30 Jun, 2024 Reviews received at journal 30 Jun, 2024 Reviewers agreed at journal 30 Jun, 2024 Reviewers invited by journal 28 Jun, 2024 Editor assigned by journal 28 Jun, 2024 Submission checks completed at journal 18 Jun, 2024 First submitted to journal 13 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4414149","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321294066,"identity":"db59c75c-cc9f-4250-ae1f-8c5335dae55c","order_by":0,"name":"Edgar Paulo da Silva Neto","email":"","orcid":"","institution":"Catholic University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Edgar","middleName":"Paulo da Silva","lastName":"Neto","suffix":""},{"id":321294067,"identity":"0724a65e-2187-4fc8-b4d9-7e48d7334fdd","order_by":1,"name":"Rafael Morriello","email":"","orcid":"","institution":"Military Police Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"","lastName":"Morriello","suffix":""},{"id":321294068,"identity":"110d2ec0-4182-447c-95e9-f63aad278e6f","order_by":2,"name":"David Romeiro Victor","email":"","orcid":"","institution":"Catholic University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"Romeiro","lastName":"Victor","suffix":""},{"id":321294069,"identity":"f65ad198-ad63-4667-9b33-d4e2caf9355f","order_by":3,"name":"Camila Mariana de Paiva Reis","email":"","orcid":"","institution":"Federal University of Juiz de Fora, Juiz de Fora","correspondingAuthor":false,"prefix":"","firstName":"Camila","middleName":"Mariana de Paiva","lastName":"Reis","suffix":""},{"id":321294070,"identity":"b9dcee22-bef7-4ed3-9695-8c10be87e76a","order_by":4,"name":"Gabriele Eckerdt Lech","email":"","orcid":"","institution":"Pontifical Catholic University of Rio Grande do Sul","correspondingAuthor":false,"prefix":"","firstName":"Gabriele","middleName":"Eckerdt","lastName":"Lech","suffix":""},{"id":321294071,"identity":"c4e66cb0-7b1c-48ec-815a-5217094a4050","order_by":5,"name":"Raquel Oliveira de Souza Silva","email":"","orcid":"","institution":"Federal University of Piaui","correspondingAuthor":false,"prefix":"","firstName":"Raquel","middleName":"Oliveira de Souza","lastName":"Silva","suffix":""},{"id":321294072,"identity":"76e0d1c7-39df-4db8-8f2b-a8f555cf3113","order_by":6,"name":"Patrícia Viana","email":"","orcid":"","institution":"University of Extreme South of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Patrícia","middleName":"","lastName":"Viana","suffix":""},{"id":321294073,"identity":"64016753-0f2b-424b-a9e4-6c1dbd534f64","order_by":7,"name":"Barbara Vieira Lima Aguiar Melao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYBACAwYGNjCDjxlIfGwAMRkbDxClhQ2ohXFmA4MEkGogUgsQM/OCtTAw4NVizn722YOfe+wS29i5Ez/b7rCp020/DLSlxiYalxbLnnRzw55nyYltzLybpXPPpEmYnUkEajmWltuAy2EH0tgkeA4wG7Mx826Qzm07LGF2AKiFseEwbi3nn7FJ/jlQD9Ky+bclSMv5hwS03Ehjk+Y5cFgOqGWbNCNIyw0CtljOeMZuLHPgOFiLZW9bmuS2G0BbEvD4xZw/je3hmwPVPPz8Zzff+Nlmw292Pv3hgw81Nji14AAJpCkfBaNgFIyCUYAGAMIvW46WP2vaAAAAAElFTkSuQmCC","orcid":"","institution":"USP Medical School","correspondingAuthor":true,"prefix":"","firstName":"Barbara","middleName":"Vieira Lima Aguiar","lastName":"Melao","suffix":""}],"badges":[],"createdAt":"2024-05-13 15:16:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4414149/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4414149/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60436589,"identity":"f5d45d53-d663-4da5-a39e-bae61fb22d26","added_by":"auto","created_at":"2024-07-16 17:34:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":293890,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram of study screening and selection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/da7663e72806249bb76dec95.png"},{"id":60436586,"identity":"9e17c385-7e85-40f3-adf1-06e570b0c35e","added_by":"auto","created_at":"2024-07-16 17:34:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":786482,"visible":true,"origin":"","legend":"\u003cp\u003eExpulsion rate in 2 weeks (2A) and 4 weeks (2B).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCaption: \u003c/em\u003e(A) Expulsion rate in 2 weeks; and (B) expulsion rate in 4 weeks.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e M-H, Mantel-Haenszel; CI, confidence interval.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/d9985e89e3502806fc4baad8.png"},{"id":60436587,"identity":"27942e9d-4899-4b91-9fd0-1007edbc602d","added_by":"auto","created_at":"2024-07-16 17:34:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":353580,"visible":true,"origin":"","legend":"\u003cp\u003eAverage expulsion time.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCaption: \u003c/em\u003eExpulsion time.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e SD, standard deviation; CI, confidence interval.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/4f0f37699f86a2c74bac9d64.png"},{"id":60436591,"identity":"a46934a2-6b96-4300-8c0d-679df5d1ac79","added_by":"auto","created_at":"2024-07-16 17:34:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":359135,"visible":true,"origin":"","legend":"\u003cp\u003eAverage number of analgesic injections.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCaption: \u003c/em\u003eAnalgesic injections.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e SD, standard deviation; CI, confidence interval.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/3db2d0a78c9219897f62ff1d.png"},{"id":60436590,"identity":"00848409-310f-4f37-8d56-da694a0abe9a","added_by":"auto","created_at":"2024-07-16 17:34:42","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":151925,"visible":true,"origin":"","legend":"\u003cp\u003eNeed for lithotripsy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCaption: \u003c/em\u003eNeed for lithotripsy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e M-H, Mantel-Haenszel; CI, confidence interval.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/20cc9287c7b818ac08bf7070.png"},{"id":60437436,"identity":"e5df6040-bf3b-4cf2-8a27-0db8862811ff","added_by":"auto","created_at":"2024-07-16 17:42:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2803956,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/fe57c25d-2638-47f5-8692-1ea1b6bfd1af.pdf"},{"id":60437435,"identity":"9cf5fef8-0d11-45f6-9416-3d918b52e6cb","added_by":"auto","created_at":"2024-07-16 17:42:42","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":245507,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYMATERIALIUN.docx","url":"https://assets-eu.researchsquare.com/files/rs-4414149/v1/ef8d4d02f4499cc71ee6e555.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is Sexual Activity an Effective Way to Expel Distal and Intramural Ureteral Stones? An Updated Systematic Review and Meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUrolithiasis stands as one of the most common urological conditions, with ureteral stones compromising 20% of all diagnosed cases. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Indeed, an estimated 11% of the United States population has experienced stone disease at least once. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] This high prevalence has continued to grow in the last decades, owing to factors such as population aging, improved detection of asymptomatic stones, dietary shifts, and higher rates of metabolic syndrome. [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Moreover, as urolithiasis is sensible to the climate\u0026rsquo;s temperature, this trend will likely be further aggravated by the effects of global warming. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] In this scenario, there is a growing need for accessible therapeutic modalities to help in its management.\u003c/p\u003e \u003cp\u003eCurrently, a range of these strategies, both invasive and non-invasive, are available. Thus, for ureteral stones requiring active removal, European Association of Urology (EAU) guidelines outline ureteroscopic lithotripsy (URS) and extracorporeal shock wave lithotripsy (ESWL) as potential treatment options. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] However, in cases where active removal is unnecessary, the guidelines suggest watchful waiting due to the high likelihood of spontaneous stone passage. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] This conservative approach should then be supplemented with medical expulsive therapy (MET) using α-blockers when stones larger than 5 mm are located in the distal ureter. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe efficacy of MET has spurred researchers to explore other alternative methods for facilitating the conservative expulsion of distally located stones. Among these methods, sexual activity or masturbation has garnered attention in the medical literature due to its apparent safety and availability. To date, two meta-analyses have been conducted to pool the results of the different trials conducted on this intervention. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Yet, the small number of studies included in each may have imposed limitations, possibly constraining their conclusions. Therefore, this systematic review and meta-analysis aim to update and reassess the current evidence through the inclusion of the most recent randomized controlled trials (RCTs).\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eThis systematic review and meta-analysis were performed and reported following the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement guidelines (\u003cem\u003eSupplemental Methods 1\u003c/em\u003e). [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The prospective protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID CRD42024506063).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source and search Strategy\u003c/h2\u003e \u003cp\u003eWe systematically searched PubMed (MEDLINE), Embase, and Cochrane Central Register of Controlled Trials in January 2024 for RCTs involving patients with distal or intramural ureteral stones who engaged in sexual activity or masturbation. The search terms included \u0026ldquo;ureterolithiasis\u0026rdquo; and \u0026ldquo;sexual behavior\u0026rdquo;. The complete search strategy is provided in \u003cem\u003eSupplemental Methods 2.\u003c/em\u003e After removing duplicates, two authors (E.P.S.N. and B.V.L.A.M.) screened titles and abstracts and independently assessed full-text articles to identify relevant works to be included according to prespecified criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEligibility Criteria\u003c/h2\u003e \u003cp\u003eInclusion in this meta-analysis was restricted to studies that met the following eligibility criteria: (1) randomized clinical trials (RCTs); (2) adult patients (\u0026gt;\u0026thinsp;18 years) with distal or intramural ureteral stones; (3) data availability of any outcome of interest; (4) patients without prior use of alpha-blocker agents. Exclusion criteria: (1) non-randomized studies; (2) studies involving pediatric or pregnant patients; (3) studies including patients with proximal or intermediate ureteral stones; (4) current use of alpha-blockers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eTwo authors (E.P.S.N. and R.M.) independently extracted the data using a standardized document to collect the following characteristics: inclusion and exclusion criteria, study design, follow-up period, population characteristics, stone size, stone site, endpoint data, and definitions. The senior author resolved discrepancies between the authors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe prespecified outcomes of interest included: (1) expulsion rate up to 2 weeks; (2) expulsion rate up to 4 weeks; (3) average quantity of analgesic injections; (4) average expulsion time; and (5) need for URS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eQuality Assessment\u003c/h2\u003e \u003cp\u003eWe assessed the risk of bias in randomized studies using version 2 of the Cochrane Collaboration\u0026rsquo;s Risk of Bias tool (RoB-2) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], according to the recommendations from the Cochrane Handbook for Systematic Reviews of Interventions. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Each trial underwent a risk of bias score assignment, indicating whether there was a high risk, low risk, or uncertain risk of bias across five domains: randomization process, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results. Two authors (E.P.S.N. and B.V.L.A.M.) independently conducted the assessment and discrepancies were resolved by consensus.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eWe estimated combined treatment effects using Odds Ratios (OR) for categorical outcomes with a 95% confidence interval (CI). Continuous endpoints were assessed using standardized mean differences (MD). Heterogeneity was examined using the Cochrane Q test and I\u003csup\u003e2\u003c/sup\u003e statistics; I\u003csup\u003e2\u003c/sup\u003e values\u0026thinsp;\u0026gt;\u0026thinsp;25% were considered significant for heterogeneity. We employed a random-effects model for all endpoints as we assumed that different studies are measuring different, but still related, treatment effects. Values of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Review Manager 5.4.1 software (Cochrane Center, The Cochrane Collaboration) was used for statistical analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection and characteristics\u003c/h2\u003e \u003cp\u003eWe identified 80 results in the initial search, and after removing duplicate records and excluding ineligible studies based on title and abstract, 10 studies remained and were reviewed in full based on inclusion criteria. After a full review, a total of 8 studies were included in this meta-analysis, all comprising RCTs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA total of 755 participants with distal or intramural ureteral stones were included, of which 685 (90.7%) were male. Approximately 383 patients (50.7%) engaged in sexual activity or masturbation varying from 2 to 4 times per week among the studies, while 372 (49.2%) patients in the control group maintained only symptomatic control with analgesics or antispasmodics and were instructed to abstain from any sexual activity during the follow-up period. Study characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The studies did not show major discrepancies regarding patient follow-up time, but the average size of the stones varied considerably among them, ranging from 4.7 to 11.1cm and from 4.9 to 11.9 in the intervention and the control group, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMain characteristics of the included studies.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDesign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRecruiting period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStones\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStone detection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExclusion criteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntervention - Sexual intercourse frequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eStone site\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDistal\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003cp\u003eI/C\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eIntramural (%)\u003c/p\u003e \u003cp\u003eI/C\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdel-Kader\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003esingle-center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eApril 2015\u003c/p\u003e \u003cp\u003e-March 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistal ureteral or intramural stones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUS, plain X-ray film or CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnmarried; ED; stones\u0026thinsp;\u0026gt;\u0026thinsp;10mm, irregular or spiky; hydronephrosis; fever; impaired renal function; previous ureteric surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u0026ndash;4 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57 / 54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e43 / 46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBayractar\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003esingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDecember 2015 - May 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRadiopaque distal ureteral stones 5-10mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX-ray, CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnmarried; ED; those who reported more than one sexual activity/ masturbation per week; stones\u0026thinsp;\u0026lt;\u0026thinsp;5mm or \u0026ge;10mm or multiple;18 years; not married; severe hydronephrosis; fever; renal insufficient; previous ureteric surgery; urinary infection; pregnancy; ureteral stenosis; VUR; neurogenic bladder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBhatti\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003esingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNovember 2021 - February 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRadiopaque distal or intramural ureteral stones 4-8mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUS, plain X-ray film or CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnmarried; ED or loss of libido; stones\u0026thinsp;\u0026lt;\u0026thinsp;4mm or multiple or spiky; hydronephrosis; impaired renal function urinary infection; neurogenic bladder; VUR; fever; skeletal deformity; renal insufficient; previous ureteric surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u0026ndash;3 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60 / 52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20 / 28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDoluoglo\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003esingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSeptember 2013 - October 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRadiopaque distal ureteral stones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUS, plain X-ray film and CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWho did not have an active sexual partner; ED; DM; stones\u0026thinsp;\u0026gt;\u0026thinsp;6mm or nonopaque or multiple; urinary infection; severe hydronephrosis; previous ureteric surgery; high creatinine; previously use of α-1 adrenergic receptor or calcium canal blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt least 3 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKhan\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003emulti-center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOctober 2021\u003c/p\u003e \u003cp\u003e- March 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistal ureteral stones 5-10mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUS, plain X-ray film and CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDM; arterial hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt least 3\u0026ndash;4 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLi\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2019*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003esingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMarch 2016\u003c/p\u003e \u003cp\u003e- January 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistal or intramural ureteral stones 7-15mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlain X-ray film and CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbnormal kidney anatomy and function; weigh\u0026thinsp;\u0026gt;\u0026thinsp;100kg; previous administration\u003c/p\u003e \u003cp\u003eof drugs that may induce stones; previous urologic surgery; hydronephrosis; coagulation dysfunction, urinary infection; tamsulosin allergy; creatinine\u0026thinsp;\u0026gt;\u0026thinsp;2 mg/dL; multiple stones; fever; hypotension; refractory pain; VUR; meurogenic bladder; DE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt least 3 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTurgut\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2021 (a)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003eSingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSeptember 2018 \u0026ndash; June 2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistal or intramural ureteral stones\u0026thinsp;\u0026lt;\u0026thinsp;10mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUS, DUSG and CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnmarried females; pregnancies; breast feeding; \u0026le; 18 years; sexual dysfunction; urinary infection; renal insufficienc; high creatinine level; severe hydroureteronephrosis; open or endoscopic ureteral surgery history; vesicoureteral reflux; neurogenic bladder; intermediate (stones on the ureter\u0026ndash;iliac artery cross) or proximal ureter stones; stones\u0026thinsp;\u0026ge;\u0026thinsp;10 mm in size; multiple ureter stones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u0026ndash;4 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60 / 57.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e40 / 42.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTurgut\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e\u003cb\u003e2021 (b)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRCT,\u003c/p\u003e \u003cp\u003eSingle center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFebruary 2018\u003c/p\u003e \u003cp\u003e- March 2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistal ureteral stones\u0026thinsp;\u0026ge;\u0026thinsp;5 mm and \u0026lt; 10 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlain X-ray, US film and CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026lt;\u0026thinsp;18 years; stones\u0026thinsp;\u0026lt;\u0026thinsp;5 mm or \u0026ge;\u0026thinsp;10 mm; intermediate (stones on the ureter\u0026ndash;iliac artery cross) or proximal ureteral; multiple ureteral stones; urinary infection; renal insufficiency; high creatinine level; severe hydroureteronephrosis; previous ureteral surgery; vesicoureteral reflux; neurogenic bladder; erectile dysfunction; inability or refusal to masturbate for any reason\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAt least 3\u0026ndash;4 times a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: RCT: Randomized Controlled Trial; US: ultrasound; CT: computed tomography; DUSG: direct urinary system graphy; ED: erectile dysfunction; VUR: vesicoureteral reflux; DM: diabetes mellitus. I: intervention; C: control.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e*All patients underwent shock wave lithotripsy within 24 hours after diagnosis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePooled analysis of all studies\u003c/h2\u003e \u003cp\u003eAll 8 included studies were included in the assessment of the expulsion rate of ureteral stones up to 2 weeks, demonstrating that sexual activity or masturbation group significantly increased the stone elimination rate ([73.8%] 283 out of 383) compared to the control group ([46.5%] 173 out of 372) (OR: 3.48; [95% CI: 2.37 to 5.11]; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;29%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). In comparison with the control group ([61.5%] 187 out of 304), the sexual activity or masturbation group ([84%] 263 out of 313) also maintained a significantly higher expulsion rate at 4 weeks (OR: 3.28; [95% CI: 2.23 to 4.83]; I\u003csup\u003e2\u003c/sup\u003e: 0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe pooled analysis of 6 studies demonstrated a significantly shorter average expulsion time of the stones in the sexual activity or masturbation group compared to the control group (MD: -3.27; [95% CI: -5.38 to -1.17]; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;77%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.002) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e Pain control in participants was measured by the average number of analgesic injections used at clinical discretion. Non-steroidal anti-inflammatory drugs or antispasmodics were administered whenever participants experienced ureteral colic. Thus, the average daily frequency of analgesic injections used by the sexual activity or masturbation group was significantly lower compared to the control group (MD: -0.6; [95% CI: -0.91 to -0.29]; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;87%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eParticipants who did not eliminate the stones by the end of 4 weeks underwent URS. When compared to the control group ([39.1%] 108 out of 276), the need for the mentioned procedure was significantly lower in the sexual activity or masturbation group ([16.4%] 47 out of 285) (OR: 0.31; [95% CI: 0.21 to 0.46]; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eThe risk of bias in individual studies was assessed using the Cochrane Collaboration\u0026rsquo;s RoB-2 tool to evaluate the bias risk in randomized studies (9), summarized in \u003cem\u003eSupplementary Fig.\u0026nbsp;2\u003c/em\u003e. Two studies were classified as high risk for not reporting relevant outcome data. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The other randomized clinical trials presented a low risk of bias (Supplementary Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity Analysis\u003c/h2\u003e \u003cp\u003eThe number of analgesic injections and the mean stone clearance time were the primary outcomes that showed high heterogeneity between studies (I\u0026sup2;=87% and I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;77%, respectively). The leave-one-out sensitivity analysis for these two outcomes revealed that no single study significantly influenced heterogeneity so that the analyses remained consistent with the overall results. In the sensitivity analysis, the OR for the number of analgesic injections and the mean stone clearance time ranged from \u0026minus;\u0026thinsp;0.71 to -0.49 and \u0026minus;\u0026thinsp;3.96 to -2.36, respectively.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis included a total of 8 RCTs yielding 755 patients. The key findings of this systematic review and meta-analysis include: (1) the stone expulsion rate at 2 weeks, as well as at 4 weeks, was significantly higher in the sexual activity or masturbation group; (2) the average time for stone elimination was shorter in the experimental group; (3) the average number of analgesic injections used for pain control during crises was lower in the sexual activity or masturbation group; and (4) the need for URS was significantly lower in participants in the sexual activity or masturbation group.\u003c/p\u003e \u003cp\u003eThe peristalsis of the distal ureter and the ureterovesical junction, as well the erection, are controlled by myogenic and neurogenic mechanisms. The neurogenic mechanisms are modulated by the autonomic nervous system through noradrenergic nerves, cholinergic nerves, and non-cholinergic non-adrenergic nerves (NANC). During erection and sexual activity, there is an increase in the release of nitric oxide, an inhibitory neurotransmitter that blocks the action of NANC, promoting relaxation of the smooth muscles in the ureteral and ureterovesical regions. This could potentially explain the contribution of sexual activity to the elimination of distal ureteral stones. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe physiological mechanisms attempting to elucidate the contribution of sexual activity or masturbation in the elimination of distal ureteral stones are well described in men. Although these mechanisms are not well-known in women, it is possible that similar mechanisms can also occur in this group of patients, which could explain similar positive results in studies that recruited women. The size and location of ureteral stones are two important predictors of spontaneous elimination. It is reported that up to 98% of stones\u0026thinsp;\u0026le;\u0026thinsp;5 mm are eliminated spontaneously. Furthermore, the more distal the stone, the higher the likelihood of spontaneous elimination, reaching a 75% chance for distal stones and a 79% chance for stones at the ureterovesical junction. [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] In our study, the size of ureteral stones ranged from 4 to 15 mm, and their location were limited to distal or intramural, encompassing patients with modest chances of spontaneous elimination.\u003c/p\u003e \u003cp\u003e The EAU guidelines advocate the use of alpha-blockers as MET for patients with stones smaller than 10 mm. A previous meta-analysis demonstrated comparable results between male sexual activity and the use of alpha-blockers. Although the expulsion rate was higher in the sexual activity group at 2 weeks (70.7% vs. 63.9%) and at 4 weeks (84.3% vs. 81.1%), the difference between the groups was not statistically significant. The average time of expulsion and the need for analgesia or additional interventions also did not differ significantly between the groups. Therefore, these results from Juman et al. suggest that sexual activity may be an alternative to pharmacological MET with alpha-blockers. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe results of our meta-analysis are consistent with the conclusions of previous meta-analyses, except for the average time of stone expulsion reported by Xu et al., that concluded that there was no statistically significant difference between the groups. In addition, none of the previous studies assessed the need for URS. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Our findings support the consideration of sexual intercourse as an alternative to the conservative treatment of distal or intramural ureteral stones, especially when alpha-blockers are contra-indicated or are associated with adverse effects and aiming to reduce costs associated with drug use and hospital procedures. It could also be a behavioral measure to be recommended in association with drug treatment and, in this case, the synergy effects must be better evaluated in further studies. Moreover, more controlled, multicenter studies with larger and more diverse population samples are needed, particularly including the female population, to minimize the impact of type I statistical errors in future assessments.\u003c/p\u003e \u003cp\u003eThis systematic review and meta-analysis had several limitations. Firstly, most of the included clinical trials were single-center and had a small and less diverse population, which could have impacted the statistical power of this study. Furthermore, the study population was predominantly male, limiting the extrapolation of results to the female population, demonstrating the need of further studies involving this subgroup. While the number of sexual activities maintained by the experimental group was nearly standardized in individual studies, the ideal number of sexual activities or masturbation for stone elimination remains uncertain. Lastly, it was not possible to assess the long-term effectiveness of sexual intercourse, beyond 4 weeks, as the included studies followed recommendations describing higher risks of hydronephrosis or even irreversible renal dysfunction in patients undergoing medical expulsive therapy for more than 4 weeks. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this meta-analysis suggest that sexual activity or masturbation contributes to expulsive treatment for distal or intramural ureteral stones, with higher expulsion rates, lower expulsion time, improved pain control, and less need for interventions. It demonstrated to be a viable alternative to conservative management of distal ureterolithiasis and patients should, therefore, be informed of its benefits; despite further studies are wanted to better select patients for this strategy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCI \u0026ndash; Confidence interval\u003c/p\u003e\n\u003cp\u003eMET \u0026ndash; Medical expulsive therapy\u003c/p\u003e\n\u003cp\u003eOR \u0026ndash; Odds ratio\u003c/p\u003e\n\u003cp\u003ePRISMA \u0026ndash;\u0026nbsp;Preferred Reporting Items for Systematic Reviews and Meta-Analysis\u003c/p\u003e\n\u003cp\u003ePROSPERO \u0026ndash;\u0026nbsp;International Prospective Register of Systematic Reviews\u003c/p\u003e\n\u003cp\u003eRCT \u0026ndash;\u0026nbsp;Randomized controlled trial(s)\u003c/p\u003e\n\u003cp\u003eRoB-2 \u0026ndash;\u0026nbsp;Cochrane risk-of-bias tool for randomized trials\u003c/p\u003e\n\u003cp\u003eURS \u0026ndash;\u0026nbsp;Ureteroscopic lithotripsy\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eE.P.S.Neto: conception and design, acquisition of data, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript. R.Morrielo: conception and design, acquisition of data, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript. D.R.Victor: conception and design, statistical analyses, drafting of the manuscript, critical revision of the manuscript. C.M.P.Reis: conception and design, acquisition of data, analysis and interpretation of data. \u0026nbsp;G.E.Lech: conception and design, acquisition of data, analysis and interpretation of data. R.O.S.Silva: conception and design, acquisition of data, analysis and interpretation of data. P.Viana: conception and design, acquisition of data, analysis and interpretation of data. B.V.L.A.Mel\u0026atilde;o: conception and design, analysis and interpretation of data, statistical analyses, drafting of the manuscript, critical revision of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e All data generated or analysed during this study are included in this published article and its supporting information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e No funds, grants, or other support was received for conducting this study.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003eAll authors declare no relationships that could be construed as a conflict of interest.\u003cbr\u003e\u0026nbsp;\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Ethical approval\u0026nbsp;\u003c/strong\u003eEthical approval was not required for a meta-analysis of previously published randomised controlled trials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResearch involving human participants and/or animals\u0026nbsp;\u003c/strong\u003eThe study did not involve human participants and/or animals.\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Informed consent\u0026nbsp;\u003c/strong\u003eNo individual participants were included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAhmed AA, Al-sayed AS. Tamsulosin versus Alfuzosin in the Treatment of Patients with Distal Ureteral Stones: Prospective, Randomized, Comparative Study. Korean J Urol 2010;51:193\u0026ndash;7. https://doi.org/10.4111/kju.2010.51.3.193.\u003c/li\u003e\n\u003cli\u003eHill AJ, Basourakos SP, Lewicki P, Wu X, Arenas-Gallo C, Chuang D, et al. Incidence of Kidney Stones in the United States: The Continuous National Health and Nutrition Examination Survey. J Urol 2022;207:851\u0026ndash;6. https://doi.org/10.1097/JU.0000000000002331.\u003c/li\u003e\n\u003cli\u003eQian X, Wan J, Xu J, Liu C, Zhong M, Zhang J, et al. Epidemiological Trends of Urolithiasis at the Global, Regional, and National Levels: A Population-Based Study. Int J Clin Pract 2022;2022:6807203. https://doi.org/10.1155/2022/6807203.\u003c/li\u003e\n\u003cli\u003eLang J, Narendrula A, El-Zawahry A, Sindhwani P, Ekwenna O. Global Trends in Incidence and Burden of Urolithiasis from 1990 to 2019: An Analysis of Global Burden of Disease Study Data. Eur Urol Open Sci 2022;35:37\u0026ndash;46. https://doi.org/10.1016/j.euros.2021.10.008.\u003c/li\u003e\n\u003cli\u003eSorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol 2017;35:1301\u0026ndash;20. https://doi.org/10.1007/s00345-017-2008-6.\u003c/li\u003e\n\u003cli\u003eBrikowski TH, Lotan Y, Pearle MS. Climate-related increase in the prevalence of urolithiasis in the United States. Proc Natl Acad Sci U S A 2008;105:9841\u0026ndash;6. https://doi.org/10.1073/pnas.0709652105.\u003c/li\u003e\n\u003cli\u003eEAU Guidelines on Urolithiasis - CITATION INFORMATION - Uroweb. Uroweb - Eur Assoc Urol n.d. https://uroweb.org/guidelines/urolithiasis/chapter/citation-information (accessed February 22, 2024).\u003c/li\u003e\n\u003cli\u003eLu Y, Zhang W, Su H, Ma C, Li H. The Efficacy of Sexual Intercourse Or Masturbation For The Expulsion Of Distal Ureteral Stones In Men: A Systematic Review And Meta-analysis Of Randomized-controlled Trials. Urol J 2022;19:246\u0026ndash;52. https://doi.org/10.22037/uj.v19i.7119.\u003c/li\u003e\n\u003cli\u003eXu B, Yan H, Zhang X, Cui Y. Meta-analysis of the efficacy of sexual intercourse for distal ureteric stones. J Int Med Res 2019;47:497\u0026ndash;504. https://doi.org/10.1177/0300060518814116.\u003c/li\u003e\n\u003cli\u003eCochrane Handbook for Systematic Reviews of Interventions n.d. https://training.cochrane.org/handbook/current (accessed February 22, 2024).\u003c/li\u003e\n\u003cli\u003ePage MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71.\u003c/li\u003e\n\u003cli\u003eHiggins JPT, Altman DG, G\u0026oslash;tzsche PC, J\u0026uuml;ni P, Moher D, Oxman AD, et al. The Cochrane Collaboration\u0026rsquo;s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. https://doi.org/10.1136/bmj.d5928.\u003c/li\u003e\n\u003cli\u003eAbdel-Kader MS. Evaluation of the efficacy of sexual intercourse in expulsion of distal ureteric stones. Int Urol Nephrol 2017;49:27\u0026ndash;30. https://doi.org/10.1007/s11255-016-1448-z.\u003c/li\u003e\n\u003cli\u003eBayraktar Z, Albayrak S. Sexual intercourse as a new option in the medical expulsive therapy of distal ureteral stones in males: a prospective, randomized, controlled study. Int Urol Nephrol 2017;49:1941\u0026ndash;6. https://doi.org/10.1007/s11255-017-1677-9.\u003c/li\u003e\n\u003cli\u003eBhatti KH, Bapir R, Bhatti WS, Muhammad HM, Abdullah HO, Abdalla BA, et al. Efficacy of sexual intercosurse in the spontaneous passage of distal or intramural ureteral stones: a randomsized controlled trial. Ann Med Surg 2012 2023;85:5972\u0026ndash;6. https://doi.org/10.1097/MS9.0000000000001414.\u003c/li\u003e\n\u003cli\u003eDoluoglu OG, Demirbas A, Kilinc MF, Karakan T, Kabar M, Bozkurt S, et al. Can Sexual Intercourse Be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled Study. Urology 2015;86:19\u0026ndash;24. https://doi.org/10.1016/j.urology.2015.03.037.\u003c/li\u003e\n\u003cli\u003eKhan SM, Omer MA, Islam SU, Imran A, Gahuri S, Goraya MIS. Role of Increased Sexual Activity in Expulsion of Distal Ureteral Stone Size 5 to 10 mmiIn Married Male. Pak J Med Health Sci 2022;16:226\u0026ndash;8. https://doi.org/10.53350/pjmhs22166226.\u003c/li\u003e\n\u003cli\u003eLi W, Mao Y, Lu C, Gu Y, Gu X, Hua B, et al. Role of Sexual Intercourse after Shockwave Lithotripsy for Distal Ureteral Stones: A Randomized Controlled Trial. Urol J 2020;17:134\u0026ndash;8. https://doi.org/10.22037/uj.v0i0.5400.\u003c/li\u003e\n\u003cli\u003eTurgut H, Sarıer M. Evaluation of the efficacy of masturbation on distal ureteral stones: a prospective, randomized, controlled study. Int Urol Nephrol 2021;53:655\u0026ndash;60. https://doi.org/10.1007/s11255-020-02672-y.\u003c/li\u003e\n\u003cli\u003eTurgut H. Evaluation of the efficacy of sexual intercourse on distal ureteral stones in women: a prospective, randomized, controlled study. Int Urol Nephrol 2021;53:409\u0026ndash;13. https://doi.org/10.1007/s11255-020-02661-1.\u003c/li\u003e\n\u003cli\u003eMastrangelo D, Baertschi AJ, Roatti A, Amherdt M, Iselin CE. Nitric oxide production within rat urothelial cells. J Urol 2003;170:1409\u0026ndash;14. https://doi.org/10.1097/01.ju.0000083492.80217.20.\u003c/li\u003e\n\u003cli\u003eFernandes VS, Hern\u0026aacute;ndez M. The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function. Basic Clin Pharmacol Toxicol 2016;119 Suppl 3:34\u0026ndash;41. https://doi.org/10.1111/bcpt.12565.\u003c/li\u003e\n\u003cli\u003eTzelves L, T\u0026uuml;rk C, Skolarikos A. European Association of Urology Urolithiasis Guidelines: Where Are We Going? Eur Urol Focus 2021;7:34\u0026ndash;8. https://doi.org/10.1016/j.euf.2020.09.011.\u003c/li\u003e\n\u003cli\u003eKnoll T, T\u0026uuml;rk C. The Role of Medical Expulsive Therapy for Ureteral Stones: Pro MET. Eur Urol Focus 2017;3:3\u0026ndash;4. https://doi.org/10.1016/j.euf.2017.01.002.\u003c/li\u003e\n\u003cli\u003eSomani BK, Aboumarzouk O, Traxer O, Baard J, Kamphuis G, de la Rosette J. Medical expulsive therapy for ureteral stones: where do we go from here? Nat Rev Urol 2016;13:608\u0026ndash;12. https://doi.org/10.1038/nrurol.2016.146.\u003c/li\u003e\n\u003cli\u003eJuman C, Bruce A, Kwan TY, Krishan A, Ehsanullah SAM, Khashaba S, et al. Comparison of the Efficacy of Male Sexual Activity Versus Alpha-Blockers in the Expulsion of Distal Ureteric Stones: A Systematic Review and Meta-Analysis. Cureus 2021;13:e19347. https://doi.org/10.7759/cureus.19347.\u003c/li\u003e\n\u003cli\u003eT\u0026uuml;rk C, Petř\u0026iacute;k A, Sarica K, Seitz C, Skolarikos A, Straub M, et al. EAU Guidelines on Diagnosis and Conservative Management of Urolithiasis. Eur Urol 2016;69:468\u0026ndash;74. https://doi.org/10.1016/j.eururo.2015.07.040.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ureterolithiasis, Ureteral Calculi, Sexual Behavior, Masturbation","lastPublishedDoi":"10.21203/rs.3.rs-4414149/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4414149/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eUreterolithiasis is a prevalent condition with a high morbidity, typically causing incapacitating pain and, if not treated correctly, can lead to renal failure. This research has sought to investigate the link between sexual activity, including masturbation, and a higher rate of spontaneous expulsion of ureteral stones.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterial and Methods: \u003c/strong\u003eWe searched PubMed, Embase, and Cochrane for randomized clinical trials (RCT) assessing the effectiveness of sexual activity or masturbation in the elimination of distal or intramural ureteral stones. Heterogeneity was assessed with I². Values of p \u0026lt; 0.05 were considered statistically significant. Statistical analysis was performed using Review Manager 5.4.1 (Cochrane Center, The Cochrane Collaboration).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We included 8 RCTs, totaling 755 patients, of which 383 (50.7%) engaged in sexual activity or masturbation 3-4 times per week for an average duration of 4 weeks. The expulsion rate at 2 weeks (OR: 3.48; [95% CI: 2.37 to 5.11]; p \u0026lt; 0.00001) and at 4 weeks (OR: 3.28; [95% CI: 2.23 to 4.83]; p \u0026lt; 0.00001) was higher in the sexual activity or masturbation group. The average time for stone expulsion (MD: -3.27; [95% CI: -5.38 to -1.17]; p \u0026lt; 0.002) was shorter in the experimental group, as well as the average number of analgesic injections (MD: -0.6; [95% CI: -0.91 to -0.29]; p \u0026lt; 0.0001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur findings suggest that sexual activity or masturbation appears to be effective as an expulsive medical therapy for patients with distal or intramural ureteral stones.\u003c/p\u003e","manuscriptTitle":"Is Sexual Activity an Effective Way to Expel Distal and Intramural Ureteral Stones? An Updated Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 17:34:37","doi":"10.21203/rs.3.rs-4414149/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-30T03:47:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-06T09:01:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258028482402090750265648178956466303105","date":"2024-06-30T22:09:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-30T10:04:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294207990551554976660630602693556632549","date":"2024-06-30T07:51:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-29T02:26:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-29T02:23:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-18T05:10:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2024-05-13T15:14:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c230705c-b6b8-47f6-abe3-286f1e50e2a7","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-08-23T02:59:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-16 17:34:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4414149","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4414149","identity":"rs-4414149","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}