The Impact of Solid Organ Transplantation on Sexual Dysfunction and Infertility in Older Men and Women: A Claims Based Study

The Impact of Solid Organ Transplantation on Sexual Dysfunction and Infertility in Older Men and Women: A Claims Based Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Impact of Solid Organ Transplantation on Sexual Dysfunction and Infertility in Older Men and Women: A Claims Based Study Akhil Muthigi, Obinna Obuekwe, Haley Clark, Gal Saffati, Tatyana Yatsenko, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6181087/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 Solid organ transplantation (SOT) is a life-saving intervention that restores organ function and enhances survival. However, its impact on sexual dysfunction and infertility remains insufficiently explored. This study aims to evaluate the impact of SOT on sexual dysfunction and infertility by comparing their prevalence before and after transplantation across different organ transplant types. We conducted a retrospective cohort study using TriNetX from June 10 to September 22, 2025. Adult patients (≥ 18 years) who underwent heart, kidney, liver, lung, or pancreas transplantation were included. Sexual dysfunction (e.g., erectile dysfunction, dyspareunia) and infertility were identified using ICD-10 codes. A pre-post analysis assessed relative risk (RR), absolute risk reduction (ARR), and relative risk reduction (RRR). Propensity score matching (PSM) adjusted for confounders between men and female patients. Statistical significance was set at p < 0.05. SOT led to a statistically significant reduction in sexual dysfunction. The prevalence of sexual dysfunction decreased in male patients more than it did in female patients. Also, the prevalence of infertility decreased in all solid organ transplant types, though only lung transplantation resulted in a statistically significant improvement. Health sciences/Diseases/Reproductive disorders/Sexual dysfunction Health sciences/Diseases/Reproductive disorders/Urogenital reproductive disorders Health sciences/Diseases/Urogenital diseases/Sexual dysfunction Health sciences/Health care/Quality of life Introduction Solid organ transplantation (SOT) has emerged as a life-saving intervention for patients with end-organ dysfunction, dramatically improving both survival rates and long-term outcomes. The United States alone has performed over one million transplants to date, yet more than 100 000 patients remain on waiting lists ( 1 ). Thanks to advances in medical technology, both the success rate of transplant procedures and post-transplant survival have increased significantly ( 2 ). As surgical techniques and post-operative care continue to improve, leading to fewer complications, greater attention is now being paid to transplant recipients' quality of life, including the crucial aspect of sexual health ( 2 ). However, while considerable research has examined fertility outcomes in transplant recipients, the impact of transplantation on sexual function—in both male and female patients—remains understudied. This gap in knowledge represents a critical oversight in understanding the complete picture of post-transplant quality of life. End-stage renal failure significantly disrupts reproductive function through its effects on the hypothalamic-pituitary-gonadal (HPG) axis, leading to anovulation and menstrual irregularities in females and decreased sperm counts and infertility in males ( 3 , 4 ). Similar HPG axis disturbances occur in end-stage liver disease, with amenorrhea affecting up to 50% of female patients ( 3 , 5 – 7 ). Fortunately, successful organ transplantation often restores fertility by reestablishing normal organ function ( 3 – 5 ). Female recipients of kidney, liver, lung, heart, and pancreas transplants typically experience a return of reproductive function within 6 to 12 months post-transplant, with some patients resuming ovulatory cycles as early as one month after surgery ( 6 , 8 , 9 ). Male transplant recipients also show improved fertility outcomes, with successful cases of fatherhood reported among kidney, heart, lung, and liver transplant patients ( 4 , 5 , 10 ). The existing literature on post-transplant sexual function offers mixed results. Some studies report improvements in sexual health: Bravata et al. ( 11 ) found significant improvement in sexual function following liver transplantation, Szpotanska-Sikorska et al. ( 12 ) reported increased sexual activity in females after the initial post-transplant period, and Schover et al. ( 13 ) observed enhanced sexual desire and erectile function (ED) post-transplant. In contrast, other studies have reported negative outcomes: Payne et al. ( 14 ) documented a high prevalence of erectile dysfunction in liver, pancreas, heart, and kidney transplant recipients, while Ho et al. ( 15 ) found a rise in sexual dysfunction following liver transplantation, from 24–47%. Similarly, Ozdemir et al. ( 16 ) reported sexual dysfunction in 69.4% of kidney transplant recipients, and Long et al. ( 17 ) noted that while sexual activity increased post-transplant, sexual dysfunction persisted in approximately 50% of patients. These conflicting findings underscore the need for further research to clarify the impact of solid organ transplantation on sexual dysfunction. This study aims to evaluate sexual dysfunction and fertility outcomes across different types of solid organ transplant recipients by comparing pre- and post-transplant prevalence rates. By addressing these aspects of post-transplant care, we aim to enhance the holistic treatment of transplant recipients and contribute to the understanding of their long-term outcomes. Materials and Methods Between June 10 and September 22, 2024, a large, retrospective cohort analysis of transplant patients within the TriNetX United States Collaborative Network was conducted. The TriNetX database is a federated database containing over 300 million patients anonymized electronic health records from participating countries around the world. The International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM), RxNorm, and TriNetX curated codes were used to identify patients and define outcomes in this study. Institutional Review Board (IRB) approval was not required for this study as it used de-identified data. Due to the anonymous nature of the data, informed consent was waived. This study was conducted and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The study included all adult patients over 18 years old who had undergone solid organ transplantation, including heart, kidney, liver, lung, and pancreas transplant patients, using ICD-10 diagnosis and procedure codes (Supplemental Table 1) ( 18 , 19 ). Patients not located geographically within the United States or who underwent solid organ transplantation over 20 years ago were excluded from the study. Demographic data, comorbidities, laboratory data, and medications were collected for each patient. The primary outcome was a composite of sexual dysfunction. For males, this included erectile dysfunction, ejaculatory dysfunction, and decreased libido. For females, outcomes included vaginismus, dyspareunia, sexual arousal disorders, and vulvar/vaginal atrophy (Supplemental Table 2). The secondary outcome was composite infertility, identified using ICD codes N46 (male infertility) and N97 (female infertility) as summarized in Supplemental Table 2. For statistical analysis, all outcomes were defined a priori , with the transplant date serving as the “index event”. The prevalence of the primary and secondary outcome was obtained before and after SOT. Relative risk (RR) of sexual dysfunction and infertility was assessed before and after SOT. These RRs were then used to calculate the relative risk reduction (RRR) and absolute risk reduction (ARR) for both outcomes following transplantation ( 20 ). A stratified analysis based on sex was performed using propensity score matching (PSM). Additional subgroup analyses were conducted to determine the risk reduction for sexual dysfunction and infertility following each type of SOT. Regarding PSM, TriNetX utilizes an input matrix of covariates specified by users to adjust for confounders. A logistic regression was applied to calculate the propensity scores for individual participants. 1:1 matching was executed using these propensity scores by employing a greedy nearest neighbor algorithm with a caliper width of 0.1 pooled standard deviations (SD). Statistical significance was defined as a two-sided p-value less than 0.05. Results A total of 64 932 solid organ transplant recipients were identified. Most patients received kidney (38 471, 59%) transplants, followed by liver (16 177, 25%), heart (4 330, 6.7%), lung (3 749, 5.8%), and pancreas (2 205, 3.4%). The mean (SD) age at transplant was 52.3 (14.1) years. 40 462 (62%) of recipients were male and 24 470 (38%) were female. Other relevant demographics are summarized in Table 1. The mean (SD) follow-up post-transplantation was 6 (3.77) years. Pre-operative comorbidities are summarized in Table 1, with essential hypertension (63.8%), diabetes mellitus (41.4%), and chronic ischemic heart disease (30.5%) being most common. Immunosuppressant use was prevalent in the cohort post-transplant, with methylprednisolone and mycophenolate mofetil being the most prescribed medications, administered to 74% and 61% of patients, respectively (Supplemental Fig. 1). Primary Analysis Solid organ transplantation (SOT) significantly reduced the risk of sexual dysfunction from 8.2–6.8%, representing an absolute risk reduction (ARR) of 1.4% (95% CI: 1.12%, 1.69%, p < 0.001) and a relative risk reduction (RRR) of 17.1%. In contrast, the impact on infertility was minimal, with only a small reduction from 0.4–0.3% (ARR = 0.049%, 95% CI: -0.012–0.109%, p = 0.115). When stratifying by gender, the effect of transplantation on sexual dysfunction was more pronounced in males (46–43.9%) compared to females (6.5–6.3%). Males experienced a significant reduction with an ARR of 2.1% (95% CI: 1.8–2.4%, p < 0.001) and RRR of 17.2%. Females showed a smaller but still significant reduction with an ARR of 0.2% (95% CI: 0.1–0.3%, p = 0.035) and RRR of 11.7%. Regarding infertility, neither males (ARR = 0.1%, 95% CI: -0.1–0.2%, p = 0.287) nor females (ARR = 0.1%, 95% CI: -0.1–0.3%, p = 0.293) showed significant changes following transplantation. Organ-stratified Analysis Solid organ transplantation generally improved sexual dysfunction and infertility across all organ types. However, only lung transplantation resulted in a statistically significant improvement in infertility, reducing its prevalence from 0.31–0.24% (ARR = 0.07%, 95% CI: -0.15–0.29%, p = 0.043) with a RRR of 22.8%. The reductions observed for heart, liver, pancreas and kidney transplantation did not achieve statistical significance. Findings are summarized in Table 2. Discussion In this extensive, retrospective cohort analysis of transplant patients, we pooled 64 932 adult patients who underwent SOT in the last 20 years within the United States to assess if SOT affected sexual dysfunction and infertility. Our results demonstrated that SOT led to a statistically significant reduction in sexual dysfunction. The prevalence of sexual dysfunction decreased in male patients more than it did in female patients. Also, the prevalence of infertility decreased in all solid organ transplant types, though only lung transplantation resulted in a statistically significant improvement. Our study’s finding that sexual dysfunction decreased after SOT is largely consistent with existing research. Several surveys demonstrated a decrease in self-reported sexual dysfunction after receiving organ transplants ( 13 , 17 , 21 ). In a questionnaire of 25 male liver transplant recipients, Coelho et al. ( 21 ) reported that following liver transplantation, all 25 men reported improvements in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction in sexual life. In a prospective study of 490 kidney transplant recipients, Long et al. ( 17 ) demonstrated that sexual bother improved after kidney transplantation and sexual activity increased following kidney transplantation. In a survey of 54 men and 36 women assessing sexual function following renal transplant, Schover et al. ( 13 ) found that SOT had a mostly positive effect on sexual function. In this survey, men and women reported improvements in libido following renal transplantation ( 13 ). Men also reported an increase in the ability to achieve erections and to achieve orgasms without coital stimulation, though they also reported a decrease in the intensity of orgasms ( 13 ). In a study reviewing 49 renal transplant patients, Flechner et al. ( 22 ) reported that all 49 recipients developed renewed interests in sexual activity. Although the majority of current research reports positive improvements in sexual function following SOT, others show mixed results. Tsujimura et al. ( 23 ) retrospectively assessed 121 male renal transplant recipients who all reported experiencing some degree of erectile dysfunction, ejaculatory dysfunction, or orgasmic dysfunction before receiving transplantation. Tsujimura et al. ( 23 ) also found that 35.5% of study participants reported improvement in sexual dysfunction following transplantation, but 28.1% reported worsening. However, the majority of study participants (39.7% − 54%) reported no change in their erectile, orgasmic, and ejaculatory dysfunction. Although not the focus of our study, Tsujimura et al. ( 23 ) demonstrated that hormones (Total Testosterone, Free Testosterone, LH, FSH, and Prolactin) normalized in all transplant recipients with abnormal hormone profiles before transplantation. Another study by El-Bahnasawy et al. ( 24 ) that assessed 400 male renal transplant recipients showed mixed results. Of the 143 transplant recipients with erectile dysfunction, 44% reported improvements in erectile function following transplantation, and 43.5% reported no change. However, 12.5% of men with normal pretransplant erections reported deterioration of their erections following transplantation, which may be due to advancing age as Bahnasawy et al. noted “highly significant association between age and ED” in their study. De novo incidence of sexual function after organ transplantation has been described in the literature. Ho et al. ( 15 ) surveyed 150 liver transplant recipients, with 62% of the participants being male. Although sexual dysfunction decreased by 9% in patients who experienced sexual dysfunction before transplantation, 42 out of 150 survey participants reported new sexual dysfunction after transplantation, and the prevalence of sexual dysfunction increased from 24–54% after transplantation. However, this data is based on a relatively small sample size and self-reporting as opposed to clinical diagnosis. In our study, men had relatively higher improvements in sexual dysfunction compared to women following SOT, although both decreases in risks were significant. This finding may be due to the finding that the prevalence of sexual dysfunction was greater in male (46%) than female (6.5%) organ transplant recipients. Other studies involving organ transplantation also show an increased prevalence of sexual dysfunction in men compared to females ( 13 , 15 , 17 ). Also, given the average age of women in this study is 51 at time of transplant, menopause and associated hormonal changes may have mitigated potential improvements in sexual dysfunction. In our study, while lung transplantation was associated with a statistically significant reduction in infertility, overall, SOT had a minimal and statistically insignificant impact. This finding contradicts existing literature, which reports that reproductive function is often restored as the transplanted organ recovers ( 3 – 5 , 9 ). Other studies even go as far as to state that "organ transplantation offers the best prospect of pregnancy in fertile women with various types of end-stage organ disease."( 25 ) Schover et al. ( 13 ) reported a 21% increase in regular menstruation in women following renal transplantation. Also, in a study of 23 men and 18 women renal transplant recipients, in which 40% of men reported infertility before transplantation and 100% of the women reported irregular menstrual, Flechner et al. ( 22 ) reported that fertility restored in all men following transplantation and regularity of menstruation was also restored in all women. Nine men went on to achieve fatherhood, and five women underwent successful pregnancies. Our study's findings on SOT impact on infertility differ from current research for several reasons. First, the prevalence of infertility in our cohort pre-SOT was very low (0.4%), making it challenging to power statistical calculations to detect significance. Second, the average age of our study's participants was 58. Most women have developed menopause at this age, and one can theorize that fertility is not a common concern for men and women of this age group, so there was less of a need for clinical assessment specifically of fertility. Additionally, the average age of participants in studies showing the return of fertility following transplantation tends to be low. One example includes the study by Flechner et al ( 22 ) in which the average age was 27. This study is novel in its use of claims-based data from the TriNetX platform to investigate sexual dysfunction and infertility in a large cohort of solid organ transplant recipients. The strengths of this study include large sample size, propensity-score matching to mitigate potential confounders, and inclusion of diverse institutional data to increase generalizability. However, several limitations must be acknowledged. First, the retrospective design relies on historical claims data, which may not capture the full complexity of patients' experiences or quality of life. Medical records depend on provider coding during healthcare encounters, and sexual dysfunction or infertility may go undocumented if not explicitly addressed. Additionally, coding variability across HCOs may introduce inconsistencies in the dataset. Second is the dynamic nature of the TriNetX platform, where data availability fluctuates based on the number of HCOs online at the time of analysis. However, we found no significant changes between repeated queries. Thirdly, TriNetX only provides aggregate data, limiting our ability to analyze individual patient-level outcomes in greater detail. Furthermore, potentially significant mechanistic data such as hormonal profiles were not readily available in this database. Nevertheless, including a large cohort with demographics similar to the U.S. population supports the generalizability of our findings. Lastly, due to limitations with the database, we could not account for de novo incidences of sexual dysfunction and infertility following transplantation. Despite the great wealth of medical knowledge that is known after solid organ transplants, sexual function and infertility are often unexplored following transplantation. In this study, we found that the prevalence of sexual dysfunction decreased after SOT; however, there were no clinically significant improvements in fertility in this population. Given the importance of sexual health to the overall quality of life, it is essential to incorporate education on these topics into pre- and post-transplant care. Our findings highlight the need for further research to better understand the long-term sexual health and reproductive outcomes of transplant patients, ultimately improving patient care and quality of life. Additional prospective studies with varying age groups, comprehensive hormonal profiling, controlled exposure data, and translational design are essential to further explore these findings and elucidate the underlying biological mechanisms by which SOT may improve sexual dysfunction and in what specific patient populations. Abbreviations ARR – Absolute risk Reduction ED – Erectile Dysfunction FSH – Follicle Stimulating Hormone HPG – Hypothalamic Pituitary Gonadal ICD-10-CM – International Classification of Disease 10th Revision, Clinical Modification LH – Luteinizing Hormone PSM – Propensity Score Matching RR – Relative Risk RRR – Relative Risk Reduction SOT – Solid Organ Transplantation Declarations Data Availability Statement All data generated or analyzed during this study are included in this published article and its supplementary information files. Acknowledgements No financial assistance was received in support of this study. Author Contribution Statement Obinna Obuekwe, Haley Clark, Gal Saffati, M.D., and Tatyana Yatsenko, M.D., wrote the original draft and played important roles in interpretating the results. Laura Oscar-Thompson, M.D., was responsible for revising the draft and data interpretation. Carlos Riveros, M.D., was responsible for conceptualization, methodology, investigation, data curation, formal analysis, review & editing, and supervision. Akhil Muthigi, M.D., was responsible for conceptualization, validation review & editing, supervision, and project administration. All authors approve the final version of this manuscript and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding No financial assistance was received in support of this study. Ethical Approval Institutional Review Board (IRB) approval was not required for this study as it used de-identified data. Due to the anonymous nature of the data, informed consent was waived. Competing Interests We confirm that there are no conflicts of interest to declare. All authors have no financial or personal relationships that could inappropriately influence this work. This article represents independent research, and we affirm that no external funding or commercial support has been involved in the preparation of this manuscript. References Dageforde LA, English RA, Kizer KW. Achieving Equity in Organ Transplantation: Recommendations for Action Based on the National Academies of Sciences, Engineering, and Medicine Report. Transplantation. 2023 Feb;107(2):291–6. Black CK, Termanini KM, Aguirre O, Hawksworth JS, Sosin M. Solid organ transplantation in the 21st century. Ann Transl Med. 2018 Oct;6(20):409. Framarino Dei Malatesta M, Rossi M, Rocca B, Iappelli M, Poli L, Piccioni MG, et al. Fertility following solid organ transplantation. Transplant Proc. 2007;39(6):2001–4. Thirumavalavan N, Scovell JM, Link RE, Lamb DJ, Lipshultz LI. Does Solid Organ Transplantation Affect Male Reproduction? Eur Urol Focus. 2018 Apr;4(3):307–10. Szymusik I, Warzecha D, Wielgoś M, Pietrzak B. Infertility in Female and Male Solid Organ Recipients - From Diagnosis to Treatment: An Up-To-Date Review of the Literature. Ann Transplant. 2020 Nov 20;25:e923592. Delesalle AS, Robin G, Provôt F, Dewailly D, Leroy-Billiard M, Peigné M. [Impact of end-stage renal disease and kidney transplantation on the reproductive system]. Gynecol Obstet Fertil. 2015 Jan;43(1):33–40. Douglas NC, Shah M, Sauer MV. Fertility and reproductive disorders in female solid organ transplant recipients. Semin Perinatol. 2007 Dec;31(6):332–8. Deshpande NA, Coscia LA, Gomez-Lobo V, Moritz MJ, Armenti VT. Pregnancy after solid organ transplantation: a guide for obstetric management. Rev Obstet Gynecol. 2013;6(3–4):116–25. Sarkar M, Bramham K, Moritz MJ, Coscia L. Reproductive health in women following abdominal organ transplant. Am J Transplant. 2018 May;18(5):1068–76. Xu LG, Yang YR, Wang HW, Qiu F, Peng WL, Xu HM, et al. Characteristics of male fertility after renal transplantation. Andrologia. 2011 Jun;43(3):203–7. Bravata DM, Olkin I, Barnato AE, Keeffe EB, Owens DK. Health-related quality of life after liver transplantation: a meta-analysis. Liver Transpl Surg. 1999 Jul;5(4):318–31. Szpotanska-Sikorska M, Mazanowska N, Staruch M, Wielgos M, Pietrzak B. The observational study of selected sexual behaviour issues in female organ transplant recipients. Sex Reprod Healthc. 2017 Jun;12:47–50. Schover LR, Novick AC, Steinmuller DR, Goormastic M. Sexuality, fertility, and renal transplantation: a survey of survivors. J Sex Marital Ther. 1990;16(1):3–13. Payne K, Popat S, Lipshultz LI, Thirumavalavan N. The Prevalence and Treatment of Erectile Dysfunction in Male Solid Organ Transplant Recipients. Sex Med Rev. 2021 Apr;9(2):331–9. Ho JK, Ko HH, Schaeffer DF, Erb SR, Wong C, Buczkowski AK, et al. Sexual health after orthotopic liver transplantation. Liver Transpl. 2006 Oct;12(10):1478–84. Ozdemir C, Eryilmaz M, Yurtman F, Karaman T. Sexual functioning after renal transplantation. Transplant Proc. 2007 Jun;39(5):1451–4. Long JJ, Gupta N, Liu Y, Hong J, Li Y, Ali NM, et al. Sexual bother and sexual activity before and after kidney transplantation. Am J Transplant. 2025 Feb;25(2):376–84. Gilmore AS, Helderman JH, Ricci JF, Ryskina KL, Feng S, Kang N, et al. Linking the US transplant registry to administrative claims data: expanding the potential of transplant research. Med Care. 2007 Jun;45(6):529–36. Wehner MR, Niu J, Wheless L, Baker LX, Cohen OG, Margolis DJ, et al. Risks of Multiple Skin Cancers in Organ Transplant Recipients: A Cohort Study in 2 Administrative Data Sets. JAMA Dermatol. 2021 Dec 1;157(12):1447–55. Barratt A, Wyer PC, Hatala R, McGinn T, Dans AL, Keitz S, et al. Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ. 2004 Aug 17;171(4):353–8. Coelho JCU, Matias JEF, Zeni Neto C, Godoy JLD, Canan Júnior LW, Jorge FMF. Função sexual de homens submetidos a transplante hepático. Rev Assoc Med Bras. 2003;49(4):413–7. Flechner SM, Novick AC, Braun WE, Popowniak KL, Steinmuller D. FUNCTIONAL CAPACITY AND REHABILITATION OF RECIPIENTS WITH A FUNCTIONING RENAL ALLOGRAFT FOR TEN YEARS OR MORE: Transplantation. 1983 Jun;35(6):572–6. Tsujimura A, Matsumiya K, Tsuboniwa N, Yamanaka M, Miura H, Kitamura M, et al. Effect of Renal Transplantation on Sexual Function. Archives of Andrology. 2002 Jan;48(6):467–74. El-Bahnasawy MS, El-Assmy A, El-Sawy E, Ali-El Dein B, Shehab El-Dein AB, Refaie A, et al. Critical evaluation of the factors influencing erectile function after renal transplantation. Int J Impot Res. 2004 Dec 1;16(6):521–6. Burra P, De Bona M. Quality of life following organ transplantation. Transplant Int. 2007 May;20(5):397–409. Tables Tables are available in the Supplementary Files section. Additional Declarations There is NO conflict of interest to disclose. Supplementary Files SOTTable1.xlsx Table 1: Patient demographics and clinical characteristics and subgroup analysis (male vs female and clinical features) of patient demographics, including follow-up data SOTTable2.xlsx Table 2: Subgroup analysis: Organ transplant effect on sexual function and infertility SOTSupplementaryTable1.xlsx Supplementary Table 1: List of ICD-10 diagnosis and procedure codes for inclusion criteria SOTSupplementaryTable2andSupplementaryFigure1.pdf Supplementary Table 2: List of ICD-10 diagnosis and procedure codes for sexual dysfunction composite; list of diagnosis and procedure codes of infertility composite Supplementary Figure 1: Immunosuppressant Use in Post-Solid Organ Transplantation Patients Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: revise 31 Mar, 2025 Review # 2 received at journal 26 Mar, 2025 Review # 1 received at journal 13 Mar, 2025 Reviewer # 2 agreed at journal 11 Mar, 2025 Reviewer # 1 agreed at journal 11 Mar, 2025 Reviewers invited by journal 11 Mar, 2025 Submission checks completed at journal 10 Mar, 2025 Editor assigned by journal 07 Mar, 2025 First submitted to journal 07 Mar, 2025 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6181087","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":426802726,"identity":"cb1d0a8d-8c8a-4685-bd59-ece973d248ca","order_by":0,"name":"Akhil Muthigi","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Akhil","middleName":"","lastName":"Muthigi","suffix":""},{"id":426802727,"identity":"c132ee8c-949f-4c88-9952-5983fd9d14aa","order_by":1,"name":"Obinna Obuekwe","email":"","orcid":"https://orcid.org/0009-0000-7202-0076","institution":"Houston Methodist Hospital","correspondingAuthor":false,"prefix":"","firstName":"Obinna","middleName":"","lastName":"Obuekwe","suffix":""},{"id":426802728,"identity":"2099e5bc-2815-4161-90c6-eca2bff6acd9","order_by":2,"name":"Haley Clark","email":"","orcid":"","institution":"School of Engineering Medicine, Texas A\u0026M University","correspondingAuthor":false,"prefix":"","firstName":"Haley","middleName":"","lastName":"Clark","suffix":""},{"id":426802729,"identity":"fd5f961e-9410-48d7-b39e-0aa103c233cf","order_by":3,"name":"Gal Saffati","email":"","orcid":"https://orcid.org/0009-0005-3053-5828","institution":"Baylor College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Gal","middleName":"","lastName":"Saffati","suffix":""},{"id":426802730,"identity":"59376f54-6b84-4f53-affd-7dc3ba7f2785","order_by":4,"name":"Tatyana Yatsenko","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tatyana","middleName":"","lastName":"Yatsenko","suffix":""},{"id":426802731,"identity":"330043b3-ae0f-49e2-b43c-52809f0001a1","order_by":5,"name":"Laura Thompson","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Thompson","suffix":""},{"id":426802732,"identity":"bdbee1dd-11ed-4e6b-a7b3-fd4447f38031","order_by":6,"name":"Carlos Riveros","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"","lastName":"Riveros","suffix":""}],"badges":[],"createdAt":"2025-03-07 22:45:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6181087/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6181087/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78450844,"identity":"d622589b-8ede-482b-8640-e262a39bb986","added_by":"auto","created_at":"2025-03-13 11:12:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":410964,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6181087/v1/79507df1-6059-4b74-9b76-524a4d065f39.pdf"},{"id":78449160,"identity":"6d6a50e4-270c-4deb-a3ce-3501bbd7b8d5","added_by":"auto","created_at":"2025-03-13 10:48:31","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":11276,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1: Patient demographics and clinical characteristics and subgroup analysis (male vs female and clinical features) of patient demographics, including follow-up data\u003c/p\u003e","description":"","filename":"SOTTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6181087/v1/43e94fd6275a7ce684ebfafd.xlsx"},{"id":78450843,"identity":"0f2e510c-46eb-4bc4-bcee-b845bc094260","added_by":"auto","created_at":"2025-03-13 11:12:31","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10807,"visible":true,"origin":"","legend":"\u003cp\u003eTable 2: Subgroup analysis: Organ transplant effect on sexual function and infertility\u003c/p\u003e","description":"","filename":"SOTTable2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6181087/v1/502f0e579f723aed56e8a7f3.xlsx"},{"id":78449162,"identity":"cd7876fe-d96c-4a6d-aa22-efdfe97d86fc","added_by":"auto","created_at":"2025-03-13 10:48:31","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10442,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Table 1: List of ICD-10 diagnosis and procedure codes for inclusion criteria\u003c/p\u003e","description":"","filename":"SOTSupplementaryTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6181087/v1/746398107f9ac2e4392546b6.xlsx"},{"id":78449155,"identity":"125e2c16-23e3-4d88-a233-fe54d1d8549c","added_by":"auto","created_at":"2025-03-13 10:48:31","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":57915,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Table 2: List of ICD-10 diagnosis and procedure codes for sexual dysfunction composite; list of diagnosis and procedure codes of infertility composite\u003c/p\u003e\n\u003cp\u003eSupplementary Figure 1: Immunosuppressant Use in Post-Solid Organ Transplantation Patients\u003c/p\u003e","description":"","filename":"SOTSupplementaryTable2andSupplementaryFigure1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6181087/v1/158e5667f01b086ea6d2abf9.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"The Impact of Solid Organ Transplantation on Sexual Dysfunction and Infertility in Older Men and Women: A Claims Based Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSolid organ transplantation (SOT) has emerged as a life-saving intervention for patients with end-organ dysfunction, dramatically improving both survival rates and long-term outcomes. The United States alone has performed over one million transplants to date, yet more than 100 000 patients remain on waiting lists (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Thanks to advances in medical technology, both the success rate of transplant procedures and post-transplant survival have increased significantly (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). As surgical techniques and post-operative care continue to improve, leading to fewer complications, greater attention is now being paid to transplant recipients' quality of life, including the crucial aspect of sexual health (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, while considerable research has examined fertility outcomes in transplant recipients, the impact of transplantation on sexual function\u0026mdash;in both male and female patients\u0026mdash;remains understudied. This gap in knowledge represents a critical oversight in understanding the complete picture of post-transplant quality of life.\u003c/p\u003e \u003cp\u003eEnd-stage renal failure significantly disrupts reproductive function through its effects on the hypothalamic-pituitary-gonadal (HPG) axis, leading to anovulation and menstrual irregularities in females and decreased sperm counts and infertility in males (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Similar HPG axis disturbances occur in end-stage liver disease, with amenorrhea affecting up to 50% of female patients (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Fortunately, successful organ transplantation often restores fertility by reestablishing normal organ function (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Female recipients of kidney, liver, lung, heart, and pancreas transplants typically experience a return of reproductive function within 6 to 12 months post-transplant, with some patients resuming ovulatory cycles as early as one month after surgery (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Male transplant recipients also show improved fertility outcomes, with successful cases of fatherhood reported among kidney, heart, lung, and liver transplant patients (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe existing literature on post-transplant sexual function offers mixed results. Some studies report improvements in sexual health: Bravata et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) found significant improvement in sexual function following liver transplantation, Szpotanska-Sikorska et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) reported increased sexual activity in females after the initial post-transplant period, and Schover et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) observed enhanced sexual desire and erectile function (ED) post-transplant. In contrast, other studies have reported negative outcomes: Payne et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) documented a high prevalence of erectile dysfunction in liver, pancreas, heart, and kidney transplant recipients, while Ho et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) found a rise in sexual dysfunction following liver transplantation, from 24\u0026ndash;47%. Similarly, Ozdemir et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) reported sexual dysfunction in 69.4% of kidney transplant recipients, and Long et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) noted that while sexual activity increased post-transplant, sexual dysfunction persisted in approximately 50% of patients. These conflicting findings underscore the need for further research to clarify the impact of solid organ transplantation on sexual dysfunction.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate sexual dysfunction and fertility outcomes across different types of solid organ transplant recipients by comparing pre- and post-transplant prevalence rates. By addressing these aspects of post-transplant care, we aim to enhance the holistic treatment of transplant recipients and contribute to the understanding of their long-term outcomes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eBetween June 10 and September 22, 2024, a large, retrospective cohort analysis of transplant patients within the TriNetX United States Collaborative Network was conducted. The TriNetX database is a federated database containing over 300\u0026nbsp;million patients anonymized electronic health records from participating countries around the world. The International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM), RxNorm, and TriNetX curated codes were used to identify patients and define outcomes in this study. Institutional Review Board (IRB) approval was not required for this study as it used de-identified data. Due to the anonymous nature of the data, informed consent was waived. This study was conducted and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.\u003c/p\u003e \u003cp\u003eThe study included all adult patients over 18 years old who had undergone solid organ transplantation, including heart, kidney, liver, lung, and pancreas transplant patients, using ICD-10 diagnosis and procedure codes (Supplemental Table\u0026nbsp;1) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Patients not located geographically within the United States or who underwent solid organ transplantation over 20 years ago were excluded from the study. Demographic data, comorbidities, laboratory data, and medications were collected for each patient. The primary outcome was a composite of sexual dysfunction. For males, this included erectile dysfunction, ejaculatory dysfunction, and decreased libido. For females, outcomes included vaginismus, dyspareunia, sexual arousal disorders, and vulvar/vaginal atrophy (Supplemental Table\u0026nbsp;2). The secondary outcome was composite infertility, identified using ICD codes N46 (male infertility) and N97 (female infertility) as summarized in Supplemental Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eFor statistical analysis, all outcomes were defined a \u003cem\u003epriori\u003c/em\u003e, with the transplant date serving as the \u0026ldquo;index event\u0026rdquo;. The prevalence of the primary and secondary outcome was obtained before and after SOT. Relative risk (RR) of sexual dysfunction and infertility was assessed before and after SOT. These RRs were then used to calculate the relative risk reduction (RRR) and absolute risk reduction (ARR) for both outcomes following transplantation (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). A stratified analysis based on sex was performed using propensity score matching (PSM). Additional subgroup analyses were conducted to determine the risk reduction for sexual dysfunction and infertility following each type of SOT. Regarding PSM, TriNetX utilizes an input matrix of covariates specified by users to adjust for confounders. A logistic regression was applied to calculate the propensity scores for individual participants. 1:1 matching was executed using these propensity scores by employing a greedy nearest neighbor algorithm with a caliper width of 0.1 pooled standard deviations (SD). Statistical significance was defined as a two-sided p-value less than 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 64 932 solid organ transplant recipients were identified. Most patients received kidney (38 471, 59%) transplants, followed by liver (16 177, 25%), heart (4 330, 6.7%), lung (3 749, 5.8%), and pancreas (2 205, 3.4%). The mean (SD) age at transplant was 52.3 (14.1) years. 40 462 (62%) of recipients were male and 24 470 (38%) were female. Other relevant demographics are summarized in Table\u0026nbsp;1. The mean (SD) follow-up post-transplantation was 6 (3.77) years. Pre-operative comorbidities are summarized in Table\u0026nbsp;1, with essential hypertension (63.8%), diabetes mellitus (41.4%), and chronic ischemic heart disease (30.5%) being most common. Immunosuppressant use was prevalent in the cohort post-transplant, with methylprednisolone and mycophenolate mofetil being the most prescribed medications, administered to 74% and 61% of patients, respectively (Supplemental Fig.\u0026nbsp;1).\u003c/p\u003e\n\u003ch3\u003ePrimary Analysis\u003c/h3\u003e\n\u003cp\u003eSolid organ transplantation (SOT) significantly reduced the risk of sexual dysfunction from 8.2\u0026ndash;6.8%, representing an absolute risk reduction (ARR) of 1.4% (95% CI: 1.12%, 1.69%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a relative risk reduction (RRR) of 17.1%. In contrast, the impact on infertility was minimal, with only a small reduction from 0.4\u0026ndash;0.3% (ARR\u0026thinsp;=\u0026thinsp;0.049%, 95% CI: -0.012\u0026ndash;0.109%, p\u0026thinsp;=\u0026thinsp;0.115). When stratifying by gender, the effect of transplantation on sexual dysfunction was more pronounced in males (46\u0026ndash;43.9%) compared to females (6.5\u0026ndash;6.3%). Males experienced a significant reduction with an ARR of 2.1% (95% CI: 1.8\u0026ndash;2.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and RRR of 17.2%. Females showed a smaller but still significant reduction with an ARR of 0.2% (95% CI: 0.1\u0026ndash;0.3%, p\u0026thinsp;=\u0026thinsp;0.035) and RRR of 11.7%. Regarding infertility, neither males (ARR\u0026thinsp;=\u0026thinsp;0.1%, 95% CI: -0.1\u0026ndash;0.2%, p\u0026thinsp;=\u0026thinsp;0.287) nor females (ARR\u0026thinsp;=\u0026thinsp;0.1%, 95% CI: -0.1\u0026ndash;0.3%, p\u0026thinsp;=\u0026thinsp;0.293) showed significant changes following transplantation.\u003c/p\u003e\n\u003ch3\u003eOrgan-stratified Analysis\u003c/h3\u003e\n\u003cp\u003eSolid organ transplantation generally improved sexual dysfunction and infertility across all organ types. However, only lung transplantation resulted in a statistically significant improvement in infertility, reducing its prevalence from 0.31\u0026ndash;0.24% (ARR\u0026thinsp;=\u0026thinsp;0.07%, 95% CI: -0.15\u0026ndash;0.29%, p\u0026thinsp;=\u0026thinsp;0.043) with a RRR of 22.8%. The reductions observed for heart, liver, pancreas and kidney transplantation did not achieve statistical significance. Findings are summarized in Table\u0026nbsp;2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this extensive, retrospective cohort analysis of transplant patients, we pooled 64 932 adult patients who underwent SOT in the last 20 years within the United States to assess if SOT affected sexual dysfunction and infertility. Our results demonstrated that SOT led to a statistically significant reduction in sexual dysfunction. The prevalence of sexual dysfunction decreased in male patients more than it did in female patients. Also, the prevalence of infertility decreased in all solid organ transplant types, though only lung transplantation resulted in a statistically significant improvement.\u003c/p\u003e \u003cp\u003eOur study\u0026rsquo;s finding that sexual dysfunction decreased after SOT is largely consistent with existing research. Several surveys demonstrated a decrease in self-reported sexual dysfunction after receiving organ transplants (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In a questionnaire of 25 male liver transplant recipients, Coelho et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) reported that following liver transplantation, all 25 men reported improvements in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction in sexual life. In a prospective study of 490 kidney transplant recipients, Long et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) demonstrated that sexual bother improved after kidney transplantation and sexual activity increased following kidney transplantation. In a survey of 54 men and 36 women assessing sexual function following renal transplant, Schover et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) found that SOT had a mostly positive effect on sexual function. In this survey, men and women reported improvements in libido following renal transplantation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Men also reported an increase in the ability to achieve erections and to achieve orgasms without coital stimulation, though they also reported a decrease in the intensity of orgasms (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In a study reviewing 49 renal transplant patients, Flechner et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) reported that all 49 recipients developed renewed interests in sexual activity.\u003c/p\u003e \u003cp\u003eAlthough the majority of current research reports positive improvements in sexual function following SOT, others show mixed results. Tsujimura et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) retrospectively assessed 121 male renal transplant recipients who all reported experiencing some degree of erectile dysfunction, ejaculatory dysfunction, or orgasmic dysfunction before receiving transplantation. Tsujimura et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) also found that 35.5% of study participants reported improvement in sexual dysfunction following transplantation, but 28.1% reported worsening. However, the majority of study participants (39.7% \u0026minus;\u0026thinsp;54%) reported no change in their erectile, orgasmic, and ejaculatory dysfunction. Although not the focus of our study, Tsujimura et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) demonstrated that hormones (Total Testosterone, Free Testosterone, LH, FSH, and Prolactin) normalized in all transplant recipients with abnormal hormone profiles before transplantation. Another study by El-Bahnasawy et al. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) that assessed 400 male renal transplant recipients showed mixed results. Of the 143 transplant recipients with erectile dysfunction, 44% reported improvements in erectile function following transplantation, and 43.5% reported no change. However, 12.5% of men with normal pretransplant erections reported deterioration of their erections following transplantation, which may be due to advancing age as Bahnasawy et al. noted \u0026ldquo;highly significant association between age and ED\u0026rdquo; in their study.\u003c/p\u003e \u003cp\u003eDe novo incidence of sexual function after organ transplantation has been described in the literature. Ho et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) surveyed 150 liver transplant recipients, with 62% of the participants being male. Although sexual dysfunction decreased by 9% in patients who experienced sexual dysfunction before transplantation, 42 out of 150 survey participants reported new sexual dysfunction after transplantation, and the prevalence of sexual dysfunction increased from 24\u0026ndash;54% after transplantation. However, this data is based on a relatively small sample size and self-reporting as opposed to clinical diagnosis.\u003c/p\u003e \u003cp\u003eIn our study, men had relatively higher improvements in sexual dysfunction compared to women following SOT, although both decreases in risks were significant. This finding may be due to the finding that the prevalence of sexual dysfunction was greater in male (46%) than female (6.5%) organ transplant recipients. Other studies involving organ transplantation also show an increased prevalence of sexual dysfunction in men compared to females (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Also, given the average age of women in this study is 51 at time of transplant, menopause and associated hormonal changes may have mitigated potential improvements in sexual dysfunction.\u003c/p\u003e \u003cp\u003eIn our study, while lung transplantation was associated with a statistically significant reduction in infertility, overall, SOT had a minimal and statistically insignificant impact. This finding contradicts existing literature, which reports that reproductive function is often restored as the transplanted organ recovers (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Other studies even go as far as to state that \"organ transplantation offers the best prospect of pregnancy in fertile women with various types of end-stage organ disease.\"(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Schover et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) reported a 21% increase in regular menstruation in women following renal transplantation. Also, in a study of 23 men and 18 women renal transplant recipients, in which 40% of men reported infertility before transplantation and 100% of the women reported irregular menstrual, Flechner et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) reported that fertility restored in all men following transplantation and regularity of menstruation was also restored in all women. Nine men went on to achieve fatherhood, and five women underwent successful pregnancies.\u003c/p\u003e \u003cp\u003eOur study's findings on SOT impact on infertility differ from current research for several reasons. First, the prevalence of infertility in our cohort pre-SOT was very low (0.4%), making it challenging to power statistical calculations to detect significance. Second, the average age of our study's participants was 58. Most women have developed menopause at this age, and one can theorize that fertility is not a common concern for men and women of this age group, so there was less of a need for clinical assessment specifically of fertility. Additionally, the average age of participants in studies showing the return of fertility following transplantation tends to be low. One example includes the study by Flechner et al (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) in which the average age was 27.\u003c/p\u003e \u003cp\u003eThis study is novel in its use of claims-based data from the TriNetX platform to investigate sexual dysfunction and infertility in a large cohort of solid organ transplant recipients. The strengths of this study include large sample size, propensity-score matching to mitigate potential confounders, and inclusion of diverse institutional data to increase generalizability.\u003c/p\u003e \u003cp\u003eHowever, several limitations must be acknowledged. First, the retrospective design relies on historical claims data, which may not capture the full complexity of patients' experiences or quality of life. Medical records depend on provider coding during healthcare encounters, and sexual dysfunction or infertility may go undocumented if not explicitly addressed. Additionally, coding variability across HCOs may introduce inconsistencies in the dataset. Second is the dynamic nature of the TriNetX platform, where data availability fluctuates based on the number of HCOs online at the time of analysis. However, we found no significant changes between repeated queries. Thirdly, TriNetX only provides aggregate data, limiting our ability to analyze individual patient-level outcomes in greater detail. Furthermore, potentially significant mechanistic data such as hormonal profiles were not readily available in this database. Nevertheless, including a large cohort with demographics similar to the U.S. population supports the generalizability of our findings. Lastly, due to limitations with the database, we could not account for de novo incidences of sexual dysfunction and infertility following transplantation.\u003c/p\u003e \u003cp\u003eDespite the great wealth of medical knowledge that is known after solid organ transplants, sexual function and infertility are often unexplored following transplantation. In this study, we found that the prevalence of sexual dysfunction decreased after SOT; however, there were no clinically significant improvements in fertility in this population. Given the importance of sexual health to the overall quality of life, it is essential to incorporate education on these topics into pre- and post-transplant care. Our findings highlight the need for further research to better understand the long-term sexual health and reproductive outcomes of transplant patients, ultimately improving patient care and quality of life. Additional prospective studies with varying age groups, comprehensive hormonal profiling, controlled exposure data, and translational design are essential to further explore these findings and elucidate the underlying biological mechanisms by which SOT may improve sexual dysfunction and in what specific patient populations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eARR \u0026ndash; Absolute risk Reduction\u003c/p\u003e\n\u003cp\u003eED \u0026ndash; Erectile Dysfunction\u003c/p\u003e\n\u003cp\u003eFSH \u0026ndash; Follicle Stimulating Hormone\u003c/p\u003e\n\u003cp\u003eHPG \u0026ndash; Hypothalamic Pituitary Gonadal\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICD-10-CM \u0026ndash; International Classification of Disease 10th Revision, Clinical Modification\u003c/p\u003e\n\u003cp\u003eLH \u0026ndash; Luteinizing Hormone\u003c/p\u003e\n\u003cp\u003ePSM \u0026ndash; Propensity Score Matching\u003c/p\u003e\n\u003cp\u003eRR \u0026ndash; Relative Risk\u003c/p\u003e\n\u003cp\u003eRRR \u0026ndash; Relative Risk Reduction\u003c/p\u003e\n\u003cp\u003eSOT \u0026ndash; Solid Organ Transplantation\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003cbr\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial assistance was received in support of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObinna Obuekwe, Haley Clark, Gal Saffati, M.D., and Tatyana Yatsenko, M.D., wrote the original draft and played important roles in interpretating the results. Laura Oscar-Thompson, M.D., was responsible for revising the draft and data interpretation. Carlos Riveros, M.D., was responsible for conceptualization, methodology, investigation, data curation, formal analysis, review \u0026amp; editing, and supervision. Akhil Muthigi, M.D., was responsible for conceptualization, validation review \u0026amp; editing, supervision, and project administration. All authors approve the final version of this manuscript and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial assistance was received in support of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board (IRB) approval was not required for this study as it used de-identified data. Due to the anonymous nature of the data, informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that there are no conflicts of interest to declare. All authors have no financial or personal relationships that could inappropriately influence this work. This article represents independent research, and we affirm that no external funding or commercial support has been involved in the preparation of this manuscript.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDageforde LA, English RA, Kizer KW. Achieving Equity in Organ Transplantation: Recommendations for Action Based on the National Academies of Sciences, Engineering, and Medicine Report. Transplantation. 2023 Feb;107(2):291\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eBlack CK, Termanini KM, Aguirre O, Hawksworth JS, Sosin M. Solid organ transplantation in the 21st century. Ann Transl Med. 2018 Oct;6(20):409. \u003c/li\u003e\n\u003cli\u003eFramarino Dei Malatesta M, Rossi M, Rocca B, Iappelli M, Poli L, Piccioni MG, et al. Fertility following solid organ transplantation. Transplant Proc. 2007;39(6):2001\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eThirumavalavan N, Scovell JM, Link RE, Lamb DJ, Lipshultz LI. Does Solid Organ Transplantation Affect Male Reproduction? Eur Urol Focus. 2018 Apr;4(3):307\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eSzymusik I, Warzecha D, Wielgoś M, Pietrzak B. Infertility in Female and Male Solid Organ Recipients - From Diagnosis to Treatment: An Up-To-Date Review of the Literature. Ann Transplant. 2020 Nov 20;25:e923592. \u003c/li\u003e\n\u003cli\u003eDelesalle AS, Robin G, Prov\u0026ocirc;t F, Dewailly D, Leroy-Billiard M, Peign\u0026eacute; M. [Impact of end-stage renal disease and kidney transplantation on the reproductive system]. Gynecol Obstet Fertil. 2015 Jan;43(1):33\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eDouglas NC, Shah M, Sauer MV. Fertility and reproductive disorders in female solid organ transplant recipients. Semin Perinatol. 2007 Dec;31(6):332\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eDeshpande NA, Coscia LA, Gomez-Lobo V, Moritz MJ, Armenti VT. Pregnancy after solid organ transplantation: a guide for obstetric management. Rev Obstet Gynecol. 2013;6(3\u0026ndash;4):116\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eSarkar M, Bramham K, Moritz MJ, Coscia L. Reproductive health in women following abdominal organ transplant. Am J Transplant. 2018 May;18(5):1068\u0026ndash;76. \u003c/li\u003e\n\u003cli\u003eXu LG, Yang YR, Wang HW, Qiu F, Peng WL, Xu HM, et al. Characteristics of male fertility after renal transplantation. Andrologia. 2011 Jun;43(3):203\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eBravata DM, Olkin I, Barnato AE, Keeffe EB, Owens DK. Health-related quality of life after liver transplantation: a meta-analysis. Liver Transpl Surg. 1999 Jul;5(4):318\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eSzpotanska-Sikorska M, Mazanowska N, Staruch M, Wielgos M, Pietrzak B. The observational study of selected sexual behaviour issues in female organ transplant recipients. Sex Reprod Healthc. 2017 Jun;12:47\u0026ndash;50. \u003c/li\u003e\n\u003cli\u003eSchover LR, Novick AC, Steinmuller DR, Goormastic M. Sexuality, fertility, and renal transplantation: a survey of survivors. J Sex Marital Ther. 1990;16(1):3\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003ePayne K, Popat S, Lipshultz LI, Thirumavalavan N. The Prevalence and Treatment of Erectile Dysfunction in Male Solid Organ Transplant Recipients. Sex Med Rev. 2021 Apr;9(2):331\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eHo JK, Ko HH, Schaeffer DF, Erb SR, Wong C, Buczkowski AK, et al. Sexual health after orthotopic liver transplantation. Liver Transpl. 2006 Oct;12(10):1478\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eOzdemir C, Eryilmaz M, Yurtman F, Karaman T. Sexual functioning after renal transplantation. Transplant Proc. 2007 Jun;39(5):1451\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eLong JJ, Gupta N, Liu Y, Hong J, Li Y, Ali NM, et al. Sexual bother and sexual activity before and after kidney transplantation. Am J Transplant. 2025 Feb;25(2):376\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eGilmore AS, Helderman JH, Ricci JF, Ryskina KL, Feng S, Kang N, et al. Linking the US transplant registry to administrative claims data: expanding the potential of transplant research. Med Care. 2007 Jun;45(6):529\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eWehner MR, Niu J, Wheless L, Baker LX, Cohen OG, Margolis DJ, et al. Risks of Multiple Skin Cancers in Organ Transplant Recipients: A Cohort Study in 2 Administrative Data Sets. JAMA Dermatol. 2021 Dec 1;157(12):1447\u0026ndash;55. \u003c/li\u003e\n\u003cli\u003eBarratt A, Wyer PC, Hatala R, McGinn T, Dans AL, Keitz S, et al. Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ. 2004 Aug 17;171(4):353\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eCoelho JCU, Matias JEF, Zeni Neto C, Godoy JLD, Canan J\u0026uacute;nior LW, Jorge FMF. Fun\u0026ccedil;\u0026atilde;o sexual de homens submetidos a transplante hep\u0026aacute;tico. Rev Assoc Med Bras. 2003;49(4):413\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eFlechner SM, Novick AC, Braun WE, Popowniak KL, Steinmuller D. FUNCTIONAL CAPACITY AND REHABILITATION OF RECIPIENTS WITH A FUNCTIONING RENAL ALLOGRAFT FOR TEN YEARS OR MORE: Transplantation. 1983 Jun;35(6):572\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eTsujimura A, Matsumiya K, Tsuboniwa N, Yamanaka M, Miura H, Kitamura M, et al. Effect of Renal Transplantation on Sexual Function. Archives of Andrology. 2002 Jan;48(6):467\u0026ndash;74. \u003c/li\u003e\n\u003cli\u003eEl-Bahnasawy MS, El-Assmy A, El-Sawy E, Ali-El Dein B, Shehab El-Dein AB, Refaie A, et al. Critical evaluation of the factors influencing erectile function after renal transplantation. Int J Impot Res. 2004 Dec 1;16(6):521\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eBurra P, De Bona M. Quality of life following organ transplantation. Transplant Int. 2007 May;20(5):397\u0026ndash;409. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"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":"international-journal-of-impotence-research","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijir","sideBox":"Learn more about [International Journal of Impotence Research](http://www.nature.com/ijir/)","snPcode":"41443","submissionUrl":"https://mts-ijir.nature.com/cgi-bin/main.plex","title":"International Journal of Impotence Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6181087/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6181087/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSolid organ transplantation (SOT) is a life-saving intervention that restores organ function and enhances survival. However, its impact on sexual dysfunction and infertility remains insufficiently explored. This study aims to evaluate the impact of SOT on sexual dysfunction and infertility by comparing their prevalence before and after transplantation across different organ transplant types. We conducted a retrospective cohort study using TriNetX from June 10 to September 22, 2025. Adult patients (\u0026ge;\u0026thinsp;18 years) who underwent heart, kidney, liver, lung, or pancreas transplantation were included. Sexual dysfunction (e.g., erectile dysfunction, dyspareunia) and infertility were identified using ICD-10 codes. A pre-post analysis assessed relative risk (RR), absolute risk reduction (ARR), and relative risk reduction (RRR). Propensity score matching (PSM) adjusted for confounders between men and female patients. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. SOT led to a statistically significant reduction in sexual dysfunction. The prevalence of sexual dysfunction decreased in male patients more than it did in female patients. Also, the prevalence of infertility decreased in all solid organ transplant types, though only lung transplantation resulted in a statistically significant improvement.\u003c/p\u003e","manuscriptTitle":"The Impact of Solid Organ Transplantation on Sexual Dysfunction and Infertility in Older Men and Women: A Claims Based Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-13 10:48:26","doi":"10.21203/rs.3.rs-6181087/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-03-31T13:23:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-03-26T14:49:01+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-03-13T04:53:49+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-03-11T20:45:25+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-03-11T09:58:09+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-03-11T09:29:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-10T15:53:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-07T22:42:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Impotence Research","date":"2025-03-07T22:42:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-impotence-research","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijir","sideBox":"Learn more about [International Journal of Impotence Research](http://www.nature.com/ijir/)","snPcode":"41443","submissionUrl":"https://mts-ijir.nature.com/cgi-bin/main.plex","title":"International Journal of Impotence Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"844fe166-2f9b-4d5b-9860-59c551e71a48","owner":[],"postedDate":"March 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":45476058,"name":"Health sciences/Diseases/Reproductive disorders/Sexual dysfunction"},{"id":45476059,"name":"Health sciences/Diseases/Reproductive disorders/Urogenital reproductive disorders"},{"id":45476060,"name":"Health sciences/Diseases/Urogenital diseases/Sexual dysfunction"},{"id":45476061,"name":"Health sciences/Health care/Quality of life"}],"tags":[],"updatedAt":"2025-06-26T14:15:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-13 10:48:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6181087","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6181087","identity":"rs-6181087","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}