Berk Hazir, Hakan Bahadir Haberal, Meylis Artykov, Muhammet Irfan Donmez, Alicia López-Abad, Alessio Pecoraro, Beatriz Bañuelos Marco, Thomas Prudhomme, Alberto Piana, Daniar Osmonov, Murat Gul, Angelo Territo
Background: End-stage renal disease (ESRD) is reported to be associated with the impairment of sex hormones, including decreased testosterone levels and increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Additionally, patients with ESRD often experience impaired spermatogenesis, leading to infertility. However, variations in study methodologies and reported outcomes make it challenging to draw definitive conclusions. Therefore, this study aims to evaluate the effects of kidney transplantation (KT) on these issues, which can be useful in counseling male patients with ESRD.
Methods: A systematic search was conducted in Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify peer-reviewed studies evaluating the impact of KT on sex hormones and reproductive parameters. A systematic review (SR) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review included English-language articles published between January 1975 and December 2024. Excluded from this search were reviews, editorials, book chapters, conference abstracts, case reports, and case series with up to four patients were excluded.
Results: A total of 2939 publications were initially identified, and 23 studies met the inclusion criteria, comprising 738 patients for analysis. Most studies reported a significant increase in testosterone levels 3, 6, and 12 months post-KT. LH and prolactin levels exhibited a trend parallel to that of testosterone. A statistically significant decrease in LH levels was observed at both 1 and 12 months post-KT, while prolactin levels showed a significant reduction at all evaluated time points from 1 to 12 months. In contrast, FSH levels fluctuated over time and did not demonstrate statistical significance at any assessment point. Additionally, KT led to improvements in testis biopsy findings, and all categories of sperm parameters.
Conclusion: This SR demonstrates that KT improves sex hormone levels, sperm parameters, and sexual function in male kidney recipients. However, to gain a more comprehensive understanding of the sexual health of male kidney recipients, the establishment of an international database with prospectively collected data is warranted.
背景:据报道,终末期肾病(ESRD)与性激素的损害有关,包括睾酮水平降低、促卵泡激素(FSH)、促黄体生成素(LH)和催乳素水平升高。此外,ESRD患者经常经历精子发生受损,导致不孕。然而,研究方法和报告结果的差异使得得出明确的结论具有挑战性。因此,本研究旨在评估肾移植(KT)对这些问题的影响,为男性ESRD患者提供咨询。方法:系统检索Web of Science、Medline(通过PubMed)和Embase(通过Scopus),以确定评估KT对性激素和生殖参数影响的同行评审研究。按照系统评价和荟萃分析(PRISMA)指南的首选报告项目进行系统评价(SR)。该综述包括1975年1月至2024年12月期间发表的英文文章。本检索排除了综述、社论、书籍章节、会议摘要、病例报告和最多4例患者的病例系列。结果:最初共纳入2939篇文献,23篇研究符合纳入标准,共纳入738例患者。大多数研究报告在kt后3、6和12个月睾酮水平显著增加。LH和催乳素水平表现出与睾酮水平平行的趋势。在kt后1个月和12个月,LH水平均有统计学意义上的显著下降,而催乳素水平在1 - 12个月的所有评估时间点均有显著下降。相比之下,FSH水平随时间波动,在任何评估点都没有统计学意义。此外,KT改善了睾丸活检结果和所有类别的精子参数。结论:本研究表明,KT可改善男性肾受体的性激素水平、精子参数和性功能。然而,为了更全面地了解男性肾受体的性健康,有必要建立一个具有前瞻性收集数据的国际数据库。
{"title":"The effects of kidney transplantation on sex hormones, sperm parameters, and fertility rate in males: A systematic review.","authors":"Berk Hazir, Hakan Bahadir Haberal, Meylis Artykov, Muhammet Irfan Donmez, Alicia López-Abad, Alessio Pecoraro, Beatriz Bañuelos Marco, Thomas Prudhomme, Alberto Piana, Daniar Osmonov, Murat Gul, Angelo Territo","doi":"10.1111/andr.70097","DOIUrl":"https://doi.org/10.1111/andr.70097","url":null,"abstract":"<p><strong>Background: </strong>End-stage renal disease (ESRD) is reported to be associated with the impairment of sex hormones, including decreased testosterone levels and increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Additionally, patients with ESRD often experience impaired spermatogenesis, leading to infertility. However, variations in study methodologies and reported outcomes make it challenging to draw definitive conclusions. Therefore, this study aims to evaluate the effects of kidney transplantation (KT) on these issues, which can be useful in counseling male patients with ESRD.</p><p><strong>Methods: </strong>A systematic search was conducted in Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify peer-reviewed studies evaluating the impact of KT on sex hormones and reproductive parameters. A systematic review (SR) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review included English-language articles published between January 1975 and December 2024. Excluded from this search were reviews, editorials, book chapters, conference abstracts, case reports, and case series with up to four patients were excluded.</p><p><strong>Results: </strong>A total of 2939 publications were initially identified, and 23 studies met the inclusion criteria, comprising 738 patients for analysis. Most studies reported a significant increase in testosterone levels 3, 6, and 12 months post-KT. LH and prolactin levels exhibited a trend parallel to that of testosterone. A statistically significant decrease in LH levels was observed at both 1 and 12 months post-KT, while prolactin levels showed a significant reduction at all evaluated time points from 1 to 12 months. In contrast, FSH levels fluctuated over time and did not demonstrate statistical significance at any assessment point. Additionally, KT led to improvements in testis biopsy findings, and all categories of sperm parameters.</p><p><strong>Conclusion: </strong>This SR demonstrates that KT improves sex hormone levels, sperm parameters, and sexual function in male kidney recipients. However, to gain a more comprehensive understanding of the sexual health of male kidney recipients, the establishment of an international database with prospectively collected data is warranted.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gonadotropins are synthesized in gonadotropes of the anterior pituitary, and they orchestrate reproductive function in vertebrates. LH and FSH share a common α-subunit that is non-covalently associated with a hormone - and receptor-specific β-subunit. Despite synthesized in the same cell, i.e., gonadotrope the trafficking and secretion patterns of LH and FSH are distinct. FSH is mostly constitutively secreted, whereas LH is stored in dense core granules and is released as a bolus via the regulated pathway in response to gonadotropin-releasing hormone.
Objective: To comparatively review the storage and secretion patterns of gonadotropins in vertebrates.
Materials and methods: Gonadotropin storage patterns are comparatively analyzed in vertebrates starting from primitive fish all the way up to higher mammals. The published work on gonadotropin trafficking/secretion patterns using in vitro and in vivo approaches is critically discussed.
Results: Primitive fish (lampreys and hagfish) express a single gonadotropic hormone. From these early vertebrates, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have evolved as two distinct hormones. In several species, including teleost fish, monohormonal gonadotropes are present that express either LH or FSH. In higher vertebrates, the majority of the gonadotropes (>90%) are bihormonal and contain both LH and FSH. Both in vitro (cell transfection and expression) and in vivo (transgenic mouse) studies identified that the LHβ caroboxy terminus heptapeptide is a gonadotrope-specific regulated pathway sorting determinant.
Discussion: When FSH is genetically rerouted from the constitutive trafficking mode and is engineered (LHβ heptapeptide fused to FSHβ subunit) to exit via the regulated pathway in gonadotropes of transgenic mice, it resulted in enhanced ovulations due to suppression of atresia and apoptosis and increased pro-survival pathways in ovaries. However, rerouted FSH expressing male mice did not demonstrate any gain of function phenotypes.
Conclusion: Understanding the basic molecular mechanisms of gonadotropin storage/trafficking and secretion may eventually lead to clinical benefits of enhancing female reproductive function and reproductive lifespan.
{"title":"Gonadotropin storage and trafficking.","authors":"Asia Ingram, T Rajendra Kumar","doi":"10.1111/andr.70094","DOIUrl":"https://doi.org/10.1111/andr.70094","url":null,"abstract":"<p><strong>Background: </strong>Gonadotropins are synthesized in gonadotropes of the anterior pituitary, and they orchestrate reproductive function in vertebrates. LH and FSH share a common α-subunit that is non-covalently associated with a hormone - and receptor-specific β-subunit. Despite synthesized in the same cell, i.e., gonadotrope the trafficking and secretion patterns of LH and FSH are distinct. FSH is mostly constitutively secreted, whereas LH is stored in dense core granules and is released as a bolus via the regulated pathway in response to gonadotropin-releasing hormone.</p><p><strong>Objective: </strong>To comparatively review the storage and secretion patterns of gonadotropins in vertebrates.</p><p><strong>Materials and methods: </strong>Gonadotropin storage patterns are comparatively analyzed in vertebrates starting from primitive fish all the way up to higher mammals. The published work on gonadotropin trafficking/secretion patterns using in vitro and in vivo approaches is critically discussed.</p><p><strong>Results: </strong>Primitive fish (lampreys and hagfish) express a single gonadotropic hormone. From these early vertebrates, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have evolved as two distinct hormones. In several species, including teleost fish, monohormonal gonadotropes are present that express either LH or FSH. In higher vertebrates, the majority of the gonadotropes (>90%) are bihormonal and contain both LH and FSH. Both in vitro (cell transfection and expression) and in vivo (transgenic mouse) studies identified that the LHβ caroboxy terminus heptapeptide is a gonadotrope-specific regulated pathway sorting determinant.</p><p><strong>Discussion: </strong>When FSH is genetically rerouted from the constitutive trafficking mode and is engineered (LHβ heptapeptide fused to FSHβ subunit) to exit via the regulated pathway in gonadotropes of transgenic mice, it resulted in enhanced ovulations due to suppression of atresia and apoptosis and increased pro-survival pathways in ovaries. However, rerouted FSH expressing male mice did not demonstrate any gain of function phenotypes.</p><p><strong>Conclusion: </strong>Understanding the basic molecular mechanisms of gonadotropin storage/trafficking and secretion may eventually lead to clinical benefits of enhancing female reproductive function and reproductive lifespan.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}