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Aleksova J, Ebeling P, Elder G. The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease. Nat Rev Endocrinol 2025; 21:301-313. [PMID: 39820573 DOI: 10.1038/s41574-024-01083-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025]
Abstract
Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.
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MESH Headings
- Humans
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/physiopathology
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/physiopathology
- Diabetes Mellitus, Type 1/metabolism
- Renal Insufficiency, Chronic/complications
- Renal Insufficiency, Chronic/physiopathology
- Renal Insufficiency, Chronic/metabolism
- Fractures, Bone/etiology
- Bone and Bones/metabolism
- Bone and Bones/physiopathology
- Bone Density/physiology
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Affiliation(s)
- Jasna Aleksova
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
- Hudson Institute for Medical Research, Clayton, Victoria, Australia.
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia.
| | - Peter Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia
| | - Grahame Elder
- Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia
- Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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Leśniak K, Lubas A, Niemczyk S. The Usefulness of Testosterone in Saliva Tests to Detect Testosterone Deficiency in Men with Advanced Chronic Kidney Disease: A Single-Center Study. J Clin Med 2025; 14:2818. [PMID: 40283649 PMCID: PMC12027738 DOI: 10.3390/jcm14082818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to serum testosterone. This study aimed to assess the usefulness of determining free testosterone concentration in saliva to detect testosterone deficiency in men with advanced CKD, including those on dialysis. Methods: A total of 77 adult, male patients (aged 41-89 years old)-30 with CKD stage G3-G4, 30 on hemodialysis (HD), and 17 on peritoneal dialysis (PD)-were evaluated. The concentration of free testosterone was determined in saliva (SalFT), while the concentration of total testosterone (TT) was determined in blood serum. Serum-free testosterone levels were calculated (cFT). Results: SalFT did not differ from cFT in the CKD (p = 0.547) and PD groups (p = 0.409). In the HD group, SalFT was higher than cFT (p = 0.009). SalFT was positively correlated with cFT (r = 0.435 in the CKD and r = 0.479 in the HD) and TT (r = 0.451 in CKD), but only in the group of patients with SalFT levels below 140 pg/mL and 120 pg/mL, respectively. A cut-off value of SalFT ≤ 60.6 pg/mL showed 73.9% sensitivity and 77.8% specificity for testosterone deficiency recognition. Conclusions: Our study supports the value of SalFT measurement as a non-invasive approach in the diagnosis of testosterone deficiency in men with advanced CKD, as well as patients on hemodialysis.
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Affiliation(s)
- Ksymena Leśniak
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine—National Research Institute, Szaserów Street 128, 04-141 Warsaw, Poland; (A.L.); (S.N.)
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Todisco T, Ubertini GM, Bizzarri C, Loche S, Cappa M. Chronic Kidney Disease and Growth Failure in Children. CHILDREN (BASEL, SWITZERLAND) 2024; 11:808. [PMID: 39062256 PMCID: PMC11274908 DOI: 10.3390/children11070808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/24/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024]
Abstract
Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3-or on dialysis older >6 months-are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population.
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Affiliation(s)
- Tommaso Todisco
- Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (T.T.)
| | - Grazia Maria Ubertini
- UOC Endocrinology and Diabetology, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy
| | - Carla Bizzarri
- UOC Endocrinology and Diabetology, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy
| | - Sandro Loche
- Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (T.T.)
| | - Marco Cappa
- Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (T.T.)
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4
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Testosterone deficiency in male organ transplant recipients. Int J Impot Res 2022; 34:679-684. [PMID: 35013565 DOI: 10.1038/s41443-021-00513-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 11/13/2021] [Accepted: 11/26/2021] [Indexed: 11/09/2022]
Abstract
Testosterone deficiency is known to affect men with increasing incidence throughout their lifespan. The clinical manifestations of testosterone deficiency, in turn, negatively impact men's quality of life and perception of overall health. The interaction of chronic systemic disease and androgen deficiency represent an area for potential intervention. Here, we explore the topic of testosterone deficiency amongst men with end-stage organ failure requiring transplantation in order to elucidate the underlying pathophysiology of androgen deficiency of chronic disease and discuss whether intervention, including testosterone replacement and organ transplantation, improve patients' outcomes and quality of life.
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Testosterone Deficiency as One of the Major Endocrine Disorders in Chronic Kidney Disease. Nutrients 2022; 14:nu14163438. [PMID: 36014945 PMCID: PMC9415930 DOI: 10.3390/nu14163438] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/11/2022] [Accepted: 08/19/2022] [Indexed: 11/28/2022] Open
Abstract
Reduced testosterone concentration is nowadays thought to be one of the main endocrine disorders in chronic kidney disease (CKD). It is caused by the dysfunction of the hypothalamic-pituitary-gonadal axis. The role of testosterone is multifactorial. Testosterone is responsible not only for reproductive processes, but it is a hormone which increases bone and muscle mass, improves lipid profile, insulin sensitivity, erythropoiesis, reduces blood pressure, and ameliorates mood and perception. The implications of hypogonadism in CKD are infertility and loss of libido, reduction of muscle mass and strength, disorders in bone mineralization, the development of sarcopenia and protein energy wasting (PEW), progression of atherosclerosis, increased visceral adiposity, insulin resistance, and anaemia. Reduced testosterone serum concentrations in CKD are associated with increased mortality rate. Testosterone supplementation improves sexual functions, reduces the level of inflammatory markers and blood pressure, stimulates muscle protein synthesis, improves insulin sensitivity and lipid profile, and increases muscle mass, bone mineral density, and haemoglobin concentration. It positively affects mood and well-being. The modes of testosterone supplementation are intramuscular injections, subcutaneous pellets, and percutaneous methods—patches and gels. Successful kidney transplantation may improve gonadal function and testosterone production, however, half of men with low testosterone concentrations before kidney transplantation do not restore hormonal function.
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Fendereski K, Ghaed MA, Calvert JK, Hotaling JM. Hypogonadism and urologic surgeries: a narrative review. Transl Androl Urol 2022; 11:1045-1062. [PMID: 35958902 PMCID: PMC9360521 DOI: 10.21037/tau-22-308] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background and Objective Previous studies indicated that the treatment of male hypogonadism can be beneficial for intraoperative and postsurgical outcomes. In this study, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provided an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without testosterone replacement therapy (TRT). Methods We performed a literature review in PubMed and Google Scholar databases for the most relevant articles pertaining to the outlined topics without placing any limitations on publication years or study designs. We included full-text English articles published in peer reviewed journals between January 1970 and March 2022. Key Content and Findings Androgen deficiency is a common finding after major urologic surgeries. Although guidelines recommend against TRT in men with prostate carcinoma, recent investigations showed no association between TRT and disease progression and recurrence. Indeed, recent evidence suggested that low androgen levels could be related to high grade prostate carcinoma and increased risk of upgrading from low to high grade disease. Investigations on the application of TRT in benign prostatic hyperplasia (BPH) patients also revealed contrasting results. While some studies suggested higher rates of prostate-related events in men who received TRT, others showed that TRT could alleviate urinary symptoms in hypogonadal men with BPH. Decreased testosterone level is commonly seen in bladder cancer patients. The treatment of perioperative androgen deficiency can reduce postoperative morbidities and lower the risk of recurrence in these patients. Low testosterone levels are observed in approximately half of the men who undergo artificial urinary sphincter (AUS) placement and can increase the risk of complications. Conclusions The role of testosterone treatment in patients with urologic diseases such as prostate carcinoma and BPH is controversial. Further investigations are needed to determine the impact of hypogonadism and TRT on the outcomes of urologic surgeries in patients with androgen deficiency.
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Affiliation(s)
- Kiarad Fendereski
- Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Mohammad Ali Ghaed
- Department of Urology, Rasoul Akram Hospital, Iran university of Medical Sciences, Tehran, Iran
| | - Joshua K Calvert
- Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - James M Hotaling
- Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA
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Gryzinski GM, Bernie HL. Testosterone deficiency and the aging male. Int J Impot Res 2022; 34:630-634. [PMID: 35393533 DOI: 10.1038/s41443-022-00555-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 01/24/2022] [Accepted: 03/07/2022] [Indexed: 11/09/2022]
Abstract
Testosterone deficiency (TD), also known as male hypogonadism, is a complex syndrome encompassing physical, biochemical, and social aspects that increasingly affects the aging population. TD has been analyzed over recent decades, with an enhanced focus on etiologies relating to aging males. There is debate whether testosterone decline leading to hypogonadism is directly and primarily related to age-specific processes or if it is the subsequent result of accumulating comorbidities throughout a lifetime. Several studies have been done to further characterize this distinction. Chronic comorbidities that have commonly been associated with TD include hypertension (HTN), cardiovascular disease (CVD), diabetes mellitus (DM), obesity, metabolic syndrome (MetS), chronic kidney disease (CKD), and tobacco use. Although clear associations between hypogonadism and aging have been biochemically demonstrated, many large studies have illustrated the concomitant effects of highly prevalent chronic diseases and social behaviors in aging men. Given the significant impact of hypogonadism on the physical and mental health of men, this paper aims to delve into these studies and further define the complex relationship of testosterone deficiency in the aging male.
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Affiliation(s)
| | - Helen L Bernie
- Department of Urology, Indiana University, Indianapolis, IN, USA.
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Hwang DB, Cha MH, Won DH, Shin YS, Kim SY, Kim C, Lee EJ, Kim YY, Yun JW. Transcriptomic analysis of rat kidney reveals a potential mechanism of sex differences in susceptibility to cisplatin-induced nephrotoxicity. Free Radic Biol Med 2021; 174:100-109. [PMID: 34384867 DOI: 10.1016/j.freeradbiomed.2021.08.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/29/2021] [Accepted: 08/07/2021] [Indexed: 12/11/2022]
Abstract
Although cisplatin is an effective platinum-based anticancer drug against solid cancer, its availability is limited owing to its adverse side effects. Our study aimed to identify the potential relationship within cisplatin-induced multi-organ physiological changes and genetic factors associated with sex differences in nephrotoxicity susceptibility. To investigate this, mice received a single intraperitoneal injection of cisplatin. Cisplatin administration resulted in renal dysfunction, as evidenced by the elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine) and the degree of histopathological alterations. In particular, along with testicular damage and low testosterone levels, we also observed a decrease in male-specific (CYP3A2) or male-dominant (CYP2B1 and CYP3A1) CYP isoforms in the livers of rats with hepatotoxicity following cisplatin treatment, which may be associated with an imbalance in male hormone regulation caused by renal and testicular injury. Notably, we found that male rats were more susceptible to cisplatin-induced nephrotoxicity, as characterized by histopathological and biochemical analyses. Therefore, RNA sequencing was performed at baseline (pre-treatment) and at 48 h following cisplatin administration (post-treatment) to identify the genes associated with sex differences in nephrotoxicity susceptibility. Gap junctions, which play a role in replenishing damaged cells to maintain tissue homeostasis, and mismatch repair associated with a pathological apoptotic mechanism against cisplatin nephrotoxicity were significantly enriched only in males following cisplatin treatment. Moreover, among the 322 DEGs showing different basal expression patterns between males and females before cisplatin treatment, the male expressed high levels of genes, which are responsible for transmembrane transport and regulation of apoptotic process, pre-cisplatin treatment; additionally, genes involved in the PI3K-Akt signaling pathway and the oxidation-reduction process were significantly lower in males before cisplatin treatment. Collectively, our comprehensive findings provided valuable insight into the potential mechanisms of sex differences in cisplatin-induced nephrotoxicity susceptibility.
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Affiliation(s)
- Da-Bin Hwang
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea
| | - Min Ho Cha
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, 41062, South Korea
| | - Dong-Hoon Won
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea
| | - Yoo-Sub Shin
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea
| | - Shin-Young Kim
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea
| | - Changuk Kim
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea
| | - Eun-Ji Lee
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, 41062, South Korea
| | - Yoon Young Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 03080, South Korea
| | - Jun-Won Yun
- Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, South Korea; Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, South Korea.
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Singh RP, Tomar V, Yadav SS. Implications of renal transplantation on serum testosterone and preoperative factors affecting its levels in the post-transplant period. JOURNAL OF CLINICAL UROLOGY 2021. [DOI: 10.1177/20514158211040712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective: Low serum testosterone is highly prevalent in chronic kidney disease patients. The objective of the study was to determine levels of serum testosterone at the time of transplantation, the prevalence of testosterone deficiency/insufficiency in the pre- and post-transplant periods, and its correlation with patients’ age, serum creatinine, duration of preoperative dialysis, human leukocyte antigen (HLA) matching, and graft outcomes. Methods: The study was conducted from January 2019 to April 2020. Forty-five male renal transplant patients were evaluated before and at one and six months following transplant for changes in testosterone and creatinine levels. Six-month follow-up was possible for 28 patients. Result: Renal transplantation resulted in significant improvement in testosterone levels as early as one month after transplantation. The duration of preoperative dialysis and HLA match had a negative and positive impact on postoperative serum testosterone levels, respectively. We did not find any impact of testosterone levels on graft function. Conclusion: Successful transplantation among the study population produced a positive impact on serum testosterone levels. The duration of preoperative dialysis and HLA match had a negative and positive impact on postoperative serum testosterone levels, respectively. Level of evidence: XXX.
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Affiliation(s)
| | - Vinay Tomar
- Department of Urology, SMS Medical College, India
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Yeo JK, Koo HS, Yu J, Park MG. Effects of Testosterone Treatment on Quality of Life in Patients With Chronic Kidney Disease. Am J Mens Health 2021; 14:1557988320917258. [PMID: 32448046 PMCID: PMC7249586 DOI: 10.1177/1557988320917258] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Testosterone deficiency (TD) is common and impairs quality of life (QoL) in
patients with chronic kidney disease (CKD). However, there are no studies about
whether testosterone replacement therapy (TRT) can improve QoL in patients with
CKD. Therefore, we investigated the effect of TRT on the QoL of patients with
CKD and confirmed the safety of TRT. Twenty-five male patients with stages
III–IV CKD whose serum testosterone levels were <350 ng/dl (TD) were enrolled
and treated with testosterone gel for 3 months (group II). Age-matched controls
with stages III–IV CKD and TD (group I) were recommended to exercise for the
same period. Before and after the treatment, the BMI and handgrip strength were
checked, serological tests were performed, and questionnaires were administered
in both groups. Compared to baseline, there was no significant difference in
serum testosterone levels, scores of the 36-Item Short Form Health Survey
(SF-36), Aging Males’ Symptoms Scale (AMS), and International Prostate Symptom
Score (IPSS), and grip strength in group I after 3 months. In group II, a
significant increase in testosterone, hemoglobin (Hb), and hematocrit (Hct) was
observed, and grip strength significantly increased after TRT. Significant
improvement in scores of SF-36, AMS, and IPSS was also confirmed after TRT in
group II. There was a significant difference in testosterone, Hb, Hct, grip
strength, and scores of SF-36, AMS, and IPSS between the two groups after 3
months. The patients in group II showed positive results and continued with TRT.
Therefore, we conclude that TRT safely improves the QoL and TD symptoms in
patients with moderate-to-severe CKD.
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Affiliation(s)
- Jeong Kyun Yeo
- Department of Urology, Inje University, Seoul Paik Hospital, Seoul, Korea
| | - Ho Seok Koo
- Department of Nephrology, Inje University, Seoul Paik Hospital, Seoul, Korea
| | - Jihyeong Yu
- Department of Urology, Inje University, Sanggye Paik Hospital, Seoul, Korea
| | - Min Gu Park
- Department of Urology, Inje University, Seoul Paik Hospital, Seoul, Korea
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Juel Mortensen L, Lorenzen M, Jørgensen A, Albrethsen J, Jørgensen N, Møller S, Andersson AM, Juul A, Blomberg Jensen M. Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men. Cancers (Basel) 2021; 13:cancers13061329. [PMID: 33809538 PMCID: PMC7999540 DOI: 10.3390/cancers13061329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/12/2021] [Accepted: 03/13/2021] [Indexed: 11/21/2022] Open
Abstract
Simple Summary The reproductive hormones luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are both agonists for the luteinizing hormone receptor (LHCGR) and essential for male reproduction during development and adulthood. LHCGR is expressed and stimulates testosterone production from the testicular Leydig cells. In this study, we demonstrate the presence of soluble LHCGR in blood, urine, and seminal fluid in both healthy boys and men, and patients with aberrations in sex-chromosomes. We show how circulating levels of sLHCGR are associated with pubertal development, testicular function, and semen quality and demonstrate that LHCGR is released from fetal human non-gonadal tissue. sLHCGR is released into serum by testis and other organs, which suggests possible extra-gonadal effects of LH or hCG in boys and men. Abstract Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are agonists for the luteinizing hormone receptor (LHCGR) which regulates male reproductive function. LHCGR may be released into body fluids. We wish to determine whether soluble LHCGR is a marker for gonadal function. Cross-sectional, longitudinal, and intervention studies on 195 healthy boys and men and 396 men with infertility, anorchia, or Klinefelter Syndrome (KS) were used to correlate LHCGR measured in serum, seminal fluid, urine, and hepatic/renal artery and vein with gonadal function. LHCGR was determined in fluids from in vitro and in vivo models of human testicular tissue and cell lines, xenograft mouse models, and human fetal kidney and adrenal glands. Western blot showed LHCGR fragments in serum and gonadal tissue of similar size using three different antibodies. The LHCGR-ELISA had no species cross-reactivity or unspecific reaction in mouse serum even after human xenografting. Instead, sLHCGR was released into the media after the culture of a human fetal kidney and adrenal glands. Serum sLHCGR decreased markedly during puberty in healthy boys (p = 0.0001). In healthy men, serum sLHCGR was inversely associated with the Inhibin B/FSH ratio (β −0.004, p = 0.027). In infertile men, seminal fluid sLHCGR was inversely associated with serum FSH (β 0.006, p = 0.009), sperm concentration (β −3.5, p = 0.003) and total sperm count (β −3.2, p = 0.007). The injection of hCG lowered sLHCGR in serum and urine of healthy men (p < 0.01). In conclusion, sLHCGR is released into body-fluids and linked with pubertal development and gonadal function. Circulating sLHCGR in anorchid men suggests that sLHCGR in serum may originate from and possibly exert actions in non-gonadal tissues. (ClinicalTrials: NTC01411527, NCT01304927, NCT03418896).
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Affiliation(s)
- Li Juel Mortensen
- Group of Skeletal, Mineral and Gonadal Endocrinology, University Department of Growth and Reproduction, Rigshospitalet, 2100 Copenhagen, Denmark; (L.J.M.); (M.L.)
| | - Mette Lorenzen
- Group of Skeletal, Mineral and Gonadal Endocrinology, University Department of Growth and Reproduction, Rigshospitalet, 2100 Copenhagen, Denmark; (L.J.M.); (M.L.)
| | - Anne Jørgensen
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; (A.J.); (J.A.); (N.J.); (A.-M.A.); (A.J.)
| | - Jakob Albrethsen
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; (A.J.); (J.A.); (N.J.); (A.-M.A.); (A.J.)
| | - Niels Jørgensen
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; (A.J.); (J.A.); (N.J.); (A.-M.A.); (A.J.)
| | - Søren Møller
- Center for Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Hvidovre Hospital, 2650 Copenhagen, Denmark;
- Department of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, 2200 Copenhagen, Denmark
| | - Anna-Maria Andersson
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; (A.J.); (J.A.); (N.J.); (A.-M.A.); (A.J.)
| | - Anders Juul
- Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; (A.J.); (J.A.); (N.J.); (A.-M.A.); (A.J.)
- Department of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, 2200 Copenhagen, Denmark
| | - Martin Blomberg Jensen
- Group of Skeletal, Mineral and Gonadal Endocrinology, University Department of Growth and Reproduction, Rigshospitalet, 2100 Copenhagen, Denmark; (L.J.M.); (M.L.)
- Division of Bone and Mineral Research, Harvard School of Dental Medicine/Harvard Medical School, Boston, MA 02115, USA
- Correspondence: ; Tel.: +45-3545-5064
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Garibotto G, Esposito P, Picciotto D, Verzola D. Testosterone Disorders and Male Hypogonadism in Kidney Disease. Semin Nephrol 2021; 41:114-125. [PMID: 34140090 DOI: 10.1016/j.semnephrol.2021.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Chronic kidney disease (CKD) causes substantial alterations in the male endocrine system, which affect puberty, libido, and sexual function. A major effect of CKD is a reduction in testosterone levels because of both primary and hypogonadotrophic hypogonadism. In addition to impairment of pubertal growth and sexual maturation in children with CKD, clinical evidence suggests that uremic hypogonadism strongly contributes to several CKD complications, including erectile dysfunction, muscle wasting and frailty, anemia, decreased bone mineralization, depression, and cognitive impairment. This review focuses on a reappraisal of the physiologic role of testosterone, with an emphasis on the hypogonadal condition linked to CKD and its complications.
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Affiliation(s)
- Giacomo Garibotto
- Division of Nephrology, Dialysis and Transplantation, University of Genova, Genova, Italy Department of Internal Medicine, Istituto di Ricerca a Carattere Scientifico Ospedale Policlinico San Martino, Genova Italy.
| | - Pasquale Esposito
- Division of Nephrology, Dialysis and Transplantation, University of Genova, Genova, Italy Department of Internal Medicine, Istituto di Ricerca a Carattere Scientifico Ospedale Policlinico San Martino, Genova Italy
| | - Daniela Picciotto
- Division of Nephrology, Dialysis and Transplantation, University of Genova, Genova, Italy Department of Internal Medicine, Istituto di Ricerca a Carattere Scientifico Ospedale Policlinico San Martino, Genova Italy
| | - Daniela Verzola
- Division of Nephrology, Dialysis and Transplantation, University of Genova, Genova, Italy Department of Internal Medicine, Istituto di Ricerca a Carattere Scientifico Ospedale Policlinico San Martino, Genova Italy
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13
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Zhou Y, Shen L, Dong B, Liu C, Lv W, Chi J, Che K, Gao Y, Wang Y, Wang Y. Elevated circulating luteinizing hormone levels are associated with diabetic macroalbuminuria in Chinese men and postmenopausal women: A cross-sectional study. J Diabetes 2020; 12:819-833. [PMID: 32475064 DOI: 10.1111/1753-0407.13073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 05/16/2020] [Accepted: 05/27/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Associations between sex hormones and diabetic vascular complications have recently been studied, but the role luteinizing hormone (LH) plays in diabetic kidney disease (DKD) remains uncertain. We aimed to investigate the relationship of LH and DKD in Chinese men and postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS Data were collected from 1775 T2DM men and postmenopausal women in hospital. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to LH quartiles were obtained by multiple logistic regression analysis. RESULTS LH levels were significantly higher in patients with macroalbuminuria than in those with microalbuminuria, but were not higher in patients with microalbuminuria than in those with normoalbuminuria. Consistently, LH in those with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 were significantly higher than in those with eGFR≥60 mL/min/1.73m2 . The prevalence of macroalbuminuria was obviously increased for subjects of the fourth quartile of LH vs the first to third quartile (20.4% vs 6.2%, 8.0%, 12.2% in men; 25.3% vs 5.5%, 3.8%, 9.3% in postmenopausal women). Multivariate logistic regression demonstrated that subjects within the highest quartile of LH had higher odds of macroalbuminuria than those within the lowest quartile (OR 4.00, 95% CI, 1.87-8.55 for men; OR 9.62, 95% CI, 3.42-27.08 for postmenopausal women), independent of age, diabetes duration, or other metabolic factors. The area under the curve for detecting macroalbuminuria based on LH was 0.662 for men, and 0.767 for postmenopausal women. CONCLUSION High LH levels are positively associated with established DKD among Chinese men and postmenopausal women. Elevated LH may be a promising clinical factor for identifying established DKD.
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Affiliation(s)
- Yue Zhou
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Liyan Shen
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Bingzi Dong
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Chuanfeng Liu
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Wenshan Lv
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Jingwei Chi
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Kui Che
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Yanyan Gao
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Yunyang Wang
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Yangang Wang
- Department of Endocrinology, Affiliated Hospital of Medical College Qingdao University, Qingdao, China
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14
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Althumairy D, Zhang X, Baez N, Barisas G, Roess DA, Bousfield GR, Crans DC. Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors. Diseases 2020; 8:E35. [PMID: 32942611 PMCID: PMC7565105 DOI: 10.3390/diseases8030035] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/22/2020] [Accepted: 08/26/2020] [Indexed: 12/14/2022] Open
Abstract
Signal transduction by luteinizing hormone receptors (LHRs) and follicle-stimulating hormone receptors (FSHRs) is essential for the successful reproduction of human beings. Both receptors and the thyroid-stimulating hormone receptor are members of a subset of G-protein coupled receptors (GPCRs) described as the glycoprotein hormone receptors. Their ligands, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a structurally related hormone produced in pregnancy, human chorionic gonadotropin (hCG), are large protein hormones that are extensively glycosylated. Although the primary physiologic functions of these receptors are in ovarian function and maintenance of pregnancy in human females and spermatogenesis in males, there are reports of LHRs or FSHRs involvement in disease processes both in the reproductive system and elsewhere. In this review, we evaluate the aggregation state of the structure of actively signaling LHRs or FSHRs, their functions in reproduction as well as summarizing disease processes related to receptor mutations affecting receptor function or expression in reproductive and non-reproductive tissues. We will also present novel strategies for either increasing or reducing the activity of LHRs signaling. Such approaches to modify signaling by glycoprotein receptors may prove advantageous in treating diseases relating to LHRs or FSHRs function in addition to furthering the identification of new strategies for modulating GPCR signaling.
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Affiliation(s)
- Duaa Althumairy
- Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA; (D.A.); (G.B.)
- Department of Biological Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Xiaoping Zhang
- Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; (X.Z.); (N.B.)
| | - Nicholas Baez
- Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; (X.Z.); (N.B.)
| | - George Barisas
- Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA; (D.A.); (G.B.)
- Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; (X.Z.); (N.B.)
| | - Deborah A. Roess
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA;
| | - George R. Bousfield
- Department of Biological Sciences, Wichita State University, Wichita, KS 67260, USA;
| | - Debbie C. Crans
- Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA; (D.A.); (G.B.)
- Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; (X.Z.); (N.B.)
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Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis. Cancers (Basel) 2020; 12:cancers12061358. [PMID: 32466562 PMCID: PMC7352821 DOI: 10.3390/cancers12061358] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/21/2020] [Accepted: 05/23/2020] [Indexed: 01/08/2023] Open
Abstract
Luteinizing hormone/choriogonadotropin receptor (LHCGR) regulates gonadal testosterone production and recent studies have suggested a growth-regulatory role in somatic cancers. Here, we established that LHCGR is expressed in a fraction of seminoma cells and germ cell neoplasia in situ (GCNIS), and the seminoma-derived cell line TCam2 released LHCGR into the medium. LH treatment induced proliferation of TCam2 cells in vitro, while hCG treatment induced a non-significant 51% increase in volume of tumors formed in a TCam2 xenograft model. A specific ELISA was used to detect a soluble LHCGR in serum. Serum concentrations of soluble LHCGR could not distinguish 4 patients with GCNIS and 216 patients with testicular germ cell tumors (TGCTs) from 297 infertile or 148 healthy young men. Instead, serum LHCGR levels were significantly higher in 112 patients with a seminoma >5 cm or elevated serum lactate dehydrogenase (LDH) compared with men harboring smaller seminomas <2 cm or normal LDH levels. Serum LHCGR levels in TGCT patients could not predict relapse irrespective whether determined pre- or post-orchiectomy. Combined, these novel findings suggest that LHCGR may be directly involved in the progression and growth of seminomas, and our retrospective pilot study suggests that serum LHCGR may have some prognostic value in men with seminoma.
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16
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Gholampour F, Malekpour Mansourkhani S, Mohammad Owji S. Amelioration of testicular damages in renal ischemia/reperfusion by berberine: An experimental study. Int J Reprod Biomed 2019; 17:799-806. [PMID: 31911962 PMCID: PMC6906871 DOI: 10.18502/ijrm.v17i10.5488] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 04/22/2019] [Accepted: 07/10/2019] [Indexed: 11/24/2022] Open
Abstract
Background Ischemic acute kidney injury is associated with an inflammatory reaction. Objective In the current study, berberine was assessed for its effect on the functional disorders and histological damages of testis induced by renal ischemia/reperfusion (I/R). Materials and Methods Twenty-eight adult male Wistar rats (260-300 gr) were equally divided into four groups (n = 7/each): sham and I/R groups which received distilled water as well as berberine (BBR) and BBR + I/R groups which received berberine (15 mg/kg/day) orally seven days before the surgery. In both groups of sham and BBR, renal arteries were not clamped. Renal I/R was induced by occluding right and left renal artery for 45 min followed by a 24 hr reperfusion period. Blood samples were taken for determining the plasma levels of creatinine, urea nitrogen, FSH (follicle stimulating hormone), LH (luteinizing hormone), and testosterone. Then the rats were killed under deep anesthesia and the left testis was immediately isolated and preserved. Results The renal I/R injury led to testicular histological damages accompanied with increased plasma levels of creatinine, urea nitrogen, LH, and FSH, as well decrease of plasma testosterone concentration at the end of 24 hr reperfusion (All p < 0.001, except for FSH p < 0.01). Berberine diminished histological damage to the testis and attenuated the increase in plasma creatinine, urea nitrogen, LH, FSH, and decrease in plasma testosterone concentration in the BBR + I/R group (All p < 0.001). Conclusion These results suggest that ischemic acute renal failure induces functional disorders and tissue damages in testis of rat, which was improved through the administration of berberine.
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Affiliation(s)
| | | | - Seyed Mohammad Owji
- Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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17
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Evenepoel P, Opdebeeck B, David K, D'Haese PC. Bone-Vascular Axis in Chronic Kidney Disease. Adv Chronic Kidney Dis 2019; 26:472-483. [PMID: 31831125 DOI: 10.1053/j.ackd.2019.09.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/30/2019] [Accepted: 09/30/2019] [Indexed: 12/13/2022]
Abstract
Patients with chronic kidney disease (CKD) are at increased risk of osteoporosis and vascular calcification. Bone demineralization and vascular mineralization go often hand in hand in CKD, similar to as in the general population. This contradictory association is independent of aging and is commonly referred to as the "calcification paradox" or the bone-vascular axis. Various common risk factors and mechanisms have been identified. Alternatively, calcifying vessels may release circulating factors that affect bone metabolism, while bone disease may infer conditions that favor vascular calcification. The present review focuses on emerging concepts and major mechanisms involved in the bone-vascular axis in the setting of CKD. A better understanding of these concepts and mechanisms may identify therapeutics able to target and exert beneficial effects on bone and vasculature simultaneously.
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18
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Abstract
PURPOSE OF REVIEW The majority of end-stage renal disease including dialysis and kidney transplant patients are men. In contrast, the incidence of chronic kidney disease (CKD) is higher in women compared with men. In this review, we dissect the sex hormone levels and its effects on experimental models and patients with CKD. RECENT FINDINGS Sex hormones are clearly involved in CKD progression to end-stage renal disease (ESRD). A significant reduction in lipid peroxidation as a mechanism of renoprotection has been observed in kidneys of streptozotocin (STZ)-diabetic ovariectomized rats after estradiol administration. Furthermore, a G-protein-coupled estrogen receptor inhibits podocyte oxidative stress maintaining the integrity of the mitochondrial membrane. Sex hormone depletion has been shown to modulate RAS system and protect against kidney injury in the male STZ-diabetic model. In human primary proximal tubular epithelial cells, a proteomic study showed that dihydrotestosterone dysregulated metabolic, suggesting that the deleterious effect of androgens within the kidney maybe related to altered energy metabolism in renal tubules. SUMMARY Male gender is associated with worse CKD progression and this fact may be ascribed to sex hormone. Although male hormones exert a deleterious effect in terms of increasing oxidative stress, activating RAS system, and worsening fibrosis within the damaged kidney, female hormones exert a renoprotective effect.
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19
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Aleksova J, Rodriguez AJ, McLachlan R, Kerr P, Milat F, Ebeling PR. Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease: a Systematic Review and Meta-Analysis. Curr Osteoporos Rep 2018; 16:674-692. [PMID: 30328552 DOI: 10.1007/s11914-018-0483-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. METHODS EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3-5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. RECENT FINDINGS Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21-3.38) and femoral neck (SMD 3.29; 95% CI 3.21-3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.
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Affiliation(s)
- Jasna Aleksova
- Department of Endocrinology, Monash Health, 246 Clayton Rd. Clayton, Melbourne, Victoria, 3168, Australia.
- Hudson Institute of Medical Reearch, Clayton, Melbourne, Australia.
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
| | - Alexander J Rodriguez
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
- Bone & Muscle Health Research Group, Department of Medicine, Monash University, Melbourne, Australia
| | - Robert McLachlan
- Department of Endocrinology, Monash Health, 246 Clayton Rd. Clayton, Melbourne, Victoria, 3168, Australia
- Hudson Institute of Medical Reearch, Clayton, Melbourne, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
| | - Peter Kerr
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
- Department of Nephrology, Monash Health, Melbourne, Australia
| | - Frances Milat
- Department of Endocrinology, Monash Health, 246 Clayton Rd. Clayton, Melbourne, Victoria, 3168, Australia
- Hudson Institute of Medical Reearch, Clayton, Melbourne, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
| | - Peter R Ebeling
- Department of Endocrinology, Monash Health, 246 Clayton Rd. Clayton, Melbourne, Victoria, 3168, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
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20
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Jalón Monzón A, Álvarez Múgica M, Gorostidi Pérez M, Escaf Barmadah S. [Sexual disorders in the renal patient]. Semergen 2018; 45:63-72. [PMID: 30482490 DOI: 10.1016/j.semerg.2018.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/04/2018] [Accepted: 09/08/2018] [Indexed: 01/23/2023]
Abstract
Quality of Life Related to Health is currently considered one of the primary therapeutic objectives in renal failure patients who need substitution treatment as life prolonging therapy. Sexual health is a basic right that positively affects the quality of life. Although a significant percentage of chronic patients have some type of sexual dysfunction, this is not openly discussed, making it important for doctors to address these issues in the clinic. A review is presented on the pathophysiology of sexual dysfunctions in both male and female chronic renal patients. The effects of dialysis and transplantation on sexual function will be addressed, as well as presenting the main sexual dysfunctions and their treatment.
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Affiliation(s)
- A Jalón Monzón
- Unidad de Gestión Clínica de Urología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, España.
| | - M Álvarez Múgica
- Servicio de Urología, Hospital Valle del Nalón, Langreo, Asturias, España
| | - M Gorostidi Pérez
- Unidad de Gestión Clínica de Nefrología, HUCA, Oviedo, Asturias, España
| | - S Escaf Barmadah
- Unidad de Gestión Clínica de Urología, HUCA, Oviedo, Asturias, España
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21
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Testosterone in renal transplant patients: effect on body composition and clinical parameters. J Nephrol 2018; 31:775-783. [DOI: 10.1007/s40620-018-0513-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022]
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22
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Sex hormone-binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy. Kidney Int 2018; 94:372-380. [PMID: 29776756 DOI: 10.1016/j.kint.2018.02.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Revised: 02/06/2018] [Accepted: 02/08/2018] [Indexed: 12/23/2022]
Abstract
Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.
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23
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Bolat MS, Özer İ, Cinar O, Akdeniz E, Aşcı R. The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end-stage renal disease. Ren Fail 2018; 39:582-587. [PMID: 28742406 PMCID: PMC6446171 DOI: 10.1080/0886022x.2017.1349678] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Erectile dysfunction (ED) is a disorder that is frequently observed in people with chronic kidney disease who undergo hemodialysis (HD). In the context of evidence-based medicine, we aimed to investigate the effect of low-dose tadalafil on sexual function in patients undergoing HD. METHODS The medical records of 30 males (aged 29-65 years) with end-stage renal disease (ESRD) on a HD program, and who had received 5 mg tadalafil twice weekly, were retrospectively evaluated. Changes in erectile and ejaculatory function were evaluated using the International Erectile Function Index questionnaire, the Erection Hardness Scale (EHS), and the Male Sexual Health Questionnaire (MSHQ). RESULTS The mean age of the patients was 47.6 ± 10.1 years, their mean body mass index was 24.3 ± 4.2 kg/m2, their mean hemoglobin was 11.9 ± 0.9 g/dL, and their mean creatinine clearance was 5.8 ± 1.1 mL/min. At the third month of treatment, 36.6% of the patients had no ED, 40% had mild ED, 10% had mild-to-moderate ED, and 13.3% had moderate ED. The mean MSHQ scores (p < .05) and the mean EHS scores (p = .001) were significantly improved. There was no significant difference between Beck's Depression Inventory scores (p > .05), but Hamilton anxiety rate scores decreased significantly (p = .001). The quality-of-life score improved throughout the study period (p < .05). CONCLUSIONS Tadalafil therapy is an effective therapeutic option in patients with ESRD who undergo HD, not only for the treatment of ED, but also for ejaculatory function, with acceptable adverse effects.
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Affiliation(s)
- Mustafa Suat Bolat
- a Department of Urology , Samsun Training and Research Hospital, Health Sciences University , Samsun , Turkey
| | - İsmail Özer
- b Department of Nephrology , Samsun Training and Research Hospital, Health Sciences University , Samsun , Turkey
| | - Onder Cinar
- a Department of Urology , Samsun Training and Research Hospital, Health Sciences University , Samsun , Turkey
| | - Ekrem Akdeniz
- a Department of Urology , Samsun Training and Research Hospital, Health Sciences University , Samsun , Turkey
| | - Ramazan Aşcı
- c Department of Urology , Ondokuz Mayıs University , Samsun , Turkey
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Edey MM. Male Sexual Dysfunction and Chronic Kidney Disease. Front Med (Lausanne) 2017; 4:32. [PMID: 28382300 PMCID: PMC5360730 DOI: 10.3389/fmed.2017.00032] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 03/06/2017] [Indexed: 12/18/2022] Open
Abstract
Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions.
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Affiliation(s)
- Matthew M Edey
- Department of Nephrology, Hull and East Yorkshire Hospitals NHS Trust, Kingston upon Hull, UK; Hull-York Medical School, Kingston upon Hull, UK
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25
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Abstract
Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psycho social factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected prior to the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men while the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed towards optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.
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Affiliation(s)
- Biff F Palmer
- Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
| | - Deborah J Clegg
- Biomedical Research Department, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, California, LA, USA
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26
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Kurita N, Horie S, Yamazaki S, Otani K, Sekiguchi M, Onishi Y, Takegami M, Ono R, Konno SI, Kikuchi SI, Fukuhara S. Low Testosterone Levels and Reduced Kidney Function in Japanese Adult Men: The Locomotive Syndrome and Health Outcome in Aizu Cohort Study. J Am Med Dir Assoc 2016; 17:371.e1-6. [PMID: 26926336 DOI: 10.1016/j.jamda.2016.01.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 01/19/2016] [Accepted: 01/19/2016] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Findings from several experimental studies in animals have suggested a protective action of testosterone on kidney function, but hard evidence for such an association in humans is scarce. We examined the association between testosterone levels and kidney function among adult men living in super-aged communities. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS We conducted cross-sectional study involving residents aged 40-80 years who participated in annual health check-ups in 2 communities. A total of 1031 men were recruited in 2010. Main exposure was salivary testosterone (sT) levels measured using an enzyme-linked immunosorbent assay. Main outcome was estimated glomerular filtration rate (eGFR) determined by age, gender, and serum creatinine levels. RESULTS For the 848 participants analyzed, median age and eGFR were 69 years and 69.1 mL/min/1.73 m(2), respectively. On comparison of 90th-percentile sT levels with lower levels, our general linear model with restricted cubic splines showed that lower sT levels were associated with decreased eGFR after adjustment for sociodemographic characteristics, comorbidities, and blood pressure. For example, fifth percentile sT was associated with decreased eGFR, with a difference in eGFR [-3.43 mL/min/1.73 m(2) (95% confidence interval, CI -6.02 to -0.84)] comparable in magnitude to the reduction in eGFR observed for a 6-year increase in age in our population. The association between low testosterone levels and decreased eGFR remained similar even when analyses were restricted to participants aged over 60 years (734 participants, median age 71 years). CONCLUSIONS Results from our study indicated that having low testosterone levels was independently associated with reduced eGFR in adult men. Our finding of this association between low testosterone levels and reduced kidney function needs to be corroborated among persons with chronic kidney disease or in a longitudinal study.
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Affiliation(s)
- Noriaki Kurita
- Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Japan; Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigeo Horie
- Department of Urology, Juntendo University School of Medicine, Tokyo, Japan
| | - Shin Yamazaki
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koji Otani
- Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Miho Sekiguchi
- Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yoshihiro Onishi
- Institute for Health Outcomes and Process Evaluation Research (i-Hope International), Kyoto, Japan
| | - Misa Takegami
- Department of Preventive Medicine and Epidemiologic Informatics, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Rei Ono
- Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - Shin-ichi Konno
- Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Shin-ichi Kikuchi
- Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Shunichi Fukuhara
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence (CIRC(2)LE), Fukushima Medical University, Fukushima, Japan.
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Gökçen K, Kılıçarslan H, Coşkun B, Ersoy A, Kaygısız O, Kordan Y. Effect of ADMA levels on severity of erectile dysfunction in chronic kidney disease and other risk factors. Can Urol Assoc J 2016; 10:E41-5. [PMID: 26858787 DOI: 10.5489/cuaj.3170] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Hormonal, neurogenic, vasculogenic, and psychogenic impairments, as well as endothelial dysfunction may play a role in erectile dysfunction (ED) in patients with chronic kidney disease (CKD). Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric oxide, which is the key element of ED. ADMA levels are increased in CKD. We aimed to evaluate the effect of serum ADMA, prolactin, testosterone, and hemoglobin levels on erectile function of patients with CKD and control subjects. METHODS A total of 42 men with CKD and 25 age-matched controls were enrolled. The patients with CKD were categorized into group 1 and group 2 based on whether they had ED according to their response to International Index of Erectile Function questionnaire (IIEF-EFD). Group 3 was a control group. Serum ADMA, total testosterone prolactin, and hemoglobin levels of the patients were evaluated. RESULTS Serum ADMA, testosterone, and hemoglobin levels were similar between group 1 and 2, serum prolactin level was significantly high in group 1 than in group 2 or 3 (control group). There was no correlation between ADMA levels and IIEF-EFD scores of patients with CKD. CONCLUSIONS The results of this study suggest serum ADMA level is not related with ED in patients with CKD. Also, low testosterone and hemoglobin levels were not significant factors. High levels of serum prolactin are related with ED in patients with CKD.
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Affiliation(s)
- Kaan Gökçen
- Cumhuriyet University, Department of Urology, Sivas, Turkey
| | | | - Burhan Coşkun
- Uludag University, Department of Urology, Bursa, Turkey
| | | | - Onur Kaygısız
- Uludag University, Department of Urology, Bursa, Turkey
| | - Yakup Kordan
- Uludag University, Department of Urology, Bursa, Turkey
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Nishida J, Kokubu N, Kawamukai M, Hashimoto A, Ohnishi H, Kouzu H, Ohnuma Y, Hasegawa T, Tsuchida A, Miura T. Does a Reduction in the Glomerular Filtration Rate Increase the Overall Severity of Coronary Artery Stenosis? Intern Med 2016; 55:871-7. [PMID: 27086798 DOI: 10.2169/internalmedicine.55.5198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis. METHODS We enrolled 1,150 patients [mean age, 68±12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution. RESULTS The log-GS was significantly larger in men than in women (2.5±1.5 vs. 1.9±1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant. CONCLUSION A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.
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Affiliation(s)
- Junichi Nishida
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Japan
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Hylander B, Lehtihet M. Testosterone and gonadotropins but not SHBG vary with CKD stages in young and middle aged men. Basic Clin Androl 2015; 25:9. [PMID: 26635963 PMCID: PMC4668662 DOI: 10.1186/s12610-015-0027-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 10/23/2015] [Indexed: 12/24/2022] Open
Abstract
Background The aim of this study was to assess the effects chronic kidney disease (CKD) had on sex hormones and lipids in a subgroup of men between 18 and 50 years old with CKD 1–5 stage without diabetes and not treated with hemodialysis. Methods Data were collected from 101 men with different CKD stages. Results Higher CKD stage (lower function) had a significant negative linear trend on total testosterone level (p < 0.01) and free testosterone level (p < 0.01), with a significant increase of luteinizing hormone (LH) (p < 0.01), and prolactin (p < 0.01), while SHBG remained unchanged between the CKD stages. Triglycerides but not total cholesterol, HDL –cholesterol or LDL-cholesterol increased with higher CKD stage. A negative correlation was observed between BMI, SHBG and free testosterone (p < 0.01 for both) but not with other sex hormones. Age per se was related to a significant decrease of total and free testosterone level (p < 0.01 for both) even after correction for BMI. Decreased levels of total testosterone and estimated free testosterone levels had a significant correlation with an increased level of triglyceride levels (p <0.01). Conclusions Our results indicate that CKD stage per se is a factor affecting testosterone levels in combination with age in men between 18 and 50 years old with CKD 1–5 stage, not treated with hemodialysis. With increased CKD stage there was a significant increase in LH level and a pattern of hypergonadotropic hypogonadism. SHBG remained unchanged between the CKD stages. Electronic supplementary material The online version of this article (doi:10.1186/s12610-015-0027-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Britta Hylander
- Department of Nephrology, Karolinska Institute and Karolinska University Hospital, Solna, Stockholm, S-17173 Sweden
| | - Mikael Lehtihet
- Department of Endocrinology, Metabolism and Diabetes, C2:94, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, S-141 86 Sweden
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Abstract
The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.
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Suzuki E, Nishimatsu H, Oba S, Takahashi M, Homma Y. Chronic kidney disease and erectile dysfunction. World J Nephrol 2014; 3:220-229. [PMID: 25374815 PMCID: PMC4220354 DOI: 10.5527/wjn.v3.i4.220] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 06/22/2014] [Accepted: 09/10/2014] [Indexed: 02/05/2023] Open
Abstract
Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack.
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Dousdampanis P, Trigka K, Fourtounas C, Bargman JM. Role of testosterone in the pathogenesis, progression, prognosis and comorbidity of men with chronic kidney disease. Ther Apher Dial 2014; 18:220-230. [PMID: 24119223 DOI: 10.1111/1744-9987.12101] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin-angiotensin system (RAS), the production of endothelin and the regulation of anti- or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.
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Ulloa-Aguirre A, Reiter E, Bousfield G, Dias JA, Huhtaniemi I. Constitutive activity in gonadotropin receptors. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2014; 70:37-80. [PMID: 24931192 DOI: 10.1016/b978-0-12-417197-8.00002-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Constitutively active mutants (CAMs) of gonadotropin receptors are, in general, rare conditions. Luteinizing hormone-choriogonadotropin receptor (LHCGR) CAMs provoke the dramatic phenotype of familial gonadotropin-independent isosexual male-limited precocious puberty, whereas in females, there is not yet any identified phenotype. Only one isolated follicle-stimulating hormone receptor (FSHR) CAM (Asp567Gly) has so far been detected in a single male patient, besides other FSHR weak CAMs linked to pregnancy-associated ovarian hyperstimulation syndrome or to impaired desensitization and internalization. Several animal models have been developed for studying enhanced gonadotropin action; in addition to unraveling valuable new information about the possible phenotypes of isolated FSHR and LHCGR CAMs in women, the information obtained from these mouse models has served multiple translational goals, including the development of new diagnostic and therapeutic targets as well as the prediction of phenotypes for mutations not yet identified in humans. Mutagenesis and computational studies have shed important information on the physiopathogenic mechanisms leading to constitutive activity of gonadotropin receptors; a common feature in these receptor CAMs is the release of stabilizing interhelical interactions between transmembrane domains (TMDs) 3 and 6 leading to an increase, with respect to the wild-type receptor, in the solvent accessibility at the cytosolic extension of TMDs 3, 5, and 6, which involves the highly conserved Glu/Asp-Arg-Tyr/Trp sequence. In this chapter, we summarize the structural features, functional consequences, and mechanisms that lead to constitutive activation of gonadotropin receptor CAMs and provide information on pharmacological approaches that might potentially modulate gonadotropin receptor CAM function.
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Affiliation(s)
- Alfredo Ulloa-Aguirre
- Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Tours, France; Research Support Network, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" and Universidad Nacional Autónoma de México, México D.F., Mexico.
| | - Eric Reiter
- Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Tours, France; BIOS Group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France
| | - George Bousfield
- Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Tours, France; Department of Biological Sciences, Wichita State University, Wichita, Kansas, USA
| | - James A Dias
- Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Tours, France; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA
| | - Ilpo Huhtaniemi
- Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Tours, France; Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
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Park M, Koo H, Lee B. Characteristics of Testosterone Deficiency Syndrome in Men With Chronic Kidney Disease and Male Renal Transplant Recipients: A Cross-Sectional Study. Transplant Proc 2013; 45:2970-4. [DOI: 10.1016/j.transproceed.2013.08.087] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Troppmann B, Kleinau G, Krause G, Gromoll J. Structural and functional plasticity of the luteinizing hormone/choriogonadotrophin receptor. Hum Reprod Update 2013; 19:583-602. [DOI: 10.1093/humupd/dmt023] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Chambers AE, Griffin C, Naif SA, Mills I, Mills WE, Syngelaki A, Nicolaides KH, Banerjee S. Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down's syndrome, preterm delivery and preeclampsia. Reprod Biol Endocrinol 2012; 10:113. [PMID: 23245345 PMCID: PMC3570453 DOI: 10.1186/1477-7827-10-113] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 12/14/2012] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. METHODS Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. RESULTS Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down's syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. CONCLUSIONS Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy.
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Affiliation(s)
- Anne E Chambers
- Department of Clinical Biochemistry, Heartlands Hospital, Birmingham, B9 5SS, UK
- Present address: Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
| | | | | | - Ian Mills
- Birmingham Women’s Hospital, Edgbaston, Birmingham, UK
| | - Walter E Mills
- Department of Clinical Biochemistry, Heartlands Hospital, Birmingham, B9 5SS, UK
- Present address: Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
| | - Argyro Syngelaki
- Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK
| | - Kypros H Nicolaides
- Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK
| | - Subhasis Banerjee
- Department of Clinical Biochemistry, Heartlands Hospital, Birmingham, B9 5SS, UK
- Present address: Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
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Carrero JJ, Stenvinkel P. The vulnerable man: impact of testosterone deficiency on the uraemic phenotype. Nephrol Dial Transplant 2012; 27:4030-41. [PMID: 22962412 DOI: 10.1093/ndt/gfs383] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Testosterone deficiency or hypogonadism is a common finding in men undergoing dialysis, to a great extent a consequence of the failing kidney per se. Testosterone restoration in hypogonadism is common practice among endocrinologists. However, there is currently little awareness of this condition among both uremic patients and nephrologists, and in many cases, testosterone deficiency remains unscreened and untreated. This review article summarizes our current understanding of the role of testosterone deficiency at the crossroad of cardiometabolic complications of patients with chronic kidney disease. Pathways discussed include, among others, the plausible role of testosterone deficiency in the development of anaemia and ESA hyporesponsiveness, muscle catabolism, endothelial dysfunction, cognitive dysfunction, decreased libido, cardiovascular disease and mortality. As there are limited sources to guide decision-making, we also review existing testosterone replacement therapy studies in the context of CKD as well as considerations for side and adverse effects. This review makes a case for consideration of screening and better management of hypogonadism in men undergoing dialysis.
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Chambers AE, Nayini KP, Mills WE, Lockwood GM, Banerjee S. Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation. Reprod Biol Endocrinol 2011; 9:161. [PMID: 22195987 PMCID: PMC3285531 DOI: 10.1186/1477-7827-9-161] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Accepted: 12/23/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Successful pregnancy via in vitro fertilization (IVF) depends on the recovery of an adequate number of healthy oocytes and on blastocyst implantation following uterine transfer. Two hormones, LH and hCG, utilize a common LH/hCG receptor (LHCGR), variations in which have profound implications in human reproduction. Soluble LHCGR (sLHCGR) is released from experimental cell lines and placental explants and it can be detected in the follicular fluid and serum. METHODS To evaluate the impact of circulating soluble LHCGR (sLHCGR) in fertility treatment, we measured sLHCGR and LH-sLHCGR complex in serum from women seeking IVF using specifically developed quantitative enzyme-linked immunosorbent assays (ELISA). Following an IVF cycle of treatment, patients were grouped according to oocyte yield into low (lower than or equal to 7 oocytes), intermediate (8-14 oocytes) and high (greater than or equal to 15 oocytes) responders and pregnancy outcome noted. RESULTS Pre-treatment sLHCGR identified many women at risk of ovarian hyperstimulation. Low levels of sLHCGR were associated with pregnancy in both high and low responders but sLHCGR did not significantly affect the treatment outcome of intermediate responders. Low responders who failed to become pregnant had high levels of circulating sLHCGR bound to LH (LH-sLHCGR). CONCLUSIONS Pre-treatment measurement of sLHCGR could be used to tailor individual fertility treatment programs and improve outcomes by avoiding ovarian hyperstimulation and poor embryo implantation.
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Affiliation(s)
- Anne E Chambers
- Department of Clinical Biochemistry, Heartlands Hospital, Birmingham B9 5SS, UK
- Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
| | | | - Walter E Mills
- Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
| | | | - Subhasis Banerjee
- Department of Clinical Biochemistry, Heartlands Hospital, Birmingham B9 5SS, UK
- Origin Biomarkers, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK
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Yilmaz MI, Sonmez A, Qureshi AR, Saglam M, Stenvinkel P, Yaman H, Eyileten T, Caglar K, Oguz Y, Taslipinar A, Vural A, Gok M, Unal HU, Yenicesu M, Carrero JJ. Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am Soc Nephrol 2011; 6:1617-25. [PMID: 21700826 DOI: 10.2215/cjn.10681210] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Deterioration of kidney function impairs testosterone production, with hypogonadism being common in men with chronic kidney disease (CKD). In nonrenal populations, testosterone is suggested to participate in the atherosclerotic process. In male dialysis patients, we showed that low testosterone increases the risk of mortality. We here studied plausible links among testosterone levels, vascular derangements, and cardiovascular events in nondialysis CKD men. DESIGN, SETTING, PARTICIPANTS, & METHODS This was a cross-sectional analysis in which flow-mediated dilation (FMD) was assessed in 239 CKD male patients (stages 1 to 5; mean age 52 ± 12 years), together with routine measurements, serum total and free testosterone, and follow-up for cardiovascular outcomes. RESULTS Total and free testosterone levels decreased in parallel with the reduction of kidney function. Multiple regression analyses showed that total and free testosterone significantly and independently contributed to explain the variance of FMD. After a median follow-up of 31 months (range 8 to 35 months), 22 fatal and 50 nonfatal cardiovascular events occurred. In Cox analysis, the risk of cardiovascular events was reduced by 22% for each nanomole-per-liter increment of total testosterone. This reduced risk persisted after adjustment for age, renal function, diabetes mellitus, previous cardiovascular history, C-reactive protein, albumin, and FMD. The same was true for free testosterone concentrations. CONCLUSIONS The reduction in endogenous testosterone levels observed with progressive CKD was inversely associated with endothelial dysfunction and exacerbated the risk of future cardiovascular events in nondialysis male CKD patients.
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Chambers AE, Stanley PF, Randeva H, Banerjee S. Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR) from transfected cells and placenta explants. Reprod Biol Endocrinol 2011; 9:64. [PMID: 21575145 PMCID: PMC3112408 DOI: 10.1186/1477-7827-9-64] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2011] [Accepted: 05/15/2011] [Indexed: 12/24/2022] Open
Abstract
Placental hCG and pitutary LH transduce signals in target tissues through a common receptor (LHCGR). We demonstrate that recombinant LHCGR proteins which include the hormone-binding domain are secreted from transfected cells and that natural LHCGR is also secreted from human placental explants. LHCGR recombinant proteins representing varying lengths of the N-terminal extracellular domain were expressed in Chinese Hamster Ovary cells in suspension culture. Secretion was minimal up to 72h but by 96h 24-37% of the LHCGR had been released into the culture medium. The secreted proteins were folded and sensitive to glycosidases suggesting N-linked glycosylation. Secretion was independent of recombinant size and was mediated via structurally defined membrane vesicles (50-150nm). Similarly cultured human early pregnancy placental explants also released LHCGR via microvesicles. These studies provide the first experimental evidence of the possible mechanistic basis of the secretion of LHCGR.
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Affiliation(s)
- Anne E Chambers
- Department of Clinical Biochemistry, Laboratory Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK
| | - Paul F Stanley
- Centre for Electron Microscopy Metallurgy and Materials Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Harpal Randeva
- Clinical Sciences Research Institute, Medical School Building, Gibbet Hill Campus, University of Warwick, Coventry, UK
| | - Subhasis Banerjee
- Department of Clinical Biochemistry, Laboratory Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK
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Abstract
Résumé
But
Le but de notre travail était d’établir le profil hormonal, érectile et spermatique chez les patients hémodialysés et de rechercher l’impact des perturbations hormonales sur la fonction érectile (FE) et les paramètres spermatiques.
Patients et méthodes
Nous avons réalisé une étude transversale chez 30 sujets hémodialysés chez qui un spermogramme a été réalisé parallèlement à un bilan hormonal qui incluait le dosage sérique de FSH (follicle-stimulating hormone) et la testostérone totale. La FE a été évaluée par l’étude de l’indice international de la FE dans sa version française (IIEF-5). Le dosage des hormones sexuelles a été fait par la technique radio-immunologique, et la pratique du spermogramme a été faite selon les recommandations de l’OMS.
Résultats
Deux patients seulement avaient un spermogramme et un bilan hormonal normaux, l’IIEF était normal chez un seul patient.
Les patients azoospermiques (16 %) présentaient un eugonadisme hypergonadotrophique. Quarante pour cent des patients avaient une hypospermie. Un tiers des patients présentait une oligozoospermie sévère associée à un taux élevé de FSH dans 77 % des cas.
La mobilité et la morphologie spermatique étaient altérées dans respectivement 96 et 50 % des cas. Le bilan hormonal montrait une élévation de la FSH (> 8,5 mUI/ml) chez 40 % des patients, et la testostéronémie était diminuée (< 3,2 ng/ml) chez 25 % des patients. Deux patients présentaient un hypogonadisme franc (testostérone < 2 ng /ml).
Discussion
Le volume de sperme était diminué de façon significative chez les patients de plus de 30 ans. La FE était perturbée dans 73 % des cas avec un IIEF moyen de 15 (IIEF normal > 20). Plusieurs auteurs ont mis en évidence une corrélation entre le dysfonctionnement gonadique et les taux élevés de gonadotrophines chez l’homme présentant une insuffisance rénale chronique, avec ou sans atrophie testiculaire. Dans notre série, la testostéronémie était normale chez nos patients malgré l’absence de prise d’androgène. Les séances d’hémodialyses permettent-elles de préserver la fonction endocrine des testicules ?
Conclusion
Les patients au stade d’hémodialyse chronique d’une durée supérieure à un an présentaient un eugonadisme hypergonadotrophique ainsi qu’une insuffisance érectile. L’ancienneté de l’hémodialyse n’altère pas de manière significative les paramètres spermatiques ni la FE. Les patients d’un âge supérieur à 30 ans présentaient une diminution significative du volume spermatique qui pourrait être un marqueur déterminant de l’atteinte de la FE et de la fonction reproductive.
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Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, Bárány P, Heimbürger O, Stenvinkel P. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol Dial Transplant 2010; 26:184-90. [PMID: 20624775 DOI: 10.1093/ndt/gfq397] [Citation(s) in RCA: 110] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Abnormally low serum testosterone levels were recently associated with an increased mortality risk in male dialysis patients. However, the prevalence of testosterone deficiency in end-stage renal disease (ESRD) is not well defined. We hereby explore the prevalence and correlates of clinical testosterone deficiency in a large cohort of ESRD male patients. METHODS Two hundred and sixty ESRD men [median age 59 (25th-75th percentile 48-67) years] were included. Testosterone concentration and testosterone deficiency (<10 nmol/L) were studied in relation to clinically evident cardiovascular disease and markers of inflammation at baseline as well as deaths registered during the following 36 months. RESULTS Testosterone deficiency was present in 44% of the patients, while 33% showed testosterone insufficiency (10-14 nmol/L), and only 23% had normal testosterone values (>14 nmol/L). Testosterone was strongly and inversely correlated to inflammatory markers (CRP, IL-6 and fibrinogen), even after correction for age and sex hormone-binding globulin. In a crude spline curve, low testosterone concentrations were associated with worse outcome. A clinical condition of testosterone deficiency was independently associated with cardiovascular co-morbidity [odds ratio (OR) 2.51; 95% confidence interval (CI) 1.32-4.76] and death (OR 2.00; 95% CI 1.01-3.97) in logistic regression analyses. CONCLUSIONS Testosterone deficiency is a common finding among male ESRD patients, and it is independently associated with inflammation, cardiovascular co-morbidity and outcome. Future studies are needed to determine the potential adverse effects of male hypogonadism in ESRD and the possibility of improving risk profile, quality of life, and ultimately outcome with testosterone supplementation in these patients.
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Schaefer F. Daily online haemodiafiltration: the perfect 'stimulus package' to induce growth? Nephrol Dial Transplant 2010; 25:658-60. [PMID: 20083477 DOI: 10.1093/ndt/gfp769] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
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45
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Sartorius GA, Handelsman DJ. Testicular Dysfunction in Systemic Diseases. Andrology 2010. [DOI: 10.1007/978-3-540-78355-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Efficacy of testosterone gel in the treatment of erectile dysfunction in hypogonadal hemodialysis patients: a pilot study. Int J Impot Res 2009; 22:140-5. [DOI: 10.1038/ijir.2009.55] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Yadav R, Mehta SN, Kumar A, Guleria S, Seenu V, Tiwari SC. A prospective analysis of testicular androgenic function in recipients of a renal allograft. Int Urol Nephrol 2008; 40:397-403. [PMID: 18392945 DOI: 10.1007/s11255-007-9277-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2007] [Accepted: 08/16/2007] [Indexed: 01/24/2023]
Abstract
Eighteen adult males with end stage renal disease (ESRD) were studied to determine the serum levels of gonadotropins (LH and FSH), prolactin (PRL) and testosterone. All of the patients were studied longitudinally while undergoing maintenance hemodialysis (HD) and six months after renal transplantation. Prior to transplantation, significantly high levels of gonadotropins and PRL were observed. During HD the serum testosterone levels tended to be subnormal in most of the uremic patients and low normal in some of the subjects. Renal transplantation led to a significant improvement (P < 0.05) in serum testosterone. Elevated gonadotropin and PRL levels observed in patients on HD returned to the normal range in most of the patients after successful renal transplantation.
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Affiliation(s)
- Rajiv Yadav
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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Schmidt RJ, Holley JL. Rehabilitation of Dialysis Patients Series Editor: Nancy G. Kutner: Sexual Function in Patients with End-Stage Renal Disease. Semin Dial 2007. [DOI: 10.1111/j.1525-139x.1998.tb00330.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
Hypogonadism is often observed in the presence of common acute and chronic illnesses in men. Low testosterone levels in these patients can be associated with loss of lean body mass and bone mass density, decline in mood, loss of energy, and sexual dysfunction. The mechanisms explaining hypogonadism and various systemic diseases are not completely understood, but these conditions are likely caused by a combination of stress, nonspecific weight loss, inflammation, and medication. Testosterone replacement can be considered in this population to improve lean body mass, bone mass density, and quality of life. More information is needed regarding the risk benefits of testosterone treatment on health outcomes in men who have systemic illness.
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Affiliation(s)
- Rita R Kalyani
- Division of Endocrinology and Metabolism, Johns Hopkins School of Medicine, 1830 E. Monument Street, Baltimore, MD 21287, USA
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Abstract
Gonadal function is significantly affected in many acute and chronic systemic diseases. As the function of the testes and the ovaries is determined by the integrity of the hypothalamic-pituitary-gonadal axis, it is obvious that a systemic disease may affect one or more levels of the axis in such a manner that the gonadal dysfunction may have various clinical and laboratory manifestations. In this brief review, the most common disturbances seen in the main systemic diseases will be discussed.
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Affiliation(s)
- Asterios Karagiannis
- Second Propedeutic Department of Internal Medicine, Division of Endocrinology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Greece.
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