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      Organ transplantation and gender differences: a paradigmatic example of intertwining between biological and sociocultural determinants

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          Abstract

          Organ transplantation, e.g., of the heart, liver, or kidney, is nowadays a routine strategy to counteract several lethal human pathologies. From literature data and from data obtained in Italy, a striking scenario appears well evident: women are more often donors than recipients. On the other hand, recipients of organs are mainly males, probably reflecting a gender bias in the incidence of transplant-related pathologies. The impact of sex mismatch on transplant outcome remains debated, even though donor-recipient sex mismatch, due to biological matters, appears undesirable in female recipients. In our opinion, the analysis of how sex and gender can interact and affect grafting success could represent a mandatory task for the management of organ transplantation.

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          The effect of donor gender on graft survival.

          Eberhard Ritz, Gerhard Opelz, B Döhler … (2002)
          Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.
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            Sex differences in myocardial metabolism and cardiac function: an emerging concept.

            Janelle M. Belanger, Daniel E L Tan, C Wittnich … (2013)
            There is substantial evidence that there are dramatic sex-related differences in the incidence of cardiovascular disease, apparently related to the presence of steroid hormones. This is supported by the discovery of steroid hormone receptors in the heart and vasculature. More controversial is the area of sex-related differences in cardiac metabolism and function. A number of human and animal studies have demonstrated that estrogen and testosterone have cardiac metabolic effects. Additionally, research shows females have higher heart rates and various indices of function, including cardiac output and stroke volume, compared with males. However, some controversy exists, as other studies report that function in isolated muscle preparations is lower in females versus males. The reasons for these differences may reflect effects of sex hormones that are dependent on the conditions being studied. Cardiac function is reduced in postmenopausal females, suggesting that female sex hormones, specifically estrogen and progesterone, influence cardiac function. Apart from its well-documented vasodilatory effects, estrogen has also been shown to have negative inotropic effects and to reduce Ca(2+) transients in cardiomyocytes. Similar results have been found for progesterone. Several studies show that testosterone administration appears to increase cardiac performance, while others show that it increases the stiffness of the ventricle due to increased collagen synthesis, thereby reducing diastolic performance. This review will discuss current evidence suggesting sex-related differences in cardiac metabolism and its energetics and function and will present the potential role of the principal sex steroid hormones.
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              Sex hormones and gender-related differences: their influence on chronic renal allograft rejection.

              V Müller, Peter A. Szabo, O Viklicky … (1999)
              Renal hemodynamics and immune responses differ between males and females. Thus, sex hormones and genetically determined gender differences may determine the process of chronic rejection to some extent.
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                Author and article information

                Contributors
                Walter Malorni: +3906 49902905 , malorni@iss.it
                Journal
                Journal ID (nlm-ta): Biol Sex Differ
                Journal ID (iso-abbrev): Biol Sex Differ
                Title: Biology of Sex Differences
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2042-6410
                Publication date (Electronic): 28 July 2016
                Publication date PMC-release: 28 July 2016
                Publication date Collection: 2016
                Volume: 7
                Electronic Location Identifier: 35
                Affiliations
                [1 ]National Transplant Center (CNT), Istituto Superiore di Sanità, Rome, Italy
                [2 ]Section of Gender Medicine, Istituto Superiore di Sanità, Rome, Italy
                [3 ]Department of Therapeutic Research and Medicine Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, viale Regina Elena 299, 00161, Rome, Italy
                Article
                Publisher ID: 88
                DOI: 10.1186/s13293-016-0088-4
                PMC ID: 4964018
                PubMed ID: 27471591
                SO-VID: 5577a818-8a0a-4c91-b49a-3c964ed4034d
                Copyright © © The Author(s). 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 11 March 2016
                Date accepted : 19 July 2016
                Categories
                Subject: Commentary
                Custom metadata
                issue-copyright-statement © The Author(s) 2016

                ScienceOpen disciplines: Human biology
                Keywords: transplantation,sex differences,gender differences
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: transplantation, sex differences, gender differences

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