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Table of Contents
EDITORIAL
Year : 2019  |  Volume : 13  |  Issue : 4  |  Page : 237-239

Men are from mars, women are from venus: Gender disparity in transplantation


Department of Nephrology, Osmania Medical College and General Hospital, Hyderabad, Telangana, India

Date of Submission18-Dec-2019
Date of Acceptance18-Dec-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Dr. Manisha Sahay
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_72_19

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  Abstract 



How to cite this article:
Sahay M. Men are from mars, women are from venus: Gender disparity in transplantation. Indian J Transplant 2019;13:237-9

How to cite this URL:
Sahay M. Men are from mars, women are from venus: Gender disparity in transplantation. Indian J Transplant [serial online] 2019 [cited 2020 Feb 26];13:237-9. Available from: http://www.ijtonline.in/text.asp?2019/13/4/237/274613



Organ transplantation is the best treatment for end-stage organ dysfunction. Organs can be obtained from live donors or deceased donors. Live donors can be live-related donors which include parents, siblings, grandparents, children, or spousal donors. Other than near-related donors include all other living donors.[1] Deceased donors are those whose organs are retrieved either after brain stem death or after circulatory death (nonheart-beating donors).

Many articles have discussed about sex and gender disparity in organ transplantation. Gender and sex are often used interchangeably. However, there is an important difference between sex and gender. Sex is the biological attribute that includes anatomical, endocrine, or genetic traits. This accounts for the medical differences between males and females and these factors are not modifiable. Gender encompasses social, cultural, and psychological identities and behaviors. Gender accounts for the social differences between men and women and these factors are modifiable.

Gender disparity is seen in the outcome of transplantation in males and females. Furthermore, there also exists a disparity in access to organ transplantation in males and females. Majority of the living-related donors are females. On the other hand, majority of the organ recipients are males. This is true across the country as shown in data by the National Organ and Tissue Transplantation Organization.[2]


  Gender Differences in Access to Transplantation Top


Factors which influence the outcomes of transplantation between males and females are as follows:

Anatomical factors

Female kidneys are smaller than male kidneys and have lesser number of nephrons. Hence, kidney transplantation from females to males may be associated with lesser dose of nephrons (nephron dosing). This may be associated with poor outcomes due to hyperfiltration and glomerulosclerosis in the long term. Analysis of the large Conflict Tactics Scale registry comprising more than 100,000 kidney transplantations from 1985 to 2000 showed inferior graft outcome when kidneys of female donors were transplanted into male recipients compared with kidney transplantation from males to females.[3] Thus, theoretically, females seem to be at anatomical advantage as they would get a bigger kidney, i.e., a higher nephron dose if donor was a male.

Physiological factors

The female kidney may be more susceptible to the effect of drugs and toxins. In addition, the metabolism of immunosuppressive drugs is different in males and females. Females may have reduced efflux of calcineurin inhibitors from cells due to the low activity of P glycoprotein, leading to greater intracellular drug exposure.[4] In addition, there is reduced activity of cytochromes 450 with increased clearance of drugs from the body in women.

Immunological factors

Literature shows that females are at immunological disadvantage. Gratwohl et al. analyzed data from the Collaborative Transplant Study and identified that female recipients of male deceased-donor kidneys had, in fact, increased risk of death-censored graft failure during the 1st year (hazard ratio of 1.11; 95% confidence interval, 1.04–1.19; P = 0.003) and between 2 and 10 years (hazard ratio of 1.10; 95% confidence interval, 1.05–1.16; P < 0.001).[5] A separate analysis of kidney allograft recipients from the US Renal Data System by Kim and Gill[6] identified increased risk of graft failure for female recipients of kidneys from male donors within the 1st year after transplant (hazard ratio of 1.12; 95% confidence interval, 1.05–1.19) but not after 10 years (hazard ratio of 1.03, 95% confidence interval, 0.98–1.07).[6] Similar adverse outcomes have been observed for female recipients of organs from male donors in the context of liver,[7] heart,[8] and lung transplant.[9] This is because of sensitization and HY antigen effect.

Sensitization in females

One of the important factors which determines the outcome of organ transplantation is the level of sensitization. Sensitization is measured by the antibodies present in the recipient against the donor antigens. These antibodies develop as a result of exposure to antigens, which may happen during blood transfusions or previous organ transplantation. Female recipients may also be at an immunological disadvantage as they become sensitized and develop antibodies against their husband's antigens during pregnancy.[10] The degree of sensitization may increase after multiple pregnancies.

HY antigen effect

In a study by Lepeytre et al.,[11] the authors showed that in the setting of a male donor, female recipients of all ages have significantly higher rates of graft failure than males. This may be explained by an immune reaction of female recipients to the HY antigen (present on all male tissues), an immune-stimulating effect of estrogen, and an immune-suppressing effect of testosterone.

The effect of HY antigen is more pronounced in younger age group who are more immunologically reactive. In the study by Lepeytre et al., the largest differences in outcomes were observed in children and the smallest differences were observed among adults >45 years. When the donor was female, only adolescent girls and young adult women (15–24 years) had higher rates of graft failure than boys and young men of the same age. There was not much difference in outcomes between males and females if the age was >45. Inferior outcomes of renal allografts in female children compared with males were also reported by the North American Pediatric Renal Trials and Collaborative Studies, without stratifying by donor sex.[12]


  Gender Differences in Access to Transplantation Top


Data from the National Organ Transplantation and Tissue Organization show that majority of living donations in India are from women and majority of organ recipients are men. Among organ transplant recipients, there are 23,682 men and a meager 5025 females.[2]

This phenomenon is seen in other countries as well though the gender disparity is less compared to that in India. In the United States also, women are more often living kidney donors than men, whereas men are more often recipients of living donor kidneys. In a study by Melk et al., from 1988 to 2017, 426,842 patients received a kidney allocated by the United Nations Organ System (UNOS), and from 2008 to 2017, 34,100 kidneys were transplanted within the Eurotransplant (ET) system. Sixty percent of the transplanted patients in the UNOS and 62% of the transplanted patients in the ET were males. At present, 103,156 patients are waitlisted in the UNOS and 11,105 in the ET (61% males in each system).[13]

Data from the UK, Europe, and Italy show a preponderance of women donors [Table 1].[14],[15],[16],[17],[18],[19],[20] Thus, gender disparity exists irrespective of whether the country is a developed or a developing country. It may vary with race or ethnicity. Race (refers to biological traits, such as skin and hair color) and ethnicity (refers to nonbiological factors such as culture, language, country of residence, or parental origin).
Table 1: Gender disparity in transplantation

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Gender disparity is more evident in certain races and ethnicities, i.e., it is more in Black race versus White race and in some ethnicities, for example, more in Africans, South Asians, Indians, and least in Caucasians. A study on 101 African patients with end-stage renal disease regarding live donor kidney transplantation (LDKT) found that women less significantly underwent LDKT than men. They were also less likely to be evaluated for a kidney transplant.[21]

Factors which influence the access to organ transplantation between males and females are as follows:

Epidemiological factors

Gender disparity in access to transplantation, i.e., more males get kidneys versus females, may be explained based on the difference in the epidemiology of end-stage kidney disease (ESKD). The incidence and prevalence of ESKD is more common in males than in females and hence there are more male recipients who undergo transplants or are waitlisted for organs.

Social factors

Females may also be at a social disadvantage as well. Whenever there is a need for organ, the women of the family are the first to be considered as organ donors. Majority of the times, if the mother is fit, she comes forward to donate her organs. If the mother is unfit, the wife is often the default donor.

Fairer sex has generally a giving nature. They give birth and bring life into this world. Many of them may come forward to donate on their own free will in order to save the life of their children or their husbands. This is true altruism and should be applauded. However, women are often coerced into donation when they do not wish to donate. In India, if the woman says no to organ donation, she is treated as a social outcast. She finds it difficult to live in the same house with other family members. However, if the male does not wish to donate, it is acceptable socially. The explanation put forth is that the male is the main breadwinner for the family and donating an organ would jeopardize his health. Women with ESKD have been found to have low self-esteem and possibly, a lack of strong social support. Lack of strong social support may explain why women less likely require LDKT in the multivariate analysis.[21] Zimmerman et al. in their study showed that there are more female donors because more wives donate to their husbands than vice versa.[22] The social differences are highlighted in an article by Phyllis August “Why can't a woman be more like a man?”[23]


  Conclusion Top


Men and women are different anatomically, physiologically, and immunologically. This may impact transplantation outcomes, with females being at an immunological disadvantage with poor transplant outcomes. This is understandable. However, what is beyond comprehension is the fact that humankind has created social differences between men and women, making women less likely to receive organs.

The society should realize that women are procreators. They are homemakers. They take care of the house and take care of the upbringing of children. They provide food for the family. They make the house a “home.” Many women work and contribute to the family's income. However, we hear of innumerable cases of violence against women, i.e., rape, dowry, and female infanticide. Coercion for organ donation is another form of female exploitation and should be strongly condemned. Women should be free to decide and exercise their free will. They should be free to say no if they do not want to donate their organs. They should be treated as equal to men. The society should not put them on pedestal and treat them as goddesses nor should treat them as slaves. This change would come only with increasing literacy among women, economic independence, and above all support from their male counterparts. Medical differences between men and women are unmodifiable, but social differences can and should be eliminated.



 
  References Top

1.
The Gazette of India. Extraordinary Transplantation of Human Organs and Tissues Rules (THOT) Ministry of Health and Family Welfare Notification. Part 2. Sec. 3. New Delhi: The Gazette of India; 2014.  Back to cited text no. 1
    
2.
Available from: https://notto.gov.in/organreport.htm. [Last accessed on 2019 Dec 15].  Back to cited text no. 2
    
3.
Zeier M, Döhler B, Opelz G, Ritz E. The effect of donor gender on graft survival. J Am Soc Nephrol 2002;13:2570-6.  Back to cited text no. 3
    
4.
Momper JD, Misel ML, McKay DB. Sex differences in transplantation. Transplant Rev (Orlando) 2017;31:145-50.  Back to cited text no. 4
    
5.
Gratwohl A, Döhler B, Stern M, Opelz G. H-Y as a minor histocompatibility antigen in kidney transplantation: A retrospective cohort study. Lancet 2008;372:49-53.  Back to cited text no. 5
    
6.
Kim SJ, Gill JS. H-Y incompatibility predicts short-term outcomes for kidney transplant recipients. J Am Soc Nephrol 2009;20:2025-33.  Back to cited text no. 6
    
7.
Candinas D, Gunson BK, Nightingale P, Hubscher S, McMaster P, Neuberger JM. Sex mismatch as a risk factor for chronic rejection of liver allografts. Lancet 1995;346:1117-21.  Back to cited text no. 7
    
8.
Prendergast TW, Furukawa S, Beyer AJ 3rd, Browne BJ, Eisen HJ, Jeevanandam V. The role of gender in heart transplantation. Ann Thorac Surg 1998;65:88-94.  Back to cited text no. 8
    
9.
Roberts DH, Wain JC, Chang Y, Ginns LC. Donor-recipient gender mismatch in lung transplantation: Impact on obliterative bronchiolitis and survival. J Heart Lung Transplant 2004;23:1252-9.  Back to cited text no. 9
    
10.
Bromberger B, Spragan D, Hashmi S, Morrison A, Thomasson A, Nazarian S, et al. Pregnancy-induced sensitization promotes sex disparity in living donor kidney transplantation. J Am Soc Nephrol 2017;28:3025-33.  Back to cited text no. 10
    
11.
Lepeytre F, Dahhou M, Zhang X, Boucquemont J, Sapir-Pichhadze R, Cardinal H, et al. Association of sex with risk of kidney graft failure differs by age. J Am Soc Nephrol 2017;28:3014-23.  Back to cited text no. 11
    
12.
Smith JM, Martz K, Blydt-Hansen TD. Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: A report of the North American pediatric renal trials and collaborative studies. Pediatr Transplant 2013;17:149-57.  Back to cited text no. 12
    
13.
Melk A, Babitsch B, Borchert-Mörlins B, Claas F, Dipchand AI, Eifert S, et al. Equally interchangeable? How sex and gender affect transplantation. Transplantation 2019;103:1094-110.  Back to cited text no. 13
    
14.
Peracha J, Hayer MK, Sharif A. Gender disparity in living-donor kidney transplant among minority ethnic groups. Exp Clin Transplant 2016;14:139-45.  Back to cited text no. 14
    
15.
Taheri S, Alavian SM, Einollahi B, Nafar M. Gender bias in Iranian living kidney transplantation program: A national report. Clin Transplant 2010;24:528-34.  Back to cited text no. 15
    
16.
Puoti F, Ricci A, Nanni-Costa A, Ricciardi W, Malorni W, Ortona E. Organ transplantation and gender differences: A paradigmatic example of intertwining between biological and sociocultural determinants. Biol Sex Differ 2016;7:35.  Back to cited text no. 16
    
17.
Øien CM, Reisæter AV, Leivestad T, Pfeffer P, Fauchald P, Os I. Gender imbalance among donors in living kidney transplantation: The Norwegian experience, nephrology dialysis. Transplantation 2005;20:783-9.  Back to cited text no. 17
    
18.
Mıhçıokur S, Ayvazoǧlu Soy EH, Türkçelik E, Akın A, Haberal M. Gender disparity and the relationship between living donors and recipients in kidney transplants in an organ transplant center in turkey. Exp Clin Transplant 2019;17:246-9.  Back to cited text no. 18
    
19.
Kayler LK, Rasmussen CS, Dykstra DM, Ojo AO, Port FK, Wolfe RA, et al. Gender imbalance and outcomes in living donor renal transplantation in the United States. Am J Transplant 2003;3:452-8.  Back to cited text no. 19
    
20.
Malattiri R, Kumar NK. Gender disparity in Indian renal transplantation. AJOB Empirical Bioethics 2014;5:1-7.  Back to cited text no. 20
    
21.
Gillespie A, Hammer H, Kolenikov S, Polychronopoulou A, Ouzienko V, Obradovic Z, et al. Sex differences and attitudes toward living donor kidney transplantation among urban black patients on hemodialysis. Clin J Am Soc Nephrol 2014;9:1764-72.  Back to cited text no. 21
    
22.
Zimmerman D, Donnelly S, Miller J, Stewart D, Albert SE. Gender disparity in living renal transplant donation. Am J Kidney Dis 2000;36:534-40.  Back to cited text no. 22
    
23.
August P, Suthanthiran M. Sex and kidney transplantation: Why can't a woman be more like a man? J Am Soc Nephrol 2017;28:2829-31.  Back to cited text no. 23
    



 
 
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