Sex-Specific Organ Transplantation Rate
Of donors from whom no organs were transplanted during the study period (11.5%, n=7182), 60.9% were male donors. Of donors from whom organs were transplanted, the crude transplantation rate from male donors was 2.92 (95% confidence interval [CI]: 2.90–2.94) organs per donor compared with 2.69 (95% CI: 2.68–2.72) organs per female donor (P<0.001; Table 2). However, this higher transplantation rate from male donors was predominantly due to the increased prevalence of young male donors. Of donors younger than 35 years, a mean of 3.89 (95% CI: 3.86–3.91) organs were transplanted from a male donor compared with 3.56 (95% CI: 3.52–3.61) organs from a female donor. In contrast, this sex difference reversed direction among donors older than 35 years, such that males contributed fewer organs per donor than female donors (male vs. female, 2.27 vs. 2.44, rate ratio (RR) 0.93; P<0.001).
Of brain-dead donors (97.5%), there was a mean of 2.95 organs transplanted per male donor compared with 2.71organs transplanted per female donor (P<0.001). Of donors younger than 35 years, there was a higher rate of organ transplanted per male donor compared with female donor (3.92 organs per male donor vs. 3.59 organs per female donor, P<0.001). Of older donors, this finding reversed direction such that there was a higher rate of transplantation from female donors (2.29 organs per male donor vs. 2.45 organs per female donor, P<0.001). Of the 1570 donors who donated following cardiac determination of death, a mean of 1.99 organs were transplanted per male donor compared with 1.85 organs per female donor (P=0.016).
Age-standardized transplantation rate declined steadily from 1994 until 1998 in both men and women, reaching a plateau between 1999 and 2002, after which the transplantation rate continued to decline (P<0.001 for both the sexes; Fig. 1). Nevertheless, the age-adjusted rate of transplantation from men was lower: men versus women, 2.78 vs. 2.85; RR 0.97; P<0.001. This sex disparity in transplantation also persisted when adjusted for differences in donor age, race, BMI, blood type, comorbidity, year of transplantation, mechanism of death, and hormonal therapy such that male sex was independently associated with 3% lower organ transplantation rate compared with female sex (adjusted rate ratio [ARR], 0.97, 95% CI: 0.96–0.98; P<0.001; Fig. 2). We found no significant interaction between donor age and gender.
Other predictors of lower adjusted rate of transplantation included age, non-white race, higher BMI, donor comorbidity, and mechanism of death (Fig. 2). In contrast, every 3-year increase in time after 1994 (ARR 1.03; 95% CI: 1.02–1.03; P<0.001), therapy with corticosteroid (ARR, 1.08, 95% CI: 1.06–1.09; P<0.001), and thyroid hormone (ARR, 1.05, 95% CI: 1.04–1.06; P<0.001) were associated with higher adjusted rate of organ transplantation.
Sex-Specific Transplantation Rate by Organ Type
Of individual organs, a higher proportion of heart (68.4% vs. 31.6%, P<0.001), lung (59.6% vs. 40.4%, P=0.002), kidney (59.3% vs. 40.7%, P<0.001), liver (58.9% vs. 41.1%, P<0.001), and pancreas (66.2% vs. 33.8%, P<0.001) were transplanted from male donors (see Table, SDC 3, http://links.lww.com/TP/A538). Figure 3 shows the longitudinal analysis of age-adjusted sex differences in organ transplantation by organ type. Among heart transplantation, the sex disparity persisted when adjusted for differences in age such that men were 20% more likely to donate hearts (age-adjusted RR 1.20; 95% CI: 1.17–1.22; P<0.001; Fig. 3). In contrast, however, this finding reversed direction among other organs such that when adjusted for differences in age, men donated a lower proportion of lungs (age-adjusted RR 0.81; 95% CI: 0.78–0.84; P<0.001), kidney (age-adjusted RR 0.98; 95% CI: 0.98–0.99; P<0.001), and liver (age-adjusted RR 0.98; 95% CI: 0.97–0.99; P<0.001).
When adjusted for differences in donor demographics, BMI, blood type, year of transplantation, and mechanism of death, a 16% higher proportion of heart (ARR 1.16; 95% CI: 1.13–1.18; P<0.001) and 7% higher proportion of pancreas (ARR 1.07; 95% CI: 1.03–1.10; P<0.001) were transplanted from male donors. In contrast, this sex difference reversed direction among all other organs such that a 20% lower rate of organs were transplanted for lung (ARR 0.80; 95% CI: 0.77–0.83; P<0.001), 1% for liver (ARR 0.99; 95%CI: 0.98–1.0; P<0.001), and 1% for kidney (ARR 0.99; 95% CI: 0.98–1.0; P<0.001) from male donors compared with female donors.
We found a sex disparity in the prevalence of deceased donors and in the rates of solid-organ transplantation in the United States. During the 12-year study period, despite a 1.5-fold higher prevalence of male donors, the transplantation rates from male donors were lower compared with that from female donors. This lower rate of transplantation was evident by 35 years of age and was persistent thereafter. After accounting for differences in demographics, donor chronic health characteristics, and processes of care, male sex was independently associated with a modestly lower rate of transplantation. This lower rate of transplantation was predominantly due to greatly decreased proportions of lung, and slightly lower liver, and kidney transplantation. In contrast, however, the proportion of heart and pancreas transplantation from male donors was higher. This study, to our knowledge, is the first to document lower covariate-adjusted transplantation rates from deceased male donors in the United States. Our findings are important given organ shortage and massive national efforts to increase organ recovery rates.
We were intrigued by these findings and considered whether the higher prevalence of male sex was explained by donor demographics, high-risk behavior, or mechanism of death. We found, however, similar sex distribution of donor demographic characteristics with the exception of age: male donors were on average 6 years younger than female donors with most of them younger than 35 years of age. Among these young male donors, we found a twofold higher prevalence of drug abuse and trauma-related death and a fivefold higher prevalence of lethal gunshot injury. Together, these findings suggest that young males were more likely to engage in high-risk lifestyles that could have accounted for higher mortality at young age and thus increased male sex prevalence.
Despite higher male prevalence, we observed a modest, yet significantly lower transplantation rate from men that persisted after controlling for most confounding factors. The overall lower adjusted rate of transplantation from male donors was predominantly due to a significantly lower proportion of lung, and modestly lower proportion of liver and kidney transplantation, which was prevalent throughout the study period. Our findings have significant implications because mitigation of the 3% difference in transplantation rates from male and female donors would result in additional recovery of organs.
We also found a higher rate of heart and pancreas transplantation from male donors. The greater proportion of heart transplantation from males could be attributed to a threefold greater prevalence of male candidates on waiting list, because same-sex heart transplantation has shown to improve recipient outcome compared with opposite sex transplantation (8). A higher rate of pancreas transplantation could be attributed to a lower prevalence of diabetes. However, in contrast, a lower rate of lung transplantation from men could be due to a combination of a higher prevalence of smoking (Table 1), size matching, and a higher prevalence of female candidates (1). Because lungs are size matched and sex matched to some extent (9), these factors might have contributed to a lower rate of lung transplantation from men.
We also found a lower rate of kidney and liver transplantation from men. The lower rate of kidney donation from men could potentially be due to a higher serum creatinine (because of increased muscle mass) compared with female donors resulting in nondonation (mean serum creatinine, male vs. female: 1.56±1.97 vs. 1.22±1.65, P<0.001). A number of unmeasured factors such as higher prevalence of alcohol and drug abuse and a positive hepatitis serology might have also contributed to a lower liver utilization from male donors.
There are important limitations to our study. First, we excluded deceased donors with missing data from our analysis that could have introduced a misclassification bias. Variables have been increasingly collected throughout the life of the UNOS database resulting in missing data for potentially relevant predictors such as BMI and mechanism of death. Given the overall high numbers of patients included in the analyses, we do not think that the frequency of missing values significantly impacted our results. Supporting this, we found no difference in the prevalence of donors by sex between our analysis cohort and that reported for all donors by the UNOS.
Second, we were unable to evaluate the influence of sex on the susceptibility to brain death and on the consent rates in our study because these data are not captured by the UNOS. Certainly, an increased male susceptibility to brain death and a higher consent rate for organ donation by males could have accounted for a higher prevalence of male donors. Nevertheless, given that the donation status is conditioned on brain death, and given the fact that most donor consent for transplantation is from surrogate consent after death (10, 11), it is unlikely that prior consent rates biased our estimates of donor prevalence. Third, we were unable to evaluate the wide variability that exists in the acceptance of an organ for transplantation depending on the preferences of the transplantation team and availability of suitable recipients, which could have affected transplantation rates. For instance, we did not account for transplant surgeon's decision to use or not to use an organ. We were also unable to evaluate whether a lower proportion of lung transplantation from men was due to lack of recipients of suitable size. However, we would not expect these factors to affect transplantation rates by sex because currently there is no a priori criteria whether to use or not to use an organ by sex.
Our study also has several strengths. Being a large and nationally representative dataset, we were able to detect small, yet important sex differences in transplantation rates and analyze longitudinal trends over a 12-year study period. Our findings are important given the severe shortage of organs (1) and national efforts to increase organ availability for transplantation (12, 13). We were able to control for many donor factors such as demographics, biometric profile, mechanism of death, and process of care variables that could have impacted transplantation rates. Given the size of our dataset, we were able to assess sex differences by individual organs with the exception of intestinal transplantation and discover differences in transplantation trends over time.
In summary, in this large-scale analysis, we found that when adjusted for differences in donor characteristics and processes of care, male sex was independently associated with overall lower rate of organ transplantation. Of individual organs, transplantation of lung, liver, and kidney from male donors was lower. In contrast, among female donors, transplantation of heart and pancreas was lower than male donors. Whether these sex differences reflect residual confounding or signal biologic differences in organ function after death need to be further clarified.
MATERIALS AND METHODS
Data Sources and Donor Selection
We conducted an analysis of the UNOS Standard Transplant Analysis and Research files from January 1994 through December 2005. We obtained deceased donor and organ transplantation data and constructed a dataset based on known mechanism of death, geographic representation, data quality, and availability. For each donor, we abstracted information pertaining to demographics (age, sex, and race), comorbid conditions, mechanism of death, blood type, biometric information, processes of care, number, and type of organs transplanted.
We selected donors 17 years of age or older and excluded donors in whom organs were recovered outside the United States or in whom the residential status was missing. We excluded donors with inconsistent coding of BMI (i.e., BMI<10 or >60 kg/m2) or missing data from the analysis. We categorized the range of solid organs that could be transplanted from a donor from 0 to 8 organs. Organs included heart, lungs, liver, intestine, pancreas, and kidneys. A value of 0 indicates that none of the organs was used for transplantation. A bilateral lung, double kidney, or segmented liver that was transplanted into a single recipient was counted as one organ. A bilateral lung, double kidney, or segmented liver that was transplanted into two different recipients were counted as two organs. The study was reviewed and approved by the Committee for Oversight of Research Involving the Dead at the University Of Pittsburgh, Pittsburgh, Pennsylvania. The requirement for written consent was waived by the committee.
Comparison of Donor Characteristics
We compared baseline characteristics between male and female donors using chi-square test for categorical variables (e.g., race, BMI, and mechanism of death) with continuity correction or Wilcoxon rank-sum test for continuous variables that were not normally distributed.
Estimating Prevalence of Donors and Rates of Transplantation
We estimated sex-specific prevalence of donors using proportions and crude age- and sex-specific rate of organ transplantation per donor by averaging the number of organs transplanted. We generated direct age-adjusted estimates of rate of organ transplantation using the study donors as the standard population. We subsequently compared temporal trends of sex differences in the prevalence of organ donors, rates of organs transplanted per donor, and type of organ transplanted from 1994 through 2005. We excluded intestinal transplantation from the analysis of sex-specific temporal trends because of small sample size.
Regression Analysis of Mean Organs Transplanted
We used log-linear regression (Poisson) with the number of organs transplanted as the outcome to compare the transplantation rates across different subgroups (e.g., men vs. women). Similarly, multivariable log-linear model was used to test for case mix differences that may have affected organ transplantation rates. We accounted for differences in donor demographics, mechanism of death, underlying donor comorbidity, BMI, blood type, hormonal therapy, and year of donation. In the Poisson regression model, the natural log of the mean number of organs transplanted is assumed to be a linear function of the donor characteristics.
Longitudinal Analysis of Rates of Transplantation
For testing the trends in age-adjusted rates of individual organ transplantation, separate regression models were fitted with age-adjusted rates as the dependent variable, and sex and year (centered to 2000), and sex and year interactions as the independent variables to see if there was a significant change in the rate of organ transplantation over time, and if so, whether the change was similar or different across male and female donors. We allowed for polynomial terms in the models to account for possible fluctuations.
Analysis of Individual Organs Transplantation
To assess the association between baseline donor characteristics and transplantation rate of individual organs, we used relative risk regression with transplantation (coded as 1, if transplanted; 0, otherwise) as the dependent variable. Use of relative risk regression provides the opportunity to obtain relative risk estimates adjusting for other donor characteristics. For all analyses, the level of statistical significance was assumed to be 5% and was performed using statistical software package SAS 9.1 (SAS, Cary, NC).
The authors thank the United Network for Organ Sharing who provided data for analysis. The data reported here have been supplied by the United Network for Organ Sharing as the Contractor for the Organ Procurement and Transplantation Network (OPTN). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government.
1. United Network for Organ Sharing: United States facts about transplantation
. Richmond, VA. Available at: www.unos.org
. Accessed April 22, 2011.
2. Sheehy E, Conrad SL, Brigham LE, et al. Estimating the number of potential organ donors in the United States. N Engl J Med
2003; 349: 667.
3. Badovinac K, Greig PD, Ross H, et al. Organ utilization among deceased donors
in Canada, 1993–2002. Can J Anaesth
2006; 53: 838.
4. Evans RW, Orians CE, Ascher NL. The potential supply of organ donors. An assessment of the efficacy of organ procurement efforts in the United States. JAMA
1992; 267: 239.
5. Murugan R, Venkataraman R, Wahed AS, et al. Increased plasma interleukin-6 in donors is associated with lower recipient hospital-free survival after cadaveric organ transplantation
. Crit Care Med
2008; 36: 1810.
6. Marino IR, Doyle HR, Aldrighetti L, et al. Effect of donor age and sex
on the outcome of liver transplantation
1995; 22: 1754.
7. Thompson TL, Robinson JD, Kenny RW. Gender
differences in family communication about organ donation. Sex Roles
2003; 49: 587.
8. Weiss ES, Allen JG, Patel ND, et al. The impact of donor-recipient sex
matching on survival after orthotopic heart transplantation
: Analysis of 18 000 transplants in the modern era. Circ Heart Fail
2009; 2: 401.
9. International Society of Heart and Lung Transplantation
Registry; Sato M, Gutierrez C, Kaneda H, et al. The effect of gender
combinations on outcome in human lung transplantation
: The International Society of Heart and Lung Transplantation
Registry experience. J Heart Lung Transplant
2006; 25: 634.
10. Zink S, Wertlieb S. A study of the presumptive approach to consent for organ donation: A new solution to an old problem. Crit Care Nurse
2006; 26: 129.
11. Truog RD. Consent for organ donation—Balancing conflicting ethical obligations. N Engl J Med
2008; 358: 1209.
12. Jacobbi LM, McBride VA, Etheredge EE, et al. The risks, benefits, and costs of expanding donor criteria. A collaborative prospective three-year study. Transplantation
1995; 60: 1491.
13. Alexander JW, Vaughn WK, Carey MA. The use of marginal donors for organ transplantation
: The older and younger donors. Transplant Proc
1991; 23: 905.
Deceased donors; Transplantation; Sex; Gender; UNOS
Supplemental Digital Content
© 2011 Lippincott Williams & Wilkins, Inc.