Article Text
PDF
Abstract
Background There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations.
Methods Retrospective analysis of pancreatitis incidence rates in transgender and GNC persons exposed and not exposed to gender-affirming hormone therapy (GAHT).
Results 7 of the 1333 patients on hormone therapy had an incidence of pancreatitis. 0 of the 615 patients with no history of GAHT use developed pancreatitis. Representing a 6.96 (95% CI 2.76 to 848.78) for the development of pancreatitis in patients with exposure to GAHT therapy.
Conclusion Clinicians working with GNC individuals should be aware of this possible association
- ACUTE PANCREATITIS
- ADVERSE DRUG REACTIONS
- PANCREAS
Data availability statement
Data are available upon reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
WHAT IS ALREADY KNOWN ON THIS TOPIC
There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming populations.
WHAT THIS STUDY ADDS
6.96 increase in relative risk for the development of pancreatitis for patients exposed to gender-affirming hormone therapy (GAHT) versus no exposure to GAHT was noted over the study period.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Clinicians working with adult patients should be aware of the possible association between GAHT and pancreatitis. Future large multicentre or national population-based analyses to further investigate this association are warranted.
Introduction
A growing appreciation for diversity and inclusion has led to an increased focus on identifying and addressing differences in the healthcare needs of sexual and gender minorities.1–4 Transgender individuals and people born with differences in sex development face even greater difficulties in obtaining compassionate, evidence-based and patient-centred care.2 This is especially pronounced in gastroenterological care, as there are limited evidence-based guidelines to help direct care and limited data on the prevalence and incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations.4
While pancreatitis is one of the most common gastrointestinal disorders encountered clinically, the incidence and prevalence estimates of pancreatitis can vary widely, with varying rates noted across geographical and socioeconomic regions.5 Identification of the incidence and prevalence of pancreatitis in transgender and GNC persons is of particular importance, as there remains significant intersectionality with GNC identity and other factors. These include race/ethnicity, socioeconomic status, culture and class, all of which can influence health behaviours. Two such examples are the use of alcohol and the prevalence of obesity,2–4 both of which are linked to the development of pancreatitis.5 Additionally, several reports have noted the association of gender-affirming hormone therapy (GAHT) with the development of hypertriglyceride-induced pancreatitis.6–8 However, whether these findings are isolated or are a part of a wider population-based phenomenon is unknown.
The aim of this study was to perform an analysis of pancreatitis incidence rates in transgender and GNC persons at our institution.
Methods
Following institutional review board approval, a retrospective chart review of all transgender and GNC persons from 09 January 2017 to 09 January 2022 was performed by the University of Virginia multidisciplinary Gender Health Program. Transgender and GNC persons were identified based on the presence of the following International Calssification of Diseases (ICD) 9 or 10 diagnosis codes (diagnosis of gender dysphoria, female-to-male trans-sexual, male-to-female trans-sexual, trans-sexualism (F64.0) or gender identity disorder not otherwise specified (NOS)). Patients were screened for a history of the diagnosis of acute pancreatitis based on diagnosis of pancreatitis per modified Atlanta criteria (presence of any two of the three parameters (1) characteristic upper abdominal pain, (2) serum amylase or lipase level of more than three times the upper limit of normal or (3) characteristic imaging findings).6 Pancreatitis aetiology was determined based on clinical grounds. Patients with pancreatitis and negative alcohol use history, normal calcium and triglyceride levels and with a lack of common bile duct pathology were deemed to be idiopathic in nature. Clinicodemographic data and a history of (or current use of) GAHT was also obtained. Statistical analysis was performed in R studio (R V.4.3.2, Boston, Massachusetts, USA).
Results
1948 patients were identified over the study period, of which 1333 were noted to have or currently be on GAHT (656 oestrogen or progesterone vs 677 testosterone derivatives). Seven of the 1333 patients on hormone therapy had an incidence of pancreatitis over the 5-year study period. Table 1 depicts the clinicodemographic data of the seven patients with pancreatitis.
Clinicodemographic data of pancreatitis patients
All were on therapy at the time of pancreatitis with a mean duration of use prior to the development of pancreatitis at 2.3 years. Zero of the 615 patients with no history of GAHT use had a history of pancreatitis. The median age for patients on hormone therapy was 28.3 versus 26.5 not on hormone therapy. There was no statistical difference between age, median body mass index (28.3 vs 27.2), smoking history or ingestion of >4 alcoholic drinks per week between patients on GAHT and patients without a history of GAHT (p<0.05).
Four GNC patients assigned female at birth and three GNC patients assigned male at birth were identified. The median age was 33. Five of the seven pancreatitis cases were noted to be idiopathic in aetiology. Four of the seven patients had three out of three modified Atlanta criteria for pancreatitis. Seven of the seven patients were noted to have characteristic imaging findings of pancreatitis. Only one patient had necrotising pancreatitis. Apart from one patient, all other patients had normal triglyceride and calcium levels. No choledocholithasis or cholelithiasis was noted in all patients. Only one patient was noted to have microlithiasis within the gallbladder without the presence of associated common bile duct pathology. Six of seven patients continued GAHT following their diagnosis of pancreatitis. Using a Haldane-Anscombe correction coefficient for zero events of 0.5, the relative risk for the development of pancreatitis in patients on GAHT was 6.96 (95% CI 2.76 to 848.78)
Discussion
To our knowledge, this represents the largest analysis of pancreatitis in a transgender or GNC individuals. The incidence rate of pancreatitis in this patient population is alarming, as with 1.3 million adults and over 300 000 youth identifying as transgender, this increased rate of pancreatitis could represent a significant unaddressed cause of morbidity and even mortality.9
1.3 million adults and over 300 000 youth identifying as transgender, this increased rate of pancreatitis could represent a significant unaddressed cause of morbidity and even mortality.9
The cause for this possible increase in incidence is currently not well established. As no patients were noted to have pancreatitis from the two most common aetiologies (alcohol and gallstone), these findings suggest alternative aetiologies, although surreptitious alcohol use is certainly possible and one patient did have evidence of microlithiasis within the gallbladder. As patients without a history of hormone therapy had no incidence of pancreatitis, hormonal therapy as a possible aetiology should be entertained. While previous reports have noted the association of GAHT with the development of hypertriglyceride-induced pancreatitis, only one such case was noted in our series. Additionally, while hormone therapy has been commonly associated with drug-induced pancreatitis, a large population-based analysis failed to note a substantial association between acute pancreatitis and the use of postmenopausal hormone therapy.10 It is unclear if GAHT is causal or serves as a proxy marker for yet unidentified alternative aetiology that contributes to the development of pancreatitis. However, no significant differences in reported alcohol or smoking history were seen between groups with and without a history of hormone use. Further investigations into this possible association, especially of younger patients on hormonal therapy are warranted.
There are several limitations to our analysis. Being a single-centre analysis, the generalisability of our findings may be limited. Moreover, the overall incidence of pancreatitis in our cohort is relatively low. Recognising the retrospective nature of our data collection, we acknowledge the possibility of missed cases, especially those that are presented outside of our institution. However, it is crucial to note that the potential under-identification of pancreatitis cases could affect both patients with and without GAHT exposure, minimising the impact on the comparative analysis between the two groups. Additionally, caution should be employed in interpreting the above incidence analysis as there exists possible selection bias that may overestimate the total risk of pancreatitis, as our analysis is unable to capture healthy GNC individuals that again do not present to our institution over the study period. Additionally, any incidence determinations likely underestimate the total population of transgender individuals, as patients may not reliably disclose their transgender status in their medical records and reliance on ICD coding for strict inclusion criteria has widely reported limitations. However, our institution has one of the nation’s only comprehensive, multidisciplinary Gender Health Program, with many transgender patients choosing our institution, specifically due to the perception of increased safety. Moreover, as hormone therapy necessitates a prescription, coupled with the low overall incidence of drug-induced pancreatitis (~ 0.1 and 2% of all pancreatitis cases),10 and that subclinical episodes of acute pancreatitis are rare, it is possible that this represents a true increase in relative risk over traditional population estimates.
The authors additionally would like to highlight that although our analysis suggests that GAHT may be associated with an increased risk of AP, these results are too preliminary to recommend withholding or restricting access to GAHT from persons or populations where it is indicated. However, given that transgender and GNC individuals make up 0.5% of US adults, clinicians working with adult patients should be aware of this possible association. Future large multicentre or national population-based analyses to further investigate this association are warranted.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
University of Virginia IRB - HSR # 24082.
Acknowledgments
A version of these results was presented at Digestive Disease Week Conference in Chicago, Illinois, May 2023.
Footnotes
X @Alexander.podboy
Contributors AP: contributed to the conception of the manuscript, interpretation of data, critical revision and final approval of the manuscript. Responsible for the overall content as guarantor. CC, RCDB, DSS, VMS and AYW: contributed to the conception of the manuscript, interpretation of data, critical revision and final approval of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.