Increased Risk of Kidney Stones in Transgender Women and Gender-Diverse Adults on Gender-Affirming Hormone Therapy: Insights from a Large Database Study.

Introduction: Transgender and gender-diverse (TGD) individuals represent a growing yet underrepresented group in medical literature. Estrogen and antiandrogens are essential in feminizing gender-affirming hormone therapy (f-GAHT) for individuals assigned male at birth (AMAB). This study examines f-GAHT effects on de novo nephrolithiasis risk in TGD individuals AMAB. Methods: This big data study utilizes medical records from the National Institutes of Health's All of Us database. The cohort includes patients AMAB who self-identified as non-binary, female, transgender women or had a relevant gender diagnosis. The cohort was divided into f-GAHT and non-f-GAHT groups. Cumulative incidence was calculated for each group. Participants were subdivided into estrogen-only f-GAHT (e-f-GAHT) and combined estrogen and antiandrogen f-GAHT (c-f-GAHT) groups. Univariate, unweighted multivariate, and weighted propensity score multivariate analyses were used to explore the association between nephrolithiasis and GAHT. Results: A total of 777 patients AMAB met our inclusion and exclusion criteria. The cumulative incidences of kidney stones were 10.3% and 4.8% in the f-GAHT and non-f-GAHT groups, respectively (p = 0.01). Kidney stone odds were 2.53 and 2.76 times greater in the unweighted and weighted regressions for f-GAHT compared with non-f-GAHT patients (p = 0.044 and p < 0.001, respectively). C-f-GAHT was associated with kidney stones in a weighted model (odds ratio [OR]: 2.63, 95% confidence interval [CI]: 1.44, 4.97, p = 0.002), whereas e-f-GAHT was not (OR = 1.88, 95% CI: 0.85, 4.32, p = 0.13). Conclusions: We observed a greater de novo incidence of nephrolithiasis among patients on f-GAHT. Antiandrogen therapy may work synergistically with estrogen to increase nephrolithiasis risk. Patients AMAB should be counseled about increased risk when starting f-GAHT, particularly if antiandrogens are included.