Effect on Kidney Function During Gender Affirming Hormonal Treatment in Transgender Individuals

Background: Accurate interpretation of laboratory values with sex-specific reference ranges presents a challenge in transgender individuals on gender affirming hormone therapy (GAHT). Creatinine (Cr), the most common marker used for kidney function, varies significantly with body mass and composition. Both Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations account for sex in estimating glomerular filtration rate. GAHT can effect Cr values in 2 potential ways: 1) by causing changes in muscle mass and body fat redistribution as early as 3 months after GAHT initiation and 2) by direct effects of sex hormones on kidney function. Previous studies have shown Cr values approaching affirmed gender identity as early as 6 months when on GAHT without mention of sex steroid levels. In this study we sought to describe the changes in serum Cr after initiation of GAHT in an effort to better understand expected changes and interpretation of lab data in TG individuals. Methods: A retrospective chart analysis on all adult TG patients initiated on GAHT at our institution from January 2011 to 2020 was completed. We reviewed demographics, baseline health information, body mass index, and lab values including Cr, sex hormone levels, A1C, and fasting blood glucose. Lab values were obtained prior to GAHT, at the start of GAHT, at 3, 6, and 12 months after GAHT. Matched pair testing was conducted with sex steroid levels and Cr values in transgender men (TM) on testosterone and transgender women (TW) on estradiol in order to compare the median pre GAHT Cr to median Cr levels at 3, 6, and 12 months. Results: 84 TW with a median age of 30 and 24 TM with a median age of 23 were included for analysis. TW and TM had a low rate of existing kidney disease (4.9%, 0%), diabetes mellitus (4.8%, 0%), and hypertension (10.8%, 4.5%) respectively. TW on GAHT achieved a goal estradiol level (≥100 pg/ml) at a rate of 37.3%, 51.7%, and 71.1% and suppressed testosterone to a goal level (<60ng/ml) at a rate of 44.4%, 54.7%, and 76.5% at 3, 6, and 12 months respectively. There was no significant change in Cr values at 3 months, but significantly decreased on average by -0.07 (p<0.001) at 6 months, and by -0.09 (p<0.001) at 12 months. TM on GAHT achieved a goal testosterone level (≥240 ng/dl) at a rate of 64.3%, 80.0%, and 72.3% at 3, 6, and 12 months respectively. Cr values increased significantly on average by 0.14 (p=0.036) at 3 months, by 0.21 (p=0.004) at 6 months, and by 0.15 (p=0.003) at 12 months. Conclusions: In TW on GAHT, clinicians can consider using affirmed gender Cr reference ranges as early as 6 months. Similarly in TM on GAHT, affirmed gender Cr reference ranges can be used as early at 3 months. It remains to be seen whether changes in Cr levels reflect changes in sex steroid levels or sex steroid direct effects. Additionally, research is needed to determine if change in Cr levels reflect true changes in GFR.