A 2020 review evaluated the evidence on the effect of gender-affirming hormone therapy on serum creatinine concentration and lean body mass. The authors observed the optimal approach to use creatinine clearance (CrCl) and ideal body weight (IBW) calculations in patients receiving hormonal gender-affirming therapy remains unclear. The effect of hormone therapy on muscle and fat distribution, and thus on CrCl and IBW calculations is unknown. In order to properly dose medications in transgender patients, a consistent recommendation for estimating CrCl and IBW is needed. Therefore, studies were identified which evaluated changes in metabolic laboratory values in transgender patients receiving hormone therapy compared to those of cisgender patients. [1, 2]
An observational, cross-sectional study of transgender women (male-to-female transition) who completed gender affirmation surgery and have taken estrogen therapy for at least two years prior to surgery found that median lean body mass was lower in transgender women than in cisgender men (51.2 kg vs 61.8 kg; p<0.001) and median serum creatinine (SCr) was also lower in transgender women (0.78 mg/dL vs 0.94 mg/dL; p<0.001). The study concluded that after gender transition, biometrics are more so similar to gender identity than sex at birth in transgender women after prolonged hormone therapy. [1]
A retrospective cohort study of transgender women and transgender men (female-to-male transition) using gender-affirming hormone therapy found that transgender women did not experience a significant change in body mass index (BMI), and SCr decreased from a baseline mean of 0.9 mg/dL to 0.85 mg/dL at follow up (p<0.05). Transgender men had a mean increase in BMI from 28.1 to 30.1 (p<0.05) and mean SCr increase from 0.73 mg/dL to 0.87 mg/dL (p<0.05). This study noted that both transgender women and transgender men experienced biomarkers changes used to calculate CrCl and IBW as soon as three months after initiation of hormone therapy. A prospective cohort study compared body weight and laboratory values before and after transgender women and transgender men had been on gender-affirming hormone therapy for four months. Mean SCr decreased in transgender women (0.97 mg/dL to 0.89 mg/dL; p<0.001) and increased in transgender men (0.87 mg/dL to 0.96 mg/dL; p<0.001). Lean body mass did not significantly decrease in transgender women (56.9 to 56.6; p= 0.56), however did increase significantly in transgender men (44 kg to 48.1 kg; p<0.001). Moreover, the mean total BMI increased in transgender women (21 to 21.9; p= 0.005) and transgender men (21.9 to 23.2; p<0.001). The study additionally showed that SCr more closely resembles gender identity than sex at birth. Another cross-sectional study of transgender women, who have been receiving estrogen therapy for at least six months, compared laboratory values (2.5th and 97.5th percentiles) to those of cisgender men and women. The percentile range for SCr in transgender women (0.55 to 1.3 mg/dL) was more similar to that in cisgender men (range 0.73 to 1.3 mg/dL) than in cisgender women (range 0.65 to 1 mg/dL). [1]
The literature summary indicates that after hormone therapy, transgender patients’ physiology reflects their gender identity more than their sex at birth. The authors recommend six months of gender-affirming therapy as the appropriate time interval before calculating CrCl and IBW according to gender identity; this is based on the time in which amenorrhea, which is a marker of successful masculinization in transgender men, most commonly occurs. The authors note that the literature provides inconsistent results of the degree of physiologic change, however this may be due to the small sample sizes, observational design of the studies, variation in human physiology, and differences in duration of hormone therapy. [1]
A letter in response to this review identifies additional considerations when assessing renal function in transgender patients including medical conditions, reproductive organ status, and medication compliance; as these factors may affect both physical goals and hormone levels. They also note that more accurate measurements of renal function may be required to appropriately manage and assess primary medical problems. [2]
A 2021 narrative review evaluated the existing literature regarding the provision of care to transgender men and women with chronic kidney disease (CKD), including dialysis and transplant, to identify specific issues related to gender-affirming therapy and chronic disease management. In general, there are two main objectives of gender-affirming hormone therapy: to decrease the levels of endogenous sex hormones and their associated secondary sex characteristics of the sex assigned at birth and to replace and shift the individual's biochemical sex hormone configuration to reflect their affirmed gender to mimic physiology as best as possible. These objectives are guided by the individual’s gender-affirming goals, while minimizing potential risks based on the clinical scenario and presence of medical comorbidities. For transgender men, exogenous testosterone therapy leads to masculine changes that typically can include voice deepening, menstrual suppression, facial and body hair growth, and increased muscle mass; body composition typically changes as body weight, and lean body mass can increase, while body fat can decrease. Female hormone therapy typically involves using exogenous estradiol which can suppress endogenous testosterone production; therapy typically leads to skin softening, breast development, decrease in body hair, increased body fat, and decreased lean body mass. Gender-affirming surgeries can also be considered, but guidelines recommend first having used hormone therapy continuously for one year and having successfully been living full-time in one’s affirmed gender role for one year as these surgeries are generally irreversible. [3]
Estimating glomerular filtration rate (GFR) is routinely estimated using creatinine and equations developed from linear regression models, including the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, both of which include sex as a covariate. Estimations using these equations are problematic in the setting of gender-affirming hormone therapy due to body composition changes, muscle mass changes, and change in SCr; however, whether there are true differences in actual GFR is unknown. Lean body mass and SCr tend to increase in transgender men and decrease in transgender women; though the clinical relevance of these changes is unknown. Cystatin C may be less affected by hormone therapy, however it is unknown if there are any differences in transgender persons compared to cisgender persons. One case report in a 36-year old transgender male showed a higher 24-hour urine for CrCl (92 mL/min) than estimated by the CKD-EPI equation using either sex (male: 81 mL/min/1.73m2; female: 61 mL/min/1.73m2); the patient’s creatinine also increased from 0.94 mg/dL to 1.3 mg/dL following 2 years of testosterone use. Due to the lack of data, the authors recommend that both male and female sexes be inputted into eGFR equations for transgender persons on gender-affirming hormone therapy to provide a range that can be narrowed by deciding which value likely represents the muscle mass of the patient to which the calculations were applied. If an accurate eGFR measurement is needed, they recommend using non-creatinine exogenous filtration markers (such as iothalamate or iohexol), however this may not be routinely feasible in clinical practice. For transgender persons not on hormone therapy, since their muscle mass is likely reflective of their sex assigned at birth, it is recommended that sex assigned at birth be used for all eGFR equations. [3]
A 2019 retrospective chart review evaluated the impact of hormone therapy (HT) on common laboratory values in transgender individuals identified at clinics at an urban county hospital and community clinic. Laboratory values were divided into four groups based on sex assigned at birth and duration of hormone therapy: transgender women taking HT > 6 months, transgender men taking HT > 6 months, transgender women with sex assigned male at birth with no history of hormone use and transgender men with sex assigned female at birth with no history of hormone use. To assess the magnitude of differences in laboratory values pre- and post-HT, the effect size was calculated using Cohen’s d index, which is a measure of the difference between two means relative to pooled standard deviation of two groups; d <0.5, d = 0.5-0.8, and d > 0.8 indicate small, moderate, and large effect sizes, respectively. Overall, 183 transgender women and 119 transgender men were identified who had laboratory data available; 87 transgender women and 62 transgender men had baseline laboratory data and data were available for 133 transender women and 89 transgender men on HT for >6 months. A significant decrease in creatinine concentrations for transgender women taking estradiol compared with baseline was observed (p<0.0001; d= 0.59); the mean creatinine concentration did not decrease to concentrations seen in the baseline transgender men group. Creatinine values in transgender men taking testosterone increased from baseline values (p<0.0001; d= 1.32) to match those observed in the baseline transgender women group (p> 0.05). No significant change in BUN concentrations in both transgender women and transgender men compared with baseline groups were identified (p> 0.05). While the study indicates significant creatinine changes in transgender men and women taking hormone therapy, correlation with actual changes in renal function was not assessed. [4]