For transgender women, taking pills of estradiol is insufficient to counteract the endogenous levels of testosterone produced by their bodies. To counteract the undesired testosterone, anti-androgens are employed. These include cyproterone acetate (approved only in Europe) or spironolactone. Spironolactone is a potassium sparing diuretic that could have unintended consequences like gynecomastia.1 This effect comes from off-target binding of spironolactone to the androgen receptor. Like the intended spironolactone target (mineralocorticoid receptor), the androgen receptor localizes to the nucleus when activated and acts as a transcription factor. Taking daily high doses of spironolactone (100mg- 300mg daily) has been shown to be safe,1 but can increase Potassium levels. In a cohort of 55 transgender women, potassium was actually not higher (Figure 1).2 This was the first time a study had rigorously measured electrolytes like potassium in transgender patients. Current guidelines recommended checking electrolyte levels in transgender women taking spironolactone.3 Full electrolytes were included for 126 TW in our study and what we found was not what we were expecting.4
We found no increased potassium levels in TW who had taken hormone therapy for at least 6 months (p>0.05). However, we did see a decrease in sodium which is consistent with the diuretic effect (p<0.0001, Figure 2).
We wondered if variability in spironolactone dosing could explain why no significant potassium change was found. Luckily, we had a large number of patients who were taking various doses of spironolactone for comparison. One-way ANOVA with Tukey post-hoc tests revealed no difference in potassium levels (p>0.05)- even between the lowest (0mg daily) and highest dose (200-300 mg daily) (Figure 3). While the sodium level trended to decrease with higher spironolactone, it was not statistically significant.
One reason that potassium levels did not increase is a difference in study populations. The original population studied for spironolactone involved patients with heart failure and hypertension whereas our study’s population was mostly in their 20’s and 30’s with very few co-morbid conditions.
Although sodium levels are decreased, they did not fall below the lower limit of normal (135 mmol/L). Low sodium would put transgender women at risk of dizziness and syncope (passing out) from low blood pressure. Thus, the takeaway is: sodium should be clinically monitored as it can decrease in transgender women.
- Clark E. Spironolactone Therapy and Gynecomastia. JAMA. 1965;193(2):163-164.
- Roberts TK et al. Interpreting Laboratory Results in Transgender Patients on Hormone Therapy. The American Journal of Medicine. 2014; 127(2): 159-162.
- Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2017
- SoRelle JA, Jiao R, Gao E et al. Impact of Hormone Therapy on Laboratory Values in Transgender Patients. Clin Chem. 2019; 65(1): 170-179.
-Jeff SoRelle, MD is a Molecular Genetic Pathology fellow at the University of Texas Southwestern Medical Center in Dallas, TX. His clinical research interests include understanding how the lab intersects with transgender healthcare and advancing quality in molecular diagnostics.