The Utility of Monitoring Potassium in Transgender, Gender Diverse, and Nonbinary Individuals on Spironolactone

Hailey Hayes; Rachel Russell; Amber Haugen; Sneha Nagavally; Jenna Sarvaideo


J Endo Soc. 2022;6(11) 

In This Article

Abstract and Introduction


Context: Current Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia.

Objective: The goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone.

Methods: Using EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin–angiotensin–aldosterone system.

Results: 318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016).

Conclusion: Our data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling.


The cost of healthcare in the United States has been steadily rising for the past 50 years. In 2020, the country spent approximately 4.1 trillion dollars in healthcare expenses.[1] To address the increasing costs, there have been numerous efforts to evaluate and address sources of superfluous healthcare spending, such as unnecessary laboratory testing.[2–4] When determining the need for laboratory testing, many physicians rely on evidence-based clinical practice guidelines. Such is the case regarding potassium monitoring in patients taking the mineralocorticoid receptor antagonist spironolactone.

Spironolactone was initially approved in the 1960s for treatment of heart failure, hypertension, edema, and primary hyperaldosteronism.[5] However, it was found to have anti-androgenic effects leading to its off-label use for acne, female pattern hair loss, and hirsutism.[6] For transgender, gender diverse, and nonbinary (TGDNB) individuals and especially transgender women in the United States, it has become a part of standard hormone therapy.

The Endocrine Society recommends that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter.[7] These guidelines were informed by studies monitoring the effects of spironolactone on heart failure patients, which indicated that spironolactone usage is associated with an increased risk of hyperkalemia within an aging population.[8–10] Conversely, guidelines released by the American Academy of Dermatology indicate that it is not necessary to screen potassium levels in healthy women who are between 18 and 45 years old and taking spironolactone, as studies have shown that the risk of hyperkalemia in this population is low.[11,12] There have been few studies directly investigating the utility of potassium monitoring in young, healthy, TGDNB individuals. Millington et al investigated the use of spironolactone specifically among adolescent transgender females (16–18 years of age) and found that there was no correlation between spironolactone dose and incidence of hyperkalemia.[13] Similarly, SoRelle et al also examined the effect of spironolactone usage on potassium levels in transgender patients through retrospective chart review and found no significant change.[14]

The goal of our study was to evaluate the incidence of hyperkalemia in TGDNB individuals taking spironolactone and to assess whether age is associated with an increased risk of hyperkalemia. We hypothesized that the risk of hyperkalemia in healthy TGDNB individuals aged ≤45 years is low; therefore, the recommended laboratory monitoring guidelines for this group may be unnecessary.