Spironolactone
Spironolactone is an antiandrogen that is often used in feminising hormone treatment to suppress testosterone. As well as suppressing the production of testosterone, spironolactone has some oestrogen-like effects, which makes it a very effective antiandrogen.
Potassium levels
As well as its antiandrogenic effect, spironolactone influences the excretion of the salts sodium and potassium by the kidneys. Specifically, spironolactone inhibits the excretion of potassium, which can result in raised levels of potassium in the blood.
While the majority of people who take spironolactone tolerate it without complications, some people on spironolactone exhibit high levels of potassium in the blood. This is known as hyperkalaemia.
Hyperkalaemia is potentially dangerous, because it can cause irregular heart rhythms, which can be life-threatening. In severe cases, hyperkalaemia can result in fatal cardiac arrest.
For this reason, spironolactone is contraindicated in people with evidence of hyperkalaemia. Also, people who are taking spironolactone are required to have regular blood testing to check their potassium levels.
Assessing potassium levels
Potassium levels can be assessed with a blood test. It is commonly part of the blood test known as urea and electrolytes.
A potassium level of 3.5mmol/l to 5.0mmol/l is considered the target healthy range. Hyperkalaemia is usually defined by a potassium level >5.5mmol/l, while a potassium level >6.5mmol/l indicates severe hyperkalaemia.
What to do if the potassium level is raised
If your potassium level is elevated beyond the healthy reference range (>5.0mmol/l), then you are at risk of hyperkalaemia, and so spironolactone is not recommended for you. If you are taking spironolactone and your potassium level is elevated, it is recommended that you stop taking spironolactone and instead consider a different antiandrogen.
If your blood test confirms hyperkalaemia (>5.5mmol/l), then it is recommended that you seek medical attention immediately or attend the emergency department so that the hyperkalaemia can be treated, as you may be at risk of a heart arrhythmia if it is left untreated.
Alternative antiandrogens
If you have had to stop spironolactone because of hyperkalaemia, alternative antiandrogens are available which do not affect potassium excretion. These include gonadotropin releasing hormone analogues (nafarelin, triptorelin, leuprorelin), 5-alpha reductase inhibitors (finasteride, dutasteride), and cyproterone acetate.
References
Deutsch, M. B. (2016). “Overview of feminizing hormone therapy”. UCSF Transgender Care. https://transcare.ucsf.edu/guidelines/feminizing-hormone-therapy
Dolovich, L., Gavura, S., and Pottie, K. (2005). “Hyperkalemia associated with spironolactone therapy”. Canadian Family Physician, 51: 357–360.
Gupta, P., Suppakitjanusant, P., Stevenson, M., Goodman, M., and Tangpricha, V. (2022). “Potassium Concentrations in Transgender Women Using Spironolactone: A Retrospective Chart Review”. Endocrine Practice, 28: 1113-1117.
Simon, L. V., Hashmi, M. F., and Farrell, M. W. (2023). “Hyperkalaemia”. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK470284/