Usually, gonadotropin releasing hormone analogues (GnRHas) would be used to block puberty. However, the provision of GnRHas for gender dysphoria has been severely restricted in some parts of the world, including the United Kingdom.
Spironolactone is a potential alternative to GnRHas for transfeminine adolescents specifically. Spironolactone has antiandrogenic effects that inhibit some of the pubertal changes in people with testes, so could potentially have a role in their gender affirming medical treatment.
What is spironolactone and how does it work?
Spironolactone is commonly used to treat conditions such as hypertension and heart failure. Spironolactone also produces feminising effects. These include suppression of testosterone production, promotion of oestrogen production, stimulation of oestrogen receptors, and stimulation of progesterone receptors.
How is spironolactone used in gender affirming medical treatment?
Spironolactone has a long history of use as an antiandrogen for transfeminine adults (Prior et al., 1989). It's effective at suppressing testosterone levels and enhancing feminising bodily changes. It's tolerated well, despite being associated with potential risks of low blood pressure and raised potassium levels.
It has also been used to inhibit the pubertal changes in transfeminine adolescents who have testes.
What is the evidence base for spironolactone in transfeminine adolescents?
Two studies have specifically examined the use of spironolactone in transfeminine adolescents.
One looked at potassium levels (Millington et al., 2019). Out of 85 transfeminine adolescents taking spironolactone at doses of 25–400mg daily, only 2.2% exhibited raised serum potassium levels (hypokalaemia).
An earlier study examined 25 transfeminine adolescents who chose spironolactone as an antiandrogen (Khatchadourian et al., 2014). All participants who were taking spironolactone had regular monitoring of their electrolyte levels and all the results remained within the target ranges.
These studies show that spironolactone is reasonably safe for transfeminine adolescents. Because of this, sources list spironolactone as a potential treatment for transfeminine adolescents (Mahfouda et al., 2017 Rosenthal, 2014).
Is spironolactone safe?
As with all medicines, spironolactone has side effects. The most significant side effects are hypotension (low blood pressure) and hyperkalaemia (high serum potassium).
Spironolactone can decrease blood pressure. We recommend having a blood pressure check before starting spironolactone, as well as regular blood pressure monitoring. The systolic pressure must be higher than 90mmHg to proceed with spironolactone.
Spironolactone can increase potassium levels, which can affect the rhythm of the heart. Before starting spironolactone, we recommend having potassium levels checked, along with regular monitoring. Potassium concentration must be in the range of 3.5–5.0mmol/l to take spironolactone.
New symptoms of headache, dizziness, fatigue, confusion, drowsiness, fainting, or decreased urination after starting spironolactone requires urgent medical attention. Anyone taking spironolactone with these symptoms should stop taking it immediately, as these indicate dangerously low blood pressure.
Spironolactone is not recommended in people with moderate to severe kidney disease without agreement by a renal specialist.
References
Khatchadourian, K., Amed, S., and Metzger, D. L. (2014). “Clinical Management of Youth with Gender Dysphoria in Vancouver”. Journal of Pediatrics, 164(4): 906–911.
Mahfouda, S., Moore, J. K., Siafarikas, A., Zepf, F. D., and Lin, A. (2017). “Puberty Suppression in Transgender Children and Adolescents”. Lancet Diabetes and Endocrinology, 5: 816–826.
Millington, K., Liu, E., and Chan, Y. M. (2019). “The Utility of Potassium Monitoring in Gender-Diverse Adolescents Taking Spironolactone”. Journal of the Endocrine Society, 3(5): 1031–1038.
Prior, J. C., Vigna, Y. M., and Watson, D. (1989). "Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism". Archives of Sexual Behavior, 18 (1): 49-57.
Rosenthal, S. M. (2014). “Approach to the Patient: Transgender Youth: Endocrine Considerations”. Journal of Clinical Endocrinology and Metabolism, 99(12): 4379–4389.