Background

Puberty blockade is an important part of gender affirming medical care for many trans adolescents. Usually, gonadotropin releasing hormone analogues (GnRHas) would be used to inhibit pubertal changes. However, the provision of GnRHas for gender dysphoria has been severely restricted in some parts of the world, including the United Kingdom.

This article examines spironolactone as a potential alternative to GnRHas for transfeminine adolescents specifically. Spironolactone has some antiandrogenic effects that inhibit some of the pubertal changes in people with testes, and so could potentially have a role in the gender affirming medical treatment of transfeminine adolescents.

What is spironolactone and how does it work?

Spironolactone is a medication that is commonly used to treat conditions such as hypertension and heart failure. Spironolactone also produces feminising effects through several mechanisms. 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 as part of feminising hormone treatment in trans women and transfeminine adults (Prior et al., 1989). It is effective at suppressing testosterone levels and enhancing feminising bodily changes. It is also tolerated well, despite being associated with potential risks of low blood pressure and raised serum potassium.

Given its safety profile and its established effectiveness at supporting feminisation in transfeminine adults, spironolactone 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.

A recent study examined the safety of spironolactone in transfeminine adolescents, specifically with regards to serum potassium levels (Millington et al., 2019). Out of 85 transfeminine adolescents who were taking spironolactone at doses of 25–400mg daily, only 2.2% exhibited raised serum potassium levels, or hypokalaemia.

An earlier study examined 25 transfeminine adolescents who chose spironolactone as an antiandrogen instead of GnRHas (Khatchadourian et al., 2014). All participants who were taking spironolactone had regular monitoring of their serum electrolytes and all the results remained within the target ranges.

The above studies provide evidence that spironolactone is reasonably safe and tolerated well in transfeminine adolescents. Accordingly, sources list spironolactone as a potential treatment option 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. Accordingly, it is recommended that the person's blood pressure is checked before commencing spironolactone. Regular monitoring of blood pressure during treatment is also recommended. The systolic pressure must be higher than 90mmHg to proceed with spironolactone.

Spironolactone can increase the level of potassium in the body, which can affect the rhythm of the heart. Accordingly, the person must have had a blood test to check serum potassium prior to commencing spironolactone. Regular monitoring of serum potassium during treatment is also recommended. The serum potassium concentration must be in the satisfactory range of 3.5–5.0mmol/l to proceed with spironolactone.

If the person experiences any new symptoms of headache, dizziness, fatigue, confusion, drowsiness, fainting, or decreased urine output after commencing spironolactone, then it is important to seek urgent medical attention and to stop taking spironolactone, as the symptoms could indicate a dangerously low blood pressure.

Spironolactone is not recommended in people with moderate to severe kidney disease without agreement by a renal specialist.

Conclusion

Spironolactone is a potential option for an antiandrogen in transfeminine adolescents when GnRHas are not available. Based on evidence from research on trans women, spironolactone is effective at suppressing testosterone and promoting the feminising effects of oestrogen. Research on transfeminine adolescents provides evidence that spironolactone is reasonably safe and tolerated well. However, given the risks of hypotension and hyperkalaemia, regular monitoring of blood pressure and serum potassium before and during treatment is recommended for everyone taking spironolactone.

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.