GnRH agonists are a class of drugs sometimes used as part of medical transition for trans people in order to block the sex hormones produced by their own bodies (Hembree et al., 2017). These are long-acting medications, typically given as a depot injection or as a subcutaneous implant. Lupron injections and histrelin implants have been used as puberty blockers for trans youth (Stevens, Gomez-Lobo, & Pine-Twaddell, 2015), and Decapeptyl and Zoladex have been used (particularly in the UK) to block testosterone in adult trans women and estrogen and progesterone in adult trans men (NGICNS, 2016). While individual treatment needs can vary – for instance, trans women will often instead take other testosterone blockers like spironolactone, and trans men may only need testosterone to suppress their estrogen – GnRH agonists are generally very effective at eliminating the body’s production of these hormones, clearing the way for cross-sex hormones to produce their desired effects.
One issue with GnRH agonists stems from their mechanism of action in regulating hormones. These medications essentially mimic the action of the body’s own gonadotropin-releasing hormone and stimulate the same receptors, resulting in an increase in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). While GnRH agonists cause the GnRH receptors to downregulate after a few weeks and shut down the body’s production of testosterone or estrogen, this initial release of LH and FSH can cause what’s known as a “flare effect”, a surge in the release of exactly the sex hormones that trans people don’t want (Magon, 2011). This effect is particularly concerning in cases where GnRH agonists are used for chemical castration in cis men with androgen-sensitive prostate cancer – other medications are often needed to blunt the initial flare of testosterone and keep this from causing progression of their disease (Pokuri et al., 2015).
More recently, a related class of medications known as GnRH antagonists have been developed. Rather than initially stimulating GnRH receptors and later causing downregulation, these antagonists have an opposite effect and directly block GnRH receptors, causing the body to stop producing sex hormones almost immediately without any flare (Weckermann & Harzmann, 2004). Unlike GnRH agonists, GnRH antagonists are not in widespread use for medical transition – but there’s no apparent reason why they couldn’t be. And a publication from earlier this year, outlining an upcoming study of trans people at the Karolinska University Hospital in Sweden, describes exactly this (Wiik et al., 2018). Under the proposed protocol, trans people presenting for treatment would be given an initial dose of the GnRH antagonist degarelix, which the authors say “results in immediate reduction in gonadotropin secretion and brings sex hormone levels (estradiol and testosterone) to castrate levels within 24 [hours]”. This would be followed a month later with depot injection of a traditional GnRH agonist, continued every three months in order to maintain the suppression of sex hormone production.
After reading this, I looked for other uses of GnRH antagonists in trans people and found a case report published in Proceedings of UCLA Healthcare in 2016 (Arasu, 2016). The report describes a trans woman who had unacceptable side effects on spironolactone, and later experienced surges in her testosterone levels when she was switched to a GnRH agonist. Finally, she was put on a monthly dose of degarelix, which provided highly effective suppression of testosterone.
While this may seem like a minor optimization on existing protocols, what it does show is that the field of transgender medicine is advancing all the time. Most hormonal medications do not work this quickly – zeroing out the hormones you don’t want within 24 hours is a big deal for trans people. Current limitations in clinical practice are being addressed, and the care that we receive is being improved upon. At one point testosterone blockers weren’t used in trans women at all; at one point blocking puberty in trans youth wasn’t even known to be possible; at one point there weren’t any medications that could eliminate the production of sex hormones immediately. In the words of a great movie: Imagine what you’ll know tomorrow. ■
References
- Arasu, A. (2016). Clinical vignette: transgender care. Proceedings of UCLA Healthcare, 20. [Full text]
- Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., . . . T’Sjoen, G. G. (2017). Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 102(11), 1–35. [Abstract]
- Magon, N. (2011). Gonadotropin releasing hormone agonists: expanding vistas. Indian Journal of Endocrinology and Metabolism, 15(4), 261–267. [Full text]
- National Gender Identity Clinical Network for Scotland (NGICNS). (2016, July 7). Endocrine management of adult transgender patients. NGICNS. Retrieved from http://www.ngicns.scot.nhs.uk [Full text]
- Pokuri, V. K., Nourkeyhani, H., Betsy, B., Herbst, L., Sikorski, M., Spangenthal, E., . . . George, S. (2015). Strategies to circumvent testosterone surge and disease flare in advanced prostate cancer: emerging treatment paradigms. Journal of the National Comprehensive Cancer Network, 13(7), e49–e55. [Abstract]
- Stevens, J., Gomez-Lobo, V., & Pine-Twaddell, E. (2015). Insurance coverage of puberty blocker therapies for transgender youth. Pediatrics, 136(6), 1029–1031. [Full text]
- Weckermann, D., & Harzmann, R. (2004). Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues. European Urology, 46(3), 279–284. [Full text]
- Wiik, A., Andersson, D. P., Brismar, T. B., Chanpen, S., Dhejne, C., Ekström, T. J., . . . Gustafsson, T. (2018). Metabolic and functional changes in transgender individuals following cross-sex hormone treatment: design and methods of the GEnder Dysphoria Treatment in Sweden (GETS) study. Contemporary Clinical Trials Communications, 10, 148–153. [Full text]
