GnRH Agonists
Overview
GnRH agonists (also called GnRH analogues) are the most effective class of anti-androgen available. They work by "turning off" the HPG axis, resulting in near-complete suppression of testosterone production. They are widely used in the UK NHS as the preferred anti-androgen.
| Property | Details |
|---|---|
| Drug class | GnRH receptor agonist |
| Mechanism | Overstimulates GnRH receptors → desensitisation → LH/FSH shut down |
| Common agents | Leuprorelin (Leuprolide), Goserelin (Zoladex), Triptorelin |
| Typical dose | Injection every 1–3 months |
| Availability | Prescription only; expensive |
How It Works
GnRH agonists work through a paradoxical mechanism:
- Initial flare (first 1–2 weeks) — GnRH agonist overstimulates the pituitary, causing a temporary surge in LH and FSH (and therefore T)
- Desensitisation — after continuous stimulation, GnRH receptors become desensitised and stop responding
- Suppression — LH and FSH production plummets, and testicular testosterone production nearly stops
Initial T flare
During the first 1–2 weeks of GnRH agonist treatment, testosterone levels may temporarily rise (the "flare" effect). This can cause a temporary increase in masculinisation symptoms. In trans women, this is usually managed by continuing estrogen therapy during this period. Some protocols add a short course of CPA or bicalutamide to block the flare.
Available Forms
| Medication | Brand Name | Dose | Frequency |
|---|---|---|---|
| Leuprorelin | Lupron, Prostap | 3.75 mg (monthly), 11.25 mg (3-month) | Subcutaneous or IM |
| Goserelin | Zoladex | 3.6 mg (monthly), 10.8 mg (3-month) | Subcutaneous implant |
| Triptorelin | Decapeptyl | 3.75 mg (monthly), 11.25 mg (3-month) | IM injection |
| Histrelin | Vantas | 50 mg implant | Subcutaneous, lasts 12 months |
Pros & Cons
| Pros | Cons |
|---|---|
| Most effective T suppression | Very expensive (often £200–500 per dose) |
| No liver toxicity | Requires injection/implant procedure |
| No potassium issues | Initial T flare (1–2 weeks) |
| No depression or mood effects | Can cause hot flashes and low energy |
| No meningioma risk | May require concurrent anti-androgen during flare |
| Once every 1–12 months dosing | Prescription-only; hard to DIY |
When GnRH Agonists Are Used
- NHS preferred anti-androgen (UK) — often the first-line choice
- Monotherapy augmentation — for people who cannot achieve T suppression with estrogen alone
- Precocious puberty — not relevant for trans HRT
- Prostate cancer — much higher doses than used in trans care
Side Effects
| Side Effect | Notes |
|---|---|
| Hot flashes | Very common (oestrogen deficiency-like) |
| Fatigue | First weeks; improves as E2 stabilises |
| Initial T flare | Temporary; managed with concurrent anti-androgen |
| Injection site pain | Minor |
| Bone density | Theoretical risk if E2 is also low (ensure adequate E2) |
References
Hembree WC, et al. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons. JCEM. https://academic.oup.com/jcem/article/102/11/3869/4157558
WPATH (2022). Standards of Care, Version 8. https://www.tandfonline.com/doi/full/10.1080/26895269.2022.2100644