Reducing Sex Hormone Production Through the Modulation of Gonadotrophin-Releasing Hormone (GnRH) Levels
In medical practice, there are two ways to influence the gonadotropin-releasing hormone (GnRH) receptor to stop the production of oestrogen by the ovaries and testosterone by the testes: you can use either GnRH agonists or antagonists.
The last government placed restrictions on new prescriptions (NHS or private) of gonatodtrophin-releasing agonists, puberty blockers, for trans people under 18 and the ban has since been extended.
Gonatodtrophin-Releasing Agonists - ‘Puberty Blockers’ Currently Banned for UK Transgender Youth
- Buserelin
- Gonadorelin
- Goserelin
- Leuprorelin acetate
- Nafarelin
- Triptorelin
These agonists are used for a variety of indications when there is a need to suppress natural hormone production, including fertility, cancer, endometriosis, fibroids, and to delay puberty or suppress hormone production in transgender people.
Gonatodtrophin-Releasing Antagonists - Not Affected by the Ban
(GnRH antagonists) are a class of medications that antagonise the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications. They have not been studied in transgender people but there is no reason why their effectiveness or safety profile would be any different to that of the agonists.
- Abarelix / Degarelix (Firmagon 80 mg) monthly injections
- Elagolix / Relugolix (Ryeqo 40mg/1mg/0.5mg film-coated tablets - contain oestrogen and progesterone and GnRH antagonist)
- Cetrorelix (Cetrotide)
- Ganirelix (daily injections for fertility)
- Linzagolix (Yselty 200 mg film-coated tablets - This medicine is subject to additional monitoring)
What Is the Difference Between an AGONIST and an ANTAGONIST?
Gonadotropin-releasing hormone (GnRH) agonists and antagonists are medications that affect the body's hormone levels, but they do so in fundamentally different ways:
GnRH Agonists: How Do They Work?
GnRH agonists initially stimulate the pituitary gland to release luteinising hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate the gonads (testes or ovaries) to produce sex hormones (testosterone and oestrogen). However, continuous stimulation with these agonists eventually leads to downregulation of GnRH receptors in the pituitary gland. This causes a significant decrease in LH and FSH secretion, leading to a dramatic reduction in sex hormone production, effectively inducing a state of chemical castration.
GnRH Antagonists: How Do They Work?
GnRH antagonists work by directly blocking the GnRH receptors in the pituitary gland, leading to an immediate drop in LH and FSH levels, and consequently a decrease in the production of sex hormones.
Both types of medications are instrumental in managing hormone-sensitive conditions, but the choice between an agonist and antagonist may depend on the need for immediate effect, potential side effects, the specific clinical scenario and the availability of them.
Are They Legal?
Although there is a ban on prescribing and dispensing GnRH agonists, this does not apply to GnRH antagonists. Suppressing the GnRH axis is a crucial aspect of care for transgender youth to prevent the unwanted effects of puberty that do not align with their gender identity.
Are They Safe?
The GnRh antagonists have not been studied in transgender youth and have only briefly been studied in cisgender youth, but there is no reason to think that they would be any less safe or effective in this patient group. The risks of prescribing new medicines to transgender young people has to be balanced with the risks of allowing pubertal development to progress.
What Are the Options to Stop Feminising Puberty?
- GnRh Agonists (injection or nasal spray) - to stop oestrogen production, in countries where there is no ban
- GnRH Antagonists (monthly injections) to stop oestrogen production
- Raloxifene - to suppress the effects of oestrogen
What Are the Options to Stop Masculining Puberty?
- GnRh Agonists (injection or nasal spray) - to stop testosterone production, in countries where there is no ban
- GnRH Antagonists (monthly injections) - to stop testosterone production
- GnRH Antagonists (pills) - contains hormones for those who are actively feminising
- Spironolactone - to reduce the effects of testosterone
- Cyproterone - to reduce the effects of testosterone
GnRH Agonists: Function
GnRH agonists play a vital role in the care of transgender youth by temporarily suppressing puberty. These medications work by regulating the release of hormones responsible for initiating puberty, such as estrogen and testosterone, thereby preventing the development of physical characteristics that do not align with the individual’s gender identity. This early intervention provides transgender youth with more time to explore their gender identity and can significantly reduce the distress associated with puberty, ultimately contributing to better mental health and well-being.
GnRH Antagonists: Function
GnRH antagonists are used in the care of transgender youth to prevent the production of sex hormones like estrogen and testosterone, thereby halting the progression of puberty. Unlike agonists, which initially cause a temporary surge in hormones, antagonists work by directly blocking the GnRH receptors, leading to an immediate reduction in hormone levels. This approach helps prevent the development of secondary sexual characteristics that conflict with the individual's gender identity, offering a more immediate and controlled way to manage puberty and support the well-being of transgender youth.
Spironolactone: Function
Spironolactone is commonly used in the care of transgender youth, particularly those assigned male at birth, to reduce the effects of testosterone. As an androgen blocker, spironolactone inhibits the action of testosterone, helping to prevent the development of masculinizing features such as facial hair and deepening of the voice. It is often used in combination with estrogen therapy to promote the development of feminine characteristics in alignment with the individual's gender identity. Spironolactone plays an essential role in supporting the physical and emotional well-being of transgender youth during their transition.
Cyproterone: Function
Cyproterone acetate is used in the care of transgender youth, especially those assigned male at birth, as an anti-androgen to block the effects of testosterone. By reducing testosterone levels, cyproterone helps prevent the development of masculinizing features, such as facial hair and voice deepening, and supports the alignment of physical characteristics with the individual's gender identity. It is often used in conjunction with estrogen therapy to enhance the development of feminine traits. Cyproterone acetate is a key component in hormone therapy, contributing to the overall well-being and mental health of transgender youth during their transition.
Raloxifene: Function
Raloxifene, a selective estrogen receptor modulator (SERM), is sometimes used in transgender care to reduce breast development and manage the endometrial lining in individuals assigned male at birth who are undergoing feminizing hormone therapy. By blocking estrogen's effects in breast tissue, raloxifene can help limit the growth of breast tissue, providing a more tailored approach to physical changes during transition. Additionally, raloxifene's effects on the endometrial lining can help manage potential complications related to estrogen therapy, offering a balanced approach to hormone management in transgender care.
If you'd like to further discuss your medical options for blocking puberty, please schedule a Doctor Consultation at your convenience. The service is available for GenderGP members and non-members.
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