Your Ad Here

Puberty Blockers – GnRH analogues – Transgender Children and Adolescents


GnRH analogues – Puberty Blockers -  Transgender Children and Adolescents

 

[Abstract] Full Text [PDF]

 Introduction

Puberty Blockers as they are now commonly known are used to withhold puberty in young people. Rather than the risky business of young people taking their mother’s or sister’s birth control pills, or self-medicating with irreversible Hormone Replacement Therapy, WPATH (World Professional Association for Transgender Health) have now recognised the importance of early intervention with this product. It is therefore essential that this medication be administered by a gender specialist. This medication is commonly prescribed to allow time for young people to make sure of their decisions before embarking on Hormones which can be irreversible.

GnRH analogues such as Zoladex (Goserelin Acetate) or Lupron (Leuprolide Acetate) dramatically reduces and in some cases stop gonadal hormone production, including testosterone, thus preventing the onset of the masculinising changes of adolescence. In the UK the use of Gonapeptyl has been trialed on young people at the Tavistock Clinic in London by The Clinical Lead Polly Carmichael.

Medication can be administered with a nasal spray, or via a weekly or monthly subcutaneous injection (Zoladex) into the abdomen.  While this treatment does not promote female physical characteristics in a girl, it does prevent or at least slow a male puberty and its physical effects – clinical studies have proven this to be very effective. However, GnRH analogues are costly, but have far better outcomes in adolescents when compared to cheaper anti-androgens such as Spironolactone and Androcur (Cyproterone Acetate) which are more often prescribed to post-puberty transsexual women. (See our Hormone Database for more on these products).

Among adolescents who are referred to gender identity clinics, the number considered eligible for early medical treatment – starting with GnRH analogues to suppress puberty in the first Tanner stages – differs among countries and centers. Not all clinics offer puberty suppression. If such treatment is offered, the pubertal stage at which adolescents are allowed to start varies from Tanner stage 2 to stage 4 (Delemarre-van de Waal & Cohen-Kettenis, 2006; Zucker et al., in press). The percentages of treated adolescents are likely influenced by the organization of health care, insurance aspects, cultural differences, opinions of health professionals, and diagnostic procedures offered in different settings.” (WPATH).

What are Puberty Blockers used for? GnRH agonists are useful in: Transgender:

  • Delaying puberty pending treatment decisions in children with gender incongruency.
  • Suppressing hormone levels in transsexuals, especially trans women.

Best known brand: Zoladex. (Click here for more information on this product). This medication can also be branded:    Avorelin,    Buserelin,    Deslorelin,    Gonadorelin,    Goserelin,    Histrelin,   Leuprorelin,    Lutrelin,    Nafarelin,    Peforelin,    Triptorelin,   Synarel,   Lupron.


Although used in young transsexuals their general use is for the following:

  • Treatment of cancers that are hormonally sensitive and where a hypogonadal state decreases the chances of a recurrence. Thus they are commonly employed in the medical management of prostate cancer and have been used in patients with breast cancer.
  • Treatment of delaying puberty in individuals with precocious puberty.
  • Management of female disorders that are dependent on estrogen productions. Women with menorrhagia, endometriosis, adenomyosis, or uterine fibroids may receive GnRH agonists to suppress ovarian activity and induce a hypoestrogenic state.
  • IVF therapy: they allow for better control of ovarian hyperstimulation during the administration of exogenous FSH. Typically, after GnRH agonists have induced a state of hypoestrogenism, exogenous FSH is given to stimulate ovarian follicle, followed by human chorionic gonadotropins (hCG) to trigger oocyte release. GnRH agonists routinely used for this purpose are: buserelin, leuprorelin, nafarelin, and triptorelin.[1] GnRH agonists are also provide a valid alternative to oocyte release triggering with HCG, resulting in an elimination of the risk of ovarian hyperstimulation syndrome.[2] The delivery rate is approximately 6% less than with hCG triggering.[2].
  • Severe cases of congenital adrenal hyperplasia.
  • Temporary Suppression of Fertility in Male Dogs.
  • Induction of Ovulation in Mares.

Women of reproductive age who undergo cytotoxic chemotherapy have been pretreated with GnRH agonists to reduce the risk of oocyte loss during such therapy and preserve ovarian function. Further studies are necessary to prove that this approach is useful.

A gonadotropin-releasing hormone analogue (GnRH analogue or analog), also known as a luteinizing hormone releasing hormone agonist (LHRH agonist) or LHRH analogue is a synthetic peptide drug modeled after the human hypothalamic gonadotropin-releasing hormone (GnRH). A GnRH analogue is designed to interact with the GnRH receptor and modify the release of pituitary gonadotropins FSH and LH for therapeutic purposes. Shortly after the discovery of GnRH by Nobel laureates Guillemin and Schally researchers tried to modify the GnRH decapeptide with the intent to synthesize stimulating and blocking variants.

Two types of analogues have to be distinguished: Agonists Gonadotropin-releasing hormone agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is an analogue that activates the GnRH receptor resulting in increased secretion of FSH and LH. Initially it was thought that agonists could be used as potent and prolonged stimulators of pituitary gonadotropin release, but it was soon recognized that agonists, after their initial stimulating action – termed a “flare” effect – eventually caused a paradoxical and sustained drop in gonadotropin secretion. This second effect was termed “downregulation” and can be observed after about 10 days. While this phase is reversible upon stopping the medication, it can be maintained when GnRH agonists use is continued for a long time.

Antagonists Gonadotropin-releasing hormone antagonist A gonadotropin-releasing hormone antagonist (GnRH antagonist) is an analogue that blocks the GnRH receptor resulting in an immediate drop in gonadotropin (FSH, LH) secretion. The GnRH antagonist is primarily used in IVF treatments to block natural ovulation. All GnRH analogues are contraindicated in pregnancy (pregnancy category X).

Dosage and contraindications Zoladex (Goserelin Acetate) Dosage and contraindications.  Administered as a depot (i.e. time-release) injection (typically 3.6mg monthly). Reported adverse effects include heart failure, obstructive pulmonary disease and severe allergic reactions as well as more minor side effects such as lethargy and nausea. In view of the fact that it is a depot injection, this drug should be treated with caution as it cannot be rapidly withdrawn should problems occur.

Citation: Transgender Zone/Delemarre-van de Waal & Cohen-Kettenis, 2006; Zucker et al., in press/WPATH/Wiki/Tavistock Clinic London.