Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents

J Sex Med. 2016 Jul;13(7):1125-32. doi: 10.1016/j.jsxm.2016.05.004.


Introduction: Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function.

Aim: To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents.

Methods: Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis.

Main outcome measures: Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry.

Results: GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased.

Conclusion: Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment.

Keywords: Gender Dysphoria; Gonadotropin-Releasing Hormone Agonist; Gonadotropins; Puberty Suppression; Sex Steroids.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Female
  • Gonadal Steroid Hormones / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / therapeutic use*
  • Gonadotropins
  • Humans
  • Male
  • Puberty
  • Puberty, Precocious / drug therapy*
  • Sexual Maturation / drug effects
  • Transsexualism / drug therapy*


  • Gonadal Steroid Hormones
  • Gonadotropins
  • Gonadotropin-Releasing Hormone