GnRHa Treatment Considered Safe and Effective for Gender Dysphoric Adolescents

GnRHa Treatment Considered Safe and Effective for Gender Dysphoric Adolescents

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

Sebastian E.E. Schagen, MD; Peggy T. Cohen-Kettenis, PhD; Henriette A. Delemarre-van de Waal, MD, PhD; Sabine E. Hannema, MD, PhD

ONLINE: July 2016 – The Journal of Sexual Medicine


Introduction and Aims

For gender dysphoric adolescents, the onset of puberty can be difficult, as the development of natal sex characteristics (e.g., breasts in natal girls, an Adam’s apple in natal boys) make it more difficult to live as the desired sex.

Gonadotropin-releasing hormone agonists (GnRHas) is a recommended approach for suppressing puberty, allowing adolescents more time to decide whether they want to proceed with more advanced treatment later. In this way, they have more time to live as their desired sex without the stress of puberty.

GnRHas have been found to benefit gender dysphoric adolescents psychologically, but the physical aspects have not been widely studied. Therefore, it is difficult to tell patients what they can expect from this treatment. In addition, it is unclear how GnRHas affect liver and kidney function in these patients and whether it is necessary to monitor these functions regularly.

The current study aimed to determine the efficacy of GnRHa treatment in this population in relation to Tanner stage, gonadotropins, and sex steroids. It also investigated the treatment’s effects on liver enzymes, renal function, and changes in body composition.


This was a observational, prospective study. Each participant received GnRHa treatment by injection of triptorelin 3.75 mg at 0, 2, and 4 weeks. From that point, injections were given every 4 weeks. Participants were evaluated every 3 months. Treatment continued until the participant was old enough to add cross-sex hormone therapy.

Data analysis included information on 49 male-to-female (MtF – median age: 13.6) and 67 female-to-male (FtM – median age: 14.2) adolescents.

The main outcome measures included the following:

Physical examination. Tanner stage was determined based on breast development in FtMs and testicular volume and genital development in MtFs. Weight, height, and body mass index (BMI) were also measured.

Laboratory investigations. Blood samples were taken at 0, 3, and 6 months of treatment and every 6 months thereafter. Levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, and creatinine were measured.

Dual-Energy X Ray Absorptiometry. This method was used to measure fat mass, fat percentage, and lean body mass percentage.

Results and Discussion

Results highlights include the following:

• Many of the FtMs were at Tanner stage 4 or 5 when the study began. Only 4 FtMs were at Tanner stage 2 at baseline and only one participant regressed to Tanner stage 1 after 6 months of treatment. Menstruation stopped for those FtMs who had begun having periods.

• For 43 of 49 MtFs, testicular volume decreased. It was unclear why volume did not change for several of these MtFs, but this result may have been due to the limited duration of treatment, the authors noted. (One individual did not adhere to treatment.)

• During the first 3 months, gonadotropin and sex steroid levels decreased and remained low after that (except in one participant who did not adhere to treatment). GnRHa doses did not need to be adjusted because of insufficient puberty suppression.

“It seems unnecessary to routinely monitor gonadotropins and sex steroids during treatment with triptorelin,” the authors wrote. “Rather, these can be measured if there are clinical signs of inadequate suppression (i.e., progressive breast development or increase in testicular volume).”

• There were no abnormalities in liver enzymes or creatinine. This result is similar to past research on GnRHa treatment in children with precocious puberty. For this reason, the authors suggested it was unnecessary to monitor renal or hepatic parameters.

• Alkaline phosphatase decreased, possibly because of slower growth velocity, as height SD scores decreased in boys and girls.

• During the first year of treatment, lean body mass percentage was significantly reduced in both boys and girls. Fat percentage increased significantly. However, because there was no control group in this study, it was unclear whether these changes were associated with treatment.

• None of the participants discontinued treatment because of side effects.

The researchers acknowledged these limitations:

• The number of participants in the early stages of puberty was small. It is unknown whether prolonged periods of puberty suppression treatment is safe.

• There was no control group.

• A limited number of safety parameters were studied. Further research may consider the effects of treatment on bone mineral density and executive function.