GnRH analogue, sex steroids during puberty have minimal impact on trans adult height

medwireNews: Most transgender adolescents treated with a gonadotropin-releasing hormone (GnRH) agonist plus oestradiol or testosterone reach an adult height that is within 2 standard deviations (SD) of that expected for their sex assigned at birth, research shows.

The impact of treatment was most apparent among trans girls who started hormone therapy early, report Pernille Badsberg Norup (Copenhagen University Hospital, Rigshospitalet, Denmark) and co-authors in The Journal of Clinical Endocrinology & Metabolism.

Their observational study included 55 transgender girls and 164 transgender boys who were all younger than 18 years of age when they began treatment with a GnRH agonist initiated with or followed by oestradiol or testosterone at a dose adjusted to serum concentrations between 0 and +2 SDs corresponding to gender identity. The median age at start of treatment was 16.4 years.

At the time of data analysis, 98.2% of trans girls and 94.5% of trans boys had an adult height that was within 2 SD of the Danish reference for cis boys and cis girls, respectively.

The height SD score (SDS), which accounts for sex and age, was a significant 0.35 points lower, on average, at adult height than at the start of treatment in trans girls and a significant 0.17 points lower in trans boys.

Six (11%) trans girls reached an adult height that was more than 2 SD above the Danish references for cis girls, while 78 (48%) trans boys had an adult height that was more than 2 SD below the reference for cis boys.

Adult height was a significant 2.7 cm shorter, on average, than target height, calculated from the height of both parents, in 18 trans girls with adequate data. For the six trans boys with data available, adult height was a nonsignificant 0.13 cm taller than target height, on average.

“The minor decline in adult height for some trans girls compared to target height, especially after oral estradiol, may be experienced as positive”, Badsberg Norup and co-authors remark.

Further analysis showed that the mean difference between adult height and target height was greatest for the three trans girls who had a bone age at or below 15 years when they started hormone treatment (–5.8 cm) and for the six trans boy who began treatment with a bone age at or below 14 years (+3.4 cm). The difference was still only significant for the trans girls, however.

Analyses of growth velocity showed a significant mean decline of 2.7 SDS per year during GnRH agonist treatment for 13 trans girls with a bone age of 15 years or younger at treatment start. When oestradiol treatment was initiated, five individuals experienced a growth spurt, with mean growth velocity at 4.4 cm/year.

By comparison, there was no decline in growth velocity during GnRH agonist treatment in a subgroup of 16 trans boys initiating treatment with a bone age of 14 years and younger, and seven of them continued to grow during the first year of testosterone treatment (mean growth velocity 1.6 cm/year).

The investigators also measured serum trajectories of insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3. All measurements were within 2 SD of the reference level for the assigned birth sex for both trans girls and trans boys.

Serum IGF-I SDS were stable after the initiation of GnRH agonists for both groups and after initiation of testosterone among trans boys.

Among the 16 trans girls receiving oral oestradiol, 13 with available data experienced an IGF-I SDS decline, at an average rate of 0.13 SDS per month. Seven of 14 trans girls given transdermal oestradiol via patches or gel also had data for IGF-I. In this group, the mean decline was 0.01 SDS per month.

Of note, height SDS declined significantly for trans girls in the orally treated group (mean slope –0.02 SDS per month) but not for those in the transdermal group (mean slope –0.01 SDS per month).

“This suggests that oral estradiol may be the preferred treatment for trans girls who do not wish to gain height,” say Badsberg Norup et al.

They also observed that IGFBP-3 increased after GnRH agonist initiation in both groups but was more pronounced among the trans girls, whereas a decline was observed after initiation of testosterone treatment for the trans boys but not after oestradiol initiation in trans girls.

The authors conclude: “Our results indicate that trans girls have a greater potential for height reduction when [hormone therapy] is started at a younger bone age. Trans boys may also have a potential for height gain, but both effects need to be investigated further.”

They add: “These changes in adult height could be beneficial for some individuals, as it would improve alignment with their gender identity.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Endocrinol Metab 2024; doi:10.1210/clinem/dgae263
Martin Savage
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