Accelerated Puberty Onset Linked to Age of GH Treatment Initiation

A comparison of 2 age groups each of girls and boys in Japan found that an earlier age at start of treatment for growth hormone deficiency (GHD) spurred earlier onset of puberty but did not have an effect on ultimate adult height, reports the study recently published in Endocrine Journal.

The girls and boys included in the study all received treatment at the Tanaka Growth Clinic in Japan between 2007 and 2017 following a diagnosis of idiopathic GHD, were initiated on treatment with growth hormone (GH) before puberty, and were followed until puberty began. Conflicting evidence on the effect of GH on final adult height spurred this study, despite there also being a positive correlation between age at puberty onset and adult height. The girls’ age groups for analysis were younger than 7 years (n = 26; Group A) and 7 to 9 years (n = 21; Group B), whereas the age groups for the boys were younger than 8 years (n = 45; Group A) and 8 to 10 years (n = 39; Group B).

“This study aimed to prove the hypothesis that early treatment might not lead to an improvement in adult height since GH treatment accelerated the delayed onset of puberty in GHD,” the authors wrote.

The overall results demonstrate that among the girls, treatment for GHD accelerated the onset of puberty by almost 2 years, with the authors noting that while the typical age of puberty onset is age 11.4 years for girls, in their study, puberty began prior to age 9.5 years. In addition, for the boys, this study showed puberty beginning before age 10 years compared with the typical age of onset of 11.7 years.

In addition, positive correlations were seen in both overall groups for ages at puberty onset and start of GH treatment:

• Girls: r = 0.302 (P < .05)
• Boys: r = 0.427 (P < .0001)

These results carried through following Mann-Whitney U and Kaplan-Meier log-rank tests, which showed that the girls and boys in the Group A age groups (<7 years and <8 years, respectively) began puberty at even earlier ages compared with those in the Group B age groups (7-9 years and 8-10 years, respectively):

• Mann-Whitney U test:
  • Girls: P < .05
  • Boys: P < .01
• Kaplan-Meier log-rank test:
  • Girls: P < .05
  • Boys: P < .01

Prior to GH treatment in the study, the boys’ mean height SD score was –2.42 SD, while the girls’ mean height SD score was –2.58 SD. During active treatment, injections were provided 7 times a week, and height and weight measures were evaluated every 3 months. In addition, quarterly bone age assessments and blood and urine tests were performed during year 1 of treatment and biannually thereafter.

The authors attributed the baseline delayed onset of puberty among their study group to several pituitary hormone deficiencies and inadequate secretion of gonadotropins; in particular, it is delayed among those with GHD vs healthy children. A direct correlation with this is that those who start GH treatment early, enter into puberty early.

Going forward, the authors recommend examining these outcomes among larger groups of patients within the same age range. They also emphasize the importance of early diagnosis and treatment, which may be able to lessen psychosocial problems that frequently occur due to being of a short stature.

Reference

Tanaka T, Soneda S, Sato N, Kishi K, Noda M, Ogasawara A. Early growth hormone treatment accelerates delayed onset of puberty in patients with growth hormone deficiency. Endocr J. Published online September 29, 2021. doi:10.1507/endocrj.EJ21-0209