Individualised vs fixed dose of oral 17β-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial

Eur J Endocrinol. 2012 Oct;167(4):523-9. doi: 10.1530/EJE-12-0444. Epub 2012 Jul 17.

Abstract

Context: Oestrogen induction of pubertal changes in Turner girls may reinforce their psychological well-being and may also optimise final height; however, oestrogen type, dose, and route are not well established.

Objective: To induce normal pubertal development in Turner girls and ovarian insufficiency with oral 17β-oestradiol (E(2)), either as individualised dose (ID) or as fixed dose (FD), and to determine whether growth is affected.

Design: Open-label randomised, parallel groups, multicentre clinical trial in 48 GH-treated Turner girls. Oral E(2) was given in tablets, either as an ID of 5-15 μg/kg per day during 2 years or as a FD of 0.2 mg daily during the first year followed by 0.5 mg daily during the second year. Main outcome measures were the event of attaining a Tanner breast staging ≥4 (primary), FSH, and auxological variables (secondary).

Results: Shorter median time to Tanner staging ≥ B4 in the FD group (733 days) compared with the ID group (818 days) (P=0.046). Higher proportion of girls with Tanner staging ≥ B4 (65%) in the FD group compared with the ID group (42%) (P=0.068). Bone age did not show inadequate acceleration and adult height prediction was maintained in both groups. No oestrogen-related adverse events were reported.

Conclusions: Two-year treatment with oral E(2) can progressively induce normal pubertal development in Turner syndrome. Low-dose oral E(2) given as a FD produces a satisfactory pubertal development not inferior to ID. Treatment was well tolerated and did not interfere with the growth-promoting effect of GH.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adolescent Development / drug effects
  • Adolescent Development / physiology
  • Body Height / drug effects
  • Body Height / physiology
  • Child
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects
  • Female
  • Humans
  • Ovulation Induction / methods*
  • Precision Medicine* / methods
  • Puberty / drug effects*
  • Puberty / physiology
  • Time Factors
  • Turner Syndrome / drug therapy*
  • Turner Syndrome / physiopathology

Substances

  • Estradiol