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

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 17b-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 mg/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 R4 (primary), FSH, and auxological variables (secondary). Results: Shorter median time to Tanner staging R B4 in the FD group (733 days) compared with the ID group (818 days) (PZ0.046). Higher proportion of girls with Tanner staging R B4 (65%) in the FD group compared with the ID group (42%) (PZ0.068). 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.

Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner's Syndrome

“…Estrogens determine epiphysis closure, inhibiting the growth; however, low estrogen doses do not interfere with GH effects on final height [25]. Moreover, the combined treatment with ultralow-dose estrogen and GH in childhood may improve the growth [26,27], and may provide other potential benefits [28]. Additionally, continuous estrogen therapy increases BMD in these subjects, and the best effects on BMD are negatively correlated with the age of start of adultdose estrogen treatment [29].…”

Muscle function in Turner syndrome: normal force but decreased power

“…The growth pattern is markedly different in patients with TS compared with healthy controls. While the height‐deficit progresses without GH treatment, the BMI rises during puberty in patients with TS . Therefore, choosing the appropriate method for comparing any parameter significantly influenced by growth remains a challenge in TS.…”

Hormone supplementation for pubertal induction in girls

“…Labarta et al treated 48 girls with Turner syndrome over 2 years using individualised or fixed dose 17β-oestradiol and described breast development to B4 in 42% and 65% of girls, respectively 15. The results from studies looking at uterine growth are variable 14 16 17.…”