Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

OBJECTIVE: The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH. PATIENTS AND DESIGN: The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradiol orally in 17 girls requesting pubertal development and with a bone age of at least 11 'years' (Group 3). RESULTS: During the first year of rhGH therapy height velocity increased significantly in all patients. Mean +/- SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age-matched girls with Turner's syndrome without puberty (8.9 +/- 1.2 vs 7.4 +/- 1.2 cm/year; P < 0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradiol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm. CONCLUSIONS: The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as possible.