ESPE Yearbook of Paediatric Endocrinology

Brief summary: This Iranian open label, quasi-experimental and matched controlled clinical trial included 59 girls with stage III–IV chronic kidney disease (CKD), short stature and delayed puberty. Patients were treated with GH (mean dose 0.05 mg/kg/day) and Ethinyl Estradiol (EE). Initial EE dose was 5 μg/day orally, doubled every 3–6 months to a maximum dose before growth plate closure 30 μg/day, and then increased gradually up to 500 μg/day. EE therapy was started at age 11 years in Group 1 and at age 13 years in Group 2. Group 3 comprised patients with short stature and pubertal delay who did not accept GH or EE therapy until age 15 years, receiving only dialysis and common renal failure treatments.

Earlier age at EE start was associated with taller final height, despite comparable mid-parental heights (mean 154.5, 151.6 and 146.1 cm in groups 1, 2 and 3, respectively). Moreover, lumbar bone mineral density was significantly higher when EE was started at the age of 11 years.

About 50% of children with end-stage renal disease have delayed puberty and reduced final height. Their pubertal growth spurts are blunted and shorter in duration. This study suggests that a relatively early start of estrogen replacement therapy could improve the growth spurt and result in taller final height. If confirmed, this finding would support the message that it is not advisable to delay the start of oestrogen therapy in order to maximise final height.

Using a quasi-experimental design, this empirical interventional study estimated the impact of an intervention on a target population without random assignment. The small sample size is a clear limitation and the different age at start and duration of GH therapy in group 1 and 2 could have influenced final heights. Furthermore, the use of oral EE to induce puberty has now been almost abandoned and replaced by the use of natural oestrogens administered transdermally. The results need to be confirmed in randomized controlled trials involving larger numbers of short girls with CKD and absent puberty, in order to evaluate the real effect of age oestrogen therapy on final height and peak bone mass accrual.