DUGi

Height outcome in boys treated with anastrozole and triptorelin for rapidly progressive early puberty and/or early puberty associated with a poor adult height prognosis: a randomised placebo-controlled clinical trial

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@26759

BACKGROUND Recent trends indicate an earlier onset of puberty in developed countries, likely linked to the increase in BMI observed in children. Early male puberty refers to pubertal onset occurring within the first half of the normal distribution and is defined by a testicular volume of ≥4 ml in boys aged 9–10 years. In addition to the psychosocial risks associated with early development, rapid pubertal progression can lead to a reduced adult height. These poor height outcomes are primarily due to premature exposure of the growth plates to pubertal oestrogens, which results their early closure and compromised growth potential. JUSTIFICATION Due to the increasing incidence of premature onset of puberty and its impact on growth, therapies have been explored for over thirty years to address this issue. GnRH analogues are commonly used to treat precocious puberty, but their role in mitigating height loss in early puberty remains understudied, with no clear consensus on their benefits. Recent data suggest that combining GnRH analogues with aromatase inhibitors may improve height outcomes. This study aims to compare the combination of these drugs with GnRH analogues alone in terms of height outcomes, specifically focusing on boys, as early puberty in males is often overlooked, with few studies addressing its impact on their growth. OBJECTIVES The primary objective of this clinical trial is to evaluate whether the combination of Tirptorelin and Anastrozole is superior to Triptorelin alone in increasing height gain in boys with rapidly progressive idiopathic early central puberty and/or early puberty associated with a poor height prognosis. Secondary objectives include comparing treatment with Anastrozole and Triptorelin to treatment with Triptorelin alone in regards of: achieved near adult height in relation to the median parental height and reducing bone age advancement, near adult height outcomes, and incidence of adverse effects. DESIGN This is a multicentre, randomized, placebo-controlled, triple blind, 9,9-year duration clinical trial PARTICIPANTS A consecutive sampling method will be used to recruit a sample of 152 boys aged 9 to 10 years (inclusive) who present early puberty and exhibit rapid progression of puberty or poor height prognosis. Informed consent will be obtained from parents, and the boys will be assessed for eligibility based on inclusion and exclusion criteria. MAIN OUTCOME MEASURES The primary outcome will be height gain, defined by the formula NAH-PAH, and will be expressed as SDS. Secondary outcomes will include ratio bone age/chronological age and near adult height expressed in SDS and defined when growth velocity is d2 cm/year. Near adult height relative to mean parental height (MPH) will be another secondary variable, determined by subtracting the SDS of MPH from the SDS of NAH. The study will also include safety variables. INTERVENTION AND METHODS Real-time stratification and adaptive randomization will be used to reduce the impact of ratio bone age/chronological age and BMI at inclusion on the outcomes. Four strata will be created, and a 1:1 allocation will assign 76 participants to the control group and 76 to the intervention group. Both groups will receive quarterly Triptorelin injections until 13,5 years of bone age are reached. The intervention group will also receive daily Anastrozole pills, while the control group will receive a placebo. Participants will have follow-up appointments every 6 months until near adult height is reached, when Anastrozole and placebo will be discontinued

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