Metformin therapy in girls to delay progression of advanced puberty and increase the adult height: a randomized trial
Year: 2016
Type: dissertation
Abstract: BACKGROUND: Currently, puberty takes place earlier, especially in those girls with elevated BMI, hyperinsulinism, insulin resistance and hyperleptinemia. Leptin and insulin seem to be implicated in this advanced activation of the hypothalamus-pituitary-ovarian axis, and moreover, insulin enhances the early secretion of estrogens. All this also causes a faster tempo of puberty that traduces a decreased adult height, and many psychological consequences.\nJUSTIFICATION: In girls with advanced puberty (8-9 years) GnRH agonists haven’t given a good response in increasing adult height, and there is a need to find an effective treatment. In LBW-PP girls, metformin has shown favourable results in delaying puberty and improve final height. Our intention is try to reproduce the results in girls without LBW or PP, but with a BMI over the mean, taking benefit of the effects of metformin in reducing weight and leptin levels, as well as insulin levels and insulin resistance, and also in reducing steroidogenesis.\nOBJECTIVES: Study if metformin therapy in girls with early puberty and with a BMI above the mean, can delay age of menarche and improve adult height, lipid profile and body composition indices (BMI and waist).\nDESIGN: Randomized double blinded clinical trial.\nPARTICIPANTS: Subjects will be Caucasian girls between the age of 8-9 years old in the beginning of puberty (Tanner 2 or 3) with a BMI in percentile 50 or over. 158 subjects will be selected (79 taking metformin and 79 taking placebo) according to inclusion and exclusion criteria.\nMAIN OUTCOME MEASURES: Primary outcome: Age of menarche. Secondary outcomes: height, BMI, waist, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides.\nINTERVENTION AND METHOD: The girls will be distributed randomly in a 1: 1 ratio to receive metformin or placebo. They will take one pill of Metformin 850 mg or placebo every day during 3 years. The total follow-up for each girl will be of 5 years. Baseline determination and visits every 6 months with new determinations in each visit will be performed.\nSETTING: Multicentre. The study will be performed in outpatient of three hospitals: Dr. Josep Trueta (Girona), Sant Joan de Déu (Barcelona) and Vall d’Hebrón (Barcelona)
Author: Laura Colet Oliver
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2529018542