Short summary

LIFE-MET is a research project under the Danish Puberty Precocity (DAPP) study. The primary aim is to investigate whether treatment with medication (Metformin) or lifestyle changes (exercise and dietary counseling) can delay pubertal development in girls aged 8 to 9 years with early puberty

Rationale

The age of pubertal onset has been decreasing worldwide, with breast development starting almost three months earlier per decade over the past 40 to 50 years. This trend may have negative consequences for the well-being and long-term health of children, as well as societal challenges. Earlier menarche has been associated with increased risk of mortality, type 2 diabetes, and cardiovascular disease. While genetics play a role in pubertal onset, lifestyle and environmental factors are believed to be major contributors. Childhood overweight is increasing globally and has been linked to early puberty. This study aims to explore the effects of metformin and lifestyle intervention on pubertal maturation in girls with overweight and early puberty. The present study postulates that pubertal onset is potentially influenced by environmental factors, specifically lifestyle and overweight, either through direct impact or via epigenetic modulation. Moreover, it is hypothesized that modification of insulin sensitivity and/or weight loss could potentially reverse this process. Participants will be randomly assigned to receive either metformin or placebo for 6 months, with follow-up assessments at 12 months and biannual questionnaires until menarche. The study will assess changes in pubertal development, metabolism, and body composition.

Description of the cohort

The participants are girls 8-9,5 years old with overweight. They will be recruited from our puberty study "DAPP". DAPP is a large national study where all children referred to a pediatric department with precocious puberty can participate. The study aims to include 80 girls from five hospitals - Herlev, Roskilde, Aalborg, Aarhus and Kolding.

Data and biological material

blood samples, questionnaire data, data from the patient journal, DXA scans

Collaborating researchers and departments

Department of Pediatrics, Zealand University Hospital, Roskilde

• Annette Korsholm Mouritsen

Department of Pediatrics, University Hospital Lillebaelt, Kolding

• Line Anker Bang Thybo

Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus

• Astrid Bruun Rasmussen

Department of Pediatrics, Aalborg University Hospital, Nord, Aalborg

• Ann-Margrethe Rønholt Christensen