A Natural History of Genetic and Environmental Predictors of Pubertal Timing Among Youth With Obesity

Study Description:

This is a longitudinal study to predict pubertal timing in 5-12-year-old girls and boys with obesity. We hypothesize that: 1) Children with obesity with exposure to estrogenic environmental compounds will demonstrate earlier puberty than those without such an exposure. 2) A polygenic risk score (PRS) of alleles that confer risk for voice break in boys will associate with age at Tanner II pubertal development in boys with obesity. 3) A polygenic risk score (PRS) of alleles that confer risk for menarche in girls will associate with age at stage II pubertal development in girls with obesity. 4) Children with obesity who demonstrate a decrease in BMI percentile of > 5 percentage points will demonstrate later stage II pubertal development than children with no change or an increase in BMI percentile but will demonstrate earlier pubertal development than peers of normal weight.

Objectives:

• Primary Objective: To identify predictors of pubertal timing in 5-12-year old children with obesity.
• Secondary Objectives: To determine the effect of obesity on reproductive hormones and adrenarche.

Endpoints:

• Primary Endpoint: pubertal markers by questionnaire, physical exam (testicular volume, breast development), and ultrasound (breast morphological stage). Pubertal development will be defined as breast morphological stage B and a testicular volume of 4 cc.
• Secondary Endpoints: Tanner pubic hair staging, reproductive hormones (luteinizing hormone (LH), Follicle-stimulating hormone (FSH), estradiol, total testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione)

• INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study, including sharing medical records
• Male or female, aged 5 to 7 years at the screening visit
• Normal weight (defined as BMI > 5th percentile and <85th percentile for age and sex) or Obese weight (defined as BMI > 95th percentile for age and sex)
• Ability of parent or guardian to understand and willingness to sign a written informed consent document. And ability of the participant (child) to provide verbal assent and/or to sign a written assent document.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Known diagnosis of syndromic/genetic form of obesity
• Current use of medications or supplements that affect reproductive hormones (e.g., estrogen, progesterone, testosterone, puberty blockers, regular use of lavender oil or tea tree oil)
• Chronic medical conditions (e.g., type 1 or type 2 diabetes, cancer, renal failure, lupus, etc.), at the discretion of the Principal Investigator
• Clinically significant abnormal laboratory values, at the discretion of the Principal Investigator
• International adoptee (associated with earlier puberty)

Individuals who do not meet the criteria for participation in this study (screen failure) because of an acute, reversible or transient medical reason may be rescreened upon reversal, improvement or stabilization of their clinical status. Participants who develop an acute, reversible or transient medical condition during the study may return upon reversal, improvement or stabilization of their clinical status.