Biochemical and Radiological Indicators of Cardiovascular Morbidity in Children With Premature Pubarche (PP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00581490
Recruitment Status : Completed
First Posted : December 27, 2007
Last Update Posted : April 4, 2017
Information provided by (Responsible Party):
Vanderbilt University Medical Center

Brief Summary:
Children with premature pubarche will have radiological and radial artery tonometry evidence of cardiovascular morbidity at diagnosis when compared to matched controls.

Condition or disease
Evidence of Cardiovascular Morbidity

Detailed Description:

Premature pubarche (PP), also called premature adrenarche (PA), is the early appearance of pubic hair before the age of 8 in girls and before 9 in boys. It had been shown that PP results from excess adrenal androgens. The terms PP and PA are used synonymously and differ from premature (precocious) puberty, the early activation of hypothalamic-pituitary gonadal axis. The incidence of PP is almost tenfold higher in girls than in boys. PP in the absence of congenital adrenal hyperplasia, virilizing ovarian or adrenal tumors has been regarded in the past as a benign phenomenon that may be associated with transient acceleration of growth and bone maturation and was not thought to have an adverse effect on the onset and progression of puberty and on final height in most patients. However, recent evidence suggests that hyperinsulinemia and obesity are common features in prepubertal and pubertal girls with a history of PP. Peri- and post-pubertal girls with PP exhibit an increase in incidence of hirsutism and polycystic ovary syndrome (PCOS). PCOS, a common hyperandrogenic disorder of women, is characterized by functional ovarian hyperandrogenism (FOH). FOH is defined as a 17-hydroxyprogesterone and/or androstenedione level >2 SD above that of the mean for control subjects after subcutaneous gonadotropin-releasing hormone agonist (GnRHa) stimulation during dexamethasone suppression of the adrenal glands. An increased risk of ovulatory dysfunction and FOH in adolescence detectable 3 years after menarche has also been reported in children diagnosed with PP. Serum triglyceride levels in premature adrenarche patients are higher when compared to controls throughout all stages of pubertal development. Boys with PP show reduced insulin sensitivity, independent of obesity, as observed in girls with PP. In Hispanic and Caribbean girls studies have shown prenatal influence on the development of PP. The lowest birth weights are found in this group of girls with PP who also have pronounced hyperinsulinism. Also, the presence of dyslipidemia in girls with PP depends on weight gain after birth. It has been shown that prepubertal girls are inherently more insulin resistant than boys which has been suggested to be related to the intrinsic difference in sex linked genes. Early metformin therapy prevents progression from PP to PCOS in a high risk group of former low birth weight girls, supporting the key role of insulin resistance in the ontogeny of PCOS.

Early intervention in PP can be initiated before marked obesity, diabetes, hypertension and increased cardiovascular morbidity related to insulin resistance become associated with endothelial dysfunction and abnormal vascular structure. Any intervention to decrease cardiovascular morbidity and mortality related to obesity and insulin resistance optimally begins in childhood. The short term goal of this proposal is to collect non-invasive evidence of cardiovascular disease morbidity risk factors at the time of PP diagnosis and to determine how they progress. Symptomatic endpoints used in most adult intervention trials, i.e. cardiac events and death, are not applicable in the setting of childhood disease.

Study Type : Observational
Actual Enrollment : 52 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Biochemical and Radiological Indicators of Cardiovascular Morbidity in Children With Premature Pubarche
Study Start Date : August 2003
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Idiopathic premature pubarche
Children with premature pubarche without precious puberty, adrenal hyperplasia or androgen secreting tumors

Primary Outcome Measures :
  1. Changes in biometric and radiological features between subjects and matched controls [ Time Frame: 6 years ]

Biospecimen Retention:   Samples With DNA
DNA sample from consented subjects and controls

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Boys below the age of 9; girls below the age of 8 if Caucasian and below age 6 if African American

Inclusion Criteria:

  • Boys and girls with isolated premature pubarche

Exclusion Criteria:

  • Congenital adrenal hyperplasia
  • Precocious puberty
  • Androgen producing tumors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00581490

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
Principal Investigator: Revi P. Mathew, M.D. Vanderbilt University

Responsible Party: Vanderbilt University Medical Center Identifier: NCT00581490     History of Changes
Other Study ID Numbers: 030292
First Posted: December 27, 2007    Key Record Dates
Last Update Posted: April 4, 2017
Last Verified: March 2017

Keywords provided by Vanderbilt University Medical Center:
Premature pubarche
Adrenal hyperandrogenism
Metabolic syndrome

Additional relevant MeSH terms:
Premature Birth
Puberty, Precocious
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Gonadal Disorders
Endocrine System Diseases