A Double Blind Randomized Controlled 12 Month Trial of Metformin for the Treatment of Premature Pubarche in Girls
Overview
- Phase
- Not Applicable
- Intervention
- Metformin, glucophage
- Conditions
- Premature Pubarche
- Sponsor
- Milton S. Hershey Medical Center
- Enrollment
- 4
- Locations
- 3
- Primary Endpoint
- Change in Serum DHEAS Levels
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary objective of this study is to determine the safety and efficacy of metformin in lowering serum DHEAS levels in girls with premature pubarche and secondary, to observe changes in hormones associated with pubertal development including gonadotropins, sex steroids, insulin, adipocytokines, and growth factors.
Investigators
Richard S. Legro, M.D.
Professor, Obstetrics and Gynecology and Public Health Sciences
Milton S. Hershey Medical Center
Eligibility Criteria
Inclusion Criteria
- •Girls aged 4-10 with pubic hair prior to 8 years of age
- •Elevated DHEAS level above age normal levels
- •Informed consent from parents and assent from the girl
Exclusion Criteria
- •Diagnosis of incomplete precocious puberty, peripheral precocious puberty, or evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid, and gonadal function other than premature secretion of adrenal androgens.
- •Chronic illness requiring treatment that may interfere with growth and development, i.e. chronic steroid use, renal failure, etc.
- •21-hydroxylase deficiency or other enzyme deficiency leading to the phenotype of congenital adrenal hyperplasia. 21-hydroxylase deficiency will be excluded in all patients by a fasting 17-hydroxyprogesterone (17-OHP) level \< 2 ng/mL. In the case of elevated fasting 17-OHP levels, an ACTH stimulation test will be performed. A 1-hour stimulated value \> 10 ng/mL will be an exclusion
- •As 21 hydroxylase deficiency is a congenital condition, any normal level in the past of 17-hydroxyprogesterone allows entry into this study.
- •Uncorrected thyroid disease (defined as TSH \< 0.2 mIU/ML or \> 5.5 mIU/mL). A normal level within the last year is adequate for entry.
- •Type I or Type II diabetes (defined as a fasting serum glucose \> 125mg/dL on two occasions 83), or patients receiving anti-diabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas; patients currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.
- •Liver disease defined as AST or ALT \> 2 times normal or total bilirubin \> 2.5 mg/dL.
- •Renal disease defined as BUN \> 30 mg/dL or serum creatinine \> 1.4 mg/dL.
- •Significant anemia (Hemoglobin \< 10 mg/dL).
- •History of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
Arms & Interventions
Metformin
2 212.5mg pill/day for 12 months
Intervention: Metformin, glucophage
sugar pill
2 pills per day for 12 months
Intervention: sugar pill
Outcomes
Primary Outcomes
Change in Serum DHEAS Levels
Time Frame: 1 year
Change in DHEAS level was constructed per subject as the 1-year measurement minus the baseline measurement. Only descriptive statistics are provided, statistical tests were not conducted given the extremely small sample size per group.