Metformin for the Treatment of Premature Pubarche in Girls

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 4

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 82. 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.
Known heart disease (New York Heart Association Class II or higher).
Enrolled simultaneously into other investigative studies that require medications, proscribe the study medications, or otherwise prevent compliance with the protocol. Patients who anticipate taking longer than a one month break during the protocol should not be enrolled.
Concomitant use other medications known to affect reproductive function or metabolism. These medications include growth hormone, IGF-1, medroxyprogesterone acetate, oral contraceptives, GnRH agonists and antagonists, anti-androgens, gonadotropins, anti-obesity drugs, somatostatin, diazoxide, ACE inhibitors, and calcium channel blockers. The washout period on all these medications will be three months.
Suspected adrenal or ovarian tumor secreting androgens or other ectopic steroid secreting tumor.
Suspected Cushing's syndrome.
Lactose intolerance (the placebo filler is lactose).
Known hypersensitivity to study medication, including ACTH and GnRH, or their excipients.
Any concomitant medical condition that in the opinion of the investigator, may expose a subject to unacceptable level of safety risk, or that affects subject compliance.
Subjects who anticipate having any surgery associated with restricted intake of fluids or radiological studies with contrast dye during the study period.
Any concomitant medical condition that in the opinion of the investigator, may expose a subject to unacceptable level of safety risk, or that affects subject compliance.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sugar pill	sugar pill	2 pills per day for 12 months
Metformin	Metformin, glucophage	2 212.5mg pill/day for 12 months

Primary Outcome Measures

Name	Time	Method
Change in Serum DHEAS Levels	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (3): Penn State Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Riley Hospital for Children, Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States