Trial Name: Insulin Resistance in Adolescents at High Risk for Polycystic Ovary Syndrome

Type of Study: Polycystic Ovarian Syndrome (PCOS)

Summary:
This study will be evaluating the following hypothesis - that a persistent insulin resistance following puberty underlies the over-production of androgen necessary for the establishment of the Polycystic Ovary Syndrome in girls genetically at highest risk (those with female first-degree relatives – older sister or mother - bearing the diagnosis of PCOS). Insulin resistance appears to be a crucial antecedent to the androgen excess of PCOS, both in vitro and in vivo. As transient insulin resistance is a metabolic characteristic of normal pubertal maturation, we hypothesize that the highly prevalent insulin resistance of PCOS must have its origins in a failure to reestablish normal insulin sensitivity at the completion of puberty.

Principal Investigator: Marcelle I. Cedars, M.D.

Study Duration: up to 5 years
Anticipated Start Date: Fall 2005
Anticipated End Date: Fall 2010

Recruitment Goal: 20 participants at UCSF (10 in each of two groups).
Group One consists of 10 subjects, who are the older sisters or mothers of the enrolled, younger girls.
Group Two consists of 10 subjects, who are pre-adolescent females of approximate age 9 to 14 years.

Qualifications:
Inclusion criteria
• Individuals will be recruited from two populations, PCOS/GI (glucose intolerant) and PCOS.
• The diagnosis of PCOS in either the mother or older post-pubertal female sibling will require the demonstration of elevations in the plasma levels of one or more androgens, including androstenedione, DHEA, and testosterone (free and/or total).
• Diagnosis will also require associated chronic oligo- or amenorrhea (defined as fewer than six menses annually).
• Adolescent girls will be included as study participants if her mother or sister has been unequivocally diagnosed with PCOS.
Exclusion Criteria
• No child enrolled in this study will be on medication known to affect either sex hormone or carbohydrate metabolism.
• No patient included will have diagnosed diabetes mellitus, Types 1 or 2.
• No enrollee will have biochemical evidence of hyperprolactinemia, thyroid disease or congenital adrenal hyperplasia, based on screening laboratory investigations.
• No patient enrolled in this study will be maintained on specialized diets or exercise regimen (except as required by the local board of education for physical education credits).

Time Requirement:
Group One / older sister or mother of enrolled pre-teen or teen (n= 10) – 1 visit
1) One-time genetic comparison to Group two.
2) If the glucose:insulin relationship has not previously been established the subject would undergo the modified oral glucose tolerance test one time only.
Group Two / pre-teen and teen study subjects (n= 10) – 2 visits/yr for up to 5 years (depending on stage of puberty at time of enrollment).
1) Body measurements (Anthropometry); 2) Blood tests; 3) Glucose tolerance test; 4) Insulin sensitivity; 5) Pelvic ultrasonography.

Reimbursement:
Adolescent participant will be paid a total of $200 for completion of the two study visits

Contact:
Gina Davis
davisg@obgyn.ucsf.edu
415-476-0742