Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Insulin Resistance
Intervention: Metformin; Dietary Restriction; Exercise Training
Intervention description: Subjects randomized to the metformin treatment group will receive 1000 mg extended release metformin hydrochloride tablets (Bristol Myers Squibb) twice per day with food approximately 8 hours apart.; Subjects randomized to the dietary restriction group will reduce their energy intake by 25% of their weight maintenance energy intake determined at baseline. Total energy expenditure as measured by a 14-day doubly labeled water (DLW) study will be used to determine the baseline energy intake of each subject. There will be no gradual ramping of dietary restriction. The 25% energy reduction goal will apply from the first day of the intervention for a period of 24 weeks. Subjects will be asked to not modify their normal level of physical activity.; For the aerobic training component, subjects are required to meet a weekly energy expenditure target of 10 kcal per kg of body weight per week (KKW).
The resistance training program will be performed 2 days a week. The resistance program includes 9 exercises. The 9 primary exercises are seated chest press, seated row, shoulder press, lat pull down, double leg press, leg extension, leg curl, back extension and abdominal crunch.
Intervention MeSH terms: Metformin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: Female
Minimum age: 20 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Exercise; Diet; Insulin resistance; Weight

Summary:

      Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women of
      reproductive age and despite decades of research the etiology the disorder is not known. The
      characteristic hyperandrogenism and anovulation is associated with abnormal neuroendocrine
      function and insulin resistance. Obesity is a common correlated phenotype of Polycystic ovary
      syndrome and weight gain worsens the reproductive and metabolic complications. Currently
      there is no evidence-based treatment plan for infertility in Polycystic ovary syndrome; yet
      weight loss by dietary restriction and regular exercise are strongly advocated. Weight loss
      and increased insulin sensitivity appear to drive improvements in reproductive outcomes in
      women with Polycystic ovary syndrome; however, the mechanism connecting these changes with
      the reproductive axis is not fully understood.
    

Eligibility criteria:

        Inclusion Criteria:

          -  20 - 40 years, inclusive

          -  Body mass index ≥ 25 kg/m2

          -  History of irregular menstrual cycles (fewer than 6 cycles in the past year)

          -  Clinical and/or biochemical androgen excess (Free androgen index>3.85 and/or
             hirsuitism rating ≥8)

          -  Anovulatory menstrual cycles (determined during screening)

        Exclusion Criteria:

          -  Ovulatory menstrual cycles (determined during screening by luteal phase serum
             progesterone >3ng/mL)

          -  History or clinical appearance of cardiovascular disease, diabetes (Type 1 or Type 2)
             and any other significant reproductive, metabolic, hematologic, pulmonary,
             gastrointestinal, neurologic, immune, hepatic, renal, urologic disorders, or cancer.

          -  Hemoglobin, hematocrit, red blood cell count, or iron level below the lower limit of
             normal at the screening visit confirmed by a test repeated within two weeks

          -  Regular use of medications for weight control, glucose intolerance, thyroid disease

          -  Use of hormonal contraception containing medroxyprogesterone acetate (A 3 month
             washout period will be permitted for oral, vaginal and transdermal contraceptives).

        Psychiatric and Behavioral Exclusion Criteria

          -  Smoking

          -  History of drug or alcohol abuse (up to 14 drinks a week are allowed) within the past
             two years

          -  History or presence of an eating disorder as determined by Interview for Diagnosis of
             Eating Disorders (IDED-IV)

          -  Beck Depression Index (BDI) score of ≥15 at screening or baseline

        Other Exclusion Criteria

          -  Individuals who have lost more than 5kg (11lbs) in the past 6 months

          -  Individuals who are pregnant or breast-feeding or whom become pregnant during the
             study

          -  Individuals engaged in a regular program of physical fitness involving some heavy
             physical activity (e.g., jogging or riding fast on a bicycle for 30 minutes or more)
             at least five times per week over the past year

          -  Individuals who have metallic objects in their body

          -  Individuals who donated blood within 30 days prior to the date of randomization

          -  Individuals unwilling to be assigned at random to either one of the intervention
             groups

          -  Unwilling or unable to adhere to the rigors of the data collection (determined by food
             and activities diaries at screening, see below) and clinical evaluation schedule over
             the entire 24 week intervention period

          -  Individuals who plan to move out of the area within the next 12 months or plan to be
             out of the study area for more than 4 weeks in the next 12 months

          -  Individuals who reside too far from Pennington