Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome, Overweight Adolescent Girls, Irregular Menstrual Cycles
Brief summary
Oral contraceptives are known to improve menstrual cycles and symptoms in PCOS, however may increase cholesterol. Metformin, a drug to improve insulin resistance, may benefit metabolic state. This study is to determine whether metformin added to oral contraceptive therapy in adolescent women with PCOS improves metabolic state.The study will also test a lifestyle improvement program to reduce weight.
Detailed description
Polycystic Ovary Syndrome (PCOS) is a heterogeneous condition characterized by chronic anovulation and androgen excess that occurs in 4-8% of unselected adult women. Although signs and symptoms of the disorder typically appear at the time of puberty, diagnosis is often delayed until adulthood. At least 50% of adult women with PCOS are obese, resulting in a more severe clinical picture. Obesity among adolescents has been increasing in recent years, with overrepresentation of females who show evidence of hyperandrogenism and irregular periods, suggesting an association of obesity and PCOS at an early age. Recent data, however, have drawn attention to the long-term risks of PCOS, including diabetes and cardiovascular disease. Insulin resistance plays a critical role in the pathophysiology of PCOS and is thought to be the metabolic abnormality most closely linked to an increased risk of diabetes and heart disease. Traditional treatments with oral contraceptives are associated with reduction in serum androgens and improvements in menstrual cycles in adolescents with PCOS, however these have not been well-studied in obese adolescents. Oral contraceptives may worsen the dyslipidemia seen in obese women with PCOS and do not address the insulin resistance. Metformin, an insulin sensitizing agent, has been shown to improve metabolic features of PCOS, but combination therapy with oral contraceptives has never been studied in the obese adolescent with PCOS. The major hypothesis of this proposal is that metformin will improve the metabolic profile of obese adolescent girls with PCOS treated with oral contraceptives. Additionally, a secondary hypothesis will be that compliance with a concurrent lifestyle modification program with be associated with the most significant improvements.
Interventions
DRUGMetformin
Metformin 500 mg. tabs 2 tabs BID for duration of study
Yasmin, drospirenone and ethinyl estradiol 28 tablets 1 tab daily for duration of study
BEHAVIORALLifestyle Management Program
Subjects and a parent/guardian will participate in a series of classes for training in diet, exercise & behavior modification skills on a regular weekly basis over the 24 week study
BEHAVIORALQuality of Life Questionnaire
Quality of Life questionnaire designed for women with Polycystic Ovary Syndrome. Questions concern health and health related issues Performed twice during study, at baseline and conclusion
PROCEDUREOral Glucose Tolerance Test
Insulin response to a glucose challenge in an oral glucose tolerance test (OGTT), as measured by area under the curve (AUC). In this study we will administer an OGTT and calculate the AUC as a measure of insulin resistance. Performed twice during study, at baseline and conclusion
PROCEDUREBlood work
Initial and conclusion blood draws include; comprehensive metabolic profile, CBC and platelet,hormonal assessment and lipids.
PROCEDUREAbdominal Ultra Sound
transabdominal transducer, which contains integrated software for volume calculation will be used to assess ovarian volume. Performed twice during study, at baseline and conclusion
Dual-energy x-ray absorptiometry (DEXA) will be used to assess percent body fat Performed twice during study, at baseline and conclusion
DRUGplacebo
placebo capsules, two capsules BID
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
Age 12-18 years; Menstrual irregularity; Overweight; Must be able to swallow capsules; At lease 6 months since onset of first menstrual cycle.
Exclusion criteria
Diabetes; Kidney or Liver disease; Tobacco use; Depression or Bipolar Disease; Contraindication to exercise; Weight \> 300 lbs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Abdominal Fat as Measured by Waist Circumference. | baseline and 24 weeks | Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight Post Minus Pre Intervention. | baseline and 24 weeks | Body mass index change in adolescents enrolled in lifestyle intervention program |
| Total Testosterone Change | baseline and 24 weeks | Change in total testosterone post minus pre intervention |
| Change in Sex Hormone Binding Globulin (SHBG) | baseline and 24 weeks | SHBG concentration post minus pre-intervention |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin Subjects given 2000mg of metformin in addition to oral contraceptive and a lifestyle program | 18 |
| Placebo Subjects given a placebo in addition to oral contraceptive and lifestyle program | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Placebo | Metformin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 18 Participants | 36 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.8 years STANDARD_DEVIATION 1.6 | 14.7 years STANDARD_DEVIATION 1.6 | 15.1 years STANDARD_DEVIATION 1.6 |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Reduction in Abdominal Fat as Measured by Waist Circumference.
Change in waist circumference measured in cms used as a measure of abdominal adiposity, pre minus post intervention
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Reduction in Abdominal Fat as Measured by Waist Circumference. | -3.9 cm | Standard Deviation 8.6 |
| Placebo | Reduction in Abdominal Fat as Measured by Waist Circumference. | -1.4 cm | Standard Deviation 10.9 |
Secondary
Change in Sex Hormone Binding Globulin (SHBG)
SHBG concentration post minus pre-intervention
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Sex Hormone Binding Globulin (SHBG) | -73.4 nmol/L | Standard Deviation 31.9 |
| Placebo | Change in Sex Hormone Binding Globulin (SHBG) | -58 nmol/L | Standard Deviation 34.3 |
Secondary
Change in Weight Post Minus Pre Intervention.
Body mass index change in adolescents enrolled in lifestyle intervention program
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Weight Post Minus Pre Intervention. | -1.9 kg/m^2 | Standard Deviation 4.7 |
| Placebo | Change in Weight Post Minus Pre Intervention. | -1.2 kg/m^2 | Standard Deviation 4.5 |
Secondary
Total Testosterone Change
Change in total testosterone post minus pre intervention
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Total Testosterone Change | -57.7 ng/dL | Standard Deviation 21.7 |
| Placebo | Total Testosterone Change | -27.6 ng/dL | Standard Deviation 30.1 |