The goal of this study is to determine the relative desirability of metformin vs. oral combined hormonal contraceptives (OCs) in treating Polycystic Ovary Syndrome (PCOS) in women of later reproductive age. Polycystic Ovary Syndrome Questionnaire (PCOSQ) score will be used as a proxy for patient satisfaction. In light of their respective effects on the classic and metabolic facets of PCOS, metformin will provide non-inferior patient satisfaction compared to OCs in later reproductive age women with PCOS.
This is a randomized, controlled, double-blinded, crossover study. The investigators will recruit women with PCOS in ages 40-49 yo. Subjects will be randomized to either receive metformin (2000 mg daily) or low dose oral contraceptives (OCs: 20 mcg ethinyl estradiol/norethindrone acetate 1mg) for a total of 6 months, and they will crossover to the other treatment for the following 6 months. Subjects will have the following assessed at baseline and 6 months after each study medication: blood pressure, weight, waist-to-hip ratio (WHR), average intermenstrual cycle length (in the previous 3 months), Ferriman-Gallwey score (as a measure of hirsutism), total testosterone (T), sex hormone binding globulin, calculated free T, fasting insulin, fasting glucose, 2-h glucose (during oral glucose tolerance test), Matsuda index, HgA1c, LDL-cholesterol, HDL-cholesterol, triglycerides, estimated cardiovascular risk (Framingham risk score), health-related quality of life using both PCOS questionnaire (PCOSQ) and the Short-Form Health Survey (SF-36), and severity of anxiety using Generalized Anxiety Disorder-7 (GAD-7) questionnaire. For safety surveillance, the investigators will measure electrolyte levels, renal function, liver function, and pregnancy tests immediately before study mediation initiation and every 3 months. For statistical analysis, per PCOSQ domain, the post-treatment QoL scores will be analyzed via a linear mixed model (LMM), in which the LMM will be specified in accordance with a 2 treatment by 2 period crossover design. The investigators determined that if 73 subjects complete the study, the investigators expect to have at least an 80% chance of rejecting the null hypothesis that QoL is inferior with metformin therapy vs. OCs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Metformin 2000 mg/day will be used in this study. Metformin is a antihyperglycemic agent that is used as a first line medical therapy to treat type 2 diabetes mellitus. It is also used to prevent progression of impaired glucose tolerance. It decrease hepatic glucose production and increase insulin sensitivity.
Oral combined hormonal contraceptive (OCs) with a combination of ethinyl estradiol 20 mcg/norethindrone acetate 1 mg will be used in this study. OCs are normally used to prevent pregnancy by suppressing ovulation and to prevent endometrial hyperplasia by inducing regular "withdrawal" bleeding. OCs help control both clinical and biochemical hyperandrogenism in PCOS and are considered first line medical therapy until the age of menopause.
University of Virginia
Charlottesville, Virginia, United States
Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ) score
It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.
Time frame: baseline
Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ) score
It is a 7-point scale questionnaire assessing health-related quality of life specific to PCOS in 5 different domains, with "7" representing optimal function and "1" representing poorest function.
Time frame: 6 months after each intervention.
Short Form (SF)-36 score
It consists of 36 items and has eight scaled scores (transformed into 0-100 scale). It assesses health related quality of life (general). The increasing score indicates better health status.
Time frame: baseline
Short Form (SF)-36 score
It consists of 36 items and has eight scaled scores (transformed into 0-100 scale). It assesses health related quality of life (general). The increasing score indicates better health status.
Time frame: 6 months after each intervention
General Anxiety Disorder (GAD)-7 score
It consists of 7 items with a scale of 0-3, and they are summed up to a total score. Increasing scores mean a greater functional impairment.
Time frame: baseline
General Anxiety Disorder (GAD)-7 score
It consists of 7 items with a scale of 0-3, and they are summed up to a total score. Increasing scores mean a greater functional impairment.
Time frame: 6 months after each intervention
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Total testosterone concentrations
ng/dL
Time frame: baseline
Total testosterone concentrations
ng/dL
Time frame: 6 months after each intervention
Calculated free testosterone concentrations
pg/mL
Time frame: baseline
Calculated free testosterone concentrations
pg/mL
Time frame: 6 months after each intervention
Sex hormone binding globulin
nmoL/L
Time frame: baseline
Sex hormone binding globulin
nmoL/L
Time frame: 6 months after each intervention
LDL cholesterol level
mg/dL
Time frame: baseline
LDL cholesterol level
mg/dL
Time frame: 6 months after each intervention
HDL cholesterol level
mg/dL
Time frame: baseline
HDL cholesterol level
mg/dL
Time frame: 6 months after each intervention
Triglyceride level
mg/dL
Time frame: baseline
Triglyceride level
mg/dL
Time frame: 6 months after each intervention
Blood pressure
mmHg
Time frame: baseline
Blood pressure
mmHg
Time frame: 6 months after each intervention
Weight
kg
Time frame: baseline
Weight
kg
Time frame: 6 months after each intervention
Body mass index
kg/meter square
Time frame: baseline
Body mass index
kg/meter square
Time frame: 6 months after each intervention
waist-to-hip ratio
It is a ratio of waist and hip circumference
Time frame: baseline
waist-to-hip ratio
It is a ratio of waist and hip circumference
Time frame: 6 months after each intervention
Matsuda index
It is an index to assess insulin sensitivity.
Time frame: baseline
Matsuda index
It is an index to assess insulin sensitivity.
Time frame: 6 months after each intervention
Fasting insulin
uIU/mL
Time frame: baseline
Fasting insulin
uIU/mL
Time frame: 6 months after each intervention
Fasting glucose
mg/dL
Time frame: baseline
Fasting glucose
mg/dL
Time frame: 6 months after each intervention
2-hour glucose level during oral glucose tolerance test
mg/dL
Time frame: baseline
2-hour glucose level during oral glucose tolerance test
mg/dL
Time frame: 6 months after each intervention
Hemoglobin A1c
percent
Time frame: baseline
Hemoglobin A1c
percent
Time frame: 6 months after each intervention
Framingham risk score
This is a risk assessing measure that estimates the 10 year cardiovascular risk for an individual. There is no scale for this. A total risk (in percentage) will be calculated.
Time frame: baseline
Framingham risk score
This is a risk assessing measure that estimates the 10 year cardiovascular risk for an individual. There is no scale for this. A total risk (in percentage) will be calculated.
Time frame: 6 months after each intervention