Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome
Brief summary
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.
Detailed description
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.
Interventions
DRUGMetformin
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.
DRUGOral combined hormonal contraceptives
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.
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized, controlled, double blinded, controlled, crossover study.
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Women with PCOS aged 40-49 years. Subject is considered to have PCOS if she has current or verifiable history of: a) clinical and/or biochemical evidence of hyperandrogenism plus b) oligomenorrhea or irregular menstruation (substantially inconsistent menstrual cycle length). Subjects with fewer than 10 menses/year or average menstrual cycle length \>35 days are allowed to participate if they have a compelling past history of oligomenorrhea (average menstrual cycle length \>45 days or fewer than 9 menses/year) or irregular menstruation. * Screening safety labs within normal reference ranges although mild abnormalities that are common in obesity and/or hyperandrogenism will not be grounds for exclusion (see
Exclusion criteria
). * Subjects must be willing and able to provide written informed consent. * Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of the study * Willingness and ability to comply with scheduled visits and study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ) score | baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Short Form (SF)-36 score | baseline | 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. |
| General Anxiety Disorder (GAD)-7 score | baseline | 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. |
| Total testosterone concentrations | baseline | ng/dL |
| Calculated free testosterone concentrations | baseline | pg/mL |
| Sex hormone binding globulin | baseline | nmoL/L |
| LDL cholesterol level | baseline | mg/dL |
| HDL cholesterol level | baseline | mg/dL |
| Triglyceride level | baseline | mg/dL |
| Blood pressure | baseline | mmHg |
| Weight | baseline | kg |
| Body mass index | baseline | kg/meter square |
| waist-to-hip ratio | baseline | It is a ratio of waist and hip circumference |
| Matsuda index | baseline | It is an index to assess insulin sensitivity. |
| Fasting insulin | baseline | uIU/mL |
| Fasting glucose | baseline | mg/dL |
| 2-hour glucose level during oral glucose tolerance test | baseline | mg/dL |
| Hemoglobin A1c | baseline | percent |
| Framingham risk score | baseline | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristine Burt Solorzano, MD
University of Virginia
Outcome results
None listed