Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS

Study Overview
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Brief Summary
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A prospective study to determine the metabolic effects of the contraceptive vaginal ring among overweight and obese women with polycystic ovary syndrome (PCOS). We will recruit a total of 40 participants and study use of the vaginal ring over a 4-month period.

Official Title
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Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Etonogestrel/ethinyl estradiol vaginal ring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PCOS according to Rotterdam criteria, with at least 2 of 3 of the following criteria: oligomenorrhea (≤8 periods per year), clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound Body mass index ≥25 and ≤45 kg/m2 In good general health according to the investigators' discretion Willing to avoid pregnancy for the duration of the study Exclusion Criteria: Current pregnancy or desire for pregnancy during course of study Current breastfeeding Second-trimester pregnancy within four weeks prior to initiation of NuvaRing or third-trimester pregnancy within 6 months prior to initiation of NuvaRing Use of hormonal contraception within four weeks prior to initiation of NuvaRing Diagnosis of metabolic syndrome. Metabolic syndrome will be defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL. Contraindications to NuvaRing use: Age ≥ 35 plus tobacco use Current or past deep vein thrombosis or pulmonary embolism Cerebrovascular disease Coronary artery disease Thrombogenic valvular or rhythm diseases of the heart (such as subacute bacterial endocarditis with valvular disease or atrial fibrillation) Inherited or acquired coagulopathy Headaches with focal neurological symptoms or migraine headaches with aura Age ≥ 35 plus any migraine headaches Liver tumors, benign or malignant Undiagnosed abnormal uterine bleeding Current or past breast cancer or other estrogen- or progestin-sensitive cancer Hypersensitivity to any of the components of NuvaRing Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir Medical comorbidities: 21-hydroxylase deficiency, congenital adrenal hyperplasia Untreated thyroid disease Untreated hyperprolactinemia Type 1 or 2 diabetes mellitus Uncontrolled liver disease Uncontrolled renal disease Current alcohol abuse Hypertension ≥ 140 mm Hg average systolic or ≥ 90 mm Hg average diastolic in women using anti-hypertensive medication Hypertension ≥ 150 mm Hg average systolic or ≥ 100 mm Hg average diastolic in women not using anti-hypertensive medication History of or current gynecologic cancer Triglycerides >=250 mg/dL Current use of lipid-lowering or weight loss agents Participation in any study of an investigational drug or device or biologic agent within 30 days Suspected adrenal or ovarian tumor secreting androgens Suspected Cushing's syndrome Bariatric surgery within 12 months Other medical concerns that in the judgment of the investigator may compromise safety of the participant or confound the reliability of compliance and information acquired in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Contraceptive Ring<br>Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing), which releases 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily. | Drug: Etonogestrel/ethinyl estradiol vaginal ring<br>* 16 weeks of continuous use of contraceptive vaginal ring<br>* Other names: NuvaRing;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Metabolic Syndrome | Metabolic Syndrome defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in low-density lipoprotein (LDL) measure |  | 4 months | 
| Change in high-density lipoprotein (HDL) measure |  | 4 months | 
| Change in triglycerides measure |  | 4 months | 
| Change in apolipoprotein A |  | 4 months | 
| Change in apolipoprotein B |  | 4 months | 
| Change in advanced lipid testing measure |  | 4 months | 
| Change in cholesterol efflux capacity |  | 4 months | 
| Change in fasting insulin level |  | 4 months | 
| Change in fasting 2 hour oral Glucose Tolerance Test result |  | 4 months | 
| Change in Testosterone |  | 4 months | 
| Change in Ferriman-Gallwey Hirsutism score | A lower score indicates less hirsutism. The F-G scoring system has a minimum value of 0, and a maximum value of 36. | 4 months | 
| Body Mass Index |  | 4 months | 
| Change in scoring on the Center for Epidemiologic Studies Depression Scale | The range of values is zero to 60, with the higher scores indicating the presence of more depressive symptoms. | 4 months | 
| Change in scoring on the State-Trait Anxiety Inventory | The State-Trait Anxiety Inventory measures both state and trait anxiety, the scores range from 20 to 80, with higher scores correlating with greater anxiety. | 4 months | 
| Change in scoring on Polycystic Ovary Syndrome Quality of Life Questionnaire | Worse quality of life is associated with a lower score on the questionnaire, with a range score from 30 to 210. | 4 months |