Low Dose OC Therapy in Women With Polycystic Ovary Syndrome (PCOS): Impact of BMI on Hyperandrogenism

Study Overview
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Brief Summary
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The classic description of polycystic ovary syndrome (PCOS) is that it is a disorder characterized by menstrual irregularity, chronic anovulation, androgen excess, and abnormal gonadotropin secretion. Use of combined oral contraceptives (OCs) in women with PCOS effectively reduces circulating androgens. Although OCs are the most common and one of the oldest symptomatic treatment modalities for androgenic skin symptoms and for irregular menstrual cycles caused by hyperandrogenism, the data concerning the effect of treatment of PCOS women with different body mass index (BMI) are limited. This study is being done to compare the hormone and metabolic changes after treatment with low-dose oral birth control regimen of DRSP 3 mg/EE 0.02mg/levomefolate calcium 0.451 mg (Beyaz™) in women with PCOS with different body weights.

Detailed Description
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Clinically, polycystic ovary syndrome (PCOS) is a heterogeneous disorder of functional androgen excess and the features of PCOS can run through a spectrum of severity. The optimal modality for long-term treatment of PCOS should positively influence androgen synthesis, sex hormone binding globulin (SHBG) production, insulin sensitivity, the lipid profile, and clinical symptoms including hirsutism and irregular menstrual cycles. Combined oral contraceptives have been a key component of the chronic treatment of women with PCOS; improving androgen excess and regulating menstrual cycles. The effect of OCs on ovarian folliculogenesis significantly decreases androgen production. This mechanism was confirmed in both healthy women and women with PCOS. In obese patients with PCOS, it is likely that the suppression of androgen production is not as significant. It is thus possible to hypothesize that the effects of OCs in PCOS could be dependent on body weight and what is needed is a head-to-head comparison. The aim of this study is to compare the effect of 6 months of a low-dose oral contraceptive regimen of 24/4 DRSP 3 mg/EE 0.02mg/levomefolate calcium 0.451 mg on androgen profiles, cardiometabolic measures, B-vitamin status, and menstrual cycle regulation in three groups, normal (BMI 18-24.9 kg/ m2) overweight (BMI 25-29.9 kg/ m2) and obese (BMI 30-35 kg/ m2) women with PCOS.

Official Title
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Positive Clinical and Hormonal Effects of Ethinylestradiol Combined With Drospirenone (EE/DRSP) in Women With Polycystic Ovary Syndrome (PCOS): Impact of Body Weight and Relevance to Hyperandrogenism

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: 3 mg DRSP/20 μg EE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Adult female-16 years to 35 years of age who have been diagnosed with PCOS desiring contraception Actual BMI >18 to <35kg/ m2 Written consent for participation in the study Patient completed lactation Exclusion Criteria: Metabolic abnormalities requiring pharmacological intervention (except controlled thyroid disease) Uncontrolled hypertension Cancer or history of hormone-dependent cancer History of cholestasis Presence of contradictions for OC administration Personal history of cardiovascular events. Use of drugs known to exacerbate glucose tolerance. No prescription or over-the-counter weight-loss drugs Diabetes Use of medications that affect blood pressure or lipid profile Smoking in past 6 months Known thrombogenic mutations (e.g. Factor V Leiden) Current or history of deep venous thrombosis/pulmonary embolism Major surgery with prolonged immobilization Injectable hormonal contraceptive use within 6 months Use of hormonal (e.g., oral contraceptive [OC] pill) or insulin-sensitizing medication unless willing to cease medications for 3 months before study measurements

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 mg DRSP/20 μg EE--normal weight<br>Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive Normal weight -BMI 18-24.9 kg/ m2 | Drug: 3 mg DRSP/20 μg EE<br>* 1 pill daily-24 days of drospirenone 3 mg (3 mg DRSP)/ethinyl estradiol 20 μg (20 μg EE)/levomefolate calcium 0.451 mg (folate) -followed by 4 days of levomefolate calcium 0.451 mg (folate)only<br>* Other names: BeYaz;|
| Experimental: 3 mg DRSP/20 μg EE- Overweight<br>Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive BMI 25-29.9 kg/ m2 | Drug: 3 mg DRSP/20 μg EE<br>* 1 pill daily-24 days of drospirenone 3 mg (3 mg DRSP)/ethinyl estradiol 20 μg (20 μg EE)/levomefolate calcium 0.451 mg (folate) -followed by 4 days of levomefolate calcium 0.451 mg (folate)only<br>* Other names: BeYaz;|
| Experimental: 3 mg DRSP/20 μg EE- Grade 1 obese<br>Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive BMI 30-34.9 kg/ m2 | Drug: 3 mg DRSP/20 μg EE<br>* 1 pill daily-24 days of drospirenone 3 mg (3 mg DRSP)/ethinyl estradiol 20 μg (20 μg EE)/levomefolate calcium 0.451 mg (folate) -followed by 4 days of levomefolate calcium 0.451 mg (folate)only<br>* Other names: BeYaz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Assessment of Hyperandrogenism | The primary outcome measure is post-treatment Free Androgen Index(FAI) which is expressed in units. FAI is calculated by taking the testosterone concentration (in nmol/l) and dividing by concentration of sex hormone binding globulin (SHBG in nmol/L)and multiplying by 100 | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiometabolic Measures | Values represent blood pressure at 24 weeks. | 24 weeks | 
| Post Therapy BMI. | Post-treatment body mass index at 24 weeks | 24 weeks | 
| Biochemical Indicator of B-vitamin Status | Post-treatment in folate concentrations after 24 weeks of treatment | 24 weeks | 
| Menstrual Cycle Regularity | Post treatment menstrual frequency over 24 weeks normalized to number of menses per year .. | 24 weeks | 
| Adrenal Androgen DHEAS | Post-treatment levels of adrenal androgen DHEAS | 24 weeks | 
| Oral Disposition Index | Post-treatment insulin secretion-sensitivity index (ISSI) calculated from the oral glucose tolerance test (OGTT). A higher value indicate improved carbohydrate metabolism | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS