Polycystic Ovary Syndrome
Conditions
Keywords
PCOS
Brief summary
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
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.
Interventions
DRUG3 mg DRSP/20 μg EE
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
Sponsors
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Woman's
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Assessment of Hyperandrogenism | 24 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post Therapy BMI. | 24 weeks | Post-treatment body mass index at 24 weeks |
| Biochemical Indicator of B-vitamin Status | 24 weeks | Post-treatment in folate concentrations after 24 weeks of treatment |
| Cardiometabolic Measures | 24 weeks | Values represent blood pressure at 24 weeks. |
| Adrenal Androgen DHEAS | 24 weeks | Post-treatment levels of adrenal androgen DHEAS |
| Oral Disposition Index | 24 weeks | Post-treatment insulin secretion-sensitivity index (ISSI) calculated from the oral glucose tolerance test (OGTT). A higher value indicate improved carbohydrate metabolism |
| Menstrual Cycle Regularity | 24 weeks | Post treatment menstrual frequency over 24 weeks normalized to number of menses per year .. |
Countries
United States
Participant flow
Recruitment details
This clinical trial was conducted from January 2012 to December 2014 Healthy, premenopausal women (n=64) with polycystic ovary syndrome (PCOS), aged between 16 and 35 years inclusive with a baseline body mass index (BMI) of \>18 to \<35kg/ m2, recruited from Woman's Metabolic Health clinic and Woman's Hospital gynecology clinics were enrolled
Pre-assignment details
Diabetic subjects, smokers, injectable hormonal contraceptive use within 6 months, or those taking sex hormones, carbohydrate metabolism, lipid-lowering and/or anti-obesity drugs within 3 months of the study were excluded
Participants by arm
| Arm | Count |
|---|---|
| 3 mg DRSP/20 μg EE--normal Weight Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive
Normal weight -BMI 18-24.9 kg/ m2
3 mg DRSP/20 μg EE: 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 | 20 |
| 3 mg DRSP/20 μg EE- Overweight Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive
BMI 25-29.9 kg/ m2
3 mg DRSP/20 μg EE: 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 | 21 |
| 3 mg DRSP/20 μg EE- Grade 1 Obese Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive
BMI 30-34.9 kg/ m2
3 mg DRSP/20 μg EE: 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 | 23 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Noncompliant | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 2 |
Baseline characteristics
| Characteristic | 3 mg DRSP/20 μg EE--normal Weight | 3 mg DRSP/20 μg EE- Overweight | 3 mg DRSP/20 μg EE- Grade 1 Obese | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 19 Participants | 19 Participants | 55 Participants |
| Region of Enrollment United States | 20 participants | 21 participants | 23 participants | 64 participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 23 Participants | 64 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 21 | 0 / 23 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 | 0 / 23 |
Outcome results
Primary
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
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Biochemical Assessment of Hyperandrogenism | 0.7 Index | Standard Deviation 0.5 |
| Obese | Biochemical Assessment of Hyperandrogenism | 0.7 Index | Standard Deviation 0.45 |
p-value: <0.0001ANOVA
Secondary
Adrenal Androgen DHEAS
Post-treatment levels of adrenal androgen DHEAS
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Adrenal Androgen DHEAS | 4.9 micromol/L | Standard Deviation 2.2 |
| Obese | Adrenal Androgen DHEAS | 4.3 micromol/L | Standard Deviation 2.3 |
p-value: <0.001ANOVA
Secondary
Biochemical Indicator of B-vitamin Status
Post-treatment in folate concentrations after 24 weeks of treatment
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Biochemical Indicator of B-vitamin Status | 65.8 Folate in nmol/l | Standard Deviation 20.4 |
| Obese | Biochemical Indicator of B-vitamin Status | 60.8 Folate in nmol/l | Standard Deviation 20.6 |
p-value: <0.001ANOVA
Secondary
Cardiometabolic Measures
Values represent blood pressure at 24 weeks.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Cardiometabolic Measures | 120 mmHg | Standard Deviation 13 |
| Obese | Cardiometabolic Measures | 125 mmHg | Standard Deviation 9 |
p-value: >0.05ANOVA
Secondary
Menstrual Cycle Regularity
Post treatment menstrual frequency over 24 weeks normalized to number of menses per year ..
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Menstrual Cycle Regularity | 11.3 number of cycles annually | Standard Deviation 1.7 |
| Obese | Menstrual Cycle Regularity | 11 number of cycles annually | Standard Deviation 1.4 |
p-value: <0.0001McNemar
Secondary
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
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Oral Disposition Index | 732 calculated index | Standard Deviation 420 |
| Obese | Oral Disposition Index | 272 calculated index | Standard Deviation 226 |
p-value: <0.04ANOVA
Secondary
Post Therapy BMI.
Post-treatment body mass index at 24 weeks
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Obese | Post Therapy BMI. | 24.6 kg/m2 | Standard Deviation 3.9 |
| Obese | Post Therapy BMI. | 32.7 kg/m2 | Standard Deviation 2.7 |
p-value: >0.05ANOVA