Polycystic Ovarian Syndrome, Vitamin D Deficiency
Conditions
Brief summary
The investigators conducted a prospective un-blinded pilot study of Vitamin D plus Calcium (Ca) supplementation in overweight (BMI \> 27) premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), as defined by the Rotterdam Criteria, 2003, and who were deficient in vitamin D as reflected by serum 25-hydroxy (25-OH) vitamin D (serum levels \< 20 ng/mL).
Detailed description
We had hypothesized that in women with PCOS, administering optimal daily doses of vitamin D3, as recommended by the National Academy of Sciences, 2000IU Cholecalciferol and 1000mg of calcium, both per oral (PO), over a three month period will improve their metabolic picture, and possibly hormone profile. Over the course of the trial, after the first 5 subjects had completed 3 month intervention,we observed that daily 2000IU D3 dosing regime was inadequate in normalizing vitamin D status in the study population; the dosing regimen was therefore modified to include weekly supplementation with 50,000IU D2 in addition to daily dosing with 2000IU D3.
Interventions
DIETARY_SUPPLEMENTVitamin D2 (Ergocalciferol)
50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months)
DRUGMedroxyprogesterone (Provera)
10mg, PO, daily for ten days
DIETARY_SUPPLEMENTVitamin D3 (Cholecalciferol)
2,000IU (or 2 tablets), PO, daily (supplements taken for three months)
DIETARY_SUPPLEMENTElemental Calcium
1,000mg (or 2 tablets), PO, daily (supplements taken for three months)
Sponsors
National Center for Research Resources (NCRR)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Premenopausal women (ages 18-40 years) with normal thyroid function and prolactin levels. * PCOS diagnosis based on Rotterdam criteria: presence of at least 2 of the following criteria: * oligomenorrhea-menstrual cycles \> 35 day intervals * hyperandrogenemia (elevated serum testosterone \[free or total\] &/or androstenedione levels) or features of hyperandrogenism i.e. acne or hirsuitism \[Ferriman-Gallaway score \> 3\] * polycystic ovaries on vaginal ultrasound as defined by ESHRE/ASRM criteria (ovarian volume ≥ 10mL or ≥ 12 follicles of diameter between 2-9mm in at least one ovary) * Overweight (BMI ≥ 27 Kg/m2) * Biochemical evidence of Vitamin D insufficiency (i.e. serum 25 OHD levels \< 20ng/mL)
Exclusion criteria
* Pregnancy * Known causes of oligomenorrhea other than PCOS, e.g. hypothyroidism/Cushing's Disease/late onset congenital adrenal hyperplasia (fasting 17-alphahydroxyprogesterone levels \< 200ng/dL) * Use of hormonal treatment (birth control pill/patch/depot medroxyprogesterone/medroxyprogesterone) within 3 months of the study onset. * Use insulin sensitizers (metformin, sulfonylureas, TZDs, incretins) within 3 months of the study onset. * Use of lipid lowering agents or medications known to influence insulin sensitivity (e.g. niacin, corticosteroids, beta blockers, calcium channel blockers, thiazide diuretics) or influence serum androgens (estrogen, anti-androgens, androgens) within 3 months of the study onset. * Known history of renal calculi or current use of Calcium and Vitamin D supplements. * Spanish Speaking.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum HbA1C at 3 Months | Completion | Fasting HbA1C levels at study completion after 3 month treatment |
| Fasting Insulin Levels at Study Completion After 3 Month Treatment | 3 months intervention | Fasting insulin levels at study completion after 3 month treatment |
| Fasting Glucose Levels at Completion of Treatment, at 3 Months | 3 months | Fasting glucose levels drawn after 3 months completion during oral GTT |
| AUC (Area Under a Curve at 0, 0.5, 1, 1.5 and 2 Hours) Insulin During 2 Hour GTT at Completion, at 3 Months | 3 months | Following 3 months intervention, AUC insulin was determined during 2 hour oral GTT |
| AUC (Area Under the Curve at 0, 0.5, 1, 1.5 and 2 Hours) During Oral GTT at Completion, at 3 Months | 3 months | AUC (Area under the curve at 0, 0.5, 1, 1.5 and 2 hours)for glucose was determined at completion of 3 months intervention for 2 hour oral GTT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of C-reactive Protein at Completion of 3 Months Treatment | 3 months | Serum levels of C-reactive protein upon completion, at 3 months |
Countries
United States
Participant flow
Recruitment details
Subjects recruited through flyers, medical clinics, internet postings May 2008-February 2010
Pre-assignment details
Some subjects did not follow through with eligibility testing or had further exclusions, such as scheduling difficulties.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months)
Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months)
Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months)
Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Vitamin D Plus Calcium (Ca) Supplementation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 26.42 years STANDARD_DEVIATION 6.11 |
| Baseline AUC for glucose | 16648.41 mg/min/120min STANDARD_DEVIATION 3949.98 |
| Baseline AUC insulin | 16136.50 µIU/ml/120 min STANDARD_DEVIATION 10086.29 |
| Baseline C Reactive protein level | 5.72 mg/L |
| Baseline glucose levels | 103.79 mg/dl STANDARD_DEVIATION 22.83 |
| Baseline HbA1C levels | 5.37 percentage STANDARD_DEVIATION 0.53 |
| Baseline insulin levels | 24.92 µIU/ml STANDARD_DEVIATION 15.42 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
AUC (Area Under a Curve at 0, 0.5, 1, 1.5 and 2 Hours) Insulin During 2 Hour GTT at Completion, at 3 Months
Following 3 months intervention, AUC insulin was determined during 2 hour oral GTT
Time frame: 3 months
Population: Number determined by completion of all study interventions and procedures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | AUC (Area Under a Curve at 0, 0.5, 1, 1.5 and 2 Hours) Insulin During 2 Hour GTT at Completion, at 3 Months | 16715.57 µIU/ml/120min | Standard Deviation 10371.76 |
Primary
AUC (Area Under the Curve at 0, 0.5, 1, 1.5 and 2 Hours) During Oral GTT at Completion, at 3 Months
AUC (Area under the curve at 0, 0.5, 1, 1.5 and 2 hours)for glucose was determined at completion of 3 months intervention for 2 hour oral GTT
Time frame: 3 months
Population: Number determined by all participants who completed all interventions and procedures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | AUC (Area Under the Curve at 0, 0.5, 1, 1.5 and 2 Hours) During Oral GTT at Completion, at 3 Months | 16726.56 mg/min/120min | Standard Deviation 3941.8 |
Primary
Fasting Glucose Levels at Completion of Treatment, at 3 Months
Fasting glucose levels drawn after 3 months completion during oral GTT
Time frame: 3 months
Population: Number determined based on all interventions and procedures completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | Fasting Glucose Levels at Completion of Treatment, at 3 Months | 103.79 mg/dl | Standard Deviation 22.83 |
Primary
Fasting Insulin Levels at Study Completion After 3 Month Treatment
Fasting insulin levels at study completion after 3 month treatment
Time frame: 3 months intervention
Population: Number determined by all those who completed all interventions and procedures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | Fasting Insulin Levels at Study Completion After 3 Month Treatment | 25.17 µIU/ml | Standard Deviation 13.67 |
Primary
Serum HbA1C at 3 Months
Fasting HbA1C levels at study completion after 3 month treatment
Time frame: Completion
Population: Number determined by those who completed all interventions and procedures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | Serum HbA1C at 3 Months | 5.55 percentage | Standard Deviation 0.66 |
Secondary
Serum Levels of C-reactive Protein at Completion of 3 Months Treatment
Serum levels of C-reactive protein upon completion, at 3 months
Time frame: 3 months
Population: All subjects who completed treatment for 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D Plus Calcium (Ca) Supplementation | Serum Levels of C-reactive Protein at Completion of 3 Months Treatment | 5.3 mg/L |