Effect of Vitamin D on Ovulation Rate in Women With Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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This is a randomized double-blind controlled trial on the effect of vitamin D supplementation to assess the ovulation rate of women with polycystic ovary syndrome (PCOS) and other reproductive, endocrine and metabolic outcomes after one year of treatment.

Detailed Description
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The hypothesis is that vitamin D supplementation results in significant improvement in the ovulation rate of women with PCOS either spontaneously or with oral ovulation induction agent. Anovulatory women with PCOS diagnosed by the Rotterdam criteria will be recruited. Participants will be randomized to the (1) vitamin D group or (2) placebo group. Those in the vitamin D group will take vitamin D 50,000 IU/ week for 4 weeks, followed by 50,000IU once every 2 weeks for 52 weeks, whereas those in the placebo group will take placebo tablets with the same external appearance. Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5mg to 7.5mg for 5 days per cycle titrated according to response) for ovulation induction. The primary outcome is the ovulation rate and will be compared between the 2 groups.

Official Title
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A Randomized Double-blind Controlled Trial on the Effect of Vitamin D on Ovulation Rate of Women With Polycystic Ovary Syndrome

Conditions
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Polycystic Ovary Syndrome, Anovulation

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal Aged 18-40 years Irregular long menstrual cycles (>35 days) PCOS according to the Rotterdam criteria Agree for transvaginal ultrasound Exclusion Criteria: Use of hormonal medication (including contraception) within 3 months prior to study inclusion, except the use of a progestogen to induce withdrawal bleeding every 3 months History of any medical condition or medications that may predispose to vitamin D sensitivity, altered vitamin D metabolism and/ or hypercalcemia, including active tuberculosis or current therapy for tuberculosis, sarcoidosis, history of renal/ ureteral stones, parathyroid disease, renal or liver failure or current use of anti-convulsants Use of insulin-sensitizing drugs, lipid lowering drugs or anti-hypertensive Anticipated to use the above medications in the coming one year Known type 2 diabetes mellitus Refusal to join the study Abnormal blood calcium level For those on supplements, we asked them to stop their own supplements.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D<br>Vitamin D 50,000 IU/ week for 4 weeks, followed by 50,000 IU once every 2 weeks for 52 weeks Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5mg to 7.5mg for 5 days per cycle titrated according to response) for ovulation induction. | Dietary Supplement: Vitamin D<br>* Vitamin D supplementation<br>|
| Placebo Comparator: Placebo<br>Placebo tablets with same external appearance for 52 weeks Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5mg to 7.5mg for 5 days per cycle titrated according to response) for ovulation induction. | Other: Placebo<br>* Placebo tablets with the same external appearance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovulation rate | Serum progesterone | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum 25(OH)D level | Serum 25(OH)D | 12 months | 
| Pregnancy rate | Positive urine or serum hCG test | 12 months | 
| Live birth rate | Delivery of a baby after 22 completed weeks of gestational age, or with birth weight of 500 grams if the gestation age is unknown, which shows evidence of life | 12 months | 
| Change in serum anti-Mullerian hormone level | serum AMH level | 12 months | 
| Change in antral follicle count | Antral follicle count measured by transvaginal/ transrectal ultrasound | 12 months | 
| Androgen indices | serum androgen and androstenedione levels, SHBG | 12 months | 
| Body mass index | Height in cm, weight in kg, to calculate the body mass index (kg/m^2) | 12 months | 
| Change in waist and hip circumference | waist and hip circumference in cm | 12 months | 
| Rate of diabetes mellitus/ impaired glucose intolerance | Measured by fasting and 2 hour glucose (post 75g OGTT) | 12 months | 
| Change in systolic and diastolic blood pressure | Blood pressure | 12 months |