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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome; Anovulation
• Intervention / Treatment: Dietary supplement: Vitamin D; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital, University of Hong Kong
    • Contact: Jennifer Ka Yee Ko, MBBS; Phone Number: 22554647; Email: jenko@hku.hk
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Princess Margaret Hospital
    • Contact: Rebecca S.F. Wan, MBBS, MRCOG
  • Hong Kong, Hong Kong
    • Recruiting
    • Kwong Wah Hospital
    • Contact: Shui Fan Lai, MBBS, MRCOG; Phone Number: +852 35175183; Email: lsf087@ha.org.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D; 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; Vitamin D supplementation
Placebo Comparator: Placebo; 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; Placebo tablets with the same external appearance

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Kwong Wah Hospital; Pamela Youde Nethersole Eastern Hospital; The Queen Elizabeth Hospital; Princess Margaret Hospital, Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Anovulation; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: UW20-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: review by investigators

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No