Vitamin D for Polycystic Ovary Syndrome Clomiphene Resistant Women
Condition: PCOS; Vitamin D Deficiency
MeSH terms: Polycystic Ovary Syndrome; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is determining the therapeutic effect of Vitamin D supplements to Pcos clomiphene
      resistant polycystic ovarian syndrome Women. Half of patients will receive Vitamin D with
      metformin while other half metformin only. Then both groups start clomiphene for 3 month
    

Detailed description: 
      Polycystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders
      affecting women in their reproductive age. Genetically it is thought to be involving defects
      in primary cellular control mechanisms resulting in expression of chronic anovulation and
      androgen excess. Being familial condition , some researches showed it is autosomal dominant
      while others thought it is complex trait with oligogenic basis.

      Diagnosing poly cystic ovary syndrome is based on finding two of three criteria according to
      Rotterdam consensus 2003 : oligo/anovulation, clinical/ biochemical signs of
      hyperandrogenism, ultrasound finding of polycystic ovaries. While insulin resistance which
      affects 50 - 70 % of PCOS patients is considered to be the main reason for hyperandrogenic
      features, PCOS also leads to various health problems including metabolic disorders (obesity -
      Diabetes Mellitus - Cardiovascular diseases) in addition to menstrual irregularities and
      infertility .

      In PCOS women there is polymorphism in Vitamin-D receptor (VDR) gene associated with vitamin
      D level in blood . This gene is isolated from the female reproductive organs . In VDR null
      mice; uterine hypoplasia, impaired folliculogenesis and infertility is noted . That's why it
      is thought to be contributing in the genomic regulation of reproduction.

      Several studies have investigated the effectiveness of Vitamin D supplementation to PCOS
      women they found that PCOS women have hypovitaminosis D3 , with increasing evidence that
      vitamin D affects insulin and glucose metabolism . vitamin D intake in PCOS women may improve
      hormonal profiles in addition to having anti-inflammatory and anti-oxidant effects . Another
      study concluded that Vitamin D and calcium supplementation to PCOS women have a positive
      effect on BMI, follicular maturation, regularity of menses, androgen related symptoms,
      infertility and insulin resistance . Moreover, Vitamin D has a crucial role in ovulation
      induction in women with PCOS.

      Vitamin D and calcium in combination with metformin have significant effect on menstrual
      regulation and follicular development.

      Insulin sensitizers such as metformin have been extensively investigated in the management of
      PCOS. Metformin decreases blood glucose levels by enhancing peripheral glucose uptake,
      decreasing intestinal glucose absorption and suppressing hepatic glucose levels. In
      anovulatory women with PCOS, metformin decreases insulin levels, luteinizing hormone (LH)
      production and circulating androgen levels.

      Clomiphene citrate is an estrogen agonist and antagonist. It works by competitively binding
      estrogen receptors in the thalamus and as it remains in place for an extended period of time,
      it depletes the body's estrogen concentration at the hypothalamic level. As the body
      perceives low levels of estrogen, gonadotropin-releasing hormone (GnRH) is released which in
      turn stimulates pituitary release of follicle stimulating hormone ( FSH) which promotes
      follicular growth and maturation. If pregnancy is not achieved by 3-6 cycles, other
      treatments should be considered.
    

Intervention name(s): Vit D; Metformin; Clomiphene
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Injection; tablets; Tablet
Other intervention name(s): Devarol-S; Glucophage extended release; Clomid
Intervention MeSH terms: Metformin; Clomiphene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment