Impact of Vitamin D Supplementation on Cardiometabolic Status and Androgen Profile in Polycystic Ovary Syndrome
Condition: Evaluations, Diagnostic Self; Treatment Adherence
MeSH terms: Polycystic Ovary Syndrome
Study type: Interventional

Summary: 
      Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive, endocrine and
      metabolic functions. Vitamin D has an influence on metabolic and reproductive functions. This
      study was designed to explore the levels of free 25 hydroxy cholecalciferol [25(OH) D] in
      PCOS patients. We also aimed to clarify the impact of vitamin D supplementation on
      cardiometabolic status, androgen profile and clinical features of PCOS.
    

Detailed description: 
      Background Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder affecting 510% of
      women of reproductive age. It is a disorder that affects the reproductive, endocrine and
      metabolic functions and is the leading cause of chronic anovulation leading to infertility.

      PCOS is characterized by hyperandrogenism, chronic oligo or anovulation, and polycystic
      ovaries. Hyperandrogenism, in particular, is a hallmark feature of PCOS because it is
      strongly implicated in the genesis of the disorder; and is also associated with metabolic
      derangements that contribute to the underlying pathophysiology. Also, it is associated with
      cardiovascular risk factors including obesity, insulin resistance (IR), dyslipidemia,
      endothelial dysfunction, and metabolic syndrome.

      Vitamin D (VD) is a fat-soluble vitamin that is naturally present in very few foods and
      available as a dietary supplement. It is a steroid hormone with pleiotropic effects. In
      addition to the main effects of VD on bone and calcium metabolism, it has other roles in the
      body, including modulation of cell growth, neuromuscular and immune function, and reduction
      of inflammation.

      VD deficiency is now recognized as pandemic disease. Its prevalence varies according to
      geographic location, season, ethnicity and the standard laboratory value; of what is
      considered normal, deficient and insufficient. VD deficiency is a risk factor for
      hypertension, diabetes, and various cancers . Accumulating evidence suggests that VD
      deficiency might be a causal factor in the pathogenesis of IR and the metabolic syndrome in
      PCOS. Carotid intima-media thickness (CIMT) measured by ultrasound is a noninvasive, safe,
      low-cost, reproducible, and well-validated marker of preclinical atherosclerosis.

      PCOS is the most frequent endocrine disorder among women of reproductive age and VD
      deficiency is a key problem in PCOS patients conversely, the basic mechanisms underlying the
      favorable effects of vitamin D in PCOS are still obscure. Resolving this mechanism may
      provide insight into the pathophysiology of this syndrome. It can also offer a new
      therapeutic option for PCOS women. Thus, in the present study was designed to explore the
      levels of free 25 hydroxyvitamin D [25(OH) D] in PCOS patients. We also aimed to clarify the
      impact of vitamin D supplementation cardiometabolic status, androgen profile and clinical
      features of PCOS. Methods This placebo-controlled trial comprised 95 women with PCO recruited
      from Outpatient Clinics of the Endocrinology Unit of Internal Medicine and Obstetrics and
      Gynecology Departments, Faculty of Medicine, Zagazig University, Egypt and 50 healthy women
      matched to PCOS women as regard age and ethnic origin. The diagnosis of PCOS was based on the
      2004 revised Rotterdam criteria .. All women underwent the menstrual history and thorough
      clinical examination. All patients were assessed at the study start on the third day of a
      spontaneous or progesterone-induced menstrual cycle. Anthropometric measures were estimated,
      including waist/hip ratio, height and weight then we calculated body mass index (BMI). We
      estimated the hirsutism score according to Ferriman and Gallwey. .Ovarian volume and antral
      follicular count (AFC) were evaluated by transvaginal ultrasound (TVS). PCOS patients were
      randomized divided to the intervention group (n=55) received vitamin D supplements (42,000 IU
      oral vitamin D per week and 500 mg calcium carbonate per day for 12-week), and
      non-intervention group (n=40) received 500 mg calcium carbonate per day for 12-week. The
      exclusion criteria for all women included a history of hyperandrogenic states (such as
      nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome,
      21-hydroxylase deficiency, or hyperprolactinemia), DM, hypertension, liver, kidney, or
      thyroid diseases. In addition, subjects on non-steroidal anti-inflammatory drugs and
      multivitamin, as well as patients treated with hormone replacement therapy. At the start of
      the study, the participants were asked to maintain their usual diet and level of physical
      activity throughout the study period as well as not to receive any lipid-lowering medications
      and medications that might affect their reproductive physiology during the 12-week
      intervention. At baseline and at the endpoint of the 12 weeks of study, anthropometrical
      measurements were estimated as well as and blood samples were collected for biochemical
      analyses. Written informed consent was taken from all of the participants after explaining
      details and benefits as well as risks to them. The ethical committee of the Faculty of
      Medicine, Zagazig University approved our study protocol.

      2.1. Sampling of blood Blood samples were drawn from all subjects during the early follicular
      phase of the menstrual cycles. One ml was collected into tubes containing fluoride for
      fasting plasma glucose (FPG). A second remaining part underwent immediate serum separation
      and was stored at -20 ◦C until analysis serum. calcium, phosphate, albumin were measured.
      Total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides levels were
      determined using routine enzymatic methods (Spinreact, Girona, Spain). Low-density
      lipoprotein (LDL) cholesterol levels were calculated using the Friedewald formula.

      2.2. Immunochemical assays: We measured prolactin, FSH, and LH levels via chemiluminescence
      immunoassays (CLIA) provided by (Immunospec Corporation, CA, USA). Serum high-sensitivity
      C-reactive protein (hs-CRP) concentrations were measured using high sensitivity enzyme-linked
      immunosorbent assays (ELISA) (Biosource, Nivelles, Belgium). We determined to fast insulin,
      FSH, LH, total and free testosterone, sex hormone-binding globulin (SHBG) levels using ELISA
      kits (DRG International, USA). We calculated insulin resistance (IR) with the homeostatic
      model assessment (HOMA-IR) index, which is defined as fasting serum insulin (FSI) value
      (µU/ml) × fasting plasma glucose value (mg/dl)/405. The B cell function was calculated using
      HOMA- B as (20× (fasting insulin µU/mL)/ (fasting glucose (mmol/l) - 3.5).

      2.3.Determination of serum vitamin D levels Serum concentrations of 25(OH)-D were tested
      using enzyme-linked immunosorbent assay, [Cat No. EQ 6411-9601, Euroimmun Medizinische
      Labordiagnostika AG, Germany]. Current recommendations define VD deficiency as serum 25(OH)-D
      levels less than 20 ng/ml and VD insufficiency less than 30 ng/ml.

      2.4. Carotid ultrasonography Carotid artery atherosclerosis was determined by one examiner
      for all patients across all six sites, using high-resolution B-mode ultrasound (M-Turbo®,
      SonoSite, Washington, Bothell, USA), according to American Society of Echocardiography
      protocol.
    

Intervention name(s): cholecalciferol (vit D3)
Intervention type(s): Dietary Supplement
Intervention description(s): 42,000 IU oral vitamin D per week and 500 mg calcium carbonate
Other intervention name(s): calcium carbonate
Intervention MeSH terms: Cholecalciferol; Vitamin D; Calcium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: PCOS; VD supplementation; androgen level; cardio metabolic