Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women

Study Overview
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Brief Summary
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Recent studies have shown that C natriuretic peptide is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors. It is suggested that produced cGMP maintains the transport of oocytes via the gap junctions and leads to a continuous increase in cyclic adenosine monophosphate (cAMP) levels in the oocyte. An important role of increased internal cAMP levels in the oocyte is shown to suppress meiotic progression. Deoxyribonucleic acid studies in animals have shown that expression of the natriuretic peptide precursor increases during the periovulatory period and shows that this increase decreases rapidly after luteinizing hormone / human chorionic gonadotropin (hCG) stimulation.Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG.Polycystic ovary syndrome (PCOS) is the most common endocrine disease in the reproductive period, characterized by hyperandrogenism, oligo-anovulation, and polycystic ovarian morphology on ultrasonography, and in an animal study investigating the relationship between CNP and PCOS, serum CNP levels were increased in polycystic ovary syndrome.CNP serum level is thought to show differences between healthy women and women with polycystic ovary syndrome.

Detailed Description
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In this prospective study, a total of 60 patients are planed to be included. PCOS group will be consisted of 30 women and control group will include 30 healthy women with regular menstruation aged between 18-40 years old. PCOS diagnosis will be made according to Rotterdam criteria. Age and body mass index of all participants will be recorded. BMI will be calculated by dividing weight by height in square meters. Then morning fasting venous blood samples will be taken from the patients between 2nd-5th day of menstruation for both groups. All blood samples will be centrifuged on the day of collection. Sera will be aliquoted into 1.5 mL Eppendorf (Eppendorf, Milano, Italy) tubes, and will be kept at -80°C until the day of CNP test. For the PCOS patients describing oligo/anovulation, after excluding pregnancy, progesterone withdrawal bleeding will be created and then the patients will be evaluated. Serum levels of LH, FSH, estradiol, thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, sex hormone binding globulin (SHBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and insulin levels will be analyzed. For insulin sensitivity, homeostatic model of insulin resistance (HOMA-IR) will be used and it will be calculated by the formula: HOMA-IR ¼ fasting blood glucose (mg/dL)fasting insulin (mIU/mL)/405. Free androgen index will be calculated by the formula 100x (Total testosteron/SHBG). Serum CNP levels of the patients will be analyzed by an enzyme-linked immunosorbent (ELISA) assay for human C-type natriuretic peptide in accordance with the manufacturer's instructions (SEA721Hu, ELISA Kit for Human C-Type Natriuretic Peptide, Wuhan USCN Business Co., Ltd., Cloud-Clone Corp., CCC, USA). Data will be analyzed using Statistical Packege for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). Independent t-test will be used to compare the parameters with normal distribution. Parameters that don't fulfill the parametric test assumptions will be compared using Mann-Whitney U test. Correlation of CNP with other parameters will be analyzed using Spearman's rank correlation test. Receiver operating characteristic (ROC) curve will be used to evaluate diagnostic sensitivity and specificity of CNP for PCOS. P values less than 0.05 will be regarded as statistically significant.

Official Title
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C Type Natriuretic Peptide and Polycystic Ovary Syndrome

Conditions
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Polycystic Ovary Syndrome, c Type Natriuretic Peptide, Menstrual Irregularity, Hyperandrogenism

Intervention / Treatment
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* Diagnostic Test: C type natriuretic peptide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCOS defined according to Rotterdam criteria Healthy normal menstruating women Exclusion Criteria: Diabetes mellitus Cardiavascular disease Renal disease Any drug usage Smoking Pregnancy

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: women with polycystic ovary syndrome<br>36 patients with PCOS | Diagnostic Test: C type natriuretic peptide<br>* Serum level of CNP in PCOS and healthy women<br>|
| Active Comparator: Healthy women of reproductive age<br>30 patients with regular normal menstrual cycle | Diagnostic Test: C type natriuretic peptide<br>* Serum level of CNP in PCOS and healthy women<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CNP Levels of PCOS and Healthy Participants | The comparison of serum levels of C type natriuretic peptide among PCOS and healthy women | Second or Third Day of Menstruation | 
| Roc Curve of CNP | We made a cut off value estimation for the diagnosis of PCOS by serum CNP levels using Receiver operator characteristics. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the CNP for diagnosing PCOS | Second or Third Day of Menstruation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of FSH and LH of PCOS and Healthy Women | Serum FSH and LH of PCOS and healthy women were compared | Second or Third Day of Menstruation | 
| Serum Estradiol Levels of PCOS and Healthy Women | Serum Estradiol levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Serum Tiroid Stimulating Hormone of PCOS and Healthy Women | serum tiroid stimulating hormone of PCOS and healthy women were compared | Second or Third Day of Menstruation | 
| Serum Prolactin Levels of PCOS and Healthy Women | serum prolactin levels of PCOS and healthy women were compared | Second or Third Day of Menstruation | 
| Serum Androstenedione Levels of PCOS and Healthy Women | Serum Androstenedione Levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Serum Dehydroepiandrosterone Sulfate (DHEAS) Levels of PCOS and Healthy Women | Serum dehydroepiandrosterone sulfate (DHEAS) Levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Serum Total Testosterone Levels of PCOS and Healthy Women | Serum Total Testosterone Levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Serum Free Testosterone Levels of PCOS and Healthy Women | Serum Free Testosterone Levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women | Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women were compared | Second or Third Day of Menstruation | 
| Free Androgen Index of Participants | Free androgen index of participants were compared. It was calculated with the formula 100XTotal testosterone/Sex hormone binding globulin | Second or Third Day of Menstruation | 
| Serum Glucose, Total Cholesterol and Triglycerides Levels of Participants | Serum glucose, total cholesterol and triglycerides levels of participants were compared | Second or third day of menstruation and morning fasting | 
| High Density Lipoprotein and Low Density Lipoprotein Levels of Participants | High density lipoprotein and low density lipoprotein levels of participants were compared | Second or Third Day of Menstruation-morning fasting | 
| Serum Insulin Levels of Participants | Serum Insulin Levels of Participants were compared | Second or Third Day of Menstruation-morning fasting | 
| Homeostatic Model Assessment of Insulin Resistance of Participants | homeostatic model assessment of insulin resistance of participants were compared. The calculation was made with formula Glucose X Insulin/405. | Second or Third Day of Menstruation-morning fasting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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c type natriuretic peptide, polycystic ovary syndrome, menstrual cycle