C Type Natriuretic Peptide and Polycystic Ovary Syndrome
Phase: NA
Conditions: Polycystic Ovary Syndrome, c Type Natriuretic Peptide, Menstrual Irregularity, Hyperandrogenism
Sponsor: Near East University, Turkey

Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary 
Syndrome Patients and Healthy Women 
NCT04006171 
Date:01.07.2021 
 
Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary 
Syndrome Patients and Healthy Women 
NCT04006171 
Date:01.07.2021 
 
Study Protocol and Statistical Analyses Plan 
Recent studies have shown that C natriuretic peptide (CNP) 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 (LH) / 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. Recently, a study on PCOS-like mouse model investigated the effect of 
CNP/ natriuretic peptide receptor 2 (NPR2) on oocyte maturation and anovulation. They 
increased the expression of CNP/NPR2 with hyperandrogenism and showed meiotic arrest 
and anovulation in the subject oocytes. Conversely, they showed that reducing CNP/NPR2 
production led to partial recovery of ovulation.CNP serum level is thought to show 
differences between healthy women and women with polycystic ovary syndrome.  
In the light of these data, we conclude that in PCOS, which is known to be associated 
with hyperandrogenism and anovulation, serum levels of CNP, which is also associated with 
these components, may be elevated. In this study, it was aimed to determine serum CNP 
levels in PCOS patients, their relationship with serum androgens, and comparison with the 
healthy group. 
In this prospective study, a total of 66 patients admitted to the Department of 
Obstetrics and Gynecology of the Near East University Hospital were included. PCOS group 
consisted of 36 women and control group included 30 healthy women with regular 
menstruation aged between 18-40 years old. PCOS diagnosis was made according to 
Rotterdam criteria. PCOS diagnosis was made in the presence of two or three of these 
findings; oligo/anovulation, polycystic ovaries on ultrasonography and clinical or biochemical 
manifestations of hyperandrogenism.  

Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary 
Syndrome Patients and Healthy Women 
NCT04006171 
Date:01.07.2021 
 
Age, body mass index (BMI), serum levels of LH, follicle stimulating hormone (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 were measured. For insulin 
sensitivity, homeostatic model of insulin resistance (HOMA-IR) was used. Free androgen 
index (FAI) was calculated for all participants.  
Exclusion criteria were as follows: age over 40 years, current pregnancy, 
hyperprolactinemia, thyroid disease, congenital adrenal hyperplasia, a history of ovarian 
surgery or any other systemic disease or drugs that could influence hypothalamic pituitary 
ovarian axis, androgen production, insulin and or/glycemic metabolism, patients with cardiac 
or renal disease and therefore drug use, patients who received any hormone therapy including 
contraceptives up to 6 months before study. 
Morning fasting venous blood samples were taken from the patients on the 2nd or 3rd 
day of the menstruation for all participants. All blood samples were centrifuged on the day of 
collection and separated serum samples and were kept at -80 degrees celcius until the day of 
CNP test. Serum CNP levels of the patients were analyzed by an enzyme‐linked 
immunosorbent (ELISA) assay for human CNP in accordance with the manufacturer's 
instructions (SEA721Hu, ELISA Kit for Human CNP, Wuhan USCN Business Co., Ltd., 
Cloud-Clone Corp., CCC, USA). 
Data were analyzed using Statistical Package for Social Sciences software (SPSS v15, 
SPSS Inc, Chicago, IL, USA). Data were presented as mean±standard deviation or median 
and interquartile range. Independent t-test was used to compare the parameters with normal 
distribution. Parameters that don’t fulfill the parametric test assumptions were compared 
using Mann-Whitney U test. Correlation of CNP with other parameters was analyzed using 
Spearman’s rank correlation test.  Receiver operating characteristic (ROC) curve was used to 
evaluate diagnostic sensitivity and specificity of CNP for PCOS. P values less than 0.05 were 
regarded as statistically significant.