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

NCT ID: NCT04006171

Last Updated: 2021-11-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-15

Study Completion Date

2020-09-01

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.

Conditions

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Polycystic Ovary Syndrome c Type Natriuretic Peptide Menstrual Irregularity Hyperandrogenism

Keywords

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c type natriuretic peptide polycystic ovary syndrome menstrual cycle

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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women with polycystic ovary syndrome

36 patients with PCOS

Group Type ACTIVE_COMPARATOR

C type natriuretic peptide

Intervention Type DIAGNOSTIC_TEST

Serum level of CNP in PCOS and healthy women

Healthy women of reproductive age

30 patients with regular normal menstrual cycle

Group Type ACTIVE_COMPARATOR

C type natriuretic peptide

Intervention Type DIAGNOSTIC_TEST

Serum level of CNP in PCOS and healthy women

Interventions

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C type natriuretic peptide

Serum level of CNP in PCOS and healthy women

Intervention Type DIAGNOSTIC_TEST

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Near East University, Turkey

OTHER

Sponsor Role lead

Responsible Party

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Ali Cenk

Medical Doctor, assistant professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Özay

Role: PRINCIPAL_INVESTIGATOR

Near East University

Locations

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Near East University Faculty of Medicine

Nicosia, , Cyprus

Site Status

Countries

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Cyprus

References

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Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010 Oct 15;330(6002):366-9. doi: 10.1126/science.1193573.

Reference Type BACKGROUND
PMID: 20947764 (View on PubMed)

Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009 Jun;136(11):1869-78. doi: 10.1242/dev.035238.

Reference Type BACKGROUND
PMID: 19429786 (View on PubMed)

Vaccari S, Weeks JL 2nd, Hsieh M, Menniti FS, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009 Sep;81(3):595-604. doi: 10.1095/biolreprod.109.077768. Epub 2009 May 27.

Reference Type BACKGROUND
PMID: 19474061 (View on PubMed)

Tsafriri A, Chun SY, Zhang R, Hsueh AJ, Conti M. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol. 1996 Sep 15;178(2):393-402. doi: 10.1006/dbio.1996.0226.

Reference Type BACKGROUND
PMID: 8812137 (View on PubMed)

Thomas RE, Armstrong DT, Gilchrist RB. Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation. Dev Biol. 2002 Apr 15;244(2):215-25. doi: 10.1006/dbio.2002.0609.

Reference Type BACKGROUND
PMID: 11944932 (View on PubMed)

Nogueira D, Albano C, Adriaenssens T, Cortvrindt R, Bourgain C, Devroey P, Smitz J. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. Biol Reprod. 2003 Sep;69(3):1042-52. doi: 10.1095/biolreprod.103.015982. Epub 2003 May 28.

Reference Type BACKGROUND
PMID: 12773402 (View on PubMed)

Lee KB, Zhang M, Sugiura K, Wigglesworth K, Uliasz T, Jaffe LA, Eppig JJ. Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells. Biol Reprod. 2013 Feb 21;88(2):42. doi: 10.1095/biolreprod.112.104810. Print 2013 Feb.

Reference Type BACKGROUND
PMID: 23255339 (View on PubMed)

Hiradate Y, Hoshino Y, Tanemura K, Sato E. C-type natriuretic peptide inhibits porcine oocyte meiotic resumption. Zygote. 2014 Aug;22(3):372-7. doi: 10.1017/S0967199412000615. Epub 2013 Jan 18.

Reference Type BACKGROUND
PMID: 23331536 (View on PubMed)

Kawamura K, Cheng Y, Kawamura N, Takae S, Okada A, Kawagoe Y, Mulders S, Terada Y, Hsueh AJ. Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes. Hum Reprod. 2011 Nov;26(11):3094-101. doi: 10.1093/humrep/der282. Epub 2011 Aug 23.

Reference Type BACKGROUND
PMID: 21865234 (View on PubMed)

Wang X, Wang H, Liu W, Zhang Z, Zhang Y, Zhang W, Chen Z, Xia G, Wang C. High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice. Clin Sci (Lond). 2018 Apr 6;132(7):759-776. doi: 10.1042/CS20171394. Print 2018 Apr 16.

Reference Type BACKGROUND
PMID: 29535265 (View on PubMed)

Reis AM, Honorato-Sampaio K. C-type natriuretic peptide: a link between hyperandrogenism and anovulation in a mouse model of polycystic ovary syndrome. Clin Sci (Lond). 2018 May 8;132(9):905-908. doi: 10.1042/CS20171491. Print 2018 May 16.

Reference Type BACKGROUND
PMID: 29739821 (View on PubMed)

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.

Reference Type BACKGROUND
PMID: 14711538 (View on PubMed)

Ozay AC, Ozay OE, Edebal OH. Role of C-type natriuretic peptide in polycystic ovary syndrome. Int J Gynaecol Obstet. 2023 May;161(2):601-606. doi: 10.1002/ijgo.14568. Epub 2022 Nov 25.

Reference Type DERIVED
PMID: 36373234 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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CNP

Identifier Type: -

Identifier Source: org_study_id