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

Polycystic Ovary Syndrome Clinical Trial

— CNP  

Official title:

C Type Natriuretic Peptide and Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04006171
• Other study ID #: CNP
• Status: Completed
• Phase: N/A
• Start date: July 15, 2019
• Est. completion date: September 1, 2020

Study information

• Verified date: October 2021
• Source: Near East University, Turkey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: September 1, 2020
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• c Type Natriuretic Peptide
• Hyperandrogenism
• Menstrual Irregularity
• Menstruation Disturbances
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Diagnostic Test:
• C type natriuretic peptide
Serum level of CNP in PCOS and healthy women

Locations

Country	Name	City	State
Cyprus	Near East University Faculty of Medicine	Nicosia

Sponsors (1)

Lead Sponsor	Collaborator
Near East University, Turkey

Country where clinical trial is conducted

Cyprus, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2003 May 28. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Serum Estradiol Levels of PCOS and Healthy Women	Serum Estradiol levels of PCOS and Healthy Women were compared	Second or Third Day of Menstruation
Secondary	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
Secondary	Serum Prolactin Levels of PCOS and Healthy Women	serum prolactin levels of PCOS and healthy women were compared	Second or Third Day of Menstruation
Secondary	Serum Androstenedione Levels of PCOS and Healthy Women	Serum Androstenedione Levels of PCOS and Healthy Women were compared	Second or Third Day of Menstruation
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum Insulin Levels of Participants	Serum Insulin Levels of Participants were compared	Second or Third Day of Menstruation-morning fasting
Secondary	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