Serum Levels of C Type Natriuretic Peptide in Different Reproductive Periods

Healthy Postmenopausal Women Clinical Trial

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Official title:

Serum Levels of C Type Natriuretic Peptide in Reproductive Age, Perimenopausal and Postmenopausal Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04000815
• Other study ID #: CenkOzay
• Status: Completed
• Phase: N/A
• Start date: July 24, 2019
• Est. completion date: January 20, 2020

Study information

• Verified date: March 2020
• 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 (CNP) is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors.It has been suggested that the transport of cGMP to oocyte via gap junctions causes a continuous increase in cyclic adenosine monophosphate (cAMP) levels within the oocyte. An important role of increased cAMP levels in oocyte is shown to suppress meiotic progression. Deoxyribonucleic acid (DNA) 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(hCG) stimulation. Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG (9).

Description:

In this prospective study, 60 patients are planned to recruite. Group 1 consists of 20 healthy reproductive aged women between 18-40 years old, with regular menstruation. Group 2 will include 20 patients in perimenopausal time period between 40-49 ages and in group 3 there will be20 postmenopausal women.

Age, gravida, parity and body mass index (BMI) data of all patients will be recorded. BMI is calculated by dividing the body weight in kilograms by the square of the height in meters. All patients will go under ultrasound examination by the same clinician (ACO). The number of antral follicles in group 1 and group 2 will be recorded. In addition, on the 2nd or 3rd day of menstruation, serum FSH, LH and E2 data of the patients in group 1 and 2 will be recorded.

For the last 6 months, patients with drug use that may affect menstruation like oral contraceptives, patients with cardiac or renal disease and therefore drug use, causes of infertility other than unexplained infertility, history of ovarian surgery, presence of polycystic ovary syndrome, and patients with irregular menstruation will be excluded for the study. In addition, patients with renal, cardiac, central nervous system and endocrine diseases will be excluded.

Morning fasting venous blood samples will be taken from the patients on the 2nd or 3rd day of the menstruation for group 1 and 2. All blood samples will be centrifuged on the day of collection and separated serum samples and will be kept at -80 degrees until the day of CNP test. Serum CNP levels of the patients will be 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 will be analyzed using Statistical Package for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). The variables will be investigated using visual and analytical methods (histograms, homogeneity of variances test, Kolmogorov-Simirnov/Shapiro-Wilk's test) to determine whether or not they are normally distributed. Patient demographics and CNP values will be presented as median ± interquartile range. Gravida and parity will be demonstrated by frequency distribution. The correlation coefficients and their significance will be calculated using the Spearman test. P-values less than 0.05 will be regarded as statistically significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: January 20, 2020
• Est. primary completion date: January 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Healthy

• Regular cyclic menstruation for reproductive age group

Exclusion Criteria:

• No systemic disease(cardiac, renal...etc)

• Smoking

• Drug usage

• Pregnancy

Related Conditions & MeSH terms

• Healthy Perimenopausal Women
• Healthy Postmenopausal Women
• Healthy Reproductive Age Women
• Serum CNP Levels

Intervention

Diagnostic Test:
• C Type Natriüretic Peptide
C Type Natriuretic Peptide will be measured with elisa method

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 (9)

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

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum C Type Natriuretic Peptide Levels	The comparison of serum levels of C type natriuretic peptide among different age groups	Second or Third Day of Menstruation
Secondary	Correlation Between Serum CNP and Follicle Stimulating Hormone and Luteinizing Hormone Levels in Groups 1 and 2	Correlations between serum CNP vs Follicle Stimulating Hormone(FSH), CNP vs Luteinizing Hormone(LH) levels in groups 1 and 2	Second or Third Day of Menstruation
Secondary	Correlation Between Serum CNP and Antral Follicle Count (AFC) in Groups 1 and 2	Correlation between serum CNP and antral follicle count (AFC) in groups 1 and 2 using Spearman test	Second or Third Day of Menstruation
Secondary	Correlation Between Serum CNP and Estradiol Levels in Groups 1 and 2	Correlation of CNP vs. Estradiol levels in reproductive age and perimenopausal women	Second or Third Day of Menstruation