Ovarian Reserve and Matrix Metalloproteinases

Oxidative Stress Clinical Trial

Official title:

Serum Prolidase Activity in Primary Ovarian Insufficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05443282
• Other study ID #: E1-20-1189
• Status: Completed
• Start date: August 10, 2021
• Est. completion date: March 7, 2022

Study information

• Verified date: June 2022
• Source: Ankara City Hospital Bilkent
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Primary Ovarian Insufficiency (POI) is dysfunction of ovaries before 40 years of age. It has been reported that genetic factors, endocrine disorders, previous pelvic surgeries, chemotherapy and radiotherapy, and autoimmune mechanisms play a role in 10%, however the etiology has not been clarified in 90% of the cases. Oxidative stress and autoimmunity has been shown to be responsible in the etiopathogenesis of POI. Prolidase is an imidodipeptidase. Prolidase was shown to be related with oxidative stress and autoimmune diseases in previous studies. In addition, it is thought that the level of prolidase plays a role both in the etiopathogenesis and progression of diseases. This study aims to investigate the level of prolidase enzyme in women with POI.

Description:

Primary Ovarian Insufficiency (POI) is dysfunction of ovaries before 40 years of age. It has been reported that genetic factors, endocrine disorders, previous pelvic surgeries, chemotherapy and radiotherapy, and autoimmune mechanisms play a role in 10%, however the etiology has not been clarified in 90% of the cases that are diagnosed as idiopathic POI. Recent studies concentrated on the role of immune mechanisms in idiopathic POI. Prolidase is a matrix metalloproteinase that plays a role in various metabolic processes and is responsible for the destruction of dipeptides containing proline and hydroxyproline. The prolidase has been shown to be related with oxidative stress and autoimmune diseases in previous studies. Prolidase was shown to be a diagnostic and prognostic value in a number of diseases. Proline and hydroxyproline are metabolites produced through the prolidase activity. Proline itself is also considered as a kind of metabolic stress indicator. On the other hand, free proline in the medium is known to inhibit the prolidase enzyme activity. Therefore, simultaneous measurement of proline and hydroxyproline levels in the medium enables to more accurately calculate the prolidase activity. This study aim to analyze the prolidase level in POI patients compared to healthy menstruating women. Besides the prolidase activity, we also aim to measure proline and hydroxyproline levels in order to provide the calibration for accurate results in terms of prolidase activity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: March 7, 2022
• Est. primary completion date: February 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of POI for study group

• Regularly menstruating women for control group

• Normally developed secondary sexual characteristics

Exclusion Criteria:

• Cardiovascular diseases including hypertension

• Type 1 or type 2 diabetes mellitus

• Morbid obesity

• Primary adrenal insufficiency

• Uterine fibroids

• Thyroid dysfunctions including Hashimoto thyroiditis and Grave's disease

• Hepatic dysfunctions

• Renal insufficiency

• Genetic disorders in chromosome constitution or karyotype analysis including monosomy X, trisomy X and gene mutations as BMP15, FMR I, POFIB, and GDF9

• Neurologic diseases

• Psychiatric disorders

• Autoimmune diseases or syndromes including Addison's disease, autoimmune syndromes, scleroderma, Sjogren's syndrome, myasthenia gravis, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and familial Mediterranean fever

• History of any malignancy

• History of exposure to chemotherapeutic agents or radiotherapy

Related Conditions & MeSH terms

• Ovarian Failure, Premature
• Ovarian Insufficiency, Primary
• Oxidative Stress
• Primary Ovarian Insufficiency

Intervention

Diagnostic Test:
• Prolidase Level
Measurement of venous blood serum level of prolidase enzyme level by ELISA method.
• Follicle Stimulating Hormone Level
Measurement of venous blood serum level of follicle stimulating hormone level.
• Estradiol Level
Measurement of venous blood serum level of estradiol hormone level.
• Proline Level
Measurement of venous blood serum level of proline level.
• Hydroxyproline Level
Measurement of venous blood serum level of hydroxyproline level.
• Anti-mullerian Hormone Level
Measurement of venous blood serum level of anti-mullerian hormone level.
• Antral Follicle Count
Ultrasonographic evaluation of antral follicle count to determine ovarian reserve.
• Prolactine Level
Measurement of venous blood serum prolactine hormone level.
• Thyroid Stimulating Hormone Level
Measurement of venous blood serum thyroid stimulating hormone level.

Locations

Country	Name	City	State
Turkey	Ankara City Hospital	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Ankara City Hospital Bilkent

Country where clinical trial is conducted

Turkey, 

References & Publications (15)

Bakalov VK, Anasti JN, Calis KA, Vanderhoof VH, Premkumar A, Chen S, Furmaniak J, Smith BR, Merino MJ, Nelson LM. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril. 2005 — View Citation

Carp HJ, Selmi C, Shoenfeld Y. The autoimmune bases of infertility and pregnancy loss. J Autoimmun. 2012 May;38(2-3):J266-74. doi: 10.1016/j.jaut.2011.11.016. Epub 2012 Jan 27. Review. — View Citation

Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol. 2014 Jul;124(1):193-197. doi: 10.1097/01.AOG.0000451757.51964.98. — View Citation

Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005 Jul-Aug;11(4):391-410. Epub 2005 May 26. Review. — View Citation

Hart RJ. Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics. Physiol Rev. 2016 Jul;96(3):873-909. doi: 10.1152/physrev.00023.2015. Review. — View Citation

Huang Y, Hu C, Ye H, Luo R, Fu X, Li X, Huang J, Chen W, Zheng Y. Inflamm-Aging: A New Mechanism Affecting Premature Ovarian Insufficiency. J Immunol Res. 2019 Jan 2;2019:8069898. doi: 10.1155/2019/8069898. eCollection 2019. Review. — View Citation

Kitchener RL, Grunden AM. Prolidase function in proline metabolism and its medical and biotechnological applications. J Appl Microbiol. 2012 Aug;113(2):233-47. doi: 10.1111/j.1365-2672.2012.05310.x. Epub 2012 May 10. Review. — View Citation

La Marca A, Broekmans FJ, Volpe A, Fauser BC, Macklon NS; ESHRE Special Interest Group for Reproductive Endocrinology--AMH Round Table. Anti-Mullerian hormone (AMH): what do we still need to know? Hum Reprod. 2009 Sep;24(9):2264-75. doi: 10.1093/humrep/de — View Citation

Luborsky J. Ovarian autoimmune disease and ovarian autoantibodies. J Womens Health Gend Based Med. 2002 Sep;11(7):585-99. Review. — View Citation

Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to iminodipeptiduria. Clin Chim Acta. 1982 Oct 27;125(2):193-205. — View Citation

Namiduru ES. Prolidase. Bratisl Lek Listy. 2016;117(8):480-5. — View Citation

Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015 Mar;103(3):e9-e17. doi: 10.1016/j.fertnstert.2014.12.093. Epub 2015 Jan 10. — View Citation

Rafique S, Sterling EW, Nelson LM. A new approach to primary ovarian insufficiency. Obstet Gynecol Clin North Am. 2012 Dec;39(4):567-86. doi: 10.1016/j.ogc.2012.09.007. Review. — View Citation

Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, Grymowicz M, Smolarczyk K, Kostrzak A, Smolarczyk R, Rudnicka E, Meczekalski B. Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge. Int J Mol Sci. 2021 Mar 5; — View Citation

Zhou F, Shi LB, Zhang SY. Ovarian Fibrosis: A Phenomenon of Concern. Chin Med J (Engl). 2017 Feb 5;130(3):365-371. doi: 10.4103/0366-6999.198931. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum prolidase level	Units per liter	10 minutes
Secondary	Serum proline level	Micromole per liter	10 minutes
Secondary	Serum hydroxyproline level	Micromole per liter	10 minutes