NCT05443282

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
133

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Aug 2021

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 10, 2021

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 12, 2022

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 7, 2022

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

June 24, 2022

Completed
11 days until next milestone

First Posted

Study publicly available on registry

July 5, 2022

Completed
Last Updated

July 5, 2022

Status Verified

June 1, 2022

Enrollment Period

6 months

First QC Date

June 24, 2022

Last Update Submit

June 29, 2022

Conditions

Oxidative StressOvarian Insufficiency, PrimaryOvarian Failure, Premature

Outcome Measures

Primary Outcomes (1)

  • Serum prolidase level

    Units per liter

    10 minutes

Secondary Outcomes (2)

  • Serum proline level

    10 minutes

  • Serum hydroxyproline level

    10 minutes

Study Arms (2)

POI group (Study group)

* The study group included 68 women with POI. * The POI cases had been diagnosed as idiopathic POI. * The POI diagnosis was based on the presence of amenorrhea before the age of 40, increased serum FSH level higher than 40 mIU/ml, and decreased estradiol levels lesser than 50 pg/mL.

Diagnostic Test: Prolidase LevelDiagnostic Test: Follicle Stimulating Hormone LevelDiagnostic Test: Estradiol LevelDiagnostic Test: Proline LevelDiagnostic Test: Hydroxyproline LevelDiagnostic Test: Anti-mullerian Hormone LevelDiagnostic Test: Antral Follicle CountDiagnostic Test: Prolactine LevelDiagnostic Test: Thyroid Stimulating Hormone Level

Normally menstruating women (Control group)

* Control group consisted of 65 healthy, regularly menstruating women. * The women were at the age of lesser than 40 years old. * The women were recruited consecutively from those that applied to outpatient clinics to get counselling for family planning.

Diagnostic Test: Prolidase LevelDiagnostic Test: Follicle Stimulating Hormone LevelDiagnostic Test: Estradiol LevelDiagnostic Test: Proline LevelDiagnostic Test: Hydroxyproline LevelDiagnostic Test: Anti-mullerian Hormone LevelDiagnostic Test: Antral Follicle CountDiagnostic Test: Prolactine LevelDiagnostic Test: Thyroid Stimulating Hormone Level

Interventions

Prolidase LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of prolidase enzyme level by ELISA method.

Normally menstruating women (Control group)POI group (Study group)
Follicle Stimulating Hormone LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of follicle stimulating hormone level.

Normally menstruating women (Control group)POI group (Study group)
Estradiol LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of estradiol hormone level.

Normally menstruating women (Control group)POI group (Study group)
Proline LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of proline level.

Normally menstruating women (Control group)POI group (Study group)
Hydroxyproline LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of hydroxyproline level.

Normally menstruating women (Control group)POI group (Study group)
Anti-mullerian Hormone LevelDIAGNOSTIC_TEST

Measurement of venous blood serum level of anti-mullerian hormone level.

Normally menstruating women (Control group)POI group (Study group)
Antral Follicle CountDIAGNOSTIC_TEST

Ultrasonographic evaluation of antral follicle count to determine ovarian reserve.

Normally menstruating women (Control group)POI group (Study group)
Prolactine LevelDIAGNOSTIC_TEST

Measurement of venous blood serum prolactine hormone level.

Normally menstruating women (Control group)POI group (Study group)
Thyroid Stimulating Hormone LevelDIAGNOSTIC_TEST

Measurement of venous blood serum thyroid stimulating hormone level.

Normally menstruating women (Control group)POI group (Study group)

Eligibility Criteria

Age18 Years - 40 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsPOI means early cessation of menses, thus it is a disease diagnosed in only females.
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Study population includes a total of 133 participants. The study group consists of 68 women with the diagnosis of idiopathic POI, and the control group consists of 65 normally menstruating women.

You may qualify if:

  • Clinical diagnosis of POI for study group
  • Regularly menstruating women for control group
  • Normally developed secondary sexual characteristics

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ankara City Hospital

Ankara, 06100, Turkey (Türkiye)

Location

Related Publications (15)

  • 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.

    PMID: 24945456RESULT

  • 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;22(5):2594. doi: 10.3390/ijms22052594.

    PMID: 33807517RESULT

  • 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.

    PMID: 23182561RESULT

  • Namiduru ES. Prolidase. Bratisl Lek Listy. 2016;117(8):480-5. doi: 10.4149/bll_2016_093.

    PMID: 27546702RESULT

  • 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.

    PMID: 28139522RESULT

  • 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.

    PMID: 27252278RESULT

  • 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.

    PMID: 22512465RESULT

  • 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.

    PMID: 25585505RESULT

  • 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. doi: 10.1016/0009-8981(82)90196-6.

    PMID: 7139961RESULT

  • 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.

    PMID: 30719458RESULT

  • 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 Oct;84(4):958-65. doi: 10.1016/j.fertnstert.2005.04.060.

    PMID: 16213850RESULT

  • Luborsky J. Ovarian autoimmune disease and ovarian autoantibodies. J Womens Health Gend Based Med. 2002 Sep;11(7):585-99. doi: 10.1089/152460902760360540.

    PMID: 12396892RESULT

  • Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005 Jul-Aug;11(4):391-410. doi: 10.1093/humupd/dmi012. Epub 2005 May 26.

    PMID: 15919682RESULT

  • 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.

    PMID: 22284905RESULT

  • 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/dep210. Epub 2009 Jun 11.

    PMID: 19520713RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

the serum samples of peripheral venous blood obtained from antecubital vein were used to analyze prolidase, proline and hydroxyproline levels.

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Condition Hierarchy (Ancestors)

Ovarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System Diseases

Study Officials

  • Esin Merve Erol Koç, MD

    Ankara City Hospital Bilkent

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor

Study Record Dates

First Submitted

June 24, 2022

First Posted

July 5, 2022

Study Start

August 10, 2021

Primary Completion

February 12, 2022

Study Completion

March 7, 2022

Last Updated

July 5, 2022

Record last verified: 2022-06

Data Sharing

IPD Sharing
Will not share

IPD are available which may be shared in necessary conditions.

Locations

TU(1)