The Cycle Disturbances, OLigomenorrhea and Amenorrhea (COLA) Study & Biobank
NCT ID: NCT02309047
Last Updated: 2021-10-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
5000 participants
OBSERVATIONAL
2004-10-31
2023-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Inclusion criteria WHO I Hypogonadotropic hypoestrogenic status (previously: "hypothalamic amenorrhea")
1. Low to normal serum follicle-stimulating hormone (FSH) concentrations
2. Low serum estradiol concentrations
WHO II
1. Amenorrhea or oligomenorrhea (mean cycle \>35 days during the last 6 months)
2. Normal serum FSH concentrations (\<12 IU/L)
3. Absence of other causes for the cycle disturbance, including: normal prolactin concentrations (\<1.0 IU/L), normal thyroid stimulating hormone (TSH) concentrations (0.2 - 4.2 milli-International unit /L), abnormalities on ultrasonography.
Within women with WHO II status, polycystic ovary syndrome (PCOS) is diagnosed when at least 2 of the following criteria are met:
1. Oligo-/anovulation
2. Clinical and/ or biochemical hyperandrogenism
3. Polycystic ovaries on ultrasonography
WHO III
1. primary ovarian insufficiency (POI): defined as secondary amenorrhea before the age of 40 years and basal FSH \> 40 IU/L.
2. incipient ovarian failure (IOF): defined as normal-ovulatory cycles with raised basal FSH \> 12 IU/L before the age of 40 years.
3. transient ovarian failure (TOF): defined as irregular cycles with raised basal FSH \> 12 IU/L before the age of 40 years.
4. Poor ovarian response: defined as less than 4 oocytes retrieved or cancellation in case of absent follicle growth after ovarian hyperstimulation with 300 IU gonadotropins.
5. Early menopause: menopause occurring between age 40 and 45 years.
6. Hypergonadotropic primary amenorrhea: primary amenorrhea with raised basal FSH \> 12 IU/L. Controls For analyses in which comparison with female controls are needed, data will be collected from existing population based cohorts, such as the EPIC cohort (Julius Center), or selected women included in the preconceptional cohort (PC, derived from the Department of Reproductive Medicine and Gynaecology in the University Medical Center Utrecht (UMCU), separate protocol in preparation).
Exclusion criteria
* Age: younger than 18 yrs.
* Regularly cycling women, with the exception of women with elevated basal FSH concentrations (IOF cases).
Study parameters In order to determine the phenotype characteristics of women with cycle disturbances, and to allow for the identification of genetic factors associated with cycle disturbances, the following parameters will be obtained.
* Age
* Ethnicity
* Social economic status and education
* Intoxications: smoking habits (previous and current), use of alcohol or drugs
* Medication and medication history
* Mental health (depression, stress and anxiety)
* Cycle regularity: age at menarche, use of (oral/intrauterine) contraceptives, mean duration of cycle, variation in cycle duration.
* Reproductive \& obstetric history: parity, time to pregnancy and pregnancy outcome, subfertility (including treatments)
* Medical history (including previous gonadotoxic treatment)
* Family history of diabetes mellitus, early menopause, cycle irregularities, subfertility, cardiovascular disease, endocrinological disease, congenital disorders
* Basic physical examination: systolic and diastolic blood pressure, height, weight (BMI), waist circumference, hip circumference
* Assessment of hirsutism, acne, Tanner sexual development stages.
* Ovarian reserve parameters: antral follicle count, ovarian volume, anti-müllerian hormone (AMH)
* luteinizing hormone (LH), FSH, prolactin, TSH, estradiol concentrations
* Androgen levels
* Lipid spectrum, glucose, insulin, High sensitivity C-reactive protein
* In POI specifically: bone density as assessed by dual-energy X-ray absorptiometry (DEXA), karyotype, fragile X premutation screening, presence of autoantibodies (against thyroid, ovaries, parietal cells and adrenal gland).
Participation in the COLA Biobank will consist of the additional withdrawal of two blood vials (one for DNA and one for serum sampling) obtained during the routine diagnostic procedure.
Relatives of the index patient:
When a familial tendency of the WHO status is suspected on the basis of family history of 1st and 2nd degree relatives, these relatives will be invited for participation of the study.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
CROSS_SECTIONAL
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
WHO anovulation
WHO I, II. III anovulation. See inclusion criteria
No interventions assigned to this group
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Low to normal serum FSH concentrations
2. Low serum estradiol concentrations
WHO II
1. Amenorrhea or oligomenorrhea (mean cycle \>35 days during the last 6 months)
2. Normal serum FSH concentrations (\<12 IU/L)
3. Absence of other causes for the cycle disturbance, including: normal prolactin concentrations (\<1.0 IU/L), normal TSH concentrations (0.2 - 4.2 milliunits/L), abnormalities on ultrasonography.
Within women with WHO II status, PCOS is diagnosed when at least 2 of the following criteria are met:
1. Oligo-/anovulation
2. Clinical and/ or biochemical hyperandrogenism
3. Polycystic ovaries on ultrasonography
WHO III
1. POI: defined as secondary amenorrhea before the age of 40 years and basal FSH \> 40 IU/L.
2. IOF: defined as normal ovulatory cycles with raised basal FSH \> 12 IU/L before the age of 40 years.
3. TOF: defined as irregular cycles with raised basal FSH \> 12 IU/L before the age of 40 years.
4. Poor ovarian response: defined as less than 4 oocytes retrieved or cancellation in case of absent follicle growth after ovarian hyperstimulation with 300 IU gonadotropins.
5. Early menopause: menopause occurring between age 40 and 45 years.
6. Hypergonadotropic primary amenorrhea: primary amenorrhea with raised basal FSH \> 12 IU/L.
Exclusion Criteria
* Regularly cycling women, with the exception of women with elevated basal FSH concentrations (IOF cases).
18 Years
45 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
UMC Utrecht
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Bart CJM Fauser
professor BCJM Fauser
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Bart CJ Fauser, professor
Role: PRINCIPAL_INVESTIGATOR
UMC Utrecht
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University Medical Center Utrecht
Utrecht, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Christ JP, Gunning MN, Meun C, Eijkemans MJC, van Rijn BB, Bonsel GJ, Laven JSE, Fauser BCJM. Pre-Conception Characteristics Predict Obstetrical and Neonatal Outcomes in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2019 Mar 1;104(3):809-818. doi: 10.1210/jc.2018-01787.
Christ JP, Gunning MN, Palla G, Eijkemans MJC, Lambalk CB, Laven JSE, Fauser BCJM. Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency. Fertil Steril. 2018 Apr;109(4):594-600.e1. doi: 10.1016/j.fertnstert.2017.11.035. Epub 2018 Mar 28.
Related Links
Access external resources that provide additional context or updates about the study.
study information
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
12-645
Identifier Type: -
Identifier Source: org_study_id