Clinical trial NCT05842096: Subclinical Hypothyroidism and Chronic Inflammation in PCOS
Official title: The Influence of Subclinical Hypothyroidism on Chronic Inflammation Activity in Women With Different PCOS Phenotypes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries
Subclinical hypothyroïdism
Hypothalamic-Pituitary-Gonadal Axis Dysfunction
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2023-05-03
Enrollment: 158
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective tertiary single-centre cohort study
Primary purpose: DIAGNOSTIC

Brief summary: Chronic inflammation in polycystic ovary syndrome (PCOS) may be the result of dysregulation of cytokine production (due to insulin resistance, excess visceral fat and hyperandrogenemia), i.e., overproduction of pro-inflammatory factors (e.g. TNF, IL-1, IL-6) in relation to anti-inflammatory ones (IL-10). This condition may be an important link between obesity and insulin resistance, which is crucial in the etiopathogenesis of the syndrome. However, it is not known whether it results from the tendency to accumulate adipose tissue or is a feature of the syndrome itself. Concomitant endocrinopathies, i.e. obesity, dyslipidemia, insulin resistance, diabetes and thyroid diseases, may additionally influence the activity of chronic inflammation. There is no data indicating the relationship between chronic inflammation and PCOS phenotypes, the severity of metabolic disorders, ovarian reserve and the influence of thyroid function on its activity in PCOS.

Detailed description: The aim of the study is:

i) to assess and compare serum concentrations of selected inflammatory markers (leucocytosis, CRP, procalcitonin, fibrinogen, ferritin, IL-1, IL-6, IL-10, TNF-alpha) in women with different phenotypes PCOS and hypothalamic-pituitary-ovarian axis dysfunction (HPOD) (control), ii) to evaluate the impact of subclinical hypothyroidism (defined as TSH\>2.5 uIU/ml, fT3 3,1-6,80 pmol/l, fT4 12,0-22,0 pmol/l), with the presence and absence of circulating antithyroid antibodies (a-TPO and a-TG), on the balance between anti- and pro-inflammatory factors in women with different PCOS and HPOD phenotypes, iii) to assess the impact of imbalance between anti- and pro-inflammatory factors in women with different PCOS and HPOD phenotypes on ovarian reserve indices, expressed as FSH and AMH concentrations.

The study population will be characterized in terms of demographic (age, BMI), gynecological (age of first and last menstrual period, cycle length, history of reproductive organ surgeries, ultrasound measurements of endometrial width, ovarian volume) and obstetrics (pregnancies, childbirth, miscarriages) data. PCOS syndrome (and its phenotypes) will be recognized by the Rotterdam criteria. HPOD will be diagnosed according to WHO criteria. During hospitalization, blood samples will be collected for scheduled analyzes (30 ml of blood in total).

Eligibility criteria: Inclusion Criteria:

* age 18-45 years,
* cycle length \<21 days or \> 35 days,
* unsuccessful attempts to conceive for at least 12 months of regular intercourse with sonographically confirmed anovulation with excluded male, tubal and uterine infertility factors.

Exclusion Criteria:

* absence of at least one ovary,
* previously diagnosed thyroid disease

Primary outcomes:
measure: Values of inflammation parameters - leukocytosis in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - CRP in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - procalcitonine in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - fibrinogen in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - ferritin in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - IL-1 in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - IL-6 in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - IL-10 in peripheral blood in both study arms
timeFrame: up to 6 months
measure: Values of inflammation parameters - TNF-alpha in peripheral blood in both study arms
timeFrame: up to 6 months
Secondary outcomes:
measure: Correlation between the concentration of TSH (mIU/l) and the parameters of inflammation - leukocytosis in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and the parameters of inflammation - CRP in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and the parameters of inflammation - procalcitonin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: fibrinogen (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: ferritin (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: il-1
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: il-6
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: il-10
timeFrame: up to 6 months
measure: Correlation between the concentration of TSH (mIU/l) and inflammatory parameters: TNF-alpha
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and the parameters of inflammation - leukocytosis in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and the parameters of inflammation - CRP in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and the parameters of inflammation - procalcitonin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: fibrinogen (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: ferritin (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: il-1 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: il-6 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: il-10 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TPO (IU/ml) and inflammatory parameters: TNF-alpha (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and the parameters of inflammation - CRP in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and the parameters of inflammation - leukocytosis in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and the parameters of inflammation - procalcitonin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: fibrinogen (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: il-1 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: il-6 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: il-10 (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: TNF-alpha (pg/ml)
timeFrame: up to 6 months
measure: Correlation between the concentration of a-TG (IU/ml) and inflammatory parameters: ferritin (μg/l)
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - leukocytosis in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - CRP in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - procalcitonin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - fibrinogen in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - ferritin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - il-1 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - il-6 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - il-10 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of AMH (pmol/l) and the parameters of inflammation - TNF-alpha in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - leukocytosis in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - CRP in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - procalcitonin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - fibrinogen in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - ferritin in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - il-1 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - il-6 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - il-10 in both arms of the study
timeFrame: up to 6 months
measure: Correlation between the concentration of FSH (IU/l) and the parameters of inflammation - TNF-alpha in both arms of the study
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Krakow
country: Poland
facility: Jagiellonian University Medical College, Department of Gynecology and Obstetrics
city: Kraków
country: Poland
facility: Jagiellonian University Medical College, Department of Gynecology and Obstetrics
Study officials:
affiliation: Jagiellonian University
name: Robert Jach, Prof., Ph.D.
role: STUDY_CHAIR
References: