Subclinical Hypothyroidism and Chronic Inflammation in PCOS

Jagiellonian University

Status: Enrolling

Conditions: Subclinical hypothyroïdism; Hypothalamic-Pituitary-Gonadal Axis Dysfunction; PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries

Treatments: Diagnostic Test: Evaluation of the impact of subclinical hypothyroidism, with present/ absent antithyroid antibodies, on the balance between anti- and pro-inflammatory factors in women in both study arms; Diagnostic Test: Measurement and comparison of leucocytosis and concentrations of CRP, procalcitonin, fibrinogen, ferritin, IL-1, IL-6, IL-10, TNF-alpha in both study arms; Diagnostic Test: Assessment of the impact of imbalance between anti- and pro-inflammatory factors in women with different PCOS and HPOD phenotypes on ovarian reserve indices

Study type: Interventional

Funder types: Other

Identifiers

NCT05842096

1072.6120.292.2022

Details and patient eligibility

About

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.

Full 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).

Enrollment: 160 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 2 patient groups

Polycystic ovary syndrome (PCOS)

Active Comparator group

Description:

Women meeting the Rotterdam-ESHRE-ASRM criteria for a diagnosis of PCOS

Treatment:

Diagnostic Test: Assessment of the impact of imbalance between anti- and pro-inflammatory factors in women with different PCOS and HPOD phenotypes on ovarian reserve indices

Diagnostic Test: Measurement and comparison of leucocytosis and concentrations of CRP, procalcitonin, fibrinogen, ferritin, IL-1, IL-6, IL-10, TNF-alpha in both study arms

Diagnostic Test: Evaluation of the impact of subclinical hypothyroidism, with present/ absent antithyroid antibodies, on the balance between anti- and pro-inflammatory factors in women in both study arms

Hypothalamic-Pituitary-Ovarian Axis Dysfunction (HPOD)

Active Comparator group

Description:

Women meeting the WHO criteria for a diagnosis of HPOD

Treatment:

Diagnostic Test: Assessment of the impact of imbalance between anti- and pro-inflammatory factors in women with different PCOS and HPOD phenotypes on ovarian reserve indices

Diagnostic Test: Measurement and comparison of leucocytosis and concentrations of CRP, procalcitonin, fibrinogen, ferritin, IL-1, IL-6, IL-10, TNF-alpha in both study arms

Diagnostic Test: Evaluation of the impact of subclinical hypothyroidism, with present/ absent antithyroid antibodies, on the balance between anti- and pro-inflammatory factors in women in both study arms