Polycystic Ovary Syndrome (PCOS)
Conditions
Keywords
Polycystic Ovary Syndrome, Brown Adipose Tissue, Infrared Thermography, Inositol, Thermogenesis, Uncoupling Protein 1 (UCP-1), Nutrition
Brief summary
This study will investigate brown adipose tissue-related physiological responses in women with polycystic ovary syndrome (PCOS). Women with PCOS who have normal body mass index, women with PCOS who are overweight or have obesity, and healthy women will be compared. Brown adipose tissue-related heat responses will be evaluated using non-invasive infrared thermography of the supraclavicular region, together with serum UCP-1 levels and metabolic measurements. Participants in the overweight/obesity PCOS group will receive an inositol supplement for 12 weeks, and measurements will be repeated after supplementation. The study will also examine possible relationships between surface temperature responses, dietary intake, physical activity, body measurements, and metabolic and hormonal markers.
Detailed description
Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder associated with reproductive and metabolic abnormalities, including insulin resistance and excess body weight. Brown adipose tissue is involved in thermogenesis and energy metabolism, and previous studies have reported reduced brown adipose tissue-related activity in women with PCOS. This study aims to further characterize brown adipose tissue-related physiological responses in women with PCOS and to examine whether these responses differ according to body mass index. Brown adipose tissue-related heat responses will be assessed using infrared thermography of the supraclavicular region. Infrared thermography is a non-invasive, radiation-free method that allows evaluation of surface temperature changes associated with thermogenic responses. Serum UCP-1, a protein associated with brown adipose tissue, will also be measured. These assessments will be considered together with anthropometric measurements, hormonal and metabolic laboratory parameters, 24-hour dietary recall, thermogenic food consumption, and physical activity. The study includes three groups: women with PCOS and normal body mass index, women with PCOS who are overweight or have obesity, and healthy women without PCOS. Participants in the overweight/obesity PCOS group will receive oral inositol supplementation for 12 weeks. In this group, brown adipose tissue-related thermal responses and relevant laboratory measures will be reassessed after the supplementation period to examine within-group changes. Infrared thermography assessments will be performed after an overnight fast and during days 4-8 of the menstrual cycle to reduce variability related to hormonal fluctuations and body temperature. Participants will first rest in a thermoneutral environment. A standardized mild cold exposure will then be applied by immersing the hands in cold water for 5 minutes. Thermal images of the supraclavicular region will be obtained using a FLIR E5 Pro thermal imaging system and analyzed using FLIR Thermal Studio software. The study is expected to provide additional information on the relationship between PCOS, body weight status, and brown adipose tissue-related physiological responses and to explore whether inositol supplementation is associated with changes in these responses.
Interventions
DIETARY_SUPPLEMENTinositol
Participants in the overweight/obesity PCOS arm (BMI ≥25 kg/m²; n=20) will receive an orally administered inositol dietary supplement for 12 weeks. The supplement will provide 700 mg of inositol twice daily (total daily dose: 1,400 mg). The intervention is based on the use of myo-inositol and D-chiro-inositol, which are commonly used in PCOS management. The product will be selected from commercially available dietary supplements approved by the Republic of Türkiye Ministry of Agriculture and Forestry and will comply with applicable national regulations. Participants will be monitored throughout the supplementation period for tolerability and adverse effects. If an adverse effect or intolerance considered related to inositol occurs, the participant will be withdrawn from the study. Study assessments in this arm will be performed at baseline and after the 12-week supplementation period.
Sponsors
Istanbul Health and Technology University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Three parallel study groups will be evaluated: women with PCOS and normal body mass index, women with PCOS who are overweight or have obesity and receive inositol supplementation, and healthy women without PCOS as a reference group. Participants will remain in their assigned group throughout the study.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participants aged 18-40 years * Premenopausal status * Ability and willingness to provide written informed consent * For the Overweight/Obesity PCOS - Inositol and Normal-BMI PCOS Reference Group arms: * Diagnosis of polycystic ovary syndrome (PCOS) established by an obstetrician and gynecologist according to the Rotterdam criteria * For the Normal-BMI PCOS Reference Group arm: * BMI 18.5-24.9 kg/m² * For the Overweight/Obesity PCOS - Inositol arm: * BMI ≥25 kg/m² * For the Healthy Control Group arm: * BMI 18.5-24.9 kg/m² * Regular menstrual cycles * Normal ovarian morphology * No diagnosis of PCOS
Exclusion criteria
* Male sex * Age ≤17 years or ≥41 years * Menopausal status * BMI \<18.5 kg/m² * Pregnancy or breastfeeding * Regular smoking or alcohol consumption * Being highly physically active, defined as regular exercise during the previous 6 months or being a professional athlete * Presence of endocrine disorders that may affect the diagnosis of PCOS, including thyroid disease, congenital adrenal hyperplasia, androgen-secreting tumors, or Cushing syndrome * Any intervention for PCOS treatment within the previous 6 months, including pharmacological treatment or alternative approaches such as acupuncture * History of ovarian surgery * Presence of any of the following conditions: * Secondary hypertension * Cardiovascular, cerebrovascular, renal, hepatic, thyroid, or pulmonary disease * Any type of cancer * Acute infection * Autoimmune disease * Severe psychological or neurological disease * Following a special diet that may affect metabolic rate, including vegetarian, vegan, diabetic, or low-calorie diets * Regular use of dietary supplements such as probiotics or prebiotics * History of obesity-specific treatment, including bariatric surgery or anti-obesity medication * Regular medication use within the previous 3 months or currently, particularly oral contraceptives, hormonal medications, or medications affecting metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Uncoupling Protein 1 (UCP-1) Level | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum UCP-1 concentration will be measured using a commercial human sandwich ELISA kit as a biochemical marker of brown adipose tissue activity and thermogenesis, and reported in ng/L. |
| Supraclavicular Skin Temperature (Tscv) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Supraclavicular skin temperature (Tscv) will be measured with a FLIR E5 Pro infrared thermal imaging camera after a standardized mild cold exposure protocol (hand immersion in cold water for 5 minutes). Mean temperatures of the right and left supraclavicular regions of interest will be averaged to obtain a single Tscv value, reported in degrees Celsius (°C), as an indicator of brown adipose tissue activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Temperature | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Body temperature will be measured and reported in degrees Celsius (°C). |
| Body Weight | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Body weight will be measured and reported in kilograms (kg). |
| Waist Circumference | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Waist circumference will be measured and reported in centimeters (cm). |
| Body Mass Index (BMI) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | BMI will be calculated as body weight in kilograms divided by the square of height in meters and reported in kg/m². |
| Body Fat Percentage | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Body fat percentage will be measured using a household-type Tanita body composition scale (bioelectrical impedance) and reported as a percentage (%) of total body weight. |
| Basal Metabolic Rate | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Basal metabolic rate will be estimated using a household-type Tanita body composition scale (bioelectrical impedance) and reported in kilocalories per day (kcal/day). |
| Systolic Blood Pressure | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Systolic blood pressure will be measured and reported in millimeters of mercury (mmHg). |
| Diastolic Blood Pressure | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Diastolic blood pressure will be measured and reported in millimeters of mercury (mmHg). |
| Serum Follicle-Stimulating Hormone (FSH) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum FSH concentration will be measured and reported in mIU/mL. |
| Serum Luteinizing Hormone (LH) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum LH concentration will be measured and reported in mIU/mL. |
| LH/FSH Ratio | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | The LH/FSH ratio will be calculated by dividing serum LH (mIU/mL) by serum FSH (mIU/mL) and reported as a unitless ratio. |
| Serum Estradiol (E2) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum estradiol concentration will be measured and reported in pg/mL. |
| Serum Thyroid-Stimulating Hormone (TSH) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum TSH concentration will be measured and reported in µIU/mL. |
| Serum Dehydroepiandrosterone Sulfate (DHEA-S) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum DHEA-S concentration will be measured and reported in µg/dL. |
| Serum Total Testosterone | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum total testosterone concentration will be measured and reported in ng/mL. |
| Modified Ferriman-Gallwey (mFG) Hirsutism Score | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Hirsutism will be assessed using the modified Ferriman-Gallwey (mFG) scoring system, in which nine androgen-sensitive body areas are each scored from 0 (no terminal hair) to 4 (maximal terminal hair growth). Item scores will be summed to obtain a total score (units on a scale). The minimum score is 0 and the maximum score is 36; higher scores indicate more severe hirsutism (worse outcome). |
| Fasting Serum Glucose | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Fasting serum glucose will be measured after an overnight fast and reported in mg/dL. |
| Hemoglobin A1c (HbA1c) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | HbA1c will be measured and reported as a percentage (%) of total hemoglobin. |
| Fasting Serum Insulin | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Fasting serum insulin concentration will be measured and reported in µIU/mL. |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | HOMA-IR will be calculated as fasting insulin (µIU/mL) × fasting glucose (mg/dL) / 405 and reported as a unitless index. |
| Serum C-Reactive Protein (CRP) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Serum CRP concentration will be measured and reported in mg/L. |
| Physical Activity Level Assessed by the International Physical Activity Questionnaire-Short Form (IPAQ-SF) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Physical activity will be assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Total physical activity will be calculated by multiplying the minutes per week spent in walking, moderate-intensity, and vigorous-intensity activities by their metabolic equivalent (MET) values (3.3, 4.0, and 8.0, respectively) and summing them, and will be reported in MET-minutes per week. The minimum value is 0, with no fixed maximum; higher values indicate greater physical activity (better outcome). |
| Dietary Intake: Daily Energy Intake | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Dietary intake will be assessed using a 24-hour dietary recall, and total daily energy intake will be reported in kilocalories per day (kcal/day). |
| Relative Supraclavicular Skin Temperature (Trel) | At baseline for all participants and repeated after the 12-week supplementation period in the inositol arm. | Relative supraclavicular skin temperature (Trel) will be calculated as the difference between Tscv and the reference skin temperature (Tref) measured over the sternal region (corpus sterni), a region without brown adipose tissue, on the same thermal image (Trel = Tscv - Tref). Values from the right and left sides will be averaged to obtain a single Trel value, reported in degrees Celsius (°C). |
Countries
Turkey (Türkiye)
Contacts
CONTACTRANA TURGUT YAMAN
PRINCIPAL_INVESTIGATORRana Turgut Yaman
Istanbul Health and Technology University
STUDY_CHAIRHayrettin Mutlu, PhD
Istanbul Health and Technology University
STUDY_DIRECTORSeda Ateş, MD
Bezmialem Vakif University
Outcome results
None listed