Introduction: The C-HEALTH study investigates how environmental and socio-economic conditions affect women's menstrual cycles and reproductive health. Aim: To compare progesterone levels during the luteal phase among women from different socio-economic backgrounds living in rural and urban areas in southern France. Methods: This is a prospective observational study involving 320 healthy women of reproductive age. * Hormones (progesterone, estradiol) will be measured daily in saliva. * Inflammation (Protéine C Réactive: CRP) will be measured five times per cycle via blood drops. * Participants will wear a smart ring to monitor body temperature and activity. * Daily symptoms and lifestyle data will be collected. * Environmental exposures (pollution, stress, living conditions) will be assessed and linked to menstrual health outcomes.
Introduction: Menstrual health is an important indicator of women's overall health, but the biological and environmental factors influencing the menstrual cycle are still poorly understood. The C-HEALTH study explores how social and ecological conditions - such as pollution, stress, socio-economic status, and living environment - affect hormonal patterns and menstrual health in women living in the Occitanie region (France). Aim: The primary objective is to compare luteal phase progesterone levels among women from different socio-economic backgrounds living in either rural or urban areas in the Occitanie region. The secondary objectives are: * To compare, according to the women's environment: levels of sex hormones (progesterone and estradiol) throughout a menstrual cycle, levels of an inflammation marker (C-reactive protein) throughout a menstrual cycle, and the description of the menstrual cycle (characteristics, possible abnormalities such as pain, abnormal bleeding, etc.). * To identify environmental factors associated with potential biological and menstrual cycle abnormalities. Methods: To meet the objectives of this research, 80 women aged 18-45 living in Occitanie (France) will be enrolled in each socioeconomic group at each location (4 groups: low-income urban, high-income urban, low-income rural, high-income rural; total n=320). After the inclusion visit (visit 1) and the training visit for self-sampling (visit 2), participants will collect their biological samples and data during one observed menstrual cycle, with a follow-up visit on day 7 of the cycle (visit 3), and will complete their participation with the collection of biological samples at home (visit 4). Biological samples (saliva and dried blood spots) will be collected no later than 30 days after the end of the collection period. The exposome matrix will be inferred using postcode and will include data from an air pollution database (Environment Data Management System - EDMS) linked primarily to traffic, industry, stationary fuel burners, forest fires and solid fuel combustion, comfort parameters (temperature, humidity), UV, pollen count, green, grey and blue spaces, vegetation, Shannon biodiversity index, noise, water quality (pesticides, heavy metals) At the end of this study: * Saliva samples will be analyzed using ELISA tests to measure steroid levels. * Dried blood spot samples will be analyzed using immunoenzymatic assays to measure CRP levels, using the ELISA technique. * The exposome will be analyzed using classical statistics, clustering/PCA (Principal Component Analysis) to assess exposure profiles, and EnWAS will be used to untangle independent associations between exposure variables and menstrual cycle parameters. A series of minimally adjusted univariate analyses will be performed and exposures significant at the false discovery rate will be retained in the cluster analysis. Within each cluster, a multivariable analysis will be performed to reduce the number of variables of interest. This will allow us to identify exposome factors independently associated with menstrual health.
Study Type
OBSERVATIONAL
Enrollment
320
Self-saliva samples are taken every day from D1 inclusive over 1 consecutive cycle, to measure progesterone (P4) and estradiol (E2) concentrations.
Self-blood sampling is done 5 times during the cycle to measure protéine C-Réactive (CRP) concentrations.
A connected ring is worn every day of the observed cycle, while maintaining lifestyle habits, to measure daily body temperature, assess heart rate variability and resting heart rate, evaluate physical activity and energy expenditure, assess stress level, and evaluate sleep quality.
An ovulation test (Ovulatest®) is carried out from day 7 until a test is positive, or until day 39 if ovulation is not detected
Institute of Evolutionary Science of Montpellier
Montpellier, France
RECRUITINGMean Luteal Phase Salivary Progesterone
Mean salivary progesterone concentration (pg/mL) measured during the luteal phase - from the day after ovulation (Day of Ovulation, Jov) to the end of the menstrual cycle, or from day 32 to 45 if ovulation is not detected. The outcome is used to compare hormonal levels between women of low vs. high socioeconomic status living in rural (Environment 1) or urban (Environment 2) areas in the Occitanie region
Time frame: One menstrual cycle (up to 45 days)
Progesterone levels
Progesterone levels (pg/ml) will be measured in saliva every day of the observed cycle. Averages will be calculated over 7 periods of the cycle: * Follicular Average * Follicular Peak Average * Luteal Average * Luteal Peak Average * Preovulatory Average\* * Periovulatory Average\* * Postovulatory Week 1 Average\* * Postovulatory Week 2 Average\* * Postovulatory Week 3 Average\* (\* for ovulatory cycles only)
Time frame: One menstrual cycle (up to 45 days)
Estradiol levels
Estradiol levels (pg/ml) will be measured in saliva every day of the observed cycle. Averages will be calculated during 7 periods of the cycle: * Follicular Average * Follicular Peak Average * Luteal Average * Luteal Peak Average * Preovulatory Average\* * Periovulatory Average\* * Postovulatory Week 1 Average\* * Postovulatory Week 2 Average\* * Postovulatory Week 3 Average\* (\* for ovulatory cycles only)
Time frame: One menstrual cycle (up to 45 days)
Protéine C Réactive (CRP) levels
CRP levels (mg/L) will be measured in the blood at 5 points during the observed cycle: * Day 2 (D2) * Day 7 (D7) * Day of ovulation (Dov) or Day 32 (D32=D45-13) if ovulation is not detected * at the Luteal Peak on Dov+7 or Day 39 (D39=D45-6) if ovulation is not detected * in the premenstrual phase on Dov+12 or Day 44 (D44=D45-1) if ovulation is not detected * Difference in CRP will be measured between D2 and Dov+7, or between D2 and D39 if ovulation is not detected
Time frame: Day 2, Day 7, Day of ovulation (or Day 32 if ovulation is not detected), 7 days after ovulation (or Day 39 if ovulation is not detected), 12 days after ovulation (or Day 44 if ovulation is not detected)
The length of cycles
The length (in days) of the 3 cycles preceding the observed cycle
Time frame: Day 0
Period frequency
Period frequency in the observed cycle (calculated as the length of a cycle: Duration between the first day of the observed cycle (D0) and the day before the first day of the next cycle). * Amenorrhea: no bleeding * Infrequent: \> 38 days * Normal: 24 to 38 days * Frequent: \< 24 days
Time frame: Day 0 and the day before the next cycle
Cycle regularity
Cycle regularity over the observed cycle and the three previous cycles: Difference (in days) between the longest and shortest cycle over four continuous cycles. * Normal or regular: difference ≤ 7-9 days) * Irregular: difference ≥ 10 days)
Time frame: Day 0 and the day before the first day of the next cycle
Duration of the period
The duration of the period in the observed cycle (in days). * Amenorrhea: 0 days * Normal: ≤ 8 days * Prolonged: \> 8 days
Time frame: Day 0 and the last day of menstruation (up to 45 days)
Flow abundance
Flow abundance (heavy/light) Heavy periods are defined as the need to change a sanitary napkin or tampon every 1 or 2 hours.
Time frame: Day 0 and the last day of menstruation (up to 45 days)
Score Higham
Score Higham is an objective assessment of menstrual blood loss based on the number of sanitary pads used and clots passed, to classify periods are light, normal or heavy. Score interpretation: * 100 points: blood loss of at least 80 mL, indicating menorrhagia. * 150 points: potential indication for surgical intervention in menometrorrhagia.
Time frame: Day 0 and the last day of menstruation (up to Day 45)
Ovulation test
Ovulatest® ovulation test performed from Day 7 until a positive test is obtained, or until Day 39 (D39=Day 45-6) if ovulation is not detected. Ovulation is considered the day following the positive test.
Time frame: Day 7 to positive test (up to Day 45) or until Day 39 if ovulation is not detected
Body temperature
Body temperature will be recorded on a smart ring throughout the observed cycle. Ovulation will be detected by an increase of at least 0.3°C by the smart ring.
Time frame: One menstrual cycle (up to 45 days)
Length of the luteal phase
Length of the luteal phase (in days), defined as the number of days between Dov (inclusive, measured by the first positive Ovulatest®) and the last day of the cycle. * ≤ 10 days: short luteal phase * \> 10 days: normal luteal phase (Practice Committees of the American Society for Reproductive Medicine and the Society for Reproductive Endocrinology and Infertility, 2021)
Time frame: First Day of ovulation and the day before the first day of the following cycle (up to Day 45), only if ovulation is detected
Intermenstrual bleeding
Presence of intermenstrual bleeding in the observed cycle (yes/no, and if yes, specify cycle day/date)
Time frame: One menstrual cycle (up to 45 days)
Premenstrual symptoms Intensity
Premenstrual symptoms intensity will be assessed over the observed cycle: * On Day 12 for the period between Days 6 and 12 (mid-follicular phase), * On Day 12 (Days 6 to 12) or Day 44 (Days 38 to 44) if ovulation is not detected. 16 symptoms (sweet cravings, increased appetite, mood swings/anxiety, fatigue, breast tenderness, weight gain, bloating, constipation or diarrhea, abdominal pain, headaches, sleep problems, inattention/distraction, hot flashes, decreased libido, oily hair, skin irritation) will be rated on a Likert scale from 1 to 5 (1=No symptoms; 2=Mild symptoms; 3=Moderate symptoms; 4=Severe symptoms; 5=Very severe symptoms).
Time frame: Day 12 and 12 days after ovulation (or Day 44 if ovulation is not detected)
Pain during menstruation
Pain during menstruation will be assessed on Day 2 of the observed cycle using a visual numeric scale (VNS) from 0 to 10.
Time frame: Day 2
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