Menstrual Cycle Symptoms and Female Health (CICLOS)

July 8, 2026 updated by: Nuria Romero Parra, Universidad Rey Juan Carlos

Prevalence of Subclinical Ovulatory Disturbances and Symptoms During the Menstrual Cycle and Their Relationship With Physical and Mental Health in Spanish Women of Reproductive Age (Prevalencia de Alteraciones Ovulatorias subclínicas y síntomas Durante el CICLO Menstrual y su relación Con la Salud física y Mental en Mujeres españolas en Edad Reproductiva).

The complexity inherent to the hormonal fluctuations associated with the female menstrual cycle (MC) has contributed, from a methodological perspective in research, to the neglect of women's physiological characteristics and to the silencing and normalization of symptoms linked to different life stages and hormonal environments. The scarce and outdated available data suggest high percentages of women experiencing perimenstrual symptoms, such as premenstrual syndrome or menstrual pain, as well as intermenstrual discomfort. These symptoms not only significantly impair daily activities but, due to their normalization, often lead to the underdiagnosis of other gynecological conditions.

Subclinical ovulatory disturbances-characterized by the suppression of ovarian hormones as an adaptive defense mechanism against various environmental stressors-are also frequently underdiagnosed. These disturbances typically do not affect MC length, making them difficult to detect, and although the process is reversible, it may initiate irreversible consequences for certain tissues, such as bone mass loss. However, neither women nor their educational, occupational, or healthcare environments appear to have the resources and/or knowledge required to adequately address these issues.

All of this may compromise women's rights to adequate sexual and reproductive health and to a dignified quality of life, as recognized under the second line of Axis 4, "Effective Rights for All Women," of the Strategic Plan for Effective Equality between Women and Men 2022-2025. Therefore, the aims of this multicenter project-carried out by a multidisciplinary research team from seven Spanish universities and three international institutions-are to describe the prevalence of symptoms and alterations related to the MC in women of reproductive age and to identify their associations with physical and mental health.

To accomplish this, an observational study will be conducted in a large sample of women of reproductive age, including multiple symptom and perceived-health questionnaires and ovulation monitoring. In addition, in a subsample of participants, bone mineral density will be assessed, blood levels of sex hormones will be monitored, and an innovative analysis of health biomarkers (glycemic and lipid profile, and inflammation) from menstrual blood will be included. This will be complemented by a qualitative study of experiences related to MC-associated symptoms and alterations, using in-depth interviews and thematic content analysis.

The findings of this project are expected to support various dissemination and educational actions, justify the design of more inclusive educational and healthcare policies, and enhance the understanding of women's needs, ultimately contributing to improved symptom management and quality of life.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain
        • Recruiting
        • Universidad Rey Juan Carlos
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Naturally menstruating females between 18 and 45 years

Description

Inclusion Criteria:

  • Females
  • Between 18 and 45 years
  • Naturally menstruating.

Exclusion Criteria:

  • Pregnant or breastfeeding.
  • Hormonal contraceptive methods during the 6 months before the study.
  • hysterectomy or ooforectomy.
  • Smoking.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Prevalence of symptoms related to menstrual cycle in naturally menstruating females
Other: Prevalence
Fulfilling the following questionnaires: Daily Record of Severity of Problems (DRSP), Menstrual Distress Questionnaire (MEDI-Q), SAMANTA Bleeding Questionnaire, Dismenorrhea symptom Interference (DSI), EQ-5D-5L questionnaire, quality of life and mental health questionnaires, urine ovulation tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of menstrual cycle-related symptoms using the Daily Record of Severity of Problems (DRSP).
Time Frame: Daily through study completion, an average of 3 months.
The DRSP is a prospective and validated questionnaire to assess the presence and severity of premenstrual symptoms. Participants rate 3 dimensions (depressive, physical and irritability) of symptoms on a 6-point Likert scale ranging from 1 (not at all) to 6 (extreme). The total symptom score is calculated by summing responses across symptom items, with higher scores indicating greater symptom severity and functional impairment.
Daily through study completion, an average of 3 months.
Menstrual cycle-related distress using the Menstrual Distress Questionnaire (MEDI-Q).
Time Frame: once, at enrollment (baseline).
The MEDI-Q is a 25-item instrument designed to assess menstruation-related distress. It evaluates symptoms including pain, discomfort, emotional and cognitive changes, gastrointestinal symptoms, and alterations in physiological functioning. The questionnaire provides a Total Score reflecting overall menstrual distress, as well as three subscales: Menstrual Symptoms (MS), Menstrual Symptoms Distress (MSD), and Menstrual Specificity Index (MESI). Higher scores indicate greater menstrual-related distress. A Total Score ≥20 has been proposed as indicative of clinically distressful menstruation.
once, at enrollment (baseline).
Dysmenorrhea using the Disnenorrhea Symptom Interference Scale (DSI)
Time Frame: Daily during bleeding days through study completion, an average of 3 days per month, 3 months.
The DSI evaluates the extent to which menstrual pain interferes with daily activities, physical functioning, emotional well-being, and social participation on a 6-point Likert scale ranging from 1 (not at all) to 6 (extreme). The total symptom score is calculated by summing responses across symptom items. Higher scores indicate greater pain-related interference.
Daily during bleeding days through study completion, an average of 3 days per month, 3 months.
SAMANTA Bleeding Questionnaire.
Time Frame: once, at enrollment (baseline).
The SAMANTA Questionnaire is a 6-item screening tool designed to identify heavy menstrual bleeding (HMB) that interferes with quality of life. Items are answered using a dichotomous yes/no format and generate a total score ranging from 0 to 10 points. Higher scores indicate greater likelihood of heavy menstrual bleeding affecting daily life. A total score of 3 or higher suggests clinically relevant heavy menstrual bleeding.
once, at enrollment (baseline).
Luteinizing hormone (LH) surge prior ovulation
Time Frame: Once a day, during three to five days prior the estimated ovulation day (around mid-cycle) according to participant's cycle retrospective count.
Urinary LH test to detect the LH hormone surge occurring 12-36 h prior ovulation.
Once a day, during three to five days prior the estimated ovulation day (around mid-cycle) according to participant's cycle retrospective count.
Ovulation
Time Frame: measured once, in days 6 to 9 after a positive urinary luteinizing hormone (LH) test during each monitored menstrual cycle.
Ovulation will be confirmed by measurement of mid-luteal serum progesterone concentration. Ovulation is considered confirmed when progesterone concentrations reach or exceed 16 nmol/L (4.61 ng/mL).
measured once, in days 6 to 9 after a positive urinary luteinizing hormone (LH) test during each monitored menstrual cycle.
Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Value
Time Frame: once, at enrollment (baseline).
The EQ-5D-5L Index Value is a standardized measure of health-related quality of life derived from five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted into a single index value, with higher values indicating better perceived health status.
once, at enrollment (baseline).
Health-related quality of life assessed using the EuroQol Visual Analogue Scale (EQ-VAS)
Time Frame: once, at enrollment (baseline).
The EQ Visual Analogue Scale (EQ-VAS) is a self-rated measure of overall health ranging from 0 (worst imaginable health) to 100 (best imaginable health). Higher scores indicate better perceived health status.
once, at enrollment (baseline).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum estradiol concentrations
Time Frame: At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum concentrations of estradiol from venous blood samples will be measured to characterize hormonal fluctuations across the menstrual cycle. Unit of measure: pg/mL (or pmol/L, depending on laboratory equipment).
At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum progesterone concentrations
Time Frame: At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum concentrations of progesterone from venous blood samples will be measured to characterize hormonal fluctuations across the menstrual cycle. Unit of measure: Unit of measure: ng/mL (or nmol/L).
At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum gonadotropin concentrations: luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
Time Frame: At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), will be measured to characterize hormonal fluctuations across the menstrual cycle. Unit of measure IU/L.
At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum testosterone concentrations
Time Frame: At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Serum concentrations of testosterone from venous blood samples will be measured to characterize hormonal fluctuations across the menstrual cycle. Unit of measure: Unit of measure: ng/mL (or nmol/L).
At 4 time points during one menstrual cycle: early follicular phase (cycle days 1-5), late follicular phase (approximately cycle days 10-14), ovulatory phase (12-36 hours after a positive urinary luteinizing hormone test), and mid-luteal phase (6-9 days)
Lipid profile biomarkers assessed from venous blood samples
Time Frame: Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Lipid health status will be assessed through measurement of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride concentrations obtained from venous blood samples. All measurements' units are mg/dL.
Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Fasting glucose concentrations
Time Frame: Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Fasting glucose concentrations to assess glycemic health status will be assessed. Unit of measure: mg/dL.
Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Fasting insulin concentrations
Time Frame: Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Fasting insulin concentrations to assess glycemic health status will be assessed. Unit of measure: µIU/mL.
Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Glycated hemoglobin (HbA1c) concentrations.
Time Frame: Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Glycated hemoglobin (HbA1c) concentrations from venus samples to assess average glycemic status will be obtained. Unit of measure: %
Once, at the mid-luteal phase of the cycle (cycle days 21-25 aproximately).
Serum high-sensitivity C-reactive protein (hs-CRP) concentrations
Time Frame: Once, at the mid-luteal phase of the cycle (cycle days 21-25, aproximately).
High-sensitivity C-reactive protein (hs-CRP) will be assessed from venous blood samples tas a marker of systemic inflammation. Unit of measure: mg/L.
Once, at the mid-luteal phase of the cycle (cycle days 21-25, aproximately).
Serum homocysteine concentrations
Time Frame: Once, at the mid-luteal phase of the cycle (days 21-25 aproximately).
Serum homocysteine will be assessed from venous blood samples as a biomarker associated with systemic inflammation and cardiometabolic health. Unit of measure: µmol/L.
Once, at the mid-luteal phase of the cycle (days 21-25 aproximately).
Bone mineral density assessed using dual-energy X-ray absorptiometry (DXA)
Time Frame: Baseline
Bone mineral density (BMD) will be assessed using dual-energy X-ray absorptiometry (DXA). BMD values will be used to evaluate bone health and to explore associations with menstrual cycle characteristics, ovulatory status, and sex hormone concentrations.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Rey Juan Carlos

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2026

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 11, 2026

First Submitted That Met QC Criteria

July 8, 2026

First Posted (Actual)

July 13, 2026

Study Record Updates

Last Update Posted (Actual)

July 13, 2026

Last Update Submitted That Met QC Criteria

July 8, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 41-01-ID25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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