Menstrual Cycle Symptoms and Female Health

Official title

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).

Overview

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 The scarce and outdated available data suggest high percentages of women experiencing perimenstrual symptoms, such as premenstrual syndrome or menstrual pain, as well as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.

Interventions

• 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.

Primary outcome measures

• 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.]
• Menstrual cycle-related distress using the Menstrual Distress Questionnaire (MEDI-Q). [Time frame: 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.]
• SAMANTA Bleeding Questionnaire. [Time frame: 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.]
• Ovulation [Time frame: 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).]
• Health-related quality of life assessed using the EuroQol Visual Analogue Scale (EQ-VAS) [Time frame: once, at enrollment (baseline).]

Secondary outcome measures (11)

• 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 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 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 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)]
• Lipid profile biomarkers assessed from venous blood samples [Time frame: 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 insulin concentrations [Time frame: 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).]
• 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).]
• Serum homocysteine concentrations [Time frame: 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 1 center

• Universidad Rey Juan Carlos — Madrid

Identifiers

NCT: NCT07699224 · 41-01-ID25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗