Iron Absorption and Variations of Iron Status, Hepcidin, Inflammation and Sex Hormones During the Menstrual Cycle

Study Overview
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Brief Summary
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Iron supplementation is the first line of treatment of iron deficiency in most women, but we do not know when the best time is to supplement in the context of the menstrual cycle. With this study, we aim to measure and compare iron status, hepcidin, inflammatory markers, hormones estrogen and progesterone and changes in iron absorption at various points throughout the menstrual cycle, with a long-term view to determine best time for iron supplementation in relation to the menstrual cycle.

Detailed Description
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To date, very few studies have assessed iron absorption in relation to a woman's menstrual cycle. Although oral iron supplementation is considered the first line of treatment for iron deficiency in most women, there is no knowledge on the relationship between this intervention in the context of the menstrual cycle, and more specifically there is no knowledge on its potential implications for the most appropriate timing of iron supplementation. A better understanding of iron absorption during the menstrual cycle as well as kinetics of key parameters could allow the design of adapted and/or new interventions (e.g., timing of iron supplementation in relation to different phases of the menstrual cycle) to mitigate iron deficiency in menstruating women and can inform programs aimed at addressing iron deficiency

Official Title
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Iron Absorption and Variations of Iron Status Parameters, Hepcidin, Inflammatory Markers and Sex Hormones During the Menstrual Cycle

Conditions
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Iron-deficiency

Intervention / Treatment
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* Other: Test meal labelled with 54Fe
* Other: Test meal labelled with 57Fe
* Other: Test meal labelled with 58Fe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, 18-30 years old Weight <70 kg Normal body mass index (18.5 - 25kg/m2) Regular menstrual cycle (self-reported cycle length between 28 and 35 days in the past 6 months) Depleted iron stores (serum ferritin ≤ 30 µg/L) Signed informed consent Able to read and understand English Exclusion Criteria: Use of hormonal contraceptives within a 3-month recall period Anemia (hemoglobin < 117 g/L) Any known major metabolic, gastrointestinal, kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer, or cardiovascular diseases (according to the participants own statement) Women with severe menstrual cramps that would prevent them from attending study meetings during menstruation (judged by the women) Consumption of iron-containing supplements within 1 month prior to the start of study Known difficulties with blood sampling Pregnancy (serum human chorionic gonadotropin (hCG) < 5 mIU/mL) Current smoking (>1 cigarette per week over a 1-month recall period) Women who are planning to get pregnant within the study period, as this would affect iron metabolism and subsequent study measurements. Inability to follow the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 54Fe<br>Participants will receive 54Fe at two time points throughout their menstrual cycle. | Other: Test meal labelled with 54Fe<br>* Each participant will receive 2 test meals containing 4mg each of isotopic tracer 54Fe<br>|
| Experimental: Experimental 57Fe<br>Participants will receive 57Fe at two time points throughout their menstrual cycle. | Other: Test meal labelled with 57Fe<br>* Each participant will receive 2 test meals containing 4mg each of isotopic tracer 57Fe<br>|
| Experimental: Experimental 58Fe<br>Participants will receive 58Fe at two time points throughout their menstrual cycle. | Other: Test meal labelled with 58Fe<br>* Each participant will receive 2 test meals containing 4mg each of isotopic tracer 58Fe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional iron absorption (%) | Fractional iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of the labelled test meals. | Day 2, 18, 22, 26 and 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin concentration (g/L) | Haemoglobin will be measured to determine presence of anaemia | Screening, day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 40 | 
| Serum ferritin (microg/L) | Iron status parameter | Screening, day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Serum transferrin receptor (mg/L) | Iron status parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Serum iron (microg/mL) | Iron status parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Serum hepcidin (nmol/L) | Hepcidin, a major regulator of iron absorption and influenced by inflammation, will be measured | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Alpha-1-acid glycoprotein (g/L) | Chronic inflammation parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| C-reactive protein (mg/L) | Acute inflammation parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Serum estradiol (pg/mL) | Hormonal parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Serum progesterone (ng/mL) | Hormonal parameter | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Total iron binding capacity (microg/mL) | Total iron binding capacity will be measured to determine the presence of iron deficiency | Day 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28 | 
| Menstrual blood volume loss/cycle | Semi-quantitative assessment to measure menstrual blood loss per cycle | Menstruation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron, Hormones, Anemia, Micronutrients, Trace elements, Menstruation