Measuring Menstrual Iron Loss Using the Iron Isotope Dilution Technique (MBL_Loss)

Quantifying Menstrual Blood Loss: Validating the Methodology for Stable Iron Isotopes Dilution Against the Alkaline Hematin Method

It is very difficult to quantify menstrual blood loss, the reference method is a tedious one. This is a problem, as it is not conducive to objectively measuring menstrual blood loss and understanding the contribution of menstrual iron loss to iron deficiency anemia. With this study, the investigators aim to investigate iron loss during the menstrual cycle and aim to validate a much simpler technique.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia; Menorrhagia
• Intervention / Treatment: Other: Iron isotope dilution; Other: Alkaline hematin method

Detailed Description

Anemia reduction efforts have largely focused on increasing iron intakes such as improving diet quality, food fortification with iron, iron supplementation, biofortification. There is little information on the contribution of menstrual iron loss to iron deficiency anemia.

Indeed, the accurate measurement of menstrual blood loss volume and iron loss is difficult. Self-perception of heavy menstrual blood loss poorly predicts actual blood loss, and the objective measurement of menstrual blood loss remains a tedious method. Various methods have been used to objectively measure menstrual blood loss volume including radioisotopes, but these methods are invasive. The investigators aim to validate a much simpler technique, namely the stable iron isotope dilution methodology. This is a promising new method for quantifying long-term body iron balance, absorption, and loss which has not been applied previously to measure menstrual iron losses. Validating this new method against the alkaline hematin reference method would be an important step to encourage menstrual blood loss measurements and shed light on the contribution of menstrual blood loss to iron deficiency and iron deficiency anemia.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8092
    • ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Female 18-30 year olds, who have already been labelled with stable iron isotopes.

Description

Inclusion Criteria:

• Female, 18-30 years old
• Already labelled with stable iron isotopes at least 12 months prior to study start
• 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)
• 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
• 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
• Inability to follow the study protocol

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants; Female 18-30 year olds, who have already been labelled with stable iron isotopes at least 12 months prior to study start.	Other: Iron isotope dilution; Menstrual blood loss will be determined using the iron isotope dilution technique and compared to the amount determined via the alkaline hematin method.; Other: Alkaline hematin method; Menstrual blood loss will be determined using the alkaline hematin method and compared to the amount determined via the iron isotope dilution technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in isotopic ratio per cycle	The change in iron losses between the time of menstruation and the remaining duration of the cycle will be measured based on the dilution of the stable iron isotopes in the blood	Screening, day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 and 85
Amount of menstrual blood lost (mL/cycle)	The amount of menstrual blood lost will be determined using the alkaline hematin reference method. All sanitary material is collected during menstruation in each cycle and the amount of blood lost is measured directly in this material. For each cycle the total amount of blood lost during this cycle is determined (there will be one value only during each cycle).	At the beginning of menstrual cycle 1 (cycle length between 28 and 35 days)
Amount of menstrual blood lost (mL/cycle)	The amount of menstrual blood lost will be determined using the alkaline hematin reference method. All sanitary material is collected during menstruation in each cycle and the amount of blood lost is measured directly in this material. For each cycle the total amount of blood lost during this cycle is determined (there will be one value only during each cycle).	At the beginning of menstrual cycle 2 (cycle length between 28 and 35 days)
Amount of menstrual blood lost (mL/cycle)	The amount of menstrual blood lost will be determined using the alkaline hematin reference method. All sanitary material is collected during menstruation in each cycle and the amount of blood lost is measured directly in this material. For each cycle the total amount of blood lost during this cycle is determined (there will be one value only during each cycle).	At the beginning of menstrual cycle 3 (cycle length between 28 and 35 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin concentration (g/L)	Hemoglobin will be measured to determine the presence of anemia and for the standardization of menstrual blood loss measurement	Screening, day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 and 85
Serum ferritin (microg/L)	Iron status parameter	Day 1 and 85
Serum transferrin receptor (mg/L)	Iron status parameter	Day 1 and 85
Alpha-1-acid glycoprotein (g/L)	Chronic inflammation parameter	Day 1 and 85
C-reactive protein (mg/L)	Acute inflammation parameter	Day 1 and 85

Collaborators and Investigators

• Sponsor: Isabelle Herter-Aeberli
• Collaborators: Kamuzu University of Health Sciences; Wageningen University and Research; Sight and Life Foundation
• Investigators: Principal Investigator: Isabelle Herter-Aeberli, PhD, ETH

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: blood loss; anemia; menorrhagia; menstruation; alkaline hematin; iron isotope dilution
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Uterine Diseases; Hemorrhage; Iron Metabolism Disorders; Menstruation Disturbances; Uterine Hemorrhage; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Menorrhagia; Iron Deficiencies
• Other Study ID Numbers: MBL_Loss

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