Rough Journey to Menopause: How Does Perimenopausal Menorrhagia Affect Women's Quality of Life and Cognitive Function?

(i) Recruitment: The investigators will recruit participants through advertisements and referrals. The investigators will utilize advertisements in Purdue Today, women's health clinics located in West Lafayette, Lafayette, and Indianapolis, and other social media platforms. Inclusion criteria are: all participants are undergoing natural perimenopause, English-speaking, and in general good health as documented by each woman's personal report that the participant is without any past history of a chronic health condition. The participants who have been using iron supplementation prior to the study may participate if the participants agree to discontinue the use of iron supplementation for the duration of the study. Lastly, individuals taking psychoactive drugs or with a history of hematological disorders will be excluded from the study.

(ii) Screening: Interested participants may either call or email the investigators using contact information found on the flyer or complete a short survey, which can be accessed via QR code on the flyer.

(iii) Randomization to treatment: Once the participants are classified as belonging to the IDA, ID, or IS groups, the participants will then be randomly assigned (within group) to receive either an iron supplement or a placebo for 4 months (previous studies have indicated a significant improvement in iron status and functional outcomes with a 4-month intervention period). FeoSol Original Iron Supplement Tablets (325 mg of ferrous sulfate containing 65 mg of elemental iron) will be used for the treatment (this have used this successfully in past studies) and 21st Century Gelatin Capsules (600 mg) will be used for the placebo (gelatin capsules have been used successfully for the placebo group, in past studies). Participants will be advised to take one capsule/tablet each day with food and store the given treatment out of the reach of children. Weekly phone calls or texts will be placed to each of the participants as a reminder to take supplements and to check tolerance to iron supplements. If intolerance to iron supplements are reported, participants may have an option to stop taking iron supplements. During weekly phone calls or texts, participants will also be asked if participants have started any new medications or become pregnant. If a participant becomes pregnant, participant's participation in the study will be terminated at that time. If a participant's physician is concerned about what the participants may be taking for this study, a participant's physician may contact either Mun Choi or Laura Murray-Kolb, whose contact information will be provided to all participants to share with physicians. Compliance will be measured through pill counts half-way through and at the end of the study. Group and treatment assignment will be blinded to the participants as well as the investigators.

(iv) Assessment of quality of life, mood, and family relationships: Assessment of these variables will take place before the blood draw at the Purdue Clinical Research Center at both baseline and endline of the study. Quality of life will be assessed using the self-administered MOS 36-Item Short Form Health Survey (SF-36) and the Menopause-Specific Quality of Life Questionnaire (MENQOL). These scales have been used extensively and shown to have good reliability with coefficients equal to or greater than 0.80 in most studies. For the assessment of mood, participants will be asked to complete the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item self-reporting questionnaire and items will be summed to create a total score with higher scores indicating higher levels of depression. It has been widely used in research and clinical settings to measure depressive symptoms according to the diagnostic criteria listed in the Diagnostic and Statistical Manual for Mental Disorders. The BDI-II has been tested for validity and reliability in different populations and has good internal consistency and reliability. Family relationships will be assessed using the Family Adaptability and Cohesion Evaluation Scale IV Short Form (FACES-IV-SF). Ratio scores that are less than 1 indicate unbalanced families, or lower quality of interactions among family members. A recent validation study showed that the FACES-IV-SF demonstrated adequate reliability and good fit to the data as evidenced by the Cronbach's alphas for the subscales ranging from 0.63 (Enmeshment) to 0.93 (Satisfaction). All family members over the age of 12 (age of 13-17) that live with participants will be asked to complete this questionnaire. For family members who are under the age of 18, parental consent will be obtained when obtaining participant's written consent and youth assent will be obtained before the administration of the FACES-IV questionnaire via Qualtrics. For family members who are at or over the age of 18, individual consent will be obtained before the administration of the FACES-IV questionnaire via Qualtrics.

(v) Computerized measures of cognitive function: Executive function is an umbrella term that is used to describe complex mental operations such as planning, time perception, working memory, inhibition, self-monitoring and regulation, motor control, regulation of emotion, and motivation. To assess multiple domains of executive function in women with perimenopausal menorrhagia, the Psychology Experiment Building Language (PEBL) platform will be utilized to evaluate cognitive domains that were shown to be affected by iron status in previous studies. The PEBL is a software package allowing the creation of computerized tests for experimental use and neuropsychological testing, and has been widely used in different populations to assess cognitive performance. Thus, the following tests will be performed through the PEBL to assess five domains of cognition in perimenopausal women in a lighting and temperature-controlled testing environment: