Clinical Research Directory

The Immunobiological Mechanisms of Depression in Perimenopause

This project aims to identify immunobiological mechanisms underlying the development of depression during the perimenopause. During the perimenopause, the risk for recurrence of depression is increased 13-fold among women who previously had depression. Moreover, perimenopause overlaps with the age span exhibiting the highest suicide rate for women. The perimenopause can last for several years and starts when estrogen and progesterone levels begin to fluctuate, gradually declining. Sex hormones are powerful modulators of the immune response and the investigators therefore propose that changes in lymphocytes play a central role in depression during this time. Notably, our previous work has demonstrated deficient regulatory T-cell responses in women with post- partum depression and identified a specific pro-inflammatory profile that predicts depression during pregnancy. Importantly, our new pilot data derived from women with severe depression in the perimenopausal age span reveals alterations in tryptophan metabolites that control T- cell responses as well as in the methylation of genes involved in T-cell fate and chromatin remodeling. Taken together, these data support the hypothesis that the perimenopausal hormonal shifts induce a pro-inflammatory state, regulated by chromatin modifications in T-cells, that triggers depression in vulnerable women. To test this hypothesis, the investigators will enroll 180 perimenopausal women aged 40-55, approximately half with depression and half without a diagnosis of depression. All participants will complete psychiatric assessments and provide blood samples to measure sex hormones, inflammation and immune cell changes. Women with depression will be reassessed approximately eight weeks later to identify blood markers that change as depressive symptoms improve. This project seeks to improve understanding of the biological mechanisms of depression during perimenopause and aid the development of predictive biomarkers and more effective treatments.

Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)

HOPES (Hops On Psychological and Estrogenic Symptoms in Menopause) is a randomized, double-blind, active-controlled nutritional intervention study in 120 peri- and postmenopausal women aged 45 to 60 years with moderate to severe menopausal symptoms. For 12 weeks, participants take one capsule per day of either a full spectrum hop (Humulus lupulus L.) extract or a soy isoflavone extract. Both products are marketed dietary supplements, and there is no placebo arm. The main question is whether the hop extract, which combines prenylated flavonoids with bitter acids, improves the psychological symptoms of menopause (depressive mood, irritability, anxiety, and physical and mental exhaustion) more than the soy extract. The main outcome is the change in the psychological subscale of the Menopause Rating Scale (MRS) from baseline to week 12. Secondary outcomes include the other MRS domains, anxiety, depressive symptoms, menopause-related quality of life, body composition, and safety.

Hemodynamics After Resistance Training

Women's blood vessel health gets worse after menopause, or "the change of life". Some women exercise less during menopause. Exercise can improve blood vessel health. The investigators want to know if resistance exercise, like lifting weights, can improve blood vessel health in women who are just starting menopause. The investigators also want to know if lifting weights can improve mood, sleep, and quality of life in women going through menopause. The investigators will have two groups of women for this study. One group will lift weights (do resistance exercise) twice per week, and the other group will get emails with information about menopause. The investigators will measure blood vessel health, sleep, mood, and menopause symptoms at the start and the end of this study and compare women who did and did not exercise.

Transcutaneous Auricular Neurostimulation (tAN) for Premenstrual Dysphoric Disorder (PMDD) and Perimenopause

Transcutaneous Auricular Neurostimulation (tAN) will be administered to women with premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and perimenopause. The investigators will examine whether tAN improves symptomology by collecting self-report data before the intervention, during the intervention, and following the intervention.

Exercise in Perimenopause to Improve Cognitive Health

Perimenopause is now considered a possible risk factor for dementia and may contribute to the fact that 2/3 of those living with Alzheimer's disease are females. Indeed, research studies show that middle-aged females demonstrate significant declines in their thinking abilities and detrimental changes in their brains as they go through perimenopause. Thus, perimenopausal females need strategies to bolster their brain health. The World Health Organization strongly recommends physical activity interventions to reduce the risk of decline in thinking abilities. However, whether exercise can improve thinking abilities and brain health in perimenopausal females has not been examined. Our research aims to address this important knowledge gap in female brain health. We will study the effects of a 6-month resistance exercise training (e.g., lifting free weights, exercise with weight machine) program on thinking abilities in 50 physically inactive perimenopausal females, aged 40 to 55 years, who are experiencing difficulties with their thinking abilities. In addition to measuring thinking abilities, we will determine if exercise benefits muscle health, heart health, sleep quality, psychological well-being, menopausal symptoms, and quality of life. We will also explore how resistance exercise training improves thinking abilities as such information can lead to new discoveries and therapies for brain health in females.

Effect of Lifestyle Intervention on Menopausal Symptoms, Sleep Quality, and Anxiety in Peri- and Postmenopausal Women

Menopause is a biological process characterized by the permanent cessation of menstruation, often accompanied by vasomotor symptoms, sleep disturbances, anxiety, and impaired quality of life. In primary healthcare settings, structured lifestyle interventions offer low-cost, safe, and sustainable non-pharmacological management strategies. The objective of this prospective, randomized controlled trial is to evaluate whether a structured lifestyle educational intervention leads to significant improvements in menopausal symptom severity, sleep quality, and anxiety levels compared with a control group receiving routine clinical care among perimenopausal and postmenopausal women aged 40 to 55 years. Primary and secondary outcomes are evaluated using the Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), and Generalized Anxiety Disorder-7 (GAD-7) at baseline and at 24 weeks.

Evaluation of the Effects of Lifestyle Medicine and Mindfulness-based Group Medical Visits on Stress, Microbiome, and Quality of Life in Women Experiencing Perimenopause and Menopause

While perimenopause and menopause are natural biological transitions, women may experience a wide range of physical, emotional, and cognitive symptoms. Although pharmacological options for symptom relief are available, these options may not be acceptable or suitable for all women. Integrative approaches for symptom relief, offered through group medical visits, may complement traditional therapies by increasing access to providers, allowing more time for focused education, and fostering supportive discussions with other women experiencing similar symptoms of perimenopause or menopause. The purpose of this study is to assess the effectiveness of eight monthly group medical visits that incorporate individual physical assessments, focused education on the foundational elements of Lifestyle Medicine relative to health and well-being, mindfulness practices, and community-building discussions with women experiencing perimenopause or menopause. Individual outcomes, obtained before the group medical visits begin, at each monthly group medical visit, and four months after the group medical visits are completed, will include measures of participants' perimenopause or menopause symptoms, stress, inflammation, microbiome (good bacteria in the body), height/weight, body mass index (BMI), systolic and diastolic blood pressure, and self-reported perceptions of physical, mental, and social health. Each 120-minute monthly group medical visit, led by a specially trained nurse practitioner and a mindfulness instructor, will include a brief physical assessment, educational discussions related to menopause and lifestyle medicine, experiential mindfulness practices, and the development of individual health and well-being goals.

Effects of a Dietary Supplement in Women With Late Perimenopause or Early Postmenopause

This study will evaluate the effects of a plant extract-based dietary supplement on menopausal symptoms and health indicators in women with late perimenopause or early postmenopause. Approximately 120 women aged 42 to 60 years will be randomly assigned to receive either the dietary supplement or a placebo daily for 12 weeks. Neither the participants nor the research team will know the assigned treatment during the study. Assessments will include the frequency and severity of hot flashes and night sweats, menopausal symptoms, quality of life, sleep quality, emotional well-being, body composition, and selected laboratory parameters.

Cuidar-ME, a Web-based Psychological Intervention for (Peri)Menopausal Women: A Pilot Randomized Controlled Trial

The Cuidar-ME program is a web-based cognitive-behavioral intervention designed to promote well-being and mental health in women during (peri)menopause. The main goal of this research is to evaluate its acceptability, feasibility and preliminary evidence of efficacy of the intervention. This pilot randomized controlled trial uses a two-arm design and serves as a preliminary step before a full-scale RCT. A sample of at least 150 (peri)menopausal women, aged 40 to 60, will be recruited online. Participants who meet the eligibility criteria will be randomly assigned to either the web-based intervention (Cuidar-ME) or a waitlist control condition (which will receive access to the program after the study concludes). Participation in this study will last approximately 3 months. Participants in both conditions will be invited by the researchers via email to complete baseline and post-intervention assessments. These assessments will include self-report questionnaires evaluating several outcomes (e.g., quality of life, menopausal symptoms, depressive and anxiety symptoms, menopause representations, etc.), potential mechanisms of treatment response (emotional regulation and self-compassion), as well as user acceptability and feasibility.

The Effect of Structured Health Information-Seeking Training on Cyberchondria and E-Health Literacy in Menopausal Women: A Randomized Controlled Trial

This randomized controlled study will examine whether two different forms of structured health information-seeking education can help women in perimenopause or postmenopause use online health information more effectively. It will assess whether video-based education and Pecha Kucha-based education reduce cyberchondria, which refers to repeated online health searches that may increase health-related worry, and improve e-health literacy and knowledge about menopause. The study will include 60 women aged 40 to 65 years. Participants will be randomly assigned in a 1:1:1 ratio to a video-based education group, a Pecha Kucha-based education group, or a control group, with 20 participants in each group. The education will cover how to identify reliable online health sources, evaluate health information, recognize misleading content, use effective search methods, and avoid online searching behaviors that may increase anxiety. The control group will not receive structured education during the study period. Outcomes will be assessed before the intervention, immediately after the intervention, and one month later. The findings will help determine which educational method is more effective in supporting safe and informed online health information-seeking among women during the menopausal transition.

Melatonin Effects on Cardiovascular Disease Mechanisms in Midlife Women: A Randomized Clinical Trial

The purpose of this research is to study the effects of 12 weeks of melatonin supplementation compared to placebo in women who are in the menopause transition (perimenopause) and have high blood pressure.

Effects of a Synbiotic Intervention on Perimenopausal/Menopausal Symptoms

FemmeBiome Meno is a synbiotic supplement, meaning it contains both probiotics (beneficial bacteria) and prebiotics (a special kind of fiber that feeds these bacteria). It is made up of: One capsule with 4 carefully selected bacterial strains and one sachet of powdered fiber. Both the capsule and the fiber sachet are taken daily. There are also placebo versions (lookalike products with no active ingredients) for use in the clinical trial. This specific combination of bacteria and fiber has not been studied before. However, previous research on the individual bacterial strains has shown several promising effects, such as: Reducing inflammation in lab tests on vaginal cells. Lowering stress-related hormones. Supporting general feelings of well-being. Helping maintain a healthy gut barrier, which is crucial for immune and digestive health. The fiber helps nourish both the added bacteria and the helpful microbes already present in the body. Some of these bacteria are believed to be reduced during menopause, especially those involved in estrogen metabolism. Why This Study Matters The aim of this study is to see whether FemmeBiome Meno can ease some of the most common and disruptive symptoms of perimenopause and menopause. In a survey of over 100 women, the top concerns were: Poor sleep Anxiety Brain fog (difficulty thinking clearly) The study also aims to examine how the supplement affects gut and vaginal health, which are both influenced by the drop in reproductive hormones during this stage of life. With so many women affected and such limited options currently available, there is a clear and urgent need for effective, science-backed natural solutions. The FemmeBiome Meno study hopes to fill that gap by providing a validated product that can genuinely support women's health during midlife and beyond.

12-week Multi-vitamin/Mineral Supplementation on Peri-menopause Symptoms, Cognition, Sleep, and Psychological Well-being.

Perimenopause is a stage of transition into menopause that is marked by menopausal symptoms while menstruation is still taking place. Perimenopause symptoms include mood changes, anxiety, sleep disruptions, hot flushes, night sweats, fatigue, and cognitive challenges. The frequency and severity of these symptoms can seriously impair women's quality of life. Even if the public's awareness on menopause has increased, there are still a lot of unanswered questions. A connection between nutrition and menopause management has been proposed in earlier research. However, there is limited research in this field, and women frequently turn to social media for supplement recommendations in order to deal with menopause-related issues. Vitamins and minerals such as vitamin D and calcium are recommended by the European Menopause and Andropause Society and there is limited evidence to suggests that soy and herbals may have a beneficial effect on menopausal symptoms, but more research is needed. The aim of this study is to investigate the effects of 12-weeks multi-vitamin/mineral and herbal extract-containing supplement on menopause symptoms, memory and concentration, sleep, and psychological well-being.

12-week Magnesium Supplementation on Peri-menopause Symptoms, Cognition, Sleep, and Psychological Well-being

Perimenopause is a transition phase into menopause, characterised by menopausal symptoms while menstrual periods are still occurring. Common symptoms of perimenopause include hot flushes, night sweats, mood swings, anxiety, sleep disturbances, fatigue, and cognitive difficulties. These symptoms can be both frequent and intense, with the potential to significantly deteriorate women's quality of life. Despite an increase in public discourse around menopause, there are still large gaps in knowledge. Previous literature has suggested a relationship between diet and menopause management. However, studies in this area are limited and women often rely on social media for advice on supplements to address menopause complaints. One supplement that has received a lot of attention with purported benefits for menopause is magnesium, primarily due to its links to energy and or/sleep, however no studies have explored psychological effects of magnesium supplementation in perimenopause. The aim of this study is to explore the effects of 12-weeks magnesium supplementation on perimenopause symptoms, cognition, sleep, and psychological well-being.

Hormone thERapy Effects on BRAin-HEART Health During the Menopausal Transition

The goal of this clinical trial is to learn whether it is feasible to conduct a larger study comparing transdermal menopausal hormone therapy (MHT) versus no hormone therapy in menopausal women with vasomotor symptoms (hot flashes and night sweats) and at least one cardiovascular risk factor. The main questions it aims to answer are: * What proportion of eligible women agree to be randomly assigned to either receive MHT or not? * How many participants complete the 12-month follow-up, including repeat heart imaging? * Does transdermal MHT affect early changes in heart muscle tissue as measured by cardiac MRI? Researchers will compare immediate initiation of transdermal estradiol (a skin gel or patch) to a no-hormone therapy strategy to see if MHT influences early cardiovascular and brain-vascular changes over 12 months. Participants will: * Be randomly assigned to start transdermal MHT within 2 weeks, or to use no hormone therapy for at least the first 3 months * Undergo a cardiac MRI and retinal eye imaging at the start of the study and again at 12 months * Complete cognitive testing and questionnaires about symptoms, sleep, and stress at both visits * Provide a blood sample for storage and future analysis of heart and brain health markers * Receive follow-up phone calls at 3, 6, and 9 months to review symptoms, medications, and any health changes

Vaginal Estradiol vs Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms and the Microbiome in Women Living With HIV

This is a research study about the effects of vaginal estradiol compared to moisturizer on vaginal symptoms of menopause and the microbiome in women with HIV. This research study aims to understand how vaginal products affect the aging of the female genital tract in women living with HIV who are menopausal or perimenopausal and have vaginal or urinary symptoms. There is a comparison group of women who are living without HIV. Participants with HIV and vaginal or urinary menopausal symptoms (e.g., dryness, irritation, soreness, itching, pain with sex, dysuria, urgency, or frequent urinary tract infections) will be asked to apply vaginal estradiol or a vaginal moisturizer (Replens). Participants who have vaginal or urinary menopausal symptoms and do not have HIV will receive vaginal estradiol.

CARAMEL Observational Study

CARAMEL is a project funded by the European Commission under the Horizon Europe programme. Its aim is to develop a personalized prevention approach based on state-of-the-art artificial intelligence models for cardiovascular risk stratification in women aged 40-60 years. These models are trained using large amounts of multi-source data and complemented by digital self-assessment and self-management tools. The CARAMEL consortium brings together a diverse group of 25 organizations, including technology companies and research centers, clinical institutions, as well as experts in ethics, law, and communication. The CARAMEL-OS study is an observational study aimed at prospectively completing the proposed personalized cardiovascular risk stratification model for women aged 40-60 years that will be developed during the earlier phases of the overall CARAMEL project (https://www.caramel-project.eu/). The study has a purely observational design, and patient stratification will not entail any clinical intervention. The data collected will be used to complete the design of the personalized stratification model, as well as to develop and validate the performance of the predictive models in an independent prospective cohort, distinct from the retrospective cohort initially used. The performance of the models developed using retrospective data will be assessed in terms of accuracy, discrimination, calibration, and other relevant metrics. In addition, the study will enable the development of new predictive models with short-term prediction horizons, incorporating additional variables that are not available retrospectively. The study population will be recruited in four European Union countries: Croatia, Spain (Andalusia and The Basque Country - Gipuzkoa), Greece and Lithuania; and in Colombia. A prospective cohort of 3,000 women aged 40-60 will be recruited, with each partner contributing 500 participants.

CREST: Samphire Guided Care Program on Wellbeing, Work Productivity, and Quality of Life

This study evaluates the feasibility and efficacy of the Samphire Guided Care (SGC) program * a 12-week structured digital health program combining clinician-led onboarding, at-home neuromodulation using the Lutea tDCS device, neuromodulation coach support, and app-based symptom tracking - on work productivity, employee wellbeing, and quality of life in individuals experiencing mood and cognitive symptoms associated with menstruation, perimenopause, or menopause.

Amygdala Insula Retraining in the Management of Perimenopause Symptoms

The goal of this study is to evaluate a neuroplasticity-based mind-body intervention, Amygdala and Insula Retraining (AIR), compared to a wait-list control in individuals experiencing perimenopausal symptoms. Our research questions include: Does AIR reduce overall perimenopausal symptom burden compared to a wait-list control? Does AIR improve sleep disturbance, vasomotor symptom interference, fatigue, mood, anxiety, and quality of life in perimenopausal individuals? Are symptom changes associated with improvements in autonomic regulation and sleep parameters, as reflected by exploratory wearable measures including heart rate variability?

Cognitive Task Sensitivity in Perimenopause and Nutritional Status

Perimenopause is when you have symptoms of menopause but your periods have not stopped. Brain-related changes are just one of the many symptoms that occur, and changes to memory and concentration ("brain fog") are frequently reported to be a challenge to those experiencing them. Diet is also understood to play an important role during menopause, however there is still more to learn about the direct impact of nutrition on brain-related symptoms associated with perimenopause. The aim of this research is to identify mental tasks capable of capturing perimenopause-related changes and to better understand how diet might account for differences in mental task performance.

Impact of Cannabinoids on Menopause Symptoms

The purpose of the study is to examine the impact of the hemp-derived minor cannabinoids on symptoms of menopause/perimenopause.

A Study to Evaluate the Efficacy of a Postbiotic Supplement on Menopausal Symptoms in Premenopausal Women

The goal of this consumer health study is to evaluate the effect of resW™ Perimenopause Postbiotic on menopausal symptom severity, menopause-related quality of life, and selected microbiome-related outcomes in generally healthy perimenopausal women aged 35 to 55 years. Participants will be randomized to receive either the active supplement or placebo daily for 4 weeks. Participants will complete electronic questionnaires at baseline and during the study. A predefined subset of participants will also complete stool and vaginal sample collection at baseline and Week 4.

Impact of a Novel Functional Snack on Perimenopausal Symptoms and Well-being

This is a clinical trial aimed to investigate if a novel phytochemical and fibre-rich snack can improve perimenopausal symptoms and well-being in perimenopausal women aged 40-55 and not on hormone replacement therapy. Hypothesis: The investigators hypothesise that the phytochemical and fibre-rich snack will improve perimenopausal symptoms via a gut microbiota mediated mechanism. Main research questions: Does eating the snack every day lower menopause symptoms such as hot flushes, night sweats, mood changes, and sleep problems? Does the snack improve mood, stress, anxiety, sleep, and overall quality of life? Does the snack improve the balance of bacteria in the gut, and could this be part of how it helps symptoms?

Our Transitions: Improving the Path to Menopause With Personal Digital Health Technologies

The goal of this observational study is to build knowledge about the path to menopause using subjective, self-reported and objectively measured information from multiple wearable study devices and a smartphone app. This study is being done in female individuals who are 35-55 years of age. The eventual aim of this work is two-fold; 1) to increase knowledge, awareness and education for individuals and clinicians about the lived experience of perimenopause and menopause through objectively measured data from digital study devices, and 2) to develop approaches to empower female individuals to manage this transition by learning what improves or worsens their symptoms.