Impact of Funcional Exercise and Supplementation in Perimenopausal Women's Health

Effects of a Nutritional Supplement and Physical Exercise on the Psycho-emotional, Cognitive, Functional, and Neuroendocrine Health of Perimenopausal Women.

The goal of this clinical trial is to learn whether a natural-origin nutritional supplement, combined with a functional exercise program, can improve psycho-emotional, cognitive, functional, and neuroendocrine health in perimenopausal women. The study will also help determine the safety of this combined intervention.

The main questions it aims to answer are:

• Does the combined intervention improve mood, sleep quality, menopausal symptoms, and cognitive performance?
• Does it enhance physical function and neuroendocrine regulation?

Researchers will compare the supplement to a placebo. All participants will follow the same supervised functional exercise program.

Participants will:

• Take a daily nutritional supplement or placebo for 10 weeks
• Attend three weekly supervised functional exercise sessions (45-60 minutes each)
• Complete pre- and post-intervention evaluations including questionnaires, physical and cognitive tests, and blood samples for biomarker analysis.

Study Overview

• Status: Recruiting
• Conditions: Aging; Perimenopause
• Intervention / Treatment: Dietary supplement: Exercise + nutritional supplement; Dietary supplement: Exercise + placebo supplement

Detailed Description

This study is a randomized, double-blind, placebo-controlled clinical trial with parallel groups, designed to evaluate the effects of a natural-origin nutritional supplement combined with a functional physical exercise program on psycho-emotional, cognitive, functional, and neuroendocrine variables in perimenopausal women. Participants will be randomly assigned to the intervention groups, with both participants and outcome assessors blinded to group allocation (double-blind design). All study groups will receive a functional exercise intervention, in addition to the nutritional supplement or placebo.

The study will last a total of 10 weeks and will include a supervised functional exercise program consisting of three weekly sessions, each lasting 45 to 60 minutes. Pre- and post-intervention assessments will be conducted, including validated questionnaires on sleep quality, mood, general well-being, and menopausal symptoms; objective cognitive tests (attention, working memory, and executive functions); physical fitness assessments (strength, agility, gait speed, body composition); and blood analyses of neuroendocrine biomarkers (cortisol, BDNF, IL-6, TNF-α, GABA, and serotonin).

This methodological design will allow for both within- and between-group comparisons and the analysis of potential interactions between the interventions, in order to determine their efficacy and safety as non-pharmacological strategies to improve the overall health of perimenopausal women.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juan Carlos Colado Sánchez, Chair full professor; Phone Number: (9639) 83470; Email: juan.colado@uv.es

Study Locations

• Spain
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Recruiting
      • Physical activity and Sport Science Faculty, Valencia, Valencia 46010
      • Contact: Juan Carlos Colado Sánchez, Chair full professor; Email: juan.colado@uv.es
      • Principal Investigator: Juan Carlos Colado Sánchez, Chair full professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women aged between 45 and 65 years.
• In the menopausal transition (defined by irregular menstrual cycles and typical symptoms within the past year) or postmenopause.
• Score ≥ 8 on the Menopause Rating Scale (MRS), indicating moderate menopausal symptom intensity.
• Regular nighttime sleep and not engaged in shift work.
• Low physical activity level: less than 150 minutes per week of moderate or vigorous physical activity, as assessed by the short-form IPAQ or a similar questionnaire.
• Body mass index (BMI) between 18.5 and 35 kg/m².
• Sufficient functional and cognitive capacity to participate in supervised physical exercise and follow the study protocol.
• Signed informed consent and availability to attend all scheduled sessions and assessments.

Exclusion Criteria:

• Current or recent (within the last 3 months) use of hormone replacement therapy (HRT).
• Surgical, induced, or early menopause (before age 40).
• Current treatment with medications that may affect mood, sleep, or vasomotor symptoms, including: antidepressants (SSRIs, SNRIs, tricyclics); anxiolytics or hypnotics; phytoestrogens, isoflavones, or other over-the-counter hormonal supplements.
• Medical diagnosis of severe or uncontrolled chronic diseases, including cardiovascular, respiratory (particularly sleep apnea), metabolic, active oncological, neurological, severe autoimmune, or psychiatric disorders.
• Regular use within the past 3 months of nutritional or sports supplements that may interfere with study outcomes (e.g., creatine, protein, omega-3, adaptogens, etc.).
• Medical contraindications for moderate-to-vigorous physical exercise, as determined by the PAR-Q+ questionnaire and/or updated medical report.
• Simultaneous participation in another clinical trial or intervention program involving drugs, supplements, or structured physical exercise of any kind.
• Known allergy or intolerance to any component of the nutritional supplement to be administered.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise + nutritional supplement (Gr 1: EXNS); Participants in this group will receive a daily dose of the natural-origin nutritional supplement in combination with a supervised functional exercise program (3 sessions per week, 45-60 minutes each) for 10 weeks.	Dietary supplement: Exercise + nutritional supplement; Participants in this group will receive an oral daily dose of the natural-origin nutritional supplement in combination with a supervised functional exercise program (3 sessions per week, 45-60 minutes each) for 10 weeks, composed by three exercise blocks: 1) joint mobility and postural control exercises block, 2) functional strength block with three sets of two explosive strength exercises using elastic bands at 70% of 1RM and, 3) coordination and agility exercises block.
Placebo Comparator: Exercise + placebo supplement (Gr 2: EXPLA); Participants in this group will receive a placebo supplement identical in appearance to the active supplement, together with the same functional exercise program for 10 weeks.	Dietary supplement: Exercise + placebo supplement; Participants in this group will receive an oral placebo supplement identical in appearance to the active supplement, together with the same functional exercise program for 10 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Brain-Derived Neurotrophic Factor (BDNF)	Serum BDNF levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state to assess neuroplasticity and cognition.	Before and after the intervention of 10 weeks
Changes in cortisol	Serum cortisol levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state to assess hypothalamic-pituitary-adrenal (HPA) axis-mediated physiological stress.	Before and after the intervention of 10 weeks
Changes in inteleukin 6 (IL-6)	Serum IL-6 levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state to assess systemic inflammation and immunity	Before and after the intervention of 10 weeks
Changes in tumor necrosis factor alfa (TNF-α)	Serum TNF-α levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state to assess chronic inflammation and immune state, which is related with fatigue and depression.	Before and after the intervention of 10 weeks
Changes in Gamma-aminobutyric acid (GABA)	Serum GABA levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state to assess the state of the central nervous system, related with relaxation, anxiety and sleep conditions.	Before and after the intervention of 10 weeks
Changes in serotonin	Serum serotonin levels will be collected through a blood sample (ELISA KIT) in the morning in a fasted state as a key neurotransmitter involved in mood regulation, sleep, and cognition.	Before and after the intervention of 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in sleep quality	Sleep quality will be assessed through the Pittsburgh Sleep Quality Index (PSQI)	Before and after the intervention of 10 weeks
Changes in perceived insomnia	Perceived insomnia will be assessed through the Insomnia Severity Index (ISI)	Before and after the intervention of 10 weeks
Changes in daytime sleepiness	Daytime sleepiness will be assessed through the Epworth Sleepiness Scale (ESS)	Before and after the intervention of 10 weeks
Changes in state-trait anxiety	State-trait anxiety will be assessed through the State-Trait Anxiety Inventory (STAI-R)	Before and after the intervention of 10 weeks
Change in depression	Depression will be assessed through the Beck Depression Inventory-II (BDI-II)	Before and after the intervention of 10 weeks
Changes in general well-being	General well-being will be assessed through the WHO-5 Well-Being Index	Before and after the intervention of 10 weeks
Changes in menopausal symptoms	Menopausal symptoms will be assessed through the Menopause Rating Scale (MRS)	Before and after the intervention of 10 weeks
Changes in global cognitive performance	Global cognitive performance will be assessed through the Montreal Cognitive Assessment (MoCA)	Before and after the intervention of 10 weeks
Changes in working memory	Working memory will be assessed through the Digit Span (WAIS-IV Digit Span subtest - forward and backward)	Before and after the intervention of 10 weeks
Changes in selective attention	Selective attention will be assessed through the Stroop Test (short version)	Before and after the intervention of 10 weeks
Changes in processing speed and cognitive flexibility	Processing speed and cognitive flexibility will be assessed through the Trail Making Test A and B (TMT-A/B)	Before and after the intervention of 10 weeks
Changes in gait speed/aerobic capacity	Gait speed/aerobic capacity will be assessed through the 6-m Walk Test	Before and after the intervention of 10 weeks
Changes in lower limb strength	Lower limb strength will be assessed through the 30-s Chair Stand Test	Before and after the intervention of 10 weeks
Changes in handgrip strength	Handgrip strength will be assessed through the Handgrip dynamometry (Jamar Hand Dynamometer).	Before and after the intervention of 10 weeks
Changes in body composition	Whole body composition will be assessed through the Bioelectrical impedance analysis (Tanita BC-418). Total body mass, fat mass, fat-free mass and percentage of fat free mass will be measured.	Before and after the intervention of 10 weeks
Adherence to supplement and exercise	Adherence to supplement and exercise will be assessed through ad hoc questionnaire	Every day for nutritional supplement and each exercise session during the 10 weeks of intervention

Collaborators and Investigators

• Sponsor: University of Valencia

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Estimated): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Cognitive function; Physical function; Functional exercise; Perimenopause; nutritional supplement; Neuroendocrine biomarkers; Psycho-emotional health; Non-pharmacological interevention; variable resistance training; Sleep and mood regulation
• Additional Relevant MeSH Terms: Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Exercise; Dietary Supplements
• Other Study ID Numbers: 2025-FIS-4025659

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No