Effect of Different Exercise Modalities on Cardiovascular and Cognitive Response in Postmenopausal Women (WOMEN-EX-MOD)

Effect of Different Exercise Modalities on Cardiovascular and Cognitive Response in Postmenopausal Women With and Without Vasomotor Symptoms

Menopause is a natural stage in female aging, increasing cardiometabolic risk and making cardio-neuro-vascular disease (CNVD) the leading cause of mortality in women over 60. Declining ovarian hormones are linked to changes in body composition, increased blood pressure, and mild cognitive impairment. Menopause also often involves significant symptoms like menopausal vasomotor symptoms (VMS), affecting 60-80% of women for 5-10 years. Women with VMS exhibit a worse cardiovascular profile and greater cognitive decline.

Physical exercise is a promising non-pharmacological option to reduce CNVD risk and limit cognitive impairment in postmenopausal women, who have a 10-year window post-menopause during which physical activity benefits vascular and possibly neurovascular health. Studies link physical activity to lower cognitive decline and improved quality of life. However, optimal exercise modalities for managing CNVD risk in postmenopausal women remain undetermined.

Study Overview

• Status: Completed
• Conditions: Menopause; Blood Pressure; Cognitive Decline
• Intervention / Treatment: Other: High intensity interval exercise session; Other: Isometric neuromuscular exercise session

Detailed Description

Menopause is a natural stage in the female aging process, resulting in increased cardiometabolic risk, making cardio-neuro-vascular disease (CNVD) the leading cause of female mortality worldwide after the age of 60. Indeed, falling ovarian hormone concentrations are associated with altered body composition, increased blood pressure, as well as mild cognitive impairment.

For some women, menopause is also accompanied by symptoms that have a significant impact on their quality of life. Among these, menopausal vasomotor symptoms (VMS - hot flushes, night sweats...) are the most frequent, affecting 60% to 80% of women for an average of 5 to 10 years. Several studies have highlighted an altered cardiovascular profile (dyslipidemia, insulin resistance, pre-hypertension/hypertension...) and a more marked decline in cognitive performance in women with VMS.

In order to reduce the risk of CNVD and limit cognitive impairment, physical exercise appears to be a particularly interesting non-pharmacological management option for postmenopausal women. Indeed, the latter seem to present a 10-year post-menopausal time window, during which physical activity has a positive vascular and probably neurovascular effect, although the latter remains to be demonstrated. Numerous studies have also shown that physical activity is associated with a lower rate of cognitive decline, and improved quality of life.

However, to date, there is little evidence to determine which exercise modalities are most effective in managing the risk of CNVD in postmenopausal women.

The aims of this study:

• To examine the effect of exercise on markers of cardio-neuro-vascular health and cognition in postmenopausal women.
• Second, to compare the differences in the cardio-neuro-vascular and cognitive response to exercise, dependent on the type of exercise, the physical fitness and the presence of menopausal symptoms.
• Third, to examine the effect of menopausal symptoms, and physical fitness on cardio-neuro-vascular health markers and cognitive health markers.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Poitiers, France, 86000
    • Faculty of Sport Science - MOVE Laboratory (UR20296)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Menopausal women (absence of menstruation for 12 consecutive months) for less than 10 years
• Women with or without vasomotor symptoms
• Women covered by the French Social Security system

Exclusion Criteria:

• Surgical menopause (oophorectomy)
• Premature ovarian failure
• Chronic renal failure
• Respiratory pathology (unstable asthma, respiratory insufficiency or pulmonary hypertension)
• Cardiovascular disease (coronary, valvular, hypertrophic, hypertensive, infiltrative, constrictive or rhythmic)
• Medically treated hypertension
• Severe obesity (BMI > 40 kg/m²)
• Hearing or vision problems that prevent reading or distinguishing colors
• Recent (< 1 year) central neurological or psychiatric disorders
• Moderate to severe cognitive impairment (MoCA < 18).
• Judicial protection or guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High intensity interval exercise session; Performed on an ergometer, the intensity of the session is adapted to the participant's physical capacity, initially assessed by the VO2max test at baseline. The session begins with a 5-minute warm-up at 50% of maximum aerobic power (MAP). The exercise then consists of 2 sets of 12 repetitions of 15 seconds each at 100% of MAP and 15 seconds of passive recovery. 2-minute of passive recovery is recommended between the two sets. The session ends with 5-minute of recovery at 50% of MAP.	Other: High intensity interval exercise session; Physical activity session supervised and adapted on ergometer
Experimental: Isometric neuromuscular exercise session; Performed with a handgrip (K-Force grip, KINVENT), the intensity of the session is adapted to the participant's capacity, initially assessed by the isometric maximal voluntary force (MVF) measurement at the beginning of the session. The session consists of 4 repetitions of 2 minutes at 30% of the isometric MVF, separated by 1 minute recovery.	Other: Isometric neuromuscular exercise session; Physical activity session supervised and adapted with a handgrip
No Intervention: Control session; Participants are seated for 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic and diastolic blood pressure (ambulatory blood pressure measurement)	Post-exercise hypotension, using the Mobil-O-Graph (mmHg).	After sessions (24 hours)
Systolic and diastolic blood pressure (resting)	Automated oscillometric tensiometer (mmHg).	Before and after sessions (15 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of cerebral oxygenation	Near-infrared spectroscopy is used to measure concentrations of oxygenated and desoxygenated hemoglobin (µmol/L).	Before, during, and after sessions (1 hour)
Working memory	2-back task (scored from 0 to 28, higher scores indicate better working memory).	Before and after sessions (10 minutes)
Episodic memory	Memory scale III (MEM-III), a story recall task taken from the test battery in the Wechsler-Memory Scale-Revised (scored from 0 to 25, higher scores indicate better episodic memory).	Before and after sessions (15 minutes)
Executive function	Stroop task, used to assess inhibitory control (scored as a ratio, negative score indicates worse inhibitory control vs. positive score indicates better inhibitory control).	Before and after sessions (15 minutes)
Perception of exertion	Modified Borg scale (scored 0 to 10, higher score indicates lower exercise tolerance).	After sessions (1 minute)
Endothelial function (brachial artery dilation capacity)	At rest, the flow-mediated dilatation technique is used with high-resolution Doppler ultrasound (CX-50 Philipps).	Baseline (30 minutes)
Baroreflex sensitivity	At rest, baroreflex sensitivity is measured using the Finapres.	Baseline (1 hour)
Aortic systolic and diastolic blood pressure	At rest, using the SphygmoCor device, which measures central blood pressure (mmHg).	Baseline (15 minutes)
Arterial stiffness (pulse wave velocity)	At rest, using the SphygmoCor device, which calculates carotid-femoral pulse wave velocity (m/s).	Baseline (15 minutes)
Physical fitness	Maximal cardiopulmonary effort test (VO2max).	Baseline (30 minutes)
Blood lipid concentrations	Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (g/L).	Baseline (5 minutes)
Blood hormone concentrations	Progesterone, 17-beta-estradiol, and follicle-stimulating hormone (ng/L).	Baseline (5 minutes)
Body weight	Total body weight, fat mass, fat-free mass and visceral-fat mass in kilograms using the Tanita impedance scale.	Baseline (1 minute)
Body composition	Percentage of body fat and fat-free mass using the Tanita impedance scale.	Baseline (1 minute)
Height	Height in meters measured with a height gauge.	Baseline (1 minute)
Body mass index	Calculated from total body weight and height (kg/m²).	Baseline (1 minute)
Cognitive assessment	Montreal Cognitive Assessment (MoCA) test (scored from 0 to 30, with higher scores indicating better cognitive function).	Baseline (15 minutes)
Menopausal rating scale	Composed of 11 items rating the severity of menopausal symptoms from 0 (no symptoms) to 4 (very severe).	Baseline (15 minutes)
Hot flash related daily interference scale	Composed of 10 items scored from 0 (no impact) to 10 (completely interferes), evaluating the impact of vasomotor symptoms on daily life.	Baseline (15 minutes)
Hospital Anxiety and Depression Scale	It provides two scores ranging from 0 to 21 that quantify anxiety and depression. Higher scores indicate more severe symptoms.	Baseline (15 minutes)
Global physical activity questionnaire	Physical activity and sedentary time assessed using the Global Physical Activity Questionnaire. Higher scores indicate better physical activity levels (categorized into high, moderate, and low physical activity levels).	Baseline (15 minutes)
Daily tobacco and alcohol use	Use daily or not use.	Baseline
Age	Age, age at menarche and menopause (in years).	Baseline
Educational level	Secondary education, high school graduate, bachelor's degree, master's or doctoral degree.	Baseline
Number of children	Self-reported.	Baseline

Collaborators and Investigators

• Sponsor: University of Poitiers
• Investigators: Principal Investigator: Laurent Bosquet, Pr, University of Poitiers - Faculty of Sport Science - MOVE Laboratory (UR20296)

Publications and helpful links

General Publications

• Greendale GA, Sternfeld B, Huang M, Han W, Karvonen-Gutierrez C, Ruppert K, Cauley JA, Finkelstein JS, Jiang SF, Karlamangla AS. Changes in body composition and weight during the menopause transition. JCI Insight. 2019 Mar 7;4(5):e124865. doi: 10.1172/jci.insight.124865. eCollection 2019 Mar 7.
• Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, Hess R, Joffe H, Kravitz HM, Tepper PG, Thurston RC; Study of Women's Health Across the Nation. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015 Apr;175(4):531-9. doi: 10.1001/jamainternmed.2014.8063.
• Armas Rojas N, Dobell E, Lacey B, Varona-Perez P, Burrett JA, Lorenzo-Vazquez E, Calderon Martinez M, Sherliker P, Bess Constanten S, Morales Rigau JM, Hernandez Lopez OJ, Martinez Morales MA, Alonso Aloma I, Achiong Estupinan F, Diaz Gonzalez M, Rosquete Munoz N, Cendra Asencio M, Peto R, Emberson J, Duenas Herrera A, Lewington S. Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study. Lancet Public Health. 2019 Feb;4(2):e107-e115. doi: 10.1016/S2468-2667(18)30210-X. Epub 2019 Jan 23. Erratum In: Lancet Public Health. 2019 Feb;4(2):e88. doi: 10.1016/S2468-2667(19)30004-0.
• Boyle CP, Raji CA, Erickson KI, Lopez OL, Becker JT, Gach HM, Kuller LH, Longstreth W Jr, Carmichael OT, Riedel BC, Thompson PM. Estrogen, brain structure, and cognition in postmenopausal women. Hum Brain Mapp. 2021 Jan;42(1):24-35. doi: 10.1002/hbm.25200. Epub 2020 Sep 10.
• Zhu D, Chung HF, Dobson AJ, Pandeya N, Anderson DJ, Kuh D, Hardy R, Brunner EJ, Avis NE, Gold EB, El Khoudary SR, Crawford SL, Mishra GD. Vasomotor menopausal symptoms and risk of cardiovascular disease: a pooled analysis of six prospective studies. Am J Obstet Gynecol. 2020 Dec;223(6):898.e1-898.e16. doi: 10.1016/j.ajog.2020.06.039. Epub 2020 Jun 23.
• Gliemann L, Hellsten Y. The exercise timing hypothesis: can exercise training compensate for the reduction in blood vessel function after menopause if timed right? J Physiol. 2019 Oct;597(19):4915-4925. doi: 10.1113/JP277056. Epub 2019 Jun 30.
• Anderson D, Seib C, Rasmussen L. Can physical activity prevent physical and cognitive decline in postmenopausal women? A systematic review of the literature. Maturitas. 2014 Sep;79(1):14-33. doi: 10.1016/j.maturitas.2014.06.010. Epub 2014 Jun 20.
• Hybholt M. Psychological and social health outcomes of physical activity around menopause: A scoping review of research. Maturitas. 2022 Oct;164:88-97. doi: 10.1016/j.maturitas.2022.07.014. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: July 19, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Physical exercise; Handgrip; High intensity interval exercise
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: WOMEN-EX-MOD

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