Cardiovascular adaptations to resistance training with different set configurations in postmenopausal women: a study protocol for a randomised controlled trial (CARE project)

Abstract

Short set configurations attenuate cardiovascular responses, reduce perceived exertion and allow for greater mechanical performance compared with longer sets. Mid-term to long-term adaptations to resistance training across set configurations remain unexplored in postmenopausal women. This study will explore cardiovascular, metabolic, neuromuscular and perceptual adaptations to 12-week resistance training programmes differing in set configuration. Forty physically active postmenopausal women will participate. After medical screening, they will complete four pretest assessments measuring cardiovascular, metabolic, neuromuscular and body composition variables. Participants will then be randomly assigned to a control group or one of two experimental groups. Each session, experimental groups will complete 36 repetitions per exercise (leg press, bench press, leg curl and lat pull-down) with a 12-repetition maximum load. The 4S group will complete nine sets of 4 reps with 45 s of rest, while the 9S group will do four sets of 9 reps with 120 s of rest. The intervention will span 12 weeks with 24 training sessions. Afterwards, all participants will repeat the initial assessments. Experimental groups will return 3 months later for follow-up evaluations of cardiovascular, metabolic and body composition outcomes. A 3×3 repeated-measures analysis of variance will be used to analyse the effects of set configuration (4S, 9S, control) over time (pretest, post-test, follow-up). The study was approved by the Galician Regional Government Ethical Committee. All participants will receive detailed oral and written information before providing informed consent. Results will be widely disseminated, including through outreach events to promote knowledge transfer. Trial registration number: NCT05544357; registration date: 7 December 2022.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Shorter set configurations in resistance training elicit lower chronotropic responses during exercise in postmenopausal women, leading to attenuated parasympathetic withdrawal, reduced baroreceptor sensitivity loss and limited increases in arterial stiffness after exercise. Postexercise hypotension, however, occurs only in hypertensive participants. The long-term adaptations to resistance training across set configurations remain unexplored in this population.

WHAT THIS STUDY ADDS

• This study represents the first investigation to examine the long-term cardiovascular, metabolic, neuromuscular and perceptual adaptations to resistance training with differing set configurations in postmenopausal women. Findings will provide evidence to inform the prescription of safer and more effective training structures, thereby optimising physiological benefits while minimising cardiovascular risk in this population.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This study helps bridge the current gap in the literature on women’s health. Its findings will provide an evidence-based framework to guide exercise professionals in prescribing safe and optimally effective training protocols for postmenopausal women, specifically to promote cardiovascular health. Furthermore, the results may inform public health strategies and policy development, supporting the implementation of targeted exercise interventions to improve health outcomes in postmenopausal women.

Introduction

The climacteric represents a critical stage in a woman’s life, marked by significant physical, psychological and social consequences that have a considerable impact on their quality of life.¹ In postmenopausal women, the decline in oestrogen contributes to the development of arterial hypertension and increases susceptibility to cardiovascular disease.² These changes highlight the importance of considering the menopausal transition as a period of heightened vulnerability for women’s health. Nevertheless, cardiovascular disease in women remains understudied, under-recognised, underdiagnosed and undertreated globally, despite being the leading cause of death among women worldwide, as emphasised by a recent Lancet Commission.³ Beyond the cardiovascular system, menopause is accompanied by additional physiological and functional changes, which include alterations in body composition, a progressive reduction in bone mineral density, increased abdominal adiposity and reduced insulin sensitivity. Sleep disturbances, impaired balance and mood disorders are also frequently observed in this population.² Collectively, these changes further complicate the health profile of postmenopausal women.

Physical activity is widely recognised as a protective factor that promotes cardiometabolic, physical and psychological health in midlife women.⁴ Engagement in regular exercise during the perimenopausal and postmenopausal years can mitigate many of the adverse physiological and functional changes associated with this life stage.⁵ Consequently, targeted interventions, particularly those incorporating structured exercise programmes, are crucial to preserve health and functional capacity in postmenopausal women. Among different exercise modalities, resistance training has emerged as an especially effective strategy to counteract or attenuate the physiological and functional declines observed in postmenopausal women.6,12 Moreover, as recently demonstrated by Le Bourvellec et al, resistance exercise is the most effective modality to induce postexercise hypotension in both premenopausal and postmenopausal women,¹³ highlighting its central role in interventions aimed at cardiovascular health during the menopausal transition.

Set configuration has been shown to modulate acute cardiovascular responses to resistance exercise in both young, physically active individuals14,22 and postmenopausal women.^{23 24} Shorter set configurations (ie, fewer than 40% of the maximum number of repetitions) attenuate acute cardiovascular responses compared with longer set configurations. Specifically, in postmenopausal women (both normotensive and hypertensive), shorter set configurations have been shown to elicit a lower chronotropic response during exercise, resulting in reduced parasympathetic withdrawal, preserved baroreceptor sensitivity and less pronounced increases in arterial stiffness. In relation to postexercise hypotension, this phenomenon has been observed primarily in postmenopausal women with hypertension.²⁴

Despite these acute effects, the chronic adaptations to resistance training under different set configurations have remained largely unexplored in postmenopausal women. To the best of our knowledge, only one study has investigated set configuration in this population, although work-to-rest ratios were not equated between protocols. Thus, most evidence comes from studies of young, healthy and active individuals that indicate resistance training does not alter cardiac autonomic modulation, blood pressure or sympathetic vasomotor tone, regardless of set configuration. Traditional longer set structures, however, may reduce cardiac baroreflex effectiveness.¹⁴ Nonetheless, these findings cannot be directly extrapolated to postmenopausal women, who are at higher cardiovascular risk, particularly those with hypertension. Consequently, while hypotheses regarding the potential effects of set configuration in postmenopausal women can be drawn from data in younger populations, their applicability remains uncertain. Furthermore, previous research suggests that longer intervention periods are required to detect meaningful long-term adaptations, especially in measures of autonomic regulation.¹⁴

Additionally, the set configuration has been found to modulate neuromuscular, metabolic and perceptual responses to and adaptations from resistance training. Shorter sets are more effective at attenuating velocity loss, power, peak force, metabolic stress and perceived exertion during resistance exercise compared with longer sets.^{25 26} Regarding mid-term adaptations, evidence indicates that both short and long set configurations produce comparable improvements in muscular strength, power, velocity, hypertrophy and muscular endurance. However, shorter set configurations may achieve these adaptations with reduced fatigue during resistance training.²⁷ It is important to note that the current evidence is based on young, healthy male participants, thereby constraining its applicability to broader populations.

Therefore, this randomised controlled trial aims to examine the cardiovascular, metabolic, neuromuscular and perceptual adaptations to a 12-week resistance training programme with differing set configurations in postmenopausal women. We expect greater cardiovascular, metabolic and neuromuscular adaptations with longer, more fatiguing training structures, resulting from sustained exposure to high physiological stress stimuli.

Methods

Study design and ethical aspects

This protocol has been developed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.²⁸ The trial is designed as a single-centre, parallel-group randomised controlled trial and is registered with the US National Library of Medicine (ClinicalTrials.gov) under the identifier NCT05544357, assigned on 7 December 2022. The design of this study was approved by the Galician Regional Government Ethical Committee (code: 2022/313) and is in accordance with the principles of the Declaration of Helsinki. Before signing an informed consent form, all participants will be provided with oral and written information detailing the study’s aim, testing procedures, experimental sessions, potential benefits and risks of their participation from two project supervisors.

The data collection and intervention protocol will be conducted in A Coruña (Spain) within the facilities of the Faculty of Sports Sciences and Physical Education of the University of Coruña. All study data will be stored in paper format at the laboratory responsible for the study and will additionally be deposited in the Zenodo repository (https://zenodo.org/communities/udc/) with pseudonymisation to ensure participant confidentiality. The results of this clinical trial will be reported following the CONSORT guidelines, and any protocol deviations will be documented and described in a dedicated section of future manuscripts.

Participants

Participants will be recruited from postmenopausal women who meet specific eligibility criteria. Women will be included if they: (1) are 55–65 years of age, (2) have experienced at least 12 months of amenorrhoea following the final menstrual period, (3) are physically active (150–300 min of moderate-intensity physical activity per week or at least 75 min of vigorous activity per week), (4) present with no more than three traditional cardiovascular risk factors, (5) are asymptomatic and free of cardiovascular (except for hypertension), metabolic or renal diseases and (6) in the case of the hypertensive subgroup, have a diagnosis of well-controlled grade 1 hypertension managed with a single antihypertensive drug. Exclusion criteria will be: (1) a diagnosis of grade 2–3 hypertension, (2) hypertension managed with multiple antihypertensive agents or with medications that may alter cardiovascular responses to exercise (eg, beta-blockers), (3) current or previous hormone replacement therapy and (4) exhibiting a hypertensive response to exercise. To participate in the study, all women will undergo a preliminary medical evaluation to determine eligibility and assess absolute and relative contraindications to exercise. This evaluation will include a treadmill ergometry test following the Bruce protocol.²⁹

The sample will be recruited from the metropolitan area of A Coruña, Spain. Outreach efforts will be directed towards public and private sports facilities to facilitate recruitment. In addition, information about the study will be disseminated through the laboratory’s official social media channels (eg, Instagram and institutional website), as well as through announcements in local print media and regional radio broadcasts.

An a priori power analysis was conducted using GPower V.3.1 (Universität Düsseldorf, Germany). Based on the study design, the sample size calculation assumed a Type I error of 0.05 and a statistical power of 80% (1–β) to detect a small-to-medium effect size (f=0.20) for the interaction between time (initial, final and follow-up measurements) and group (experimental groups with different set configurations and control group) in a repeated-measures design, with a pre–post correlation of 0.7. This analysis indicated a required total sample size of 33 women. To account for potential dropouts, we will enrol around 40 women in total, which represents an anticipated 21% increase over the minimum required sample size.

Experimental procedures

At the beginning of the study, each woman will undergo a medical evaluation to confirm eligibility based on the inclusion criteria. Subsequently, all participants will complete four pretest sessions to assess cardiovascular, metabolic, neuromuscular and body composition parameters. After baseline assessments, participants will be randomly assigned to the control group (CON) or to one of two experimental groups differing in set configuration: short set configuration (4S) or long set configuration (9S). The intervention period will last 12 weeks, comprising 24 resistance training sessions (two per week). Participants in the CON group will be instructed to maintain their habits throughout the 12 weeks. Following the intervention, all participants will complete four post-test sessions identical to the pretest sessions. Finally, only participants in the experimental groups will return to the laboratory 3 months after the end of the intervention period for a follow-up assessment of cardiovascular, metabolic and body composition outcomes. Figure 1 provides a detailed overview of the study design, including the specific resistance training protocols to be conducted. The SPIRIT figure (table 1) illustrating the participant’s timeline presents the study’s overall structure and the timing of outcome measurements.

Figure 1. Schematic representation of the study. (A) Study design; (B) training protocols for experimental groups. 4S: short set configuration training group consisting of 9 sets of 4 repetitions and 45 s rest; 9S: long set configuration training group consisting of 4 sets of 9 repetitions and 120 s rest.

Table 1. Participant timeline: schedule of enrolment, interventions and assessments.

	Enrolment	Allocation	Preintervention	Intervention	Postintervention	Follow-up
Timepoint	t−1	t0	S1–S7	S8–S28	S32	S33
Enrolment
Informed consent	X
Eligibility criteria	X	X
Medical evaluation	X	X
Assessments
Cardiac autonomic control and baroreflex			X		X	X
Haemodynamic and arterial stiffness			X		X	X
Metabolic responses and lipid profile			X		X	X
Body composition and musculoskeletal characteristics			X		X	X
Health-related quality of life, physical activity and dietary habits			X		X	X
Neuromuscular performance and balance			X		X
Neuromuscular fatigue				X
Randomisation		X	X		X
Intervention/comparator
4S training group
9S training group
Control group			X		X

4S, short set configuration training group; 9S, long set configuration training group; S, Session.

Medical evaluation

The medical evaluation session will include a detailed anamnesis, followed by a comprehensive physical examination and complementary assessments, including a resting ECG and spirometry. If a participant meets the inclusion and exclusion criteria, she will be thoroughly informed about the experimental protocol both verbally and in writing. oOn agreement, informed consent may then be signed.

Pretest assessments

Session 1

Participants will arrive in the morning and will be instructed to maintain a minimum fasting period of 2 hours, to avoid consuming caffeinated beverages, alcohol or drugs within 48 hours of the session, and not to perform strenuous exercise within 24 hours of testing. The session will begin with a lipid profile assessment from a finger-prick blood sample. Calcaneus bone mineral density will then be estimated, followed by a 60 min cardiovascular and metabolic evaluation at rest. Participants will lie supine on a stretcher with a 45° trunk inclination in a quiet room, avoiding movement. Immediately afterwards, arterial stiffness and body composition will be assessed in a horizontal lying position. Participants will also complete questionnaires to assess health-related quality of life, physical activity and dietary habits. Health-related quality of life (HRQoL) will be evaluated using the Short Version of the Cervantes Scale (Cervantes-SV),³⁰ physical activity will be assessed with the International Physical Activity Questionnaire (IPAQ)³¹ and dietary habits will be evaluated using the Short Diet Quality Screener (sDQS).³²

At the conclusion of the session, participants will undergo familiarisation with the isokinetic dynamometer. They will perform two isometric contractions, each lasting 5 s, followed by a set of two dynamic repetitions at angular velocities of 30°/s and 300°/s for both unilateral knee extension and unilateral elbow flexion exercises. A rest period of 1 min will be provided between sets, and 2 min between different conditions and exercise types. The chair position, dynamometer configuration and attachment arm length will be individually adjusted to align the anatomical axes of the knee and elbow joints with the lever arm’s rotational axis, ensuring accurate biomechanical alignment.

Session 2

Following device adjustments and familiarisation trials, the knee extensors and elbow flexors of the dominant limb will be evaluated using an isokinetic dynamometer at angular velocities of 30°, 60°, 120°, 180°, 240°, 300°/s and 400°/s. The range of motion (ROM) for knee extension will span from 0° (full extension) to 80° (flexion), while elbow flexion will be assessed from 20° (nearly full extension) to 120° (flexion). Maximum isometric torque will be measured at 60° and 90° joint positions for knee extensors and elbow flexors, respectively. Three attempts will be recorded for each condition, with 2 min of rest between attempts and conditions.

Session 3

Ultrasound recordings will be acquired to assess muscle volume and cross-sectional area of the biceps brachii and vastus lateralis in the dominant limb. Subsequently, participants will complete a 12-repetition maximum (12RM) test for each exercise included in the intervention. For each exercise, the load that the participant can lift 12 times but not 13 times will be determined. Before 12RM testing, participants will warm up on a stationary bicycle for 5 min at 60–80 rpm, followed by two sets of 12 repetitions with 2 min of rest between sets, corresponding to a perceived exertion of 6 and 8 on the OMNI-RES scale (0–10). The load will then be progressively increased. Participants will then perform the first 12RM attempt. If the participant completes 13 repetitions during the initial set, the load will be progressively increased. Following a 6 min rest period, a subsequent attempt will be made. Muscle failure will be determined either by the inability to lift the prescribed load or by the failure to complete the full ROM required for the exercise.

Session 4

The session will begin with a stationary balance test (the modified Clinical Test of Sensory Interaction on Balance (mCTSIB)).³³ Four tests of 30 s each will be conducted in a standing position, with eyes open and eyes closed, on stable and unstable surfaces. Then, a second 12RM test of each exercise will be conducted, following the same procedures as described in the previous session.

Resistance training interventions for experimental groups: 4S and 9S (sessions 5–28)

During the intervention, participants in the 4S or 9S groups will warm up in a similar manner. After 5 min on a cycle ergometer at 60–80 rpm and 5 min of joint mobility and core exercises, participants will perform a specific warm-up for the four resistance exercises, consisting of 10 repetitions at 70% of the 12RM load. Subsequently, participants will engage in the experimental sessions, during which the exercises will be executed in the following sequence: (1) horizontal leg press (Sportsart N956, Switzerland), (2) bench press (Multipower Shock (Model SH004/0), Telju Fitness, Toledo, Spain), (3) prone leg curl (Biotech Fitness Solutions, Brazil) and (4) lat pull-down (Biotech Fitness Solutions, Brazil). Resistance training sessions will be performed with the previously determined 12RM load. All resistance training sessions will comprise 36 repetitions and 360 s of rest for each exercise. Participants in the 4S group will complete nine sets of four repetitions (ie, 33% of the effort intensity) with 45 s of interset rest for each exercise. Regarding the 9S group, sessions will entail four sets of 9 repetitions (ie, 75% of the effort intensity) per exercise, with an inter-set rest of 120 s. During sessions, the mean propulsive velocity of each repetition will be recorded. After each set, supervisors will record the perceived exertion using the OMNI-RES scale. For all resistance training sessions, a 4 min recovery will be established between exercises. In week 6, a midintervention 12RM test will be conducted to recalibrate the training load for all participants across all exercises.

All intervention sessions will be closely supervised by the project leader alongside sport science researchers with expertise in resistance training. During resistance exercises, participants will receive specific instructions from supervisors to ensure a controlled eccentric phase, followed by a concentric phase performed at the intended maximal velocity for each repetition.

Participants assigned to the control group will be instructed to maintain their usual lifestyle habits, including the physical exercise routine they followed before enrolling in the study.

Post-test assessments (session 29–32)

Sessions 1, 2 and 3 (corresponding to sessions 29, 30 and 31, respectively) will be repeated at the end of the intervention for all participants enrolled in the study. Additionally, a final session (ie, 32) will be conducted to explore muscle endurance adaptations. During this session, participants will perform a test to determine the maximum repetitions with the preintervention 12RM load, following the same procedures described previously. For each exercise, participants will be instructed to complete as many repetitions as possible in a single set, continuing until volitional muscular failure.

Follow-up assessments: session 33

Three months after the end of the intervention, participants enrolled in the experimental groups (4S and 9S) will be contacted to complete a follow-up assessment. The procedures conducted during the first pretest session will be repeated to assess the residual effect of the intervention on the project’s primary variables (ie, cardiovascular and metabolic outcomes).

Outcomes 

Tables2 3 summarise the primary and secondary outcomes that will be recorded in this study. Along the different time points (pre, post and follow-up), the following outcomes will be recorded (see table 1).

Table 2. Summary of primary outcomes and time points of measurements.

Primary outcomes
Outcome		Parameter	Description	Data recording
Cardiovascular outcomes
Cardiac autonomic control	Time domain	SDNN	SD of all NN intervals (ms)	5 min epochs
		RMSSD	Square root of the mean of the sum of the squares of differences between adjacent NN intervals (ms)
	Frequency domain	LF	Power of the low frequency range in absolute values (ms2)
		HF	Power of the high frequency range in absolute values (ms2)
		LF n.u.	Power of the low frequency range in normalised units
		HF n.u.	Power of the high frequency range in normalised units
		Ratio LF/HF	Ratio
	Entropy	AmpEn	Approximate entropy
		SampEn	Sample entropy
Cardiac baroreflex		BRScount	Number of baroreflex sequences detected (n)	10 min epochs
		BRSslope	Magnitude of the baroreflex sensitivity (ms·mm Hg−1)
		BEI	Baroreflex effectiveness index (%)
Sympathetic vasomotor tone		LFsBP	Low frequency of systolic blood pressure (mm Hg2)
Haemodynamics		SBP	Systolic blood pressure (mm Hg)
		DBP	Diastolic blood pressure (mm Hg)
		MAP	Mean arterial pressure (mm Hg)
		HR	Heart rate (bpm)
		RPP	Rate pressure product (bpm·mm Hg)
Arterial stiffness		f-t PWV ft-PWV	Finger-toe pulse wave velocity (m·s−1)	Single assessment
		f-t TT; ft-TT	Finger-toe transit time (ms)
Resting metabolic outcomes
Metabolic responses		VO2	Oxygen uptake (mL·kg−1·min−1)	10 min epochs
		VCO2	Carbon dioxide production (mL·kg−1·min−1)
		RER	Respiratory exchange ratio

Table 3. Summary of secondary outcomes and time points of measurements.

Secondary outcomes
Neuromuscular fatigue outcomes
Mechanical performance	VM	Mean velocity (m·s−1)	Each repetition
	PM	Mean power (m·s−1)
	FM	Mean force (N)
	RPE	Rate of perceived exertion
Body composition and musculoskeletal characteristics
Body composition	Weight	(kg)	Single assessment
	Height	(cm)
	BMI	Body mass index (weight (kg); (height (m)2)) kg·m−2
	% fat mass	(%)
	% fat-free mass	(%)
	SOS	Speed of sound
	BUA	Broadband ultrasound attenuation
	BQI	Bone quality index
Musculoskeletal characteristics	CSA	Cross-sectional area of vastus lateralis and biceps brachii (cm2)
	MV	Muscle volume of vastus lateralis and biceps brachii (cm3)
Lipid profile
Biochemical parameters	CHOL	Total cholesterol (mg·dL−1)	Single assessment
	HDL	High-density lipoprotein cholesterol (mg·dL−1)
	TGL	Triglycerides (mg·dL−1)
	CHOL/HDL ratio	A ratio of total cholesterol to high-density lipoprotein cholesterol (%)
	LDL	Low-density lipoprotein cholesterol (mg·dL−1)
Health-related quality of life, physical activity and dietary habits
Health-related quality of life (Short Version of the Cervantes Scale)	Global score	Overall perceived quality of life related to menopausal status	Single assessment
	Menopause and health dimension	Composed of three subdimensions (vasomotor symptoms, health and ageing) Vasomotor symptoms: assesses the intensity and frequency of menopausal symptoms such as hot flushes and night sweats General health: evaluates the woman’s overall health status and the presence of physical complaints or discomfort Ageing: explores perceptions and the impact of age-related changes on daily life
	Psychological dimension	Emotional and psychological well-being, including mood and anxiety
	Sexuality dimension	Sexual function and satisfaction
	Couple relations dimension	Perceived impact of menopause on couples and social relationships
Physical activity (International Physical Activity Questionnaire)	Vigorous activity	(min/week)
	Moderate activity	(min/week)
	Walking	(min/week)
	Sitting time	(min/day)
	Total physical activity	(MET-min/week)
	Physical activity category	Physical activity level is classified as low, moderate or high
Dietary habits (Short Diet Quality Screener)	Frequency	Frequency of consumption of food groups
	Total score	Overall diet quality
	Adherence	Degree of adherence to healthy dietary guidelines
Neuromuscular performance and balance
Strength performance	12RM	12 repetitions maximum load (kg) for each exercise (ie, horizontal leg press, bench press, leg curl, lat pull-down)	Single assessment
	nRM	Maximal number of repetitions with the 12RM load in the pretest assessment for each exercise (ie, horizontal leg press, bench press, leg curl, lat pull-down)
Isometric and isokinetic performance	Tisom	Isometric torque (N·m) for unilateral elbow flexors (90°) and knee extensors (60°)
	RFD	Rate of force development (N·s−1) for unilateral elbow flexors (90°) and knee extensors (60°)
	T30	Peak torque at 30°/s (N·m) for unilateral elbow flexors and knee extensors
	T60	Peak torque at 60°/s (N·m) for unilateral elbow flexors and knee extensors
	T120	Peak torque at 120°/s (N·m) for unilateral elbow flexors and knee extensors
	T180	Peak torque at 180°/s (N·m) for unilateral elbow flexors and knee extensors
	T240	Peak torque at 240°/s (N·m) for unilateral elbow flexors and knee extensors
	T300	Peak torque at 300°/s (N·m) for unilateral elbow flexors and knee extensors
	T400	Peak torque at 400°/s (N·m) for unilateral elbow flexors and knee extensors
Balance	APmax	Maximum antero-posterior displacement of the centre of pressure (mm)
	MLmax	Maximum medio-lateral displacement of the centre of pressure (mm)
	VCoP	Mean velocity of the centre of pressure (cm·s−1)

Primary outcomes

The primary outcomes will be evaluated during pre, post and follow-up assessments. These primary data will include the cardiovascular and resting metabolic adaptations (table 2). Regarding cardiovascular outcomes, cardiac autonomic control, cardiac baroreflex, sympathetic vasomotor tone and haemodynamic parameters will be evaluated with the Task Force Monitor (CNSystems, Graz, Austria). Moreover, arterial stiffness will be assessed via pOpmètre (Axelife SAS, France). This assessment requires a prior blood pressure measurement obtained with an oscillometric device (Omron MIT Elite Plus, Kyoto, Japan) with the cuff on the left arm. A mobile gas analyser (MetaMax 3b; Cortex Biophysik, Leipzig, Germany) will be used to assess resting metabolic outcomes.

Secondary Outcomes

Secondary outcomes will primarily be assessed at preintervention and postintervention time points, and in certain cases, during follow-up evaluations. Additionally, specific data were recorded throughout the training sessions (table 3).

Lipid profile, quality of life, physical activity level, dietary habits, body composition, musculoskeletal characteristics and physical fitness of the sample will be recorded. To assess participants’ lipid profile, a capillary blood sample will be collected from the ear and analysed with a portable Mission Cholesterol analyser (ACON Laboratories, Inc, USA). Cervantes-SV, IPAQ and sDQS questionnaires will be provided to the participant to assess HRQoL, physical activity level and dietary habits, respectively. A multifrequency bioimpedance device (Bodystat Quadscan 4000, UK) will be used to assess body composition, and bone mineral density of the calcaneus will be estimated using an ultrasound bone densitometer (Sonost 3000; Osteosys Corp., Korea). Moreover, musculoskeletal characteristics will be assessed via ultrasound recordings with a Versana Active device (GE HealthCare, USA) and a linear probe (12L-RS; GE HealthCare, USA) to calculate muscle volume and the cross-sectional area of the biceps brachii and vastus lateralis. To assess physical fitness through the muscular component, some strength tests will be performed: (1) the 12RM load will be determined for the horizontal leg press, bench press, leg curl and lat pull-down exercises; (2) an isometric and isokinetic test will be conducted using a Humac Norm isokinetic dynamometer (Humac Norm, CSMI, USA). The strength of the elbow flexors and knee extensors of the dominant limbs will be assessed. Finally, neuromuscular fatigue will be evaluated by recording mechanical performance through a linear velocity transducer (T-Force System; Ergotech, Murcia, Spain), while perceived exertion following each exercise will be assessed using the OMNI-RES scale.

Statistical analysis

Descriptive statistics will be reported as means and SD (mean±SD). All statistical analyses will be conducted using the statistical package of SPSS V,25.0 (SPSS, IBM, Armonk, New York, USA) and R V.4.2.1 (R Foundation, Vienna, Austria). For each variable, the Shapiro-Wilk test will be used to check the normality of the data distribution, and the homogeneity will be examined using Levene’s Test. If the data present a normal distribution, a two-way repeated-measures factorial analysis of variance (ANOVA) will be conducted. Specifically, a 3×3 repeated-measures ANOVA will be performed to analyse the effects of set configuration (ie, 4S, 9S and CON) across time points (ie, pretest, post-test and follow-up). If a significant interaction is detected, pairwise comparisons using the Bonferroni post-hoc test will be conducted to examine the statistical differences between set configurations and times. In cases of missing data (ie, missing data for a specific participant at a particular time point or condition), this analysis will be performed using linear mixed models. Conversely, when the assumption of normality is violated, non-parametric ANOVA-type statistics will be used.³⁴ This non-parametric analysis is similar to parametric ANOVA but uses rank-based calculations to determine the relative marginal effects.³⁴ If a significant interaction is found, paired comparisons within groups will be conducted using the Wilcoxon signed-rank test with Bonferroni’s adjustment. For all statistical analyses, significance will be set at p≤0.05.

To assess the magnitude of differences for parametric variables, two effect size measures will be employed: partial eta squared (ηp²) and Hedge’s g with 95% CIs. Additionally, the matched-pairs rank-biserial correlation will be used to estimate effect sizes in non-parametric contrasts.

Dissemination

The results of this study will be disseminated to a wide range of audiences, including the scientific community, exercise science professionals and related fields, as well as the general population. Dissemination will include publication in peer-reviewed scientific journals, presentation at national and international scientific conferences and registration of findings in clinical trial databases. Furthermore, both scientific and outreach events will be organised to facilitate knowledge transfer to society. In addition, individual reports will be prepared and provided to study participants.

Discussion

To the best of our knowledge, this is the first study specifically designed to investigate how the set configuration of resistance training influences chronic adaptations in postmenopausal women, including both normotensive and hypertensive individuals. The primary objective is to determine whether distinct set configurations elicit differential cardiovascular, metabolic, neuromuscular and perceptual adaptations between these groups, while also exploring the underlying mechanisms. Moreover, the study will assess the residual effects of resistance training through follow-up evaluations conducted after a detraining period, thereby providing insight into the persistence of training-induced adaptations.

By employing a comprehensive, multifactorial approach, this study seeks to advance the understanding of the interactions among key physiological systems in this population. Such knowledge is expected to guide exercise professionals and postmenopausal women, enhancing the effectiveness and safety of exercise prescriptions and fostering long-term adherence.

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.