Purpose: The aims of the study are to investigate the effects of high-intensity resistance training (HIRT) with or without creatine monohydrate (CM) supplementation on three key areas: muscle characteristics, brain health, and metabolism/protein dynamics.

Participants: 51 healthy, perimenopausal women between 38-60 years old. Procedures: In a randomized double-blind, placebo-controlled design, participants will either consume creatine (CM), a placebo (PL), or no supplement (CON). CM and PL groups will be assigned a HIRT protocol, and the CON will do no training.

Over one million women in the U.S. transition through menopause each year, a phase marked by significant hormonal fluctuations (estrogen, progesterone, luteinizing hormone) and associated with increased cardiometabolic and cardiovascular risks. Research from our lab has identified key metabolic disruptions during the perimenopausal (PERI) period, including reduced protein balance, increased abdominal fat, decreased strength, and impaired metabolic flexibility. Additionally, women as early as age 35 may experience menopause-related symptoms such as cognitive decline, mood disturbances, and sleep disruptions.

Skeletal muscle health, critical for lifelong function, often begins to decline during PERI. While resistance training is known to improve muscle strength and body composition in older women, limited research has focused specifically on the PERI stage. High-intensity resistance training (HIRT) offers a time-efficient strategy to address these issues. Creatine monohydrate (CM) supplementation, traditionally used to enhance muscle performance, has shown potential benefits for cognitive function, mood, fatigue reduction, and overall metabolic health-effects particularly relevant to PERI women.

This pilot study aims to evaluate the preliminary effects of six weeks of HIRT, with or without CM supplementation, on muscle characteristics, brain health, and metabolism in women around PERI age. The study uses a randomized, double-blind, placebo-controlled design with broad inclusion criteria to enhance generalizability. Participants will undergo a 5-day supplementation phase followed by a 6-week training phase. Outcomes will include assessments of muscle quality and strength, cognitive function, brain oxygenation, metabolic rate, and protein turnover, while accounting for hormonal fluctuations.

This trial will provide foundational data to inform a larger, more comprehensive study and aims to identify effective, accessible interventions to support health and quality of life in women during the menopause transition.

Inclusion Criteria:

• Women transitioning through perimenopause (defined by the North American Menopause Society Menopause Health Questionnaire), with or without hormone therapy or experiencing two or more perimenopause-related symptoms, as determined from the validated North American Menopause Society
• Women ≥38-60 yrs.
• Recreationally active [(≥30 minutes of moderate-intensity physical activity per week and <3 times per week of progressive resistance training, as defined by the International Physical Activity Questionnaire (IPAQ)]
• Body mass index of 18.5-34.9 kg/m^2
• Is at risk or has a current chronic disease that is not contraindicated by exercise, and could be improved by resistance exercise (i.e. type 2 diabetes, heart disease, hypertension, hypercholesterolemia, hyperthyroidism, depression, osteoporosis, etc.)

Exclusion Criteria:

• Experienced a musculoskeletal injury within the past three months that inhibits participation in the study.
• Has chronic kidney disease, liver disease, chronic obstructive pulmonary disease, or cancer
• Currently using medications that may directly impact the primary outcomes including: diuretics and corticosteroids).
• Currently using creatine monohydrate or other performance-enhancing supplements
• Has a self-identified or clinically diagnosed eating disorder
• Currently pregnant or planning to become pregnant (determined from urine pregnancy test)
• Currently nursing or have had a child within the previous 6 months
• Has participated in another clinical trial within four weeks prior to enrollment that in the opinion of the PI would influence the results.
• Has severely impaired hearing or speech or inability to speak English.
• Unwilling or unable to comply with the study protocol, including abstaining from caffeine, tobacco, alcohol, and physical activity before testing days.

Female

This is pilot data and therefore may not be powered for secondary analyses