Low creatinine-to-cystatin C ratio linked to postmenopausal muscle loss

Low creatinine-to-cystatin C ratio linked to postmenopausal muscle loss | Image Credit: © javiindy - © javiindy - stock.adobe.com.

Postmenopausal women with a reduced creatinine-to cystatin C ratio (CCR) are more likely to have decreased muscle volume and gait speed, according to a recent study published in Menopause, the journal of The Menopause Society.¹

Impact of estrogen on muscle mass and strength

Estrogen plays a key role in bone density, muscle mass, and muscle strength. When estrogen declines during menopause, these characteristics are also reduced, while visceral fat mass increases, potentially leading to immobility and associated health concerns.¹

“Little is known about the longitudinal associations between CCR with muscle volume and function during the menopausal transition,” wrote investigators.² Therefore, the study was conducted to determine the impact of baseline CCR on muscle strength after 6.6 years.

Study methodology

Integrated Women's Health Programme participants attending baseline and follow-up visits were included in the analysis. These women were aged a mean 56.2 ± 6.0 years at baseline and had their muscle strength measured through physical performance assessments and magnetic resonance imaging (MRI).²

Investigators divided the creatinine in mg/dL by the cystatin C in mg/L in these patients to determine the creatinine to cystatin C ratio. Those with low CCR of under 8.16 were categorized in the lowest tertile, and the link between baseline CCR with muscle volumes and function after 6.6 years was determined through multivariable regression analyses.²

Key findings

An association was reported between low CCR at baseline and reduced muscle volume measured through MRI after 6.6 years. Additionally, patients with reduced baseline CCR reported a decrease in physical function during follow-up.²

The low CCR group reported a 0.350 L lower average fat-free thigh muscle volume vs the high CCR group following adjustments for covariates. This group also had a slower mean usual gait speed by 0.029 m/s and mean narrow gait speed by 0.049 m/s.²

No association was reported between low CCR and reduced handgrip strength, repeated chair stands, or one-leg stand test. However, patients with low CCR had an overall reduced muscle volume and gait speed after 6.6 years.²

Need for simpler muscle mass measurement

Muscle mass measurement has traditionally been performed using 3D-imaging technologies, but high costs and the need for a trained expert pose significant barriers to evaluation.¹ Additionally, specially trained personnel are needed for alternate measuring methods such as hand-grip strength.

These issues highlight the need for simpler methods. Based on the study data, CCR may be utilized as a biomarker of muscle mass and function.¹

Importance of physical function

Physical function is vital to understand in older women, as it may be linked to multiple health concerns, such as fracture risk in women with type 2 diabetes (T2D).³ A study published in 2024 noted 6.9% lower 25-hydroxyvitamin D3 levels, 4.7% higher creatinine, 1.6% higher calcium, and 23.8% higher glycated hemoglobin among T2D patients, alongside a hazard ratio of 1.26 for any fracture across a median 7.3 years.

“Regardless of baseline risk, all midlife women should strive to mitigate loss of muscle mass with regular resistance training and adequate dietary protein intake to help prevent frailty as they age," said Stephanie Faubion, MD, MBA, medical director for The Menopause Society.¹

References

1. New study identifies potential predictive biomarker for sarcopenia in midlife women. The Menopause Society. March 19, 2025. Accessed March 19, 2025.
2. Tan DYZ, Wong BWX, Shen L, Li LJ, Yong EL. Low creatinine to cystatin C ratio is associated with lower muscle volumes and poorer gait speeds in the longitudinal Integrated Women's Health Program cohort. Menopause. 2025. doi:10.1097/GME.0000000000002524
3. Krewson C. Reduced physical function linked to fracture risk in older women with T2D. Contemporary OB/GYN. August 12, 2024. Accessed March 20, 2025. https://www.contemporaryobgyn.net/view/reduced-physical-function-linked-to-fracture-risk-in-older-women-with-t2d.