HOT OFF THE PRESS FROM THE MENOPAUSE SOCIETY

New Study Identifies Potential Predictive Biomarker for Sarcopenia in Midlife Women

Low creatinine-to cystatin C ratio associated with lower muscle volumes and poorer gait speeds 

CLEVELAND, Ohio (March 19, 2025)—Menopause is associated with a decline in estrogen, which increases visceral fat mass and decreases bone density, muscle mass, and muscle strength. This can lead to immobility and related health problems. A new study suggests there may be an easy way to predict which women are most at risk—low creatinine-to-cystatin C ratios. Results of the study are published online today in Menopause, the journal of The Menopause Society.

Women are more vulnerable to decline in muscle mass and function after menopause. Not only does that make them frailer, but it also increases their risk of developing other adverse health outcomes such as diabetes, malnutrition, and mortality. Losing muscle function can seriously affect a woman’s quality of life and ability to live independently. It can also create a significant financial burden.

To date, muscle mass is most accurately measured with 3D-imaging technologies, such as magnetic resonance imaging (MRI). The problem is that these tests are expensive and rely on highly trained staff to compute highly technical calculations. Other types of available diagnostics, such as measures of handgrip strength and physical performance, are time-consuming and require specially trained personnel. There is a need for simpler and more practical methods that can simultaneously assess total skeletal muscle mass and function.

Researchers in a new study that followed nearly 900 women over 6.6 years suggested that a woman’s creatinine-to-cystatin C ratio (CCR) might be associated with muscle volume and gait speeds. They found very limited research in this area because there did not appear to be any relevant studies previously conducted.

Creatinine is generated by skeletal muscles as a waste product of muscle metabolism. It is typically filtered through the kidneys and excreted in urine and provides the energy transfer mechanism for muscle contraction. Cystatin C is a protein produced by cells in the body.

On completion of their study, the researchers concluded that, together, creatinine and cystatin C provided a reliable biomarker of total skeletal muscle mass and function that is independent of kidney function. They assessed MRI-measured muscle volumes, as well as muscle strength, using multiple measures. Their findings showed that a low CCR at baseline was associated with lower fat-free muscle volumes and poorer gait speeds 6 years later.

Survey results are published in the article “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.”

“Because both muscle volume and poorer gait speed are constituents of current diagnostic criteria of sarcopenia, CCR may be a tool to help identify midlife women at risk of developing early sarcopenia and associated probability of adverse health outcomes. 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,” says Dr. Stephanie Faubion, medical director for The Menopause Society.

For more information visit www.menopause.org.

Are You Just Tired or Are You Menopause Tired?

New study demonstrates need for more attention on bleeding changes during the menopause transition because abnormal uterine bleeding during that time is linked to greater risk of fatigue 

CLEVELAND, Ohio (March 12, 2025)—Multiple menopause symptoms can make women feel fatigued. Hot flashes, sleep problems, pain, and depression are just a few. A new study suggests that heavy or prolonged menstrual bleeding may increase fatigue, which helps to explain why midlife women are two-to-four times more likely to experience debilitating forms of syndromic fatigue. Results of the study are published online today in Menopause, the journal of The Menopause Society.

Most women transitioning through menopause experience changes in the amount and duration of menstrual flow, with many reporting episodes of prolonged (PMB) or heavy (HMB) menstrual bleeding that meet the criteria for abnormal uterine bleeding (AUB). The Study of Women’s Health Across the Nation (SWAN) revealed that one in three women transitioning through menopause had episodes of AUB.

Despite the high occurrence of AUB, only a few prior studies have focused on the problem, and no known studies have attempted to link AUB during the menopause transition with fatigue or an overall decreased quality of life. Heavy menstrual bleeding, in particular, is linked to iron deficiency anemia, a well-recognized cause of fatigue.

In this new large-scale study, daily menstrual calendar data from more than 2,300 midlife women were assessed to determine whether HMB or PMB recorded during the 6 months before a follow-up visit were associated with the reporting of four specific symptoms of fatigue (feeling worn out, feeling tired, not feeling full of pep, or not having energy). Based on the results, the researchers concluded that HMB and PMB during the menopause transition were associated with an increased risk of fatigue, even after adjusting for other causes. They suggest that greater clinical awareness is required of bleeding changes during this life stage, especially when fatigue is also reported.

Because iron deficiency and related anemia can be readily treated, an early assessment and remediation in women with these symptoms would be helpful. To date, however, limited attention has been paid to bleeding problems during the menopause transition—in research, the lay press, and social media.

Survey results are published in the article “Abnormal uterine bleeding is associated with fatigue during the menopause transition.”

“This study highlights the need for greater clinical awareness of abnormal uterine bleeding, particularly given the increased frequency during the menopause transition and its association with low energy or fatigue symptoms. Educating women about the possibility of prolonged or heavy menstrual bleeding during the menopause transition and the potential health consequences is also needed,” says Dr. Stephanie Faubion, medical director for The Menopause Society.

To learn more, visit menopause.org.