Understanding the Connection Between Hormone Levels and Muscle Loss During Menopause

Estrogen’s Impact on Muscle Health in Women

The Effects of Menopause Beyond Hot Flashes

Menopause is often associated with well-known symptoms such as hot flashes and mood fluctuations. However, one less recognized change during this period is the decline in muscle health in women, which includes a reduction in muscle mass and strength. As women age, both muscle strength and the regenerative capacity of muscle cells diminish. While the relationship between sex hormones and muscle strength has been extensively researched in men, it remains less explored in women. A key female sex hormone that declines with age is estrogen.

Estrogen Deficiency and Its Consequences

Decreasing levels of estrogen are connected to a slower metabolism, an increased likelihood of cardiovascular disease, and osteoporosis. Additionally, a deficiency in estrogen contributes to the reduction of skeletal muscle mass in women. It is widely believed that low estrogen levels hinder the body’s ability to store and utilize protein, which subsequently leads to diminished muscle mass. Recent research from the University of Minnesota’s Medical School, published in Cell Reports, highlights estrogen’s vital role in muscle strength at a cellular level, particularly in the maintenance and function of muscle stem cells.

Muscle Stem Cells and Their Importance

The Role of Muscle Stem Cells

Throughout a person’s life, skeletal muscles experience various injuries, and the maintenance and repair of these muscles rely heavily on muscle stem cells. However, the pool of these stem cells decreases with age, partly due to hormonal changes, including shifts in sex hormones. Researchers, including lead authors Dawn Lowe, Ph.D., and Michael Kyba, Ph.D., have demonstrated that estrogen is crucial in sustaining the number of muscle stem cells in women. Their research indicates that estrogen signaling pathways play a significant role in the self-renewal, regeneration, and cell death of these stem cells.

Impact of Estrogen Deficiency on Stem Cell Numbers

In studies measuring stem cell populations across five different muscles, it was found that mice lacking estrogen exhibited a 30 to 60 percent reduction in stem cell numbers compared to their normal counterparts. Furthermore, estrogen deficiency impaired the remaining cells’ ability to recover from injury, resulting in a 20 to 30 percent decrease in strength recovery. Additional experiments revealed a connection between estrogen deficiency and increased programmed cell death among muscle stem cells, contributing to the observed decrease in cell numbers.

Muscle Stem Cell Reduction During Menopause

Research Findings on Menopausal Changes

The researchers were the first to document that muscle stem cell numbers decline by approximately 15% during the transition from perimenopause to post-menopause. This conclusion was drawn from a longitudinal study that involved muscle biopsies from women undergoing the menopausal transition. Dr. Lowe noted, “This is the first work to show that estrogen deficiency affects the number as well as the function of satellite [muscle stem] cells.”

Advancements in Hormone Therapy

Potential of Selective Estrogen Receptor Modulators

Estrogen replacement therapy has the potential to help maintain muscle health in women; however, it is also associated with an elevated risk of cancer due to its influence on cell growth, particularly in breast and endometrial tissues. A new class of FDA-approved medications, known as selective estrogen receptor modulators (SERMs), selectively modify estrogen receptor activity in various tissues. One such drug, bazedoxifene, has been shown to activate estrogen signaling pathways, thereby restoring the muscle stem cell pool in estrogen-deficient mice. This suggests that SERMs may serve as a treatment option for muscle loss related to menopause, minimizing the risks tied to traditional hormone replacement therapy.

Implications for Future Research

This study marks a significant advancement in understanding the role of sex hormones in women’s muscle health. Dr. Lowe emphasized, “It has long been known that male sex hormones promote muscle health, but we have been in the dark about what happens when females age. What estrogen does in women in terms of reproduction has been known for decades. Now we’re learning what estrogens do in women’s muscles.”

References

Collins BC, Arpke RW, Larson AA, Baumann CW, Xie N, Cabelka CA, Nash NL, Juppi HK, Laakkonen EK, Sipilä S, Kovanen V, Spangenburg EE, Kyba M, Lowe DA. Estrogen regulates the satellite cell compartment in females. Cell Rep. 2019 Jul 9;28(2):368-381.
Glynn K. UMN medical school researchers explain muscle loss with menopause. EurekAlert! https://www.eurekalert.org/news-releases/479935. Published July 18, 2019.
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