Active Voice: Estrogen, Like Androgen, Can Affect Muscle Strength
By Dawn Lowe, PhD, FACSM

Active Voice is a column by ACSM experts in science, medicine, and allied health. The viewpoints expressed do not necessarily reflect positions or policies of ACSM.

Dawn Lowe, PhD, FACSM, is Associate Professor in the Department of Physical Medicine & Rehabilitation, University of Minnesota. Her research focuses on cellular and molecular mechanisms underlying skeletal muscle deterioration in relation to age, injury and disease. See the April 2010 issue of ACSM's Exercise and Sports Sciences Reviews for a related research review she coauthored: "Mechanisms Behind Estrogen's Beneficial Effect on Muscle Strength in Females."

Estrogens and androgens are the primary sex hormones of females and males, respectively, and these hormones are quite different. Right? We recognize androgens as anabolic steroids that influence the response of skeletal muscle to exercise in males. But what about estrogen’s influence on exercise and skeletal muscle in women? If you are not so sure about this answer, you are not alone.

The literature on women is mixed, with some studies finding benefits of estrogens on skeletal muscle and exercise responses while many others not. Animal models are often used in research to address questions related to exercise and muscle adaptations, but thus far they have not added clarity to these estrogen questions. A main reason for this is that the preponderance of rodent studies are conducted on male rats and mice. This is particularly true when the scientific question revolves around aging. I remember as a post-doctoral associate causally asking senior investigators, “Why do you use male mice/rats?”, and inevitably the answer would be something like, “So that we don’t have to deal with fluctuating/changing hormones that would add variability to …” This seems reasonable given that a big advantage of using rodents in the first place is to reduce biological and environmental heterogeneity that is inherent to studies on humans. Then again, fluctuations and age-related changes in the sex hormones are biological reality.

A major interest in my laboratory is determining mechanisms underlying age-related muscle weakness and investigating what can be done to slow, prevent or reverse the occurrence. Our earlier work on age-induced alterations in the structure-function of myosin (the “molecular motor” of skeletal muscle) indeed was conducted on male rodents. The fact that essentially all work in this area had been conducted on male rodents became crystal-clear to me when I added a “Gender” column to my spreadsheet where I was summarizing previous papers that had reported age-related decrements in skeletal muscle function. At the time, 26/27 of the papers on my list reported results from studies on young versus aged male rats or mice. So began a nice research project for the first graduate student in my lab!

What we have learned on this topic over the past few years is that the temporal loss of muscle strength differs between aging male and female mice and that estrogens are implicated. These observations are not restricted to mice; the collective literature shows similar results in men and women and that hormone replacement is favorable for muscle strength of women. We have referred to this estrogenic effect as being qualitative as opposed to quantitative because estrogens do not appear to impart muscle strength by making more contractile machinery or by making muscle fibers larger, but rather by making those fibers and the force-generating molecules within them functionally better. This is in contrast to androgens where strength improvements can be attributed to the hormones’ anabolic effects. While our data support estrogens’ qualitative influences, an anabolic role for these hormones shouldn’t be dismissed. The cattle industry has used low-level estrogens to enhance muscle quantity, i.e., beef production, for decades. Bottom line, we need to know more about these hormones and their mechanisms of action in non-reproductive tissues, particularly in regard to how they influence exercise-induced adaptations.

As we continue to follow our questions of estrogens’ influences on exercise and skeletal muscle in females, we also need to consider a) estrogen and estrogen-like effects in males, b) whether or not effects are the same in pre-elderly adults and the aged, and c) muscles’ neighboring tissues that are also impacted by exercise and by the presence or absence of estrogens. Considering the last point, the skeleton is a prime example because it is also affected by exercise and estrogens. The combined influences that estrogens have on muscle and adipose tissue and their interactions is another good example, particularly from metabolic and energetic standpoints. I was excited to see symposia at the recent 2010 Annual Meeting of the ACSM on these and similar topics because I also remember being told as a junior investigator that studying sex differences was descriptive. I think we are realizing that this is not true, particularly when we can delve into the cellular and molecular mechanisms by which sex hormones influence exercise-induced adaptations of cells and tissues and impact health.