Muscle Mass and Perimenopause

Debunking the viral claim

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There are viral claims that women lose a lot of muscle mass, even up to 10%, during the menopause transition, a.k.a perimenopause. I've seen several iterations of this, but here is one of the rather alarming quotes that I was sent and that prompted this piece:

Starting with perimenopause, we begin to lose muscle at an incredibly fast rate. We lose twice as much muscle during perimenopause and menopause as during any other time of life- up to 10% between early and late perimenopause.

There are also claims that the clear answer to this dramatic loss of muscle is menopause hormone therapy, which means that without MHT, women are destined to become feeble.

How accurate is this?

I was naturally skeptical for two reasons. One is that it is fear-based messaging, which gets far more attention on social media. The second is that studies tell us that metabolism doesn’t change during the menopause transition. As muscle contributes significantly to metabolism, if a lot of women were really losing 10% of their muscle mass or close to that percentage during the menopause transition, I would think that we should expect to see a change in metabolism.

But thinking isn’t knowing. And as a woman of science I am always open to quality data. Admittedly, I had not taken a deep dive into the literature on muscle mass and menopause in a while, so, I thought now would be a good time to do just that.

Let’s get into it!

Muscle and Aging

Both men and women lose muscle mass with age, but do the hormone changes of the menopause transition add to this equation for women?

Muscle mass is relatively stable from age 18 to 30, and around age 30, age-related muscle loss begins; it is about 0.37% per year for women and 0.47% per year for men.^1,2 (There is some controversy about the age at which this loss of muscle starts, and while that isn’t the point of this piece and doesn’t really factor in here, I just wanted to add it for completeness). Once we are over 75, muscle loss accelerates to 0.64-0.7% per year for women and 0.8-0.98% per year for men.¹

I asked Dr. Lauren Colenso-Semple, a PhD scientist in female physiology, exercise, and nutrition, about age-related muscle loss (she is a great evidence-based follow on Instagram). She said, “Depending on the measurement technique, the rate of muscle loss is ~0.05% to ~1% per year. Aging and reduced physical activity often go hand in hand, so muscle loss in individuals over 75 tends to be greater than muscle loss in individuals in their early 60s.

Menopause, Aging, and Muscle

We’ve established that loss of muscle mass will occur over time for women in their 30s and above, but does menopause affect that trajectory? Some cross-sectional studies suggest a relationship between menopause and loss of lean mass over and above aging, while others suggest no association. The issue with cross-sectional studies is they don’t follow the same women over time; they choose groups of women who are still having regular menstrual cycles, those in their menopause transition (perimenopause), and those past their final period and compare their muscle mass. But we can’t conclude that people lose muscle mass over time by measuring different people.

These cross-sectional studies can look impressive and many may be hypothesis-generating, we can’t use them to inform us about what happens over time. Here’s an example. In one of the larger cross-sectional studies that did show a difference

between pre and post-menopause, age range 47-55, appendicular lean mass went from 18.6 kg premenopause to 17.8 kg post-menopause, which is a change of 4%.³ But the authors offer a caution, and we need to take them at their word:

The main limitation of this study is the cross‐sectional design with group comparisons and correlative analysis, which do not enable causal interpretations. We may also have failed to take into account all of the important confounding factors, for example, individual genetic factors that may have an effect on muscle mass and bone density. Our earlier studies among postmenopausal women show that 60% of the variance in lower limb bone strength and 31% of that in knee extension strength are explained by genetic factors and that the association between muscle mass and bone strength derives from both genetic and environmental factors.

With a cross-sectional study, we can’t assume, even when matched for factors like level of physical activity, that the women who are 47 years old will be exactly like another group of women who are 55 when they reach that age because genetics plays a major role. In addition, physical activity is a very important mitigating factor in the loss of muscle mass, so when it is recorded via a questionnaire instead of a pedometer, that might also affect the results. And again, not all of the cross-sectional studies show a menopause-transition-specific impact, so it’s important not to cherrypick the ones that reinforce our bias.

To determine whether the menopause transition contributes to muscle loss above and beyond age, we must follow women over time and compare what they lose with age to what they lose as their hormones change.

Hughes et al. enrolled men, with an average age of 61.1, and women, with an average age of 60, followed them for 9.5 and 9.9 years, respectively.⁴ The men lost 1.2 kg of fat-free mass (FFM) per decade, and the women lost 0.1 kg FFM per decade. While most of the participants were past the menopause transition and so not of great help, nine were in the menopause transition at enrollment. During the study, there was no loss in fat-free mass among this small group of women who transitioned from premenopause to post-menopause, but nine women does not a robust argument make.

The Women’s Health Initiative (yes, the WHI) followed a subset a women over time with DEXA scans to evaluate changes in body composition. Women had three scans over six years, one at baseline and two in follow up. Now all these women were in menopause by definition, so it doesn’t quite tell us about the menopause transition, but the women are grouped by age and there were 2,715 women between ages 50 and 59 at enrollment, and so some were very likely in early menopause at the start of the study. There was no change in lean mass for this group over 6 years.⁵

The Fels longitudinal study followed women and men with a number of evaluations, including underwater weighing for fat-free mass every two years.⁶ Of the men and women aged 45-65, 75% of participants had done three or more exams, so, this study is poised to tell us something about the menopause transition. The average change in fat-free mass per year for women ages 45-65 was a surprising zero, and a loss of 0.13 kg/year for men. However, this paper doesn’t tell us if any women were using menopause hormone therapy (MHT), so it should be interpreted with caution as the publication date was 1998, and about 40% of women were using MHT at that time, which might potentially affect results.

Fortunately, another analysis of the Fels data includes information about menopause status and estrogen, and, sure enough, 45% of the group used MHT.⁷ The average age of women in this paper was 45.5 at the start and 53.6 years at the end. On average, for men, there was a loss of fat-free mass of 0.07 kg/year; for women, it was about 0.11 kg per year, and the authors report there “were no apparent effects of menopausal status on FFM.” They did report that women who had used estrogen for more than 5 years had higher fat-free mass, which should not be interpreted as cause and effect as the type and dose of hormones were not reported, and women were not randomly assigned to hormone therapy.

(Side note: the two studies above have slightly different results; for example, in the first, men lost 0.13 kg/year of fat-free mass, and in the second one, with the same study, they lost 0.07 kg/year, which is a good demonstration of how analysis can affect results).

Fortunately, we have SWAN, the Study of Women’s Health Across the Nation. In SWAN, 1,246 women were evaluated annually using DEXA scans and they were followed before they went through the menopause transition, through the transition, and then for years after menopause, so this study is poised to tell us exactly what happens during the menopause transition for women not taking hormone therapy.⁸ For this study, they defined the menopause transition as starting 2 years before the final menstrual period. SWAN found an average increase in lean mass of 0.2% per year until 2 years before the final period, and then lean mass decreased by 0.2% per year, and this trend persisted until two years after the final period. At this point, lean mass stabilized below the premenopausal levels. While statistically significant, the absolute change was relatively small: a net loss of 0.2 kg of muscle over four years. This is not 10%, not even 1%; it is 0.5%. And remember, some loss of muscle mass every year is expected due to age.

Here is the relevant graph from SWAN; the straight blue line (second from the bottom) is what is important for this discussion about muscle mass:

It is way more than a stretch to call that blue line an “incredibly fast” loss of muscle mass.

The accelerated gain two years before the menopause transition and then the accelerated loss during the menopause transition is a fascinating biological phenomenon and statistically significant, but beyond that, the implications are unknown. Remember, over 4 years, we should expect an age-related loss in muscle mass; if a loss of 0.37% per year is accurate for women, that puts the net 0.5% loss over the four year menopause transition in perspective.¹

(This doesn’t mean that women lose less muscle than expected, given the different measurement techniques we are going to see differences in muscle loss study to study).

Cherry-picking a Bad Paper

There is a rather bizarre research letter called Menopause and the Loss of Skeletal Muscle Mass in Women, published in a relatively obscure journal, Iran J Public Health, in 2021.⁹ One of the findings is that the appendicular lean mass index was “10 and 9 % lower in late peri- and postmenopausal women.” This sounds scary, but there are issues with this conclusion.

First of all, weirdly, this research letter isn’t a new study; it’s a summary of a paper already published in 2020, which, if someone didn’t look closely, would make it seem like two papers were claiming a 9-10% loss of muscle mass, when there is only one.¹⁰ The next issue is that the study from 2020 is cross-sectional, so women in different phases of their reproductive life were evaluated and compared with each other. It is not as good as following one group of women over time, like SWAN. Finally, the 2020 paper is a secondary analysis of data from a study published in 2012 that looked at the mechanisms of cardiovascular dysfunction with aging and menopause, and this original study was not powered to detect differences in appendicular lean mass index.¹¹ The authors of the 2020 paper even state:

…the present study was a secondary analysis of body composition data from an investigation of the biological mechanisms underlying cardiovascular dysfunction with aging and estrogen deficiency in healthy women. As such, the present study was not powered to detect differences in ALMi and to make correlations between ALMi and other variables, and the results should be interpreted cautiously. Third, the cross-sectional design precludes discussion of causality.

We should take their word that the study didn’t have the power to conclude anything about muscle loss and can’t ascribe cause and effect to the menopause transition. If anyone shares this 2021 research letter or the 2020 article as “proof” of muscle loss during the menopause transition, alarm bells should be going off.

What Can I Do to Protect My Muscles as I Age?

Based on the published research, there is no good data to support the idea that women lose a clinically significant amount of muscle during the menopause transition. To make sure I wasn’t missing anything, I checked back with Dr. Colenso-Semple, who told me, “There is nothing to suggest that the menopause transition specifically exacerbates muscle loss."

Is there a group of women who may be more vulnerable to loss of muscle mass during the menopause transition or early menopause? Sure, but as we don’t have a study that has evaluated this hypothesis, it should be just that, a hypothesis. Interestingly, a study was recently published looking at biomarkers to predict sarcopenia, a loss of muscle mass and strength.¹¹ Among women aged 45-69, a low creatinine-cystatin C ratio (CCR), which indicates a lower muscle volume, correlates with lower muscle volume and poorer physical function an average of 6.6 years later. This isn’t surprising that lower muscle volume is a risk factor for sarcopenia. Based on what we know, women with lower muscle volume are likely at greater risk as they have less muscle to lose.

The good news is based on what we know: the menopause transition is not a cause of a significant loss of muscle mass, and resistance training is the best thing for muscles at any age. Exercise can prevent or slow much of the age-related muscle loss, which is fantastic! In fact, many women can make incredible gains with muscle mass in menopause with resistance training. It’s also essential to make sure you are getting enough protein.

Study after study shows that it the basics that matter, but it’s also really important not to confuse basic with easy, because they are not the same thing. And it’s true that symptoms in the menopause transition and menopause, like hot flashes, disrupted sleep, joint pain, and brain fog, can make it harder to be active, and so treatment of those symptoms may make it easier for some women to start resistance training.

References

1. Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012 Jul 11;3:260. doi: 10.3389/fphys.2012.00260. PMID: 22934016; PMCID: PMC3429036.

2. Volpi E, Nazemi R, Fujita S. Muscle tissue changes with aging. Curr Opin Clin Nutr Metab Care. 2004 Jul;7(4):405-10. doi: 10.1097/01.mco.0000134362.76653.b2. PMID: 15192443; PMCID: PMC2804956.

3. Sipilä S, Törmäkangas T, Sillanpää E, Aukee P, Kujala UM, Kovanen V, Laakkonen EK. Muscle and bone mass in middle-aged women: role of menopausal status and physical activity. J Cachexia Sarcopenia Muscle. 2020 Jun;11(3):698-709. doi: 10.1002/jcsm.12547. Epub 2020 Feb 3. PMID: 32017473; PMCID: PMC7296268.

4. Hughes,V.A.,Frontera,W.R., Roubenoff,R.,Evans,W.J.,and Singh,M.A. Longitudinal changes in body composition in older men and women:role of body weight change and physical activity. 2002. Am.J.Clin.Nutr. 76, 473–481.

5. Sims ST, Kubo J, Desai M, Bea J, Beasley JM, Manson JE, Allison M, Seguin RA, Chen Z, Michael YL, Sullivan SD, Beresford S, Stefanick ML. Changes in physical activity and body composition in postmenopausal women over time. Med Sci Sports Exerc. 2013 Aug;45(8):1486-92. doi: 10.1249/MSS.0b013e31828af8bd. PMID: 23439422; PMCID: PMC3715578.

6. Siervogel RM,Wisemandle W, Maynard LM, et al. Serial changes in body composition throughout adulthood and their relationships to changes in lipid and lipoprotein levels. The FELS Longitudinal Study. Arterioscler Thromb Vasc Biol 1998;18:1759–64.

7. Shumei S Guo, Christine Zeller, William Cameron Chumlea, Roger M Siervogel, Aging, body composition, and lifestyle: the Fels Longitudinal Study. The American Journal of Clinical Nutrition, Volume 70, Issue 3, 1999, Pages 405-411, ISSN 0002-9165 https://doi.org/10.1093/ajcn/70.3.405.

8. Greendale GA, Sternfeld B, Huang M, et al. Changes in body composition and weight during the menopause transition. JCI Insight. 2019;4(5):e124865. https://doi.org/10.1172/jci.insight.124865.

9. Jupil Ko, Young-Min Park. Menopause and the Loss of Skeletal Muscle Mass in Women. Iran J Public Health, Vol. 50, No.2, Feb 2021, pp.413-414

10. Park YM, Jankowski CM, Ozemek C, Hildreth KL, Kohrt WM, Moreau KL. Appendicular lean mass is lower in late compared with early perimenopausal women: potential role of FSH. 2020. J Appl Physiol 128:1373-1380.

11. Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab 97: 4692–4700, 2012. doi:10.1210/jc.2012-2244

Post was updated March 31 to include the data from the WHI.