The Truth About Intermittent Fasting for Women Over 40, Part 2: Autophagy, Cortisol, and the Sign It Isn't Working for You
5min read
In this second part of the series, I'm looking at what's actually known about intermittent fasting for women in perimenopause and menopause, the claims around autophagy and longevity, cortisol and belly fat, and why a strict fasting routine might not be right for most women, who'd do better approaching it carefully and paying attention to their own response.
You'll find part one here, where I covered weight management, muscle preservation, and metabolism.
If you read nothing else, read this
One thing worth knowing: If you're on a GLP-1 medication, such as semaglutide (Ozempic, Wegovy) or the dual GLP-1/GIP medication tirzepatide (Mounjaro, Zepbound), think twice before adding fasting on top, and talk to your prescriber first. These medications already suppress appetite enough to cause malnutrition, in some cases.
One thing to ponder: What's your overall stress load right now, and how much room do you actually have to take on more?
One thing to experiment with: Instead of removing a meal or trying to manage calories and macros, try adding more fruit and vegetables to your meals, slow down while you eat, and notice how you feel.
What autophagy actually is
Autophagy is your body's ongoing way of clearing out damaged or worn-out parts of cells. It's running at a low level all the time, not just when you fast. What changes with fasting or exercise is the rate of this process, not whether it happens at all. Two switches drive this: AMPK senses when the body's energy is low and turns autophagy up directly, while mTOR normally holds it back and switches off when food is scarce, releasing that brake [1]. Fasting engages both. Exercise turns AMPK on too, through the energy demand of working muscle [2].
Human studies have found markers of increased autophagy activity after both fasting and exercise [2][3]. The strongest human evidence used a proper measure of the process itself, not just gene activity, and it came from one intensive protocol, three near-fasting days a week, not a daily pattern that one can typically manage [4]. The fasting-mimicking diet, a structured 5-day very-low-calorie plan followed monthly, has shown real benefits in a randomised trial, including better insulin sensitivity, less fat in the liver, and markers of slower biological ageing, independent of weight loss [5].
Whether fasting longer or more often increases the autophagy benefit further, it hasn't actually been tested.
Belly Fat in Midlife: What Actually Drives It
You'll often hear that stress and cortisol cause "meno belly." It's worth separating fact from popular claim here, because the evidence for each part of this story isn't equally strong.
In perimenopause, oestrogen doesn't decline steadily, it swings unpredictably, with high points and sudden drops, while trending downward overall, reaching its lowest point at menopause [6]. This fat redistribution itself is well supported in menopause. Oestrogen normally favours storing fat under the skin, around the hips and thighs, and supports the breakdown of stored fat for energy. As oestrogen declines, that effect weakens, and fat shifts toward the abdomen instead, including visceral fat, the kind around your organs [7].
The evidence for cortisol's role is weaker. Despite how often it's blamed for abdominal fat specifically, the evidence doesn't support a direct causal link. Dr Rexford Ahima, an endocrinologist at Johns Hopkins, states plainly that the idea that chronic stress and high cortisol drive abdominal fat "is not supported by evidence" [8]. What the research does show is an association, women with more central fat tend to have a stronger cortisol response to stress, but that's two things occurring together, not proof that cortisol causes the fat [9]. The one clear exception is Cushing's syndrome, a rare condition of genuinely excess cortisol production, which does reliably cause central fat gain, but that's a medical condition, not the everyday stress most women experience.
Poor sleep adds to this picture, and it is affected by our stress levels. Sleep deprivation raises hunger, weakens the signal that tells you you're full, worsens blood sugar handling, and increases stress reactivity [10].
Loss of muscle matters too, since muscle burns much of your energy at rest, and losing it means the same food intake is more likely to be stored as fat [11].
The honest summary: declining oestrogen is the best-supported driver of midlife belly fat. MHT is licensed for managing menopausal symptoms and protecting bone health, not for treating fat gain, though some studies have found it's also linked to a reduction in central fat as part of that treatment [12]. Cortisol gets blamed constantly for abdominal fat specifically, but the evidence for that link is weaker than its reputation suggests.
What reliably supports healthy body composition and metabolic health in midlife is the same as at any other stage: whole-food nutrition, regular movement, good sleep, and managing stress, with sleep and nutrition standing out as the most consistently supported factors across the research [18][19].
Restriction itself is a stressor
Postmenopausal women who deliberately limited their food to manage weight had higher cortisol than women who didn't, even though their weight, exercise, and reported stress were the same [13]. The restriction itself seemed to be the difference.
Whether fasting is suitable for you depends on your individual stress levels and tolerance, your sleep, and your other recovery practices, not on theories about hormones. If your stress is generally manageable and your sleep's reasonable, fasting may be worth trying. If not, it's one more demand on a body that's already stretched.
GLP-1 medications and fasting
If you're on semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound, which acts on both the GLP-1 and GIP receptors), combining either with fasting needs real caution. These medications suppress appetite as their actual mechanism, not as a side effect, which means hunger isn't a reliable signal that something's wrong. This isn't theoretical: one study found people on GLP-1 medications were over six times more likely to show signs of malnutrition before surgery than people not on them [14], a study of over 450,000 people on these medications found 22 percent developed a nutritional deficiency within a year, most often vitamin D [15], and people managing treatment without nutrition guidance often cut their intake further than they realise [16]. Watch for fatigue, hair thinning, low energy, or trouble concentrating, and talk to your prescriber before even considering adding fasting, just because you are not that hungry any more.
Watch for this
Food restriction doesn't just affect how the body works, it can change how someone relates to food itself. The classic demonstration of this is the Minnesota Starvation Experiment, where 36 men followed a semi-starvation diet for six months, roughly half their previous intake, and lost about a quarter of their body weight. Many became preoccupied with food, dreaming about it, talking about it constantly, and collecting recipes [17].
This kind of preoccupation tends to show up more in women with a longer history of dieting, the pattern seems easier to trigger once it's been triggered before. Women without that history often find fasting genuinely unremarkable.
If fasting leaves you constantly thinking about food, that's worth paying attention to. It's a sign worth discussing with a coach or healthcare provider rather than something to push through alone.
In summary
Autophagy happens in your body all the time. Fasting and exercise both seem to turn up its activity, but the evidence is limited, and more fasting hasn't been shown to result in more benefit.
Declining oestrogen is the best-supported driver of midlife belly fat. Cortisol is associated with it but isn't a proven direct cause, and sleep, nutrition, and muscle preservation matter at least as much.
Restriction itself raises cortisol, regardless of any hormone theory. Whether fasting suits you depends on your stress levels and quality of sleep.
Combining fasting with a GLP-1 medication needs real caution. Hunger won't warn you reliably to recognise your body’s needs, fatigue and hair loss are better signs to watch, but in any case make sure you work with a coach or nutritionist so that you get adequate nutrition through regular meals.
If you are looking for support to reach your health and fitness goals in midlife, improve your menopause experience and enjoy life, I will be honoured to be your coach. Book a free discovery call to see if we are a good fit.
References
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[2] Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training-induced increase in autophagy markers in human skeletal muscle. Physiological Reports. 2018;6(7):e13651. https://pmc.ncbi.nlm.nih.gov/articles/PMC5889490/
[3] Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients. 2019;11(6):1234.
[4] Bensalem J, Teong XT, Hattersley KJ, et al. Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis. Journal of Physiology. 2025;603(10):3019-3032. https://pubmed.ncbi.nlm.nih.gov/40345145/
[5] Wei M, Brandhorst S, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine. 2017;9(377):eaai8700.
[6] Grub J, Süss H, Willi J, Ehlert U. Steroid Hormone Secretion Over the Course of the Perimenopause: Findings From the Swiss Perimenopause Study. Frontiers in Global Women's Health. 2021;2:774308. PMID: 34970652; PMCID: PMC8712488.
[7] Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA, Richelsen B. Estrogen controls lipolysis by up-regulating α2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor α. Journal of Clinical Endocrinology and Metabolism. 2004;89(4):1869-1878.
[8] Ahima RS, quoted in: Cortisol Belly: Causes and Symptoms. WebMD. Verify exact publication date and full citation before publication.
[9] Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat. Psychosomatic Medicine. 2000;62(5):623-632.
[10] Covassin N, Singh P, McCrady-Spitzer SK, et al. Effects of experimental sleep restriction on energy intake, energy expenditure, and visceral obesity. Journal of the American College of Cardiology. 2022;79(13):1254-1265. https://pubmed.ncbi.nlm.nih.gov/35361348/
[11] Lower resting and total energy expenditure in postmenopausal compared with premenopausal women matched for abdominal obesity. PMC4153012.
[12] Clinical review: Menopause hormone therapy in weight management. ScienceDirect. 2026. Verify exact authors and full citation before publication.
[13] Rideout CA, Linden W, Barr SI. High cognitive dietary restraint is associated with increased cortisol excretion in postmenopausal women. Journal of Gerontology: Series A. 2006;61(6):628-633. https://academic.oup.com/biomedgerontology/article/61/6/628/589490
[14] Jodoin Z, Young WH, Sheikh D, et al. Malnutrition is common in patients utilizing glucagon-like peptide-1 agonists prior to total joint arthroplasty. Arthroplasty Today. 2025.
[15] Butsch WS, Sulo S, et al. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists. Obesity Pillars. 2025;15:100186.
[16] Mogna-Peláez P, Guasch-Ferré M. Avoiding malnutrition in the era of GLP-1 medications: emerging evidence and opportunities for integrated nutrition care. The Journal of Nutrition. 2026; In Press, Journal Pre-proof, 101684. https://www.sciencedirect.com/science/article/pii/S0022316626003330
[17] Kalm LM, Semba RD. They starved so that others be better fed: remembering Ancel Keys and the Minnesota Experiment. Journal of Nutrition. 2005;135(6):1347-1352.
[18] Sleep, health, and metabolism in midlife women and menopause: food for thought. PMC6338227.
[19] Well-being predictors of body composition and associated behavioral risk factors in midlife/older women participating in a meditative movement intervention: an exploratory analysis. PMC10523288.