According to Dr Sarah Merran, menopause marks a loss of systemic signalling: falling oestrogen lifts a metabolic shield that protected women before the age of 50. The risk of metabolic syndrome can then double. With 1.2 billion postmenopausal women expected by 2030, the cardiometabolic stakes are considerable.
Metabolic syndrome: the criteria
The central element is an increase in abdominal fat (a waist circumference above 80 cm in women), combined with at least two of the following: raised triglycerides, blood pressure at or above 130/85 mmHg, low HDL and raised blood glucose. The consequences are serious: a sharply increased risk of type 2 diabetes, higher cardiovascular and stroke risk, and excess all-cause mortality.
Why perimenopause changes everything
Perimenopause combines a decline in progesterone, then a fall in oestrogen, relative hyperoestrogenism and a gradual rise in FSH. This shift alters energy homeostasis and slowly establishes an unfavourable terrain. Hence the value of acting early, before metabolic syndrome is fully established.
A network of mechanisms
Metabolic syndrome does not rest on a single mechanism. Insulin resistance is the central piece, alongside low-grade systemic inflammation and chronic NF-κB activation. Added to that are disturbances in adipose tissue, muscle, liver and pancreas; a gut contribution (metabolic endotoxaemia, reduced short-chain fatty acids, disrupted bile acids, impaired barrier function); neuroendocrine changes (HPA axis, autonomic nervous system, renin-angiotensin-aldosterone system); reduced mitochondrial efficiency; and the role of sleep, endocrine disruptors and epigenetics.
Oestrogen receptors everywhere
Oestrogens act well beyond the reproductive sphere: their receptors are present in the brain, adipose tissue, liver, muscle, pancreas, endothelium and heart, kidneys, bone and immune system. This distribution explains the broad impact of oestrogen deficiency.
Pancreas
17β-oestradiol supports insulin biosynthesis and secretion, protects beta cells from apoptosis linked to oxidative stress, and improves insulin sensitivity. As it falls, glucose-stimulated insulin secretion and beta cell survival both decline.
Liver
When oestrogen falls, the liver switches into storage mode: more de novo lipogenesis, less beta-oxidation, higher glucose output and more VLDL/triglycerides, lower HDL and hepatic insulin resistance. This context favours steatosis, dyslipidaemia and fibrosis.
Muscle
Muscle loses regenerative capacity and glucose uptake (less membrane GLUT4), with a build-up of intramuscular lipids and a risk of sarcopenia, which is common after menopause.
Adipose tissue
Distribution moves from a gynoid pattern (hips, thighs) to an android one (visceral fat). The adipose secretome changes: less adiponectin, leptin resistance, more resistin and cytokines, macrophage infiltration. The tissue becomes hypertrophic, hypoxic and inflammatory.
Mitochondria
Mitochondria carry oestrogen receptors too. Their deficiency reduces mitochondrial biogenesis and the efficiency of the respiratory chain, lowers ATP, increases free radicals and promotes tissue lipotoxicity.
Gut, microbiota and estrobolome
The estrobolome (the bacterial genes able to metabolise oestrogens via beta-glucuronidase) directly influences circulating oestrogen levels. Postmenopausal deficiency reduces microbial diversity and the production of butyrate, propionate and acetate (hence poorer GLP-1 signalling and postprandial hyperglycaemia) and alters bile acids (FXR and TGR5 signalling, permeability). It also disturbs the tryptophan-serotonin-kynurenine axis, which contributes to emotional vulnerability, brain fog and anxiety, and amplifies the metabolic terrain.
Sleep, cortisol and thyroid
The fall in oestrogen and progesterone has knock-on effects on clock genes, sleep quality and satiety: fragmented sleep, higher ghrelin, snacking on sugary foods, higher basal cortisol and more visceral adiposity. A fall in T3 and in basal metabolic rate is also commonly seen, along with frequent thyroid dysfunction.
The window of opportunity in perimenopause
The first signs (persistent fatigue, brain fog, poorer sleep, recent-onset anxiety, hot flushes, weight gain and a change in body shape, shorter cycles) signal this shift. Acting at that moment means intervening before metabolic syndrome is fully established.
Nutritional and lifestyle levers
- Macronutrients and timing: adequate protein intake (of the order of 1 g/kg/day), protein in the morning, a low insulin index, fewer ultra-processed foods, fast sugars and less alcohol, and a 10 to 12 hour overnight fasting window.
- Liver and metabolic support: olive leaf, artichoke, chrysanthellum, garlic, milk thistle, berberine, chromium, cinnamon.
- Cofactors and micronutrition: vitamins B9, B12 and B6, carnitine, polyphenols, EPA and DHA, GLA/DGLA, vitamin D, zinc, selenium.
- The gut-microbiota axis: fibre, targeted probiotics, prebiotics, glutamine, and phytoestrogens depending on the context.
- Sleep, stress and the autonomic system: cardiac coherence breathing, morning light, fewer screens in the evening, rhodiola, holy basil, saffron, glycine, magnesium.
- Physical activity: regular aerobic work, resistance training, HIIT for mitochondrial quality, and cutting sedentary time (active breaks).
Putting it into practice with Simplycure
To support women from perimenopause onwards and build a clear metabolic protocol, from liver support to omega 3 and the microbiota, Simplycure brings together the protocols and products of more than 300 brands on a single platform. Create your practitioner account to compare and recommend in a few clicks.
