If you're struggling to lose weight despite eating well and exercising, hormonal imbalances, particularly those related to estrogen, might be the culprit. Hormones act as messengers in your body, influencing when you burn or store fat and how hungry or full you feel. When these hormones are out of sync due to factors like age, stress, or lifestyle changes, weight loss can become challenging.
The Role of Hormones in Weight Management
Hormones play a significant role in regulating appetite, metabolism, and fat storage. Understanding how different hormones affect your body can provide valuable insights into weight management.
- Insulin: This hormone helps cells absorb sugar from the bloodstream for energy or storage. High insulin levels, often caused by frequent eating or a diet high in refined carbohydrates and sugar, can lead to increased fat storage and reduced fat burning. Balanced insulin levels promote the use of fat as an energy source.
- Leptin: Produced by fat cells, leptin signals the brain that you've had enough to eat. Leptin resistance, where the brain doesn't receive this message, can result in overeating.
- Ghrelin: Known as the hunger hormone, ghrelin is released in the stomach and rises before meals, signaling the body to eat. Dieting can increase ghrelin levels, making you hungrier and hindering weight loss efforts.
- Cortisol: This is the body’s stress hormone. Elevated cortisol levels can increase food cravings, encourage belly fat storage, and slow down fat burning.
- Thyroid Hormones: Produced by the thyroid gland, these hormones control how quickly the body burns energy. Low thyroid hormone levels can slow metabolism and lead to weight gain, while high levels accelerate it, potentially contributing to weight loss.
- Estrogen: This hormone influences where the body stores fat. Low estrogen levels often result in fat storage around the abdomen, making weight loss more challenging and altering body shape.
- Testosterone: Crucial for building and maintaining muscle mass, which is essential for a healthy metabolism. Low testosterone levels can lead to muscle loss and increased body fat.
- Gut Hormones: These hormones send signals to the brain indicating satiety after eating, regulate blood sugar, and aid digestion. Higher levels make portion control easier and reduce overeating.
- Adiponectin: Produced by fat cells, adiponectin helps regulate blood sugar and fatty acid breakdown. Higher levels promote better fat burning and reduce the risk of obesity.
Estrogen's Impact on Weight and Metabolism
Estrogens are sex hormones that strongly influence body fat distribution and adipocyte differentiation. While both estrogens and testosterone affect adipocyte physiology, the role of estrogens in the development of metabolic diseases during menopause is a subject of debate. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances in estrogen signaling can lead to metabolic syndrome and increased cardiovascular risk in women.
The absence of estrogens is a significant factor in the onset of cardiovascular disease during menopause, characterized by lipid profile variations and abdominal fat accumulation. However, the direct relationship between estrogen deficiency and increased obesity in menopausal women is not entirely clear.
Estrogen Receptors and Adipocyte Function
Estrogens function through nuclear receptors, specifically estrogen receptors (ERs) alpha (ERα) and beta (ERβ). These receptors act as transcription factors, influencing gene expression and affecting adipocyte activity.
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Human subcutaneous and visceral adipose tissues express both ERα and ERβ, while only ERα mRNA has been identified in brown adipose tissue. ERα plays a major role in adipocyte activity and the sexual dimorphism of fat distribution. Studies on mice lacking ERα showed that both female and male mice have central obesity, have severe insulin resistance, and are diabetic.
Estrogen's Role in Fat Distribution and Lipolysis
Estrogen seems to promote the typical female fat distribution pattern, characterized by adipose tissue accumulation, especially in subcutaneous fat depots, with limited intra-abdominal fat accumulation. Estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in subcutaneous adipocytes. In contrast, visceral adipocytes exhibit a high α2A/β ratio and are stimulated by epinephrine; no effect of estrogen on α2A-adrenergic receptor mRNA expression was observed in adipocytes from the intra-abdominal fat depot. The effects of estrogens differ on the route of administration and the lipolytic influence of estrogens on fat accumulation affects specific regions of the body.
Estradiol (E2) may also increase beta adrenoreceptor expression through ERα, facilitating fat oxidation in the muscle by inhibiting lipogenesis in the liver and muscle through the regulation of peroxisome proliferator-activated receptor γ (PPARγ) and increasing LPL expression. E2 also increases muscle oxidative capacity by regulating acyl-CoA oxidase and uncoupling proteins (UCP2-UCP3), enhancing fatty acid uptake without lipid accumulation.
Estrogen and Hypothalamic Control of Obesity
The hypothalamus, a critical brain center for coordinating food consumption, body weight homeostasis, and energy expenditure, is influenced by estrogens. Areas within the hypothalamus, such as the ventromedial (VMN), arcuate (ARC), and paraventricular (PVN) nuclei, regulate physiological events that control weight.
Estrogens modulate the activity of molecules involved in orexigenic action, which can induce an increase in food intake. However, estrogen receptors regulate the neuronal activity of energy homeostasis and reproductive behaviors. While ERα is abundantly expressed in the rodent brain in VMN and ARC, PVN, and the medial preoptic area, ERβ is found in the same hypothalamic nuclei, but ERβ expression is significantly lower relative to ERα.
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Impact on POMC and NPY Neurons
Within the ARC, proopiomelanocortin (POMC) neurons modulate food intake, energy expenditure, and reproduction. ARC POMC ERα mRNA levels fluctuate over the course of the estrous cycle, with the most dramatic increase on the day of proestrus, when E2 concentration is highest. Estrogens directly act on POMC neurons and regulate their cellular activity. Deletion of ER in POMC neurons in mice leads to hyperphagia without directly influencing energy expenditure or adipose tissue distribution.
Neuropeptide Y (NPY) is a potent orexigenic that increases food intake during fasting conditions and after food consumption by acting primarily on the ARC and PVN in the hypothalamus. NPY exhibits decreased orexigenic activity after exposure to estrogens due to the estrogen modulation of NPY mRNA expression and receptor activity.
Ghrelin and Melanin-Concentrating Hormone (MCH)
Ghrelin, produced by parietal cells in the stomach, regulates feeding behaviors by sensing carbohydrate and lipid levels via stimulation of the growth hormone receptor. Ghrelin antagonizes leptin action through the activation of the hypothalamic neuropeptide Y/Y1 receptor pathway, augmented NPY gene expression, and increased food intake. Estrogen hormone replacement therapy induces a decrease or no change in ghrelin activity.
Melanin-concentrating hormone (MCH) promotes food consumption by acting directly on the lateral nucleus of the hypothalamus. Nerves that stimulate the MCH activity arise from the ARC nucleus and contain POMC, NPY, and Agouti-related protein (AgRP).
Estrogen and Insulin Sensitivity
Estradiol (E2) administered to ovariectomized (OVX) mice fed with a high-fat diet preserved improved glucose tolerance and insulin sensitivity in wild-type mice but not in ERα -/- mice, suggesting that targeting of the ERα could represent a strategy to reduce the impact of high-fat diet induced in type 2 diabetes mellitus (DM).
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Insulin resistance is a central disorder in the pathogenesis of type 2 DM and a feature observed in metabolic syndrome. Excess accumulation of adipose tissue in the central region of the body (intra-abdominal, "android," or male-pattern obesity) correlates with increased risk of and mortality from metabolic disorders, including type 2 DM.
As women enter menopause, there is a decline in circulating estrogen, accompanied by alterations in energy homeostasis that result in increases in intra-abdominal body fat. OVX rats, which are induced to exhibit obesity, regain normal weight after estrogen replacement. Although OVX induces a transient increase in food intake, hyperphagia does not fully account for changes in metabolism and development obesity after OVX.
Regulation of Glucose/Energy Metabolism
Estrogens regulate glucose/energy metabolism via the direct and indirect control of the expression of enzymes involved in this process, such as hexokinase (HK), phosphoglucoisomerase (PGI), phosphofructokinase (PFK), aldolase (AD), glyceraldehyde 3-phosphate dehydrogenase (GAPD), phosphoglycerate kinase (PK) 6-phosphofructo 2-kinase, fructose 2,6-bisphosphatase, and glucose transporters Glut 3 and Glut 4.
Estradiol availability affects the regulation of enzymes involved in tricarboxylic acid cycle activity. E2 enhances the glycolytic/pyruvate/acetyl-CoA pathway to generate electrons required for oxidative phosphorylation and ATP generation to sustain utilization of glucose as the primary fuel source.
Lipoprotein Lipase (LPL) Modulation
Lipoprotein lipase (LPL) is a key-regulating enzyme for energy metabolism that breaks down plasma triglycerides into free fatty acids and glycerol. Estradiol modulates the activity of LPL wherein the promoter region contains estrogen response elements that interact with the estrogen receptor and inhibit mRNA expression in 3T3 cells and patients undergoing therapy with estradiol patches.
Mitochondrial Function
The role of estrogens in mitochondria, which generate more than 90% of cellular ATP, must also be recognized. The mitochondria play an important role in the regulation of cell survival and apoptosis, and the respiratory chain is the primary structural and functional component that is influenced by estrogen activity.
The Impact of Menopause on Weight
During perimenopause and menopause, many women experience weight gain, particularly around their midsection, due to declining and fluctuating hormone levels, including estrogen and progesterone. This hormonal shift leads to a decrease in muscle mass, which results in fewer calories being burned by the body. The impact of menopause symptoms such as poor sleep, aches, pains, and hot flashes can further reduce energy levels, leading to a more sedentary lifestyle and poorer food choices.
The hormone 17 beta-estradiol encourages fat to be held around the hips and thighs. As this hormone declines, it naturally starts to change body shape. The International Menopause Society (IMS) stated that "menopause does not cause weight gain but does increase ‘belly fat’". This increase in abdominal fat, also known as visceral fat, can contribute to metabolic syndrome.
Hormone Replacement Therapy (HRT) as a Potential Solution
Hormone replacement therapy (HRT) can help your body find its balance, especially during menopause when hormonal changes make weight difficult to manage. While it’s not a quick fix for losing weight, HRT can support your metabolism, help your body respond more effectively to insulin, preserve muscle, and even help regulate your appetite.
HRT can help your body find its balance, especially during menopause when hormonal changes make weight difficult to manage. While it’s not a quick fix for losing weight, HRT can support your metabolism, help your body respond more effectively to insulin, preserve muscle, and even help regulate your appetite.
- Improve metabolism: By restoring regular hormone levels, HRT can help prevent the accumulation of abdominal fat, which often occurs during menopause. A regular metabolism can result in a higher calorie usage, leading to increased fat burn.
- Enhance insulin sensitivity: Menopause often upsets your body’s insulin response, leading to increased fat storage. Balancing hormone levels may enable your body to regulate blood sugar levels better and reduce fat deposition.
- Promote muscle mass: Estrogen, a key hormone in HRT treatment, can help preserve and even increase muscle mass. The effect may be a boosted metabolism that supports weight management.
- Regulate appetite: Hormonal changes can affect appetite and food cravings. HRT can help regulate hunger, thereby controlling your ability to manage calorie intake.
- Improve energy levels: Symptoms like fatigue and mood swings can impact food choices. Easing these symptoms through hormone replacement therapy can promote healthier food choices, which in turn contribute to better weight control.
- Better sleep: Sleep disturbances are common when hormones are out of sync, which can contribute to weight gain. HRT improves your quality of sleep, which has a positive impact on your overall health.
Types of HRT and Their Effects on Weight
HRT is not primarily intended nor prescribed for weight loss, but it can help indirectly by improving overall well-being.
- Oestrogen: Some evidence suggests that oestrogen hormone therapy increases a woman's resting metabolic rate (energy expenditure), which might help slow weight gain.
- Testosterone: Testosterone replacement therapy can be beneficial for women during menopause struggling with low libido. It can also impact body composition and weight by increasing lean muscle mass and influencing metabolism, fat storage, and energy levels.
- Thyroid hormone: The thyroid gland produces hormones that regulate the metabolism of the body’s cells. Thyroid hormone replacement can lead to weight loss if the thyroid is underactive.
HRT and Weight Gain: Addressing Concerns
Most evidence-based data suggest that HRT does not cause weight gain. Metabolic changes associated with menopause primarily influence weight gain. If HRT is used to manage menopausal symptoms, many women find their weight easier to manage and may even lose weight as HRT shifts metabolism back towards a pre-menopausal state.
While progesterone (and synthetic progestogens) can sometimes lead to fluid retention, mimicking weight gain, adjustments to HRT regimes can minimize this impact.
What is Estrogen Dominance or Unopposed Estrogen?
One of the most common hormonal imbalances is estrogen dominance, estrogen excess or unopposed estrogen. This means that estrogen levels are too high relative to progesterone (this can also include testosterone).
Estrogen Detoxification
The role of estrogen detoxification is vital for overall hormone health. Estrogen detoxification occurs in three stages:
- Phase 1: Enzymes called the CYP family of detoxification enzymes take estrogens through a process called hydroxylation and prepares them for Phase 2 detoxification.
- Phase 2: Methylation is the transformation of estrogen so it can be removed. If there is poor methylation status in the body it can lead to hormone imbalance, poor detoxification, poor sleep, mood changes and low energy.
- Phase 3: The safe removal of estrogen from the body via bile, urine and stool. If phase 3 is not working properly, it can lead to the unpacking of your estrogen (by an enzyme called beta-glucoronidase) and can lead to your estrogen being reabsorbed in the body again = resulting in high estrogen.
Lifestyle Strategies to Complement HRT
While HRT can be a valuable tool in managing weight during menopause, it is most effective when combined with healthy lifestyle habits.
- Balanced Diet: A diet rich in vegetables, fruits, whole grains, and lean proteins can stabilize blood sugar, prevent energy dips, and reduce cravings for high-sugar snacks. Protein is particularly important for maintaining muscle mass, and healthy fats provide satiety and support hormone production.
- Hydration: Staying hydrated is essential for digestion, metabolism, and appetite control. Drinking water before meals can help you feel fuller and reduce overall calorie intake.
- Regular Exercise: A combination of cardio, strength training, and flexibility exercises is crucial for managing weight, supporting muscle health, and reducing the risk of heart problems. Aim for at least 150 minutes of moderate-intensity exercise weekly, plus two days of muscle-strengthening activities.
- Stress Reduction: Chronic stress can lead to weight gain, especially around the abdominal area, due to increased cortisol levels. Incorporating relaxation techniques, hobbies, or social connections can lower stress and improve overall well-being.
- Optimize Sleep: Quality sleep regulates hunger hormones and supports metabolism. Aim for 7-8 hours of sleep each night and establish a calming bedtime routine.
The Mediterranean Diet
The Mediterranean diet can help lower the risk of cardiovascular disease, metabolic syndrome, osteoporosis, dementia and certain cancers, in addition to supporting a healthy balance of gut flora to help with digestion. The plant-forward diet, filled with anti-inflammatory foods, limits sugar, sodium, processed carbohydrates, trans and saturated fats, and processed foods. It includes whole foods rich in nutrients, fiber and antioxidants that work together to optimize health and maintenance of a healthy weight.
Other Strategies to Help
Personalized weight-loss medications like GLP-1s, even in microdoses, can help, and some women are finding benefits from combining GLP-1s with HRT.
Supplements, like fiber and berberine have been shown to help aid in weight loss. Research suggests that making the single change of eating more fiber helps you lose weight, according to a study in The Journal of Nutrition. Berberine, now dubbed “nature’s Ozempic,” may also help aid in weight loss by improving overall health, and it has been shown in several studies to help lower blood sugar levels and improve cholesterol levels-two health markers exacerbated in menopause.