The Relationship Between Hormones & Metabolic Syndrome

Understanding Metabolic Health and Metabolic Syndrome

To fully understand metabolic health, we need to start with understanding metabolism. Metabolism is the sum of all chemical reactions in your body that use energy from food for cellular growth, movement, reproduction, and repair and break down dead and damaged tissue. When these chemical reactions efficiently and effectively convert energy from food to fuel for bodily processes, this is called metabolic health. Metabolic health is essential for overall fitness and well-being.

Metabolic health is defined by having optimal values for 6 markers for metabolic health without using medications. If you have suboptimal values for three or more of these markers, then you meet the criteria for metabolic syndrome. (One marker of metabolic health, uric acid, is not included in the criteria to define metabolic syndrome) 

Criteria for metabolic syndrome: 

• A waistline of 35 inches or more for women, or 40 inches or more for men
• Fasting blood glucose above 100 mg/dL
• Triglycerides above 150 mg/dL
• High density lipoproteins (HDL) (good) cholesterol less than 40 mg/dL in men or less than 50 mg/dL in women
• Blood pressure consistently 130/85 mm Hg or higher

Metabolic syndrome is a constellation of risk factors that increase your likelihood of developing coronary heart disease, stroke, type 2 diabetes, nonalcoholic fatty liver disease, and other serious health conditions. 

<p class="pro-tip"><strong>Learn more about the </strong> <a href="/blog/signs-metabolic-health-out-of-balance">warning signs your metabolic health is out of balance</a>.</p>

Body weight, dietary choices, physical activity levels, age, and genetic predisposition are all contributory causes of metabolic syndrome. Complex interactions between hormones secreted by abdominal (visceral) fat, insulin resistance, and low levels of inflammation cause metabolic syndrome.¹Many of these factors overlap and amplify each other. 

Environmental factors (physical inactivity, smoking, consuming energy-dense foods, and stress) interact with genetic factors (having the thrifty genetic profile, i.e., holding on to calories and energy) to create a positive energy imbalance. This energy excess leads to increased adipose (fat) tissue, which changes fatty acid metabolism and increases the release of adipokines (hormones released by fat cells).²Excess free fatty acids in the blood inhibit insulin action in the muscles and liver. This results in:

• Damage to the inner lining of blood vessels.
• Abnormal blood lipids: increased Low-density lipoproteins (LDL) (bad) and decreased HDL (good) cholesterol. 
• Insulin resistance.
• High blood pressure.
• Increased tendency to have blood clots.
• Low-grade inflammation.

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How Different Types of Hormones Can Affect Metabolic Health

Metabolic syndrome, insulin resistance, and obesity are three chronic conditions that are linked and share many risk factors, but the metabolic, immune, endocrine, and chemical molecules that connect these conditions are not fully understood. 

The tissues and organs in your body communicate via three systems:

• Nervous system: The nervous system gathers sensory information inside and outside the body and quickly responds to it. 
• Endocrine system: Hormones are protein and lipid molecules secreted by endocrine glands that bind to receptors throughout the body, including other endocrine glands, and elicit a response. Depending on the target organ, hormones can have many different effects throughout the body. 
• Local responses: Cells secrete chemicals that allow them to communicate with other nearby cells. This is called autocrine (stimulates self) and paracrine (stimulates nearby cells) signaling. 

The endocrine and nervous systems are linked by the hypothalamus, a brain structure that is directly connected to the pituitary gland, the master gland of the endocrine system. Together, they control sleep, hunger, thirst, and libido (plus many other bodily functions) by either secreting hormones that act on target tissues or regulating the synthesis and action of other hormones. 

The interactions between the nervous and endocrine systems are not fully understood. Scientists can identify correlations and trends, but not causes. While more research is needed to understand which hormones cause metabolic syndrome and how they do it, links between hormones and metabolic changes in the body have been identified, and the network of connections between these two systems that are understood is growing. 

Here are examples of these correlations:

• Chronic stress increases cortisol levels and is associated with abdominal obesity, insulin resistance, and higher blood lipids, all factors associated with metabolic syndrome. 
• Most people with metabolic syndrome also have insulin resistance, suggesting that insulin plays a role in developing metabolic syndrome, but the relationship is unclear.
• As men age, the sex hormone testosterone decreases, and there is an increased prevalence of metabolic syndrome. 
• Women with polycystic ovary syndrome (PCOS) have increased androgens (male sex hormones) and are at an increased risk of insulin resistance, obesity, and metabolic syndrome. 

<p class="pro-tip"><strong>Key takeaways: </strong> Knowledge about the connections between the endocrine and nervous systems is growing. Researchers use clinical trials and research studies to test these connections with the goal of developing effective medications to treat metabolic syndrome.</p> 

Steroid Hormones

Steroid hormones are secreted by the adrenal cortex, testes, ovaries, and placenta during pregnancy. All steroid hormones are derived from cholesterol. 

Steroid hormones are divided into two major classes:

• Corticosteroids: glucocorticoids and mineralocorticoids
• Sex steroids: progesterone, androgens, and estrogens

Glucocorticoids, such as cortisol:

• Respond to stress.
• Are involved in the immune response feedback system.
• Mediate inflammation.
• Are involved in carbohydrate metabolism and protein breakdown.
• Regulate blood electrolytes.
• Are involved in behavior.

Mineralocorticoids:

• Maintain salt and water balance in the body.

Stress Hormones

Cortisol (stress hormone) is produced in the adrenal glands, which are small glands located just above the kidneys. When stressful situations arise, the part of the brain that processes this information activates the hypothalamic-pituitary-adrenal gland (HPA) axis. Signals from the hypothalamus stimulate the secretion of adrenocorticotropin hormone (ACTH) from the pituitary gland. ACTH then prods the adrenal gland to produce cortisol. Persistent activation of the HPA axis may lead to metabolic syndrome.

The HPA axis acts in concert with the sympathetic nervous system. These two systems work together to flood your bloodstream with glucose to provide the energy you need to fight or flee in stressful situations. Other hormones that contribute to the stress response and increase blood glucose include epinephrine, growth hormone, and glucagon. After the stress subsides, you get hungry as your body attempts to restore its glucose reserves. Prolonged stress increases abdominal fat because the calories consumed are not fully used. Abdominal fat secretes hormones and chemicals that cause metabolic syndrome.³A cycle of increased stress, followed by increased appetite, low physical activity, and increasing abdominal fat, causes insulin resistance, obesity, and higher blood lipids. These factors cause metabolic syndrome. 

Researchers have found some differences between the stress response in men and women, suggesting that sex hormones are also involved. Women have a greater stress response than men, but men have a higher baseline level of cortisol.⁴

<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/what-is-cortisol">cortisol, and why managing it matters</a>.</p>

Stress increases cortisol release and activates the sympathetic (fight-or-flight) nervous system. Long-term exposure to stress can cause:⁴

• Increased abdominal (visceral) fat.
• Insulin resistance.
• Increased blood insulin levels.
• Impaired glucose tolerance.
• Type 2 diabetes.
• Enhanced response to stimulation for cortisol release.
• Reduced sex hormone production.
• Altered cholesterol and lipid profiles.
• Increased incidence of cardiovascular disease.

<p class="pro-tip"><strong>Key takeaways: </strong>Chronic stress increases cortisol release, which leads to metabolic syndrome, obesity, and insulin resistance. Managing stress can help reduce your risk for these three chronic diseases.</p>

<p class="pro-tip"><strong>Read more about </strong> <a href="/blog/how-to-manage-stress">how to manage stress and cortisol levels</a>.</p>

Sex Hormones

The male sex hormones, testosterone and dihydrotestosterone, and the female sex hormones, estrogen and progesterone, drive many bodily changes over the lifespan. All adults have androgens (male sex hormones) and estrogens, though the amounts of each type vary by sex. 

Predominant metabolic syndrome traits differ by age and sex, which provides support for the key role sex hormones play in metabolic control:⁵

• The most common symptom cluster in younger women is increased triglycerides, decreased HDL cholesterol, and increased waist circumference. 
• The most common symptom cluster in younger men is increased triglycerides, low HDL cholesterol, and increased blood pressure. 
• All five traits used to diagnose metabolic syndrome were equally prevalent in older men and women. 

<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/lower-blood-sugar-cholesterol">how cholesterol and blood sugar are connected</a>.</p>

Dehydroepiandrosterone (DHEA)

Dehydroepiandrosterone (DHEA) is an androgen produced by the adrenal glands and is the most abundant sex steroid. DHEA levels peak in your mid-20s and then begin to decline. Scientists are investigating potential connections between DHEA and metabolic syndrome.

When DHEA supplements were used to restore DHEA levels to the levels found in young adults, researchers noted:⁶

• Increases in testosterone levels in women but not in men.
• Increases in estradiol (estrogen) in both men and women.
• Small but significant increases in insulin growth factor-1 concentrations.
• Significant decreases in abdominal fat over six months.
• A significant increase in insulin sensitivity.

However, other studies have not replicated these results.^7-9

DHEA is converted to androstenedione, which is converted to testosterone or estrone (an estrogen). Testosterone and estrogen are also produced by the sex organs (gonads). Testosterone can also be converted to estrogen in fat tissue.  

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Most testosterone and estrogen travel through the bloodstream bound to albumin or sex hormone-binding globulin (SHBG). Small amounts are unbound or free testosterone or estrogen. Bioavailable (active) testosterone and estrogen include unbound hormones and hormones bound to albumin. About 50% of total estrogen and 30% of total testosterone are bioavailable. Sex hormone levels decline with age. It is unclear whether ratios of sex hormones, biologically active sex hormones, or levels of SHBG affect glucose metabolism.¹⁰

Testosterone

Testosterone is an androgen that is predominantly produced in the testes in men and in the adrenal gland and ovaries in women. Androgens are both anabolic and androgenic. Testosterone helps maintain and support:¹¹

• Muscle mass.
• Muscle strength.
• Fat distribution.
• Bone density, thickness, and strength.
• Libido.
• Red blood cell production.
• Body and facial hair.

Testosterone production begins at puberty and declines by about 1% each year, starting around age 30.¹²There are contradictory research results on whether testosterone has an age-dependent decrease and, if so, what the significance of this decrease is.¹³

In one study, researchers found that low total testosterone is associated with an increased risk of metabolic syndrome, even in healthy weight, middle-aged men, and independent of other cardiovascular risk factors, including insulin resistance. Low testosterone levels are also associated with increased insulin resistance. High testosterone is associated with a decreased risk of metabolic syndrome and insulin resistance.¹³

<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/age-glucose-levels">how aging affects blood glucose levels</a>.</p>

An analysis of multiple studies showed inconsistencies regarding a relationship between metabolic syndrome and testosterone in men:¹⁰

• Six studies showed an association between low total testosterone levels and metabolic syndrome.
• Two studies showed no association.
• One study showed an association between low free testosterone and metabolic syndrome.
• Four studies showed no association between low free testosterone and metabolic syndrome.

Because research results are inconsistent, more research into the relationship between testosterone and metabolic syndrome is needed.¹³

Some studies have indicated that testosterone supplementation may improve metabolic health.¹⁴Weight loss increases free and total testosterone and SHBG in men with obesity. Restoring testosterone in men with low testosterone increases muscle mass, decreases fat mass, and improves lipid levels. It is important to keep in mind that the effects of increased body fat on insulin resistance overwhelm any effects from lower testosterone or SHBG.¹⁰

Polycystic ovary syndrome (PCOS) is characterized by having high androgen levels, especially free testosterone.⁴Women with high testosterone levels have an increased risk of metabolic syndrome and type 2 diabetes. This is the opposite of the relationship between testosterone and metabolic syndrome in men. 

<p class="pro-tip"><strong>Read about </strong> <a href="/blog/weight-loss-pcos">how to lose weight when you have PCOS</a>.</p>

Three studies investigated the relationship between metabolic syndrome and testosterone in women:¹⁰

• Two studies showed no association between total testosterone and metabolic syndrome.
• One study showed an association between free testosterone and metabolic syndrome.
• One study showed no association between free testosterone and metabolic syndrome. 
• One study found that a higher testosterone to estrogen ratio was associated with metabolic syndrome.

Estrogen and Progesterone

Estrogens—estrone (E1), estradiol (E2), and estriol (E3)—are the predominant female sex hormones, 

Estradiol is produced in the ovaries and testes. It regulates the female reproductive system and influences the endocrine, skeletal, adipose, and cardiovascular systems.¹⁵  Estrogen promotes energy storage as fat (but only in certain locations), regulates some aspects of glucose and lipid metabolism, decreases hunger, and increases water and salt retention.¹⁶

Progesterone is a steroid sex hormone produced in the ovary, placenta, and adrenal glands. Progesterone increases hunger and energy usage. As long as estrogen and progesterone levels are balanced, estrogen's fat storage effects are balanced by progesterone's energy-burning effects.¹⁷

Estrogen declines after menopause are associated with increased body fat, especially abdominal fat, decreased lean body mass, increased blood lipids, impaired glucose metabolism, and insulin resistance.¹⁰

Many women opt for hormone replacement therapy to compensate for decreasing estrogen levels. Estrogen and progesterone combinations may vary when used for hormone replacement and oral contraception, but they are used to replace estrogen, progesterone, or both.  A meta-analysis of 49 studies found no real evidence to suggest a link between estrogen-progesterone contraceptives and weight gain.¹⁸

<p class="pro-tip"><strong>Read more about </strong> <a href="/blog/weight-loss-menopause">weight loss and menopause</a>.</p>

The relationship between estrogen levels and carbohydrate metabolism varies based on hormone ratios and the type of estrogen. The relationship between estrogen supplementation and insulin sensitivity is inconsistent in studies. Several studies show improved insulin sensitivity with estrogen supplementation, but at least one study showed no association. Studies have used oral estrogen supplementation, and the results cannot be translated to transdermal patches.¹⁰ Some studies have also indicated an increased risk of metabolic syndrome after using oral contraception.¹⁹ More research is needed to better understand the relationship between estrogens and risk factors for metabolic syndrome.

Follicle-Stimulating Hormones (FSH)

The pituitary gland secretes follicle-stimulating hormone (FSH). It stimulates the maturation of the ovarian follicles. FSH increases at menopause because no follicles are left; therefore, there is nothing to halt FSH production. Since metabolic syndrome increases post-menopause, several studies have investigated potential links between FSH and metabolic syndrome. So far, the results have been inconclusive.²⁰

Currently, there is no consensus on how to measure sex hormones. An important step towards understanding the effect of sex hormones on metabolic health is developing a standardized measurement method. There is interest in exploring the potential to use sex hormone supplementation to improve carbohydrate metabolism and metabolic health.¹⁰However, a better understanding of normal trends in sex hormones over a lifespan and the effects of these trends is needed. 

<p class="pro-tip"><strong>Key takeaways: </strong>Sex hormones play a key role in developing metabolic syndrome, though how this occurs is not fully understood. Decreased testosterone and SHBG in men and decreased estrogen and increased testosterone in women contribute to the increased prevalence of metabolic syndrome in middle age. It is unclear whether sex hormone supplementation would have the same effects on metabolism as natural physiological changes. Standards are not yet set for sex hormones based on age, and the risks of supplementing sex hormones versus the potential metabolic benefits are not fully understood.¹⁰</p>

<p class="pro-tip"><strong>Read more about </strong> <a href="/blog/hormones-and-weight-loss">hormones and weight loss</a>.</p>

Thyroid Hormones

The thyroid gland is a butterfly-shaped gland on the front of the neck. Thyroid hormone controls metabolism by increasing and decreasing thyroid hormone secretion. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary gland to secrete thyroid-stimulating hormone (TSH). After being stimulated by TSH, the thyroid gland secretes some of its stored supply of iodine-containing hormones T4 (tetraiodothyronine, also known as thyroxine) and T3 (triiodothyronine). Inactive T4 is converted to active T3. More recently discovered pathways that affect metabolism may help explain the connections between thyroid function and aspects of metabolic disease.²¹

Thyroid hormones regulate metabolism in every cell in the body, regulate appetite control, and activate the sympathetic nervous system.²²Thyroid hormone influences every aspect of metabolism. 

Thyroid hormone:

• Increases metabolic rate.
• Increases use of glucose and fatty acids for energy.
• Increases glucose production in the liver.
• Increases breathing rate.
• Maintains alertness, wakefulness, and responsiveness to external stimuli.
• Increases body temperature.
• Increases protein synthesis.
• Speeds up the heart rate.
• Strengthens heart muscle contractions.
• Influences how fast food and liquids pass through the digestive tract.
• Affects brain development.

Thyroid hormone affects glucose metabolism by regulating the transporters that usher glucose from the bloodstream into body cells.²³The effect of thyroid hormone on insulin sensitivity varies by body tissue. For example, thyroid hormone increases glucose uptake in muscle but reduces it in the liver. Both hyperthyroidism (too much thyroid hormone) and hypothyroidism (too little thyroid hormone) increase insulin resistance, although the mechanisms differ.²⁴The incidence and prevalence of type 2 diabetes  are higher among people with hypothyroidism and hyperthyroidism than in the general population. ²⁵

Too much thyroid hormone can cause these factors associated with metabolic syndrome:²¹

• Increased glucose production in the liver
• Increased glucose absorption from the gut
• Increased insulin degradation
• Increased systolic blood pressure
• Increased appetite
• Increased fat breakdown in fat stores
• Increased triglyceride production in the liver

Too little thyroid hormone can cause these factors associated with metabolic syndrome:²⁶

• Reduced glucose uptake into body cells
• Increased LDL (bad) cholesterol
• Increased diastolic blood pressure

The thyroid gland plays an important role in metabolic regulation. Thyroid hormones affect glucose and lipid metabolism and energy consumption. People with hypothyroidism and subclinical hypothyroidism have an increased risk of metabolic syndrome.²⁷When thyroid hormone production is low, TSH increases to prod the thyroid to produce more thyroid hormone. In a study of over 7,000 people with normal thyroid function, increasing TSH levels were associated with an increase in the factors associated with metabolic syndrome.²⁸Further research is needed to understand the effects of TSH, T4, and T3 on different body tissues and how this increases the risk of metabolic syndrome.

Hypothyroidism and metabolic syndrome are both common disorders that increase with age. Researchers are investigating the idea that not only is metabolic syndrome a result of thyroid dysfunction but also a cause of thyroid dysfunction. A potential link may be fat cells. Adipose tissue (fat cells) secretes chemicals such as leptin that influence thyroid hormone production. Leptin binds to receptors in the hypothalamus and increases TRH, which increases TSH, which increases thyroid hormone and therefore increases metabolism. Low thyroid hormone predisposes to increased fat cells due to decreased metabolic rate.²⁶This relationship may set up a cycle of decreasing thyroid function and increasing abdominal fat.

<p class="pro-tip"><strong>Key takeaways: </strong>Resistance to the effects of thyroid hormone is associated with obesity, metabolic syndrome, diabetes, and diabetes-related mortality. There appears to be a bidirectional relationship between metabolic syndrome and thyroid disease.</p>

Growth Hormone

Growth hormone is produced in the pituitary gland, secreted into the bloodstream, and promotes the growth of body tissues by stimulating the liver to secrete insulin-like growth factor 1 (IGF1). Growth hormone is an anabolic hormone. It promotes protein synthesis and growth of body tissue. 

Growth hormone: 

• Stimulates fat cells to break down fat to provide fuel for growth.
• Increases the uptake of amino acids from the blood to build proteins.
• Stimulates the release of glucose from the liver to provide energy for growth. 

Growth hormone supports longitudinal growth throughout childhood and adolescence and plays an important role in maintaining body composition during adulthood. However, growth hormone levels decline with age, causing symptoms such as:²⁹

• Decreased muscle mass 
• Decreased muscle strength 
• Increased abdominal fat 
• Increased risk of metabolic syndrome 
• Reduced stamina

Researchers are investigating the link between decreased IGF1 and metabolic syndrome. IGF1 has many similarities to insulin and seems to play a key role in developing obesity. Low IGF1 levels are associated with insulin resistance, glucose intolerance, and type 2 diabetes.³⁰People with a genetic change that caused 18% lower IGF1 levels were 2.7 centimeters shorter than the control group and had a 1.7 times higher rate of developing type 2 diabetes after age 60.³¹

Recombinant forms of IGF1 are FDA-approved for specific uses. These products, and others, are being tested and improved. Results so far are promising. Exercise also increases IGF1 and remains the recommended treatment for people with metabolic syndrome and obesity.³⁰

<p class="pro-tip"><strong>Key takeaways: </strong>Low IGF1 is associated with abnormal lipid and carbohydrate metabolism, cardiovascular disease, and diabetes. Researchers are investigating its role in causing metabolic syndrome.³⁰</p>

<p class="pro-tip"><strong>Read more about </strong> <a href="/blog/metabolic-advantages-of-cardio">how cardio benefits metabolic health</a> and <a href="/blog/metabolic-health-strength-training">how strength training improves metabolic health</a>.</p>

Hormones Secreted by Fat Tissue

Adipose (fat) tissue is stored in three body compartments, under the skin (subcutaneous fat), in the bones (marrow fat), and around internal organs (visceral fat). Visceral fat is metabolically active. It secretes hormones such as leptin and adiponectin, peptides that affect blood pressure, and inflammatory cytokines, all of which play a major role in insulin resistance and metabolic syndrome. 

Leptin tells your brain you are full. Leptin release is proportional to the amount of fat stored as energy. Decreased leptin levels stimulate appetite. When body energy stores are adequate, leptin suppresses appetite, stimulates energy expenditure, and controls glucose homeostasis and insulin sensitivity. Leptin levels do not fluctuate from meal to meal. They act over a longer period. Leptin may link obesity, metabolic syndrome, and cardiovascular disease.³²

In people with obesity, enlarged fat cells secrete more leptin but less adiponectin. Increased leptin secretion is associated with:³³

• Increased oxidative stress
• Increased inflammation
• A switch from glucose metabolism to fatty acid metabolism

Adiponectin is a hormone and adipokine protein that increases insulin sensitivity and reduces inflammation. Lower than normal adiponectin levels are associated with obesity, type 2 diabetes, and metabolic syndrome. 

Fat cells release other biologically active adipokines. These free fatty acids and other chemicals promote inflammation. Adipokines integrate the endocrine system and the local signals (autocrine and paracrine) to mediate:²

• Insulin sensitivity
• Oxidative stress
• Energy metabolism
• Blood clotting
• Inflammation

<p class="pro-tip"><strong>Key takeaways: </strong>Fat tissue is biologically active. It secretes adipokines such as leptin and adiponectin and other biologically active hormones and metabolites that influence carbohydrate and fat metabolism. </p>

How to Improve Hormonal Balance and Metabolic Health

Your best strategies to reduce your risk of metabolic syndrome and naturally balance your hormones are lifestyle modifications such as: 

• Choose whole foods that are healthy sources of fat.
• Pair carbohydrates with proteins, fiber, and fat to reduce glucose spikes. 
• Increase protein in your diet.
• Make time for at least two strength-building exercise sessions each week.
• Aim for 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity each week, or a combination of both.
• Cut back on alcohol use.
• Ask your doctor if any of your medications may contribute to your symptoms or cause a decrease in testosterone as a side effect.
• Avoid endocrine disruptors.
• Avoid tobacco and drug use.
• Aim for 7 to 9 hours of restful sleep each night.
• Boost your vitamin D by getting 20 minutes of exposure to ultraviolet (UV) light from the sun twice weekly unless you are at increased risk for skin cancer. 
• Prioritize time for meditation, gardening, yoga, massage therapy, breathing exercises, or a favorite hobby to reduce stress.
• Monitor your blood glucose levels to see how your lifestyle changes affect your blood glucose. 

<p class="pro-tip"><strong>Keep reading: </strong> <a href="/blog/blood-sugar-metabolic-health">how blood glucose and metabolic health are related</a>.</p>