Hormones play a vital role in our health – and knowledge of any imbalance can guide the treatment of hormones’ role in metabolic syndrome

This 59-year-old lady presented with a history of increasing lethargy and weight gain.  She was also noted to be irritable and forgetful, with mood swings.  She complained bitterly about nocturnal symptoms of hot flushes and excessive sweating, disturbing her sleep, together with visiting the toilet several times a night.  I suspected that hormones were playing their part in her metabolic syndrome. 

She reported to her GP surgery and was found to have gained nearly two stone in weight; her blood pressure was running high at 145/90, and her blood sugar was in the prediabetic range (6.6). Her lipid profile reported high cholesterol, high triglycerides, and low protective HDL (the good guy.)

This is an excellent example of a postmenopausal metabolic syndrome that affects 60% of ladies.  She was postmenopausal as she had not had a period for more than 12 months.  Her symptoms started three years previously whilst she was heading towards the life change.

(Challenging life events in women, such as pregnancy and menopause, can result in changes in gonadal hormones associated with insulin resistance.  Similarly, women’s pathological conditions, such as PCOS and gestational diabetes, can also result in insulin resistance and metabolic syndrome.)

This lady had reached a state of energy imbalance, with increased appetite and reduced energy expenditure.  She was eating energy-dense food whilst being physically less active.  Her weight gain was around her middle, her waist measurement being high at 39 inches and hip at 41 inches, giving an abnormal WHR ratio of 0.95.

Increased deposition of fat in the abdominal area (visceral fat) had triggered inflammation, which coincided with a significant decline in her ovarian oestradiol, the natural anti-inflammatory protection.  Transdermal oestrogen supplementation has helped her to lose weight and reclaim her health and vitality.

This article will look at hormones, which play a significant role in our health (or lack of it), and which we test routinely as part of our assessment of patients with metabolic syndrome.  Such information usually gives these patients more insight into their problems and offers more effective health management with better lasting results. 

Insulin resistance – obesity – metabolic syndrome – health problems

Insulin resistance is the central feature of obesity and metabolic syndrome.  In practical terms, this shows up early on in those with waist sizes larger than 100cm in men and 88cm in women.  This progresses to include other risk factors – high blood pressure and high blood sugar, abnormal blood fat characterised by high triglyceride and low HDL (the good guy), to symptoms of the metabolic syndrome.  From there, it can escalate further to inflammation of blood vessels and the deposition of cholesterol plaque to cause vascular diseases.

For instance, I am sure many of us are familiar with the fact that an underactive thyroid gland is almost always associated with obesity and metabolic syndrome.  This is due to the fact that the thyroid hormone (thyroxine) and its active form (T3) activate the genes involved in the energy production in every body cell to produce enough energy (ATPs) to keep us warm and comfortable.

Besides weight gain, the metabolic type of abnormal lipid profile is an early feature of an underactive thyroid patient.  The other components follow later.  Therefore, sorting out your thyroid status may be the most important step to normalise your metabolism and resolve your metabolic syndrome.

Various hormones and their effect on us

Just like insulin, amylin and incretin are two hormones produced by the pancreas.  They act very similarly to insulin but are unique in suppressing glucagon release and slowing gastric (stomach) emptying, a key determinant of post-prandial glucose concentration.  This also highlights the importance of oral feeding to have an adequate insulin response.  A study confirmed more insulin is released when the food was taken orally, compared with a dose of intravenous glucose infusion.

Leptin is a hormone produced by fat tissues in response to having an abundance of energy and triglyceride.  It acts upon receptors in the hypothalamus (appetite centre) to reduce appetite and prompt you to stop eating.

Leptin plays an important role in the pathophysiology of metabolic syndrome.  Altered leptin levels affect energy expenditure, glucose, and lipid metabolism.  Leptin should be considered as a predictive clinical marker for obesity and type 2 diabetes mellitus (T2DM).

Leptin resistance occurs due to a loss of leptin sensitivity, like insulin resistance, when the pancreas produces more insulin to compensate for the loss of insulin sensitivity.  Leptin resistance means that the body produces large amounts of leptin but does not respond to it.

High leptin levels reduce your appetite, so you do not eat much.  When your leptin is low, the food tastes good, and you want to eat more of it.  However, leptin resistance is when leptin is high, but your brain cannot respond to it.  In this case, you lose control and continue to eat beyond your needs.  This results in consuming more energy to store as fat, central obesity and metabolic syndrome.  Taking leptin supplements, in this case, does not make sense due to our brain cells’ impaired response.

The best approach to leptin resistance is to reduce your sugar and refined carbohydrate intake, take more fibre, and lose weight.

Low leptin levels are associated with infertility since a low-fat mass is an indication that your body is declaring starvation.  As we have not enough fat (energy) to run a big project like pregnancy, low fertility ensues.

Leptin is a digestible protein, which enters the bloodstream, so it can’t be taken as a supplement form.  Atkinson, the famous New York physician, says. “If you were to take it as a pill, it’s just like eating chicken or beef.  It’s a protein, and your body would just break it up, so you wouldn’t absorb it from a pill.”

Ghrelin is a hormone produced in the stomach, which travels in the bloodstream, to stimulate the hypothalamus (appetite centre) in the brain to eat more food and store more fat.  Ghrelin is produced when the stomach is empty, and, as the level goes up, you feel hungrier, and you want to eat more.

Ghrelin levels increase before eating and decrease after your stomach is full.  Ghrelin levels become elevated when you go on a diet.  Ghrelin levels are not necessarily high in obese people as some are more sensitive to its effect.

So, it would be beneficial to lower Ghrelin levels if you want to lose weight and reverse your metabolic syndrome.

How to lower Ghrelin levels

You can do this by prioritising sleep, as poor sleep increases your hunger and causes weight gain.  Strength training increases your muscle mass, which lowers your Ghrelin levels.  Take protein (animal or plant) with every meal.  Cycle your calories: periods of higher calorie intake can reduce hunger and increase leptin.  One study found two-week periods on 29 to 45% more calories reduce Ghrelin levels by 18%.

Glucagon is produced from the alfa cells in the pancreas in response to hypoglycaemia.  Glucagon tends to find energy resources to cover the emergency situation of low blood sugar (hypoglycaemia.)  In the liver, Glucagon breaks down stored glycogen into glucose and activates the process of making glucose from other resources (gluconeogenesis.)  It also breaks down amino acids and fatty acids to produce ketone bodies to be available as an alternative fuel.

Glucagon injections are used routinely as emergency measures to save a life in patients presenting with severe hypoglycaemia (low blood sugar.)  Glucagon injections restore the blood glucose level faster than an intravenous glucose infusion.

Diabetogenic hormones

This is a group of hormones known to impair your ability to deal with sugar and hence increase the potential of causing diabetes and metabolic syndrome.  These include growth hormone, cortisol, Glucagon, and adrenaline.  Growth hormone and cortisol impair the liver’s uptake of glucose and reduce periphery use of glucose to raise blood sugar.

Adrenaline and glucagon act to release glucose stored as glycogen in the liver and to switch the liver to make more glucose from other sources such as protein, a process known as (gluconeogenesis).  Therefore, all these hormones work to increase blood sugar, and this trend pushes us towards metabolic syndrome or even diabetes.  We also know that diabetic control gets worse with stress due to the release of adrenaline and cortisol.

I have met many patients presenting with high levels of these hormones in clinical practice.  Cushing’s syndrome (high cortisol) and acromegaly (high growth hormone) are good examples.  They present with a clinical picture of metabolic syndrome, i.e. high blood pressure, high blood sugar, high fat mass, and abnormal lipid profile, all attributable to the effect of these hormones.

Using this information in emergency situations, we find variations in the effect of these hormones on blood sugar.  Adrenaline and Glucagon are fast, and hence they are used in emergency situations to restore blood sugar.  However, growth hormone and cortisol take several hours to act and hence they are not useful for this purpose.

Although Cushing’s syndrome and acromegaly are rare, there are 2.5% of the population on steroid therapy for various clinical conditions, making them insulin resistant and at risk of obesity and metabolic syndrome due to exogenous steroid therapy.  This is a major health issue.

Moreover, chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased production of adrenal cortisol.  This leads to central obesity, high blood pressure, high blood sugar, and metabolic lipid profile.  This is another public health issue that needs attention.

High levels of cortisol are particularly associated with a unique body habitat of central obesity and thin extremities (limbs).  This makes it easy for me to identify patients presenting with chronic stress and those on steroid therapy.

Glucagon may be considered catabolic (breaking down body mass) and insulin anabolic (maintaining or building mass.)  Insulin promotes body gain by stimulating protein and fat synthesis.  Growth hormone increases protein retention and decreases fat deposition.  Growth hormones can alter the sensitivity of tissues to insulin.  In contrast, catabolic hormones such as Glucagon, epinephrine, and glucocorticoids are provided for the mobilisation of energy reserves to allow the organism to survive (deal with) adverse situations.

How can you reverse metabolic syndrome?

Metabolic syndrome is treated by tracking individual risk factors until they normalise.  You need to lower insulin resistance to reduce the risk of diabetes and heart disease.

Weight loss is a key target to resolve metabolic syndrome.  You need to avoid sugar and refined carbohydrates and eat lean meat, beans, nuts and seeds, and low-carb fruit such as berries.

Your exercise program should consist of 30 minutes of your preferred cardio – walking, jogging, swimming, or dancing – five times a week, together with strength building for 20 minutes twice a week.  Building your muscle mass makes you more insulin sensitive.

Losing weight, your blood pressure and blood sugar will come down, and your lipid profile will normalise over time, and your metabolic syndrome disappears.

Once you reach your desired weight, then you can switch to the Mediterranean diet, which will help you sustain your healthy weight.

So, my friends, whilst knowledge of a specific hormonal imbalance can help guide treatment, as in the case of the lady we discussed first, the right course of action will always include the right food and regular exercise!  Please do share your thoughts and questions by commenting on this piece, and do subscribe to the newsletter so that you don’t miss further vital information.  Thank you!



Growth hormone and that metabolic syndrome


Thyroid hormones and the metabolic syndrome


Mechanisms in endocrinology: Metabolic syndrome through the female life cycle


Leptin as a predictive marker for metabolic syndrome


Facts on leptin: the truth about the hormone leptin and obesity https://www.webmd.com/diet/obesity/features/the-facts-on-leptin-faq#1

Serum leptin is associated with cardio metabolic risk and predicts metabolic syndrome in Taiwanese adults


Ghrelin: the “hunger hormone” explained


Diagnosed with Metabolic syndrome?  Why it’s a call for action you should take seriously


The role of insulin and the other related hormones in energy metabolism – a review


Hormonal regulation of metabolism


Glucose metabolism and regulation: beyond insulin and Glucagon – amylin & incretin