Endometriosis and Prostaglandins

Endometriosis and Prostaglandins

Endometriosis and the relevance of Prostaglandins

Prostaglandins are very relevant for women with Endometriosis because of the critical reaction and inter-action between endometrial tissue, digestive enzymes, pain and inflammation and various prostaglandin activities.

Introduction to Prostaglandins

Prostaglandins were first discovered and isolated from human semen in the 1930s by Ulf von Euler of Sweden. Thinking they had come from the prostate gland, he named them prostaglandins. It has since been determined that they exist and are synthesised in virtually every cell of the body. Prostaglandins are like hormones in that they act as chemical messengers, but they do not move to other places in the body. They work right within the cells where they are made.

Functions of Prostaglandins - some basics

They have a variety of physiological effects on the body including:
- Activation of the inflammatory responses at the sites of damaged tissue, and production of pain and fever. When tissues are damaged, white blood cells flood the site to try to minimise tissue destruction. Prostaglandins are produced as a result.

- Blood clots form when a blood vessel is damaged. A type of prostaglandin called thromboxane stimulates constriction and clotting of platelets. Also the opposite happens and protastaglandin 12 (PG12) is produced on the walls of blood vessels where clots should not be forming. ( The body is very, very clever. It knows what to do, where to do it and when.)

- Certain prostaglandins are involved with the introduction of labour and other reproductive processes, and the role of fertility. PGE2 causes uterine contractions and has been used to induce labour.

- Prostaglandins are involved in several other organs and systems such as the gastrointestinal tract, cell growth and the immune system response.

Dictionary Definition

Prostaglandins - any of a group of about a dozen compounds synthesised from fatty acids in mammals as well as in lower animals. Prostaglandins are highly potent substances that are not stored but are produced as needed by cell membranes in virtually every body tissue. Different prostaglandins have been found to raise or lower blood pressure and regulate smooth muscle activity and glandular secretions. One such substance, which stimulates contraction of the uterus, is used clinically to induce labour; another has been in experimental use as a birth control agent. Prostaglandins also control the substances involved in the transmission of nerve impulses, participate in the body’s defences against infection, and regulate the rate of metabolism in various tissues.

Several prostaglandins have been shown to induce fever, possibly by participating in the temperature-regulating mechanisms in the hypothalamus; they also play a part in inflammation. Many naturally occurring prostaglandins as well as many artificial forms have been synthesised in the laboratory

Chemical Messengers

Prostaglandins vary somewhat from one another based upon subtle differences in their chemical structures. These small variations are believed to be responsible for the immense diversity of effects they have on the body. In general, prostaglandins act in a manner similar to that of hormones, by stimulating target cells into action. However, they differ from hormones in that they act locally, near their site of synthesis, and they are metabolised very rapidly. Interestingly, the same prostaglandins act differently in different tissue. (The in-built intelligence of the human body, that we will never understand)!

Research into Prostaglandins

Early studies of prostaglandins carried out by researchers revealed that these substances were active, and capable of producing many actions in the body including lowering blood pressure and instigating the contraction of uterine tissue. Later research revealed much more, including the fact that they can be found in almost all body tissue since they are not restricted to specific organs.

Prostaglandins, it was also discovered, are only active for a short period of time before they are modified into a non-functional form and are subsequently excreted from the body. So tissue cannot store prostaglandins, but must instead synthesise them in a nearby area when needed.

Approximately a dozen different prostaglandins have been identified to date, each of which is associated with different kinds of activities and effects on various kinds of tissue. One important activity of a group of prostaglandins is facilitating the relaxation of the muscle walls and the delineate blood vessels, effectively dilating them. Working in conjunction with thromboxanes, prostaglandins play an equally important role in blood clotting, and the balance between the two kinds of substances essentially control whether or not coagulation occurs. Also, many prostaglandins induce inflammation and the constriction of muscle tissue, while certain prostaglandins are believed to be involved in the inhibition or promotion of activities such as ion transport, cell growth, temperature regulation, and immune system response.

Prostaglandins in bite sizes!

Prostaglandins are a subset of a larger family of substances called eicosanoids
Other subgroups include thromboxanes, leukotrienes and lipoxins (just out of interest!)
Eicosanoids are localised tissue hormones that seem to be the fundamental regulating molecules in most forms of life
Prostaglandins are chemical mediators, or ‘local’ hormones. Whereas hormones circulate in the blood stream to influence distant tissues, prostaglandins act locally on adjacent cells
Prostaglandins serve as a catalyst for a large number of processes including the movement of calcium and other substances into and out of cells, dilation and contraction, inhibition and promotion of blood clotting, regulation of secretions including digestive juices and hormones, control of fertility, cell division and growth
Prostaglandins are produced in the cells by the action of enzymes on essential fatty-acids
From the discoveries to date of the number and complexity of prostaglandins, they have been divided into ‘Series’ type prostaglandins. Most commonly known to women with endometriosis are the prostaglandin Series 1 and Series 2 for their opposing effects or cause on pain messengers and inflammation
In simple terms, the Series 2 prostaglandins play a role in swelling and inflammation at sites of damage or injury. They also play a role in inducing birth, in regulating temperature, lowering blood pressure, and in the regulation of platelet forming and clotting. The role of Series 2 Prostaglandins does serve a vital role for the body for without it you would bleed to death from the slightest cut. However, in excess, these prostaglandins are harmful and many diseases are directly linked to excessive inflammation and blood clotting
Series 1 prostaglandins have the opposite effect of the Series 2 prostaglandins. Series 1 reduce inflammation, dilate blood vessels, and inhibit blood clotting. The strong anti-inflammatory properties help the body recover from injury by reducing pain, swelling and redness.
No doubt this is a simplistic definition of the role of these different substances, which will be more complex and subtle, but research is still being done into how prostaglandins work.
More recent research has focused on the balance between Series 2 and Series 3 prostaglandins. The Series 2 group is involved in intense actions, often in response to some emergency such as injury or stress. The Series 3 group has a modulating effect.
The Series 3 prostaglandins are formed at a slower rate and work to deal with excessive Series 2 prostaglandin production.
Many of you will have heard the term ‘Antagonistic Prostaglandins’ - in simple terms this means unfriendly prostaglandins
Antagonistic prostaglandins are made from a fatty acid called arachidonic acid (I can’t help thinking of spiders when that term is used - arachnid being the generic term for spiders, but this word seems relevant as spiders and other arachnids like scorpions are classed as ‘8 legged aggressive predators’. The same can be said of the predatory nature of antagonistic prostaglandins.)
Aracidonic acid is obtained from animal products - meat and dairy
Arachidonic acid can also be made from another fatty acid linoleic acid, through the animal food chain consumption
Linoleic acid is a fatty acid found in plant oils, such as corn oil, soybean oil, and other light vegetable oils. We also obtain linoleic acid from meat and dairy products (because the animals eat plants and store Linoleic acid)
Beneficial prostaglandins are made from a fatty acid found mostly in marine plants and fish known as EPA (eicosapentaenoic acid)
EPA is the most important member of an exclusive group of three fatty acids called the "omega-3 fatty acids"
This group includes alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)
ALA is made in the chloroplasts of green plants from linoleic acid. In mammals, linoleic acid is converted to arachidonic acid that is used to make the antagonistic prostaglandins. BUT, in the green plant the same linoleic acid is converted into the beneficial ALA
ALA is important because it serves as the building material for EPA
EPA is the most critical of the omega 3 fatty acids. It is the only material that our bodies use to make the beneficial prostaglandins that help reduce inflammation
DHA is another omega 3 fatty acid. It is an integral part of eye and brain tissue. It is made by marine algae, plankton, fish and mammals from EPA. Fish accumulate DHA in their oily tissue, along with EPA
It is now known that an excess of oleic acid (found chiefly in olive oil and nuts), known as the essential fatty acid group (EFA), will inhibit the prostaglandin pathway. But the block being set up is one which will inhibit the Series 2 prostaglandins - the ones which cause inflammation and swelling. Which is why women with endometriosis are advised to change the oil in their diet to only include the oils which will block Series 2. Evening Primrose Oil, Fish Oils, Flax seed oil, and Borage oil, which contain omega-3 fatty acids are also used by women with endometriosis to help shift the balance of prostaglandins and reduce the inflammatory action caused by Series 2 prostaglandins
Aspirin, a non-steroidal anti-inflammatory, was discovered over 100 years ago. It works by blocking prostaglandins that are produced in inflamed or injured tissues and cause the sensation of pain. It also acts centrally: the salicylate and acetate parts of aspirin's chemical structure (aspirin is acetyl salicylic acid) cross separately into the brain and spinal cord. There they act on prostaglandins in sites in the central nervous system known to be involved in both the perception and transmission of pain.
Prostaglandins are released by the endometrium during the menstrual cycle. Some women release more prostaglandin during menstruation than other women. These higher levels of prostaglandins in women with severe dysmenorrhea (painful periods) results in increased uterine contractions and muscular spasm.

Summary

There are 2 groups of prostaglandins which are most relevant to endometriosis - Good or Bad.

Good - take part in the normal functions of the body without contributing to the processes which cause the negative effects of endometriosis

Bad - take part in the functions of the body which contribute to endometriosis symptoms and its negative effects i.e. pain, inflammation, digestive disturbance, connective tissue damage

The way your body produces different types of prostaglandins can be controlled by what you include in your diet by consumption of different oils and foods. Some foods and oils will promote the negative prostaglandins because of subtle chemical reactions. In turn, other foods and oils will block that chemical reaction and stop the negative prostaglandins from being produced.

These potent chemicals act at an atomic level and are not always present in the body. They are produced in reaction to a sudden change or shock or injury in the body. Our bodies will produce them to act as warning signals, or to provide support to damaged tissue. The dual roles of prostaglanin Series 1 and 2 seem to be contradictory, but we obviously need both types of prostaglandins for the repair, maintenance and survival of the body.

If we did not suffer pain then we would not be alerted to the problem of damage within the body. Suffering pain is distressing, but in turn it is also telling us that something is wrong. It is fortunate that we now know how these particular prostaglandins work (be it in simple terms), so that women with endometriosis are able to alter the balance of prostaglandin production to reduce their symptoms by reducing the Series 2 prostaglandins, and aim to increase the Series 1 prostaglandins through their diet and with supplements.

PART TWO

Prostaglandins and pain messengers

Prostaglandins serve a variety of regulatory functions within the body. One of these functions is to assist the transmission of pain signals to the brain so that you are readily alerted that damage or dysfunction has occurred within the body.

When damage occurs to the body, certain prostaglandins are formed from the unsaturated fatty acids released by damaged cells. The production of a particular group of prostaglandins amplifies the amount of pain experienced by serving as a pain activator. They increase the sensitivity of the nerves to pain impulses. By reducing the synthesis of prostaglandins, the amount of pain stimuli sent to the brain is correspondingly reduced. This is usually achieved by the use of aspirin which blocks the production of pain messenger prostaglandins.

Alternatively, by making changes in your diet you can shift the prostaglandin production from the negative inflammatory prostaglandins to the anti-inflammatory prostaglandins.

Prostaglandins and inflammation

Prostaglandins are known as local hormones - they are released from cells and bring about changes in neighbouring cells that carry specific prostaglandin receptors in their membranes.

The influence which prostaglandins have depends upon the type of tissue they are acting upon. Such action may be direct, or as a result of modifying the actions of other signalling molecules.

As well as signalling and influencing pain messengers to the brain, prostaglandins will interact with other chemicals in the body when there is damage. They will also intensify the effects of other chemical mediators such as histamine.

Acting in concert these substances can bring about vasodilatation and an increase in the permeability of capillaries supplying the damaged area, encouraging the migration of phagocytes (Phagocytes are leukocytes - white blood cells - that engulf invading micro-organisms, and then kill them. They are part of our natural defence against infection ) from the blood through capillary walls into the damaged tissue. As a result of these changes, the blood supply to the area increases, the tissues swell, causing inflammation and pain subsequently occurs.

Phagocytes in more detail

Phagocytes are large white cells that can engulf and digest foreign invaders.They include monocytes, which circulate in the blood, and macrophages, which are found in tissues throughout the body, as well as neutrophils, cells that circulate in the blood but move into tissues where they are needed. Macrophages are versatile cells; they act as scavengers, they secrete a wide variety of powerful chemicals, and they play an essential role in activating T cells (part of your immune system).

Neutrophils are not only phagocytes but also granulocytes: they contain granules filled with potent chemicals. These chemicals, in addition to destroying micro-organisms, play a key role in acute inflammatory reactions.

There are two main types of phagocytes: neutrophills and macrophages.

Neutrophils:

Are made in bone marrow throughout life.
Make up 60% of white blood cells.
Travel through the blood.
Are short lived.
Squeeze through capillary walls to patrol tissue.
Released in large numbers during infection.
Dead neutrophils make pus.

Macrophages:

Are made in bone marrow throughout life.
Leave bone marrow and travel in blood as monocytes.
Are longer lived than neutrophils.
Are found in organs such as: lungs, liver, kidney, spleen, lymph nodes.

Prostaglandins and womb contractions

Primary dysmenorrhoea (painful periods) is caused by cramping in the uterine muscles — the uterus is a muscle and like all muscles it contracts and relaxes! Women don’t usually feel these muscles contract, unless it is a particularly strong contraction. With endometriosis the pain associated with menstrual cramps is usually very intense and painful. During a contraction, blood supply to the uterus can be temporarily cut off. This deprives the muscle of oxygen, which causes pain. But why do the uterine muscles contract?

It is caused by the series two prostaglandins. Series two prostaglandins help the uterus to shed the womb lining during menstruation by causing the contraction of the uterine muscles. Understandably, if too many of these prostaglandins are produced, then the contractions will be more severe and cause painful menstrual cramps — primary dysmenorrhoea.

However, not all prostaglandins have this effect on the involuntary uterine muscles, which is why diet can play a big role in minimising the production of series two prostaglandins. The types of fatty acids included in your diet influence the types of prostaglandins made. For example, series two prostaglandin (the type that trigger powerful contractions of the uterus) levels are increased when animal fat is included in the diet. In contrast, series one and series three prostaglandins (the type that don’t cause uterine contractions) are produced when the diet is higher in linoleic acid, which is found naturally in tuna and salmon oil. Evening primrose oil and starflower oil are also rich sources of linoleic acid, which is why they are often recommended for women suffering from period cramps and are especially helpful for women with endometriosis.

Prostaglandins and infertility

One major group of hormones secreted by the normal endometrium is that of prostaglandins. Prostaglandins are required for many bodily processes, including several stages of the menstrual cycle and pregnancy.

Prostaglandins are required for ovulation, regression of the corpus luteum (i.e., ending the monthly menstrual cycle), sperm motility, immune interaction, contraction of the uterus at birth and menstrual cramps. Endometrial implants and the endometrium of the uterus are the richest source of prostaglandin production in the body.

However, the problem with endometrial implants includes:

- Prostaglandins are released into the abdomen instead of inside the womb
- Prostaglandins release by the implants seem to be out of phase with their release by the uterus
- Prostaglandins are produced at the wrong time sending the wrong message

For instance, there is a normal surge in prostaglandin F production at the end of the menstrual cycle, causing the effect of the corpus luteum of the ovary to die down and signalling the start of a new menstrual cycle. The implants of endometriosis produce their own prostaglandin surge several days after that of the womb lining. This may be one of the main causes of very early miscarriage.

If a women is a few days pregnant then the endometriosis implants producing prostaglandin F would incorrectly signal the ovary to start a new menstrual cycle, causing the womb lining with the implanted egg to be expelled - and the consequence is an early miscarriage.

Prostaglandins also play an important role in the contractions of womb and fallopian tubes. During the normal menstrual cycle, the gentle contraction of the womb and fallopian tube aids the movement of egg and sperm to the outer third of the fallopian tube where fertilisation occurs. High concentrations of endometriosis implants may prevent fertilisation. An excess of PGF2 and PGE2 could cause contractions that are too strong and expel the egg too quickly.

Prostglandins and Diet

You should all have had it ‘drummed into you’ by now that the KEY way to shift the production of prostaglandins from the negative (inflammatory / pain messenger / womb contracting type) to the positive (anti-inflammatory / suppress womb contractions and pain messenger type), is through your diet, and most crucially by the types of fats and oils you include in your diet.

Several enzymes take part in the process that transforms fats into prostaglandins. These enzymes act as gatekeepers, channelling fats into the making of different prostaglandins. Like other enzymes in the body, they require specific nutrient coenzymes to do their job.

The enzyme delta-6-desaturase acts on linoleic acid - from most vegetable, nut and seed oils - to transform it to gamma-linoleic acid (GLA). GLA is used to make the anti-inflammatory series 1 prostaglandins and also supports healthy nervous system function.

The activity of delta-6-desaturase is affected by dietary factors. Trans-fatty acids from hydrogenated oils, too much saturated fat (found in meats, fried foods, junk foods and dairy products) in the diet, high stress, too much sugar or refined flours in the diet all slow down this enzyme down.

Trans-fatty Acids

Many processed foods contain trans-fatty acids. These fats slow down the activity of delta-6-desaturase. They are manufactured from vegetable oils in a process called hydrogenation, which involves the bombardment of liquid oils with hydrogen atoms to make them solid and prevent them going rancid. These trans-fats have harmful effects on the stability of cell membranes and the structure of nerve and brain cells. They also interfere with the formation of anti-inflammatory prostglandins.

B Vitamins

The B vitamins are crucial for the conversion of linoleic acid to GLA, which is necessary to produce beneficial prostaglandins. Linoleic acid is an essential fatty acid (EFA), and it is found in foods such as fresh nuts and seeds, safflower oil, and Evening Primrose Oil.

The B vitamins are required to convert this essential oil into a form that can be used by the body to produce the good prostaglandins.

Bromelain and prostaglandins

The enzyme bromelain from the stem of the pineapple, is also effective in inhibiting the inflammatory prostaglandins. In an extensive five-year study of more than 200 people experiencing inflammation as a result of surgery, traumatic injuries and wounds, 75 percent of the study participants had good to excellent improvement with bromelain; a much higher rate than that afforded by drugs. Most of the people in this study were discharged from the hospital in only eight days—half the usual amount of time. They also experienced no side effects.

To conclude ….

Along with hormones, these are very powerful and complex substances and can be easily influenced by outside factors through diet. It could be that our emotions as well as stress could alter and influence the way these natural bodily chemicals work. Many of us have felt and witnessed the changes in our hormones brought about by stress and emotions.

‘You are what you eat’ - we have all heard that phrase. Our bodies react to what we eat. It sometimes seems incredible that the body can differentiate between the chemical and molecular structure of 2 different oils (its only food!) - but our bodies are very clever and NOTHING goes unnoticed. It may not show up immediately, but if you feed your body with things it does not like or need, eventually you will get signals.

Fortunately, due to huge advances in understanding the body and how it works, we now have a better awareness how correct diet is crucial to the health of the body. And women with endometriosis can take advantage of the discoveries and knowledge about the role of diet in controlling their symptoms and shifting the levels of prostaglandins from the bad ones to the good ones.

As it is mentioned above - we do need prostaglandins - both types - they are all part of the complex and intricate orchestra of the body. But it does seem apparent from research that women with endometriosis are producing too many of the negative prostaglandins, which is the cause of many symptoms.

If you take these findings on board then you are part way to taking control of this disease, rather than IT taking control of you.

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