This page demonstrates why insulin resistance is only part of the problem. Not the problem.
Note: cutting sugar will only help you feel better. It will not cure estrogen dominance. You need to cut out transfats (IN PROCESSED FOODS), eat omega 3's, Vitamin B's, and bromelain (enzyme in pineapples).
Like previously mentioned, cutting out sugar isn't enough.
THIS IS A MUST READ. For every woman regardless if you have PCOS/Endometriosis or not.
http://www.endo-resolved.com/prostaglandins.html
http://www.endo-resolved.com/prostaglandins.html
Most of this blog will be notes taken out from this page, this information is money.
I already blogged on the link between inflammation and estrogen dominance.
First of all, without these T-cells, none of these ovarian cysts would happen. (I can't make this up.)
"A study of female mice is suggesting that ovarian cysts may at least partially be the result of an immune system dysfunction. The gland involved is the thymus gland, which is responsible for the management of major aspects of your immune system. One of the functions of the thymus gland is to produce T-cells, which are white blood cells that help protect you from infection and also perform other important activities.
The researchers reported that ovarian cysts in the female mice did not develop unless there was an absence of regulatory T-cells."
http://www.ovarian-cysts-pcos.com/news81.html
The cellular biology is complex but this is incredibly good research. Diet is our only defense against it at this time, however if Big Pharma figures out how to combat the cause of inflammation, their products will be demand inelastic. It may be a bigger hit than a cancer cure.
Inflammatory issues and auto-immune disease are not limited to PCOS, inflammation also contributes to things like allergies (think about those sinuses) and celiac disease which is very common in women with PCOS.
NOTES:
PROSTAGLANDINSProstaglandins 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.- 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, thesame prostaglandins act differently in different tissue. (The in-built intelligence of the human body, that we will never understand)!FUNCTION OF PROSTAGLANDINS- 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.)(Does anyone have Factor 2 or Factor 5 type blood? This might be WHY!)- 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.THE SERIES 1 and SERIES 2 PROSTAGLANDINSProstaglandins 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 (it's said that calcium and Vitamin D helps the uterus with contractions, Notice the mention of control of insulin release and elimination of bad free radicals in this source. Free Radicals contribute to inflammation.) -dilation and contraction -inhibition and promotion of blood clotting -regulation of secretions including digestive juices and hormones -control of fertility -cell division -growth Prostaglandins are produced in the cells by the action of enzymes on essential fatty-acid 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.
-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"
-OMEGA-3 FATTY ACIDS - includes alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)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. 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.‘Antagonistic Prostaglandins’ - in simple terms this means unfriendly prostaglandins.
Antagonistic prostaglandins are made from a fatty acid called arachidonic acid.
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)Alpha Linoleic Acid (ALA)-on ALA-it's 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 EPAEicosapentaenoic Acid (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 inflammationDocosahexaenoic Acid (DHA)-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 EPAOleic Acid (EFA)-found chiefly in olive oil and nuts-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
- Borage oil
ASPRIN- 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.
"I define an activated essential fatty acid as any essential fatty acid that has this new double bond inserted by the delta-6-desaturase enzyme. This is because this new double bond starts bending the essential fatty acid to get the appropriate spatial configuration required to make an eicosanoid. Once this new double bond has been inserted into a short-chain essential fatty acid, then very small amounts of these activated essential fatty acids can profoundly affect eicosanoid balance in your body.
However, there are many factors that can decrease the activity of delta-6-desaturase enzyme. The most important factor is age itself. There are two times in your life during which this enzyme is relatively inactive. The first is at birth. For the first six months of life, the activity of this key enzyme in the newborn is relatively low. But this is also the time at which maximum amounts of long-chain essential fatty acids are required by the child since the brain is growing at the fastest possible rate, and these long-chain essential fatty acids are the key structural building blocks for the brain. Nature has developed a unique solution to this problem: mother's breast milk. Breast milk is very rich in GLA and other long-chain essential fatty acids such as the EPA and DHA. By supplying these activated essential fatty acids through the diet, this early inactivity of the delta-6-desaturase enzyme is overcome.
The second time in your life during which the activity of this enzyme begins to decrease is after the age of 30. Eicosanoids are critical for successful reproduction. Since the primary child-bearing years for women are between the ages of 18 and 30, it makes good evolutionary sense to start turning down the activity of a key enzyme needed to make the precursors of eicosanoids required for fertility after age 30.
The delta-6-desaturase enzyme can also be inhibited by viral infection. The only known anti-viral agents are "good" eicosanoids such as PGA1 because of their ability to increase cyclic AMP levels that keep viral replication under control. On the other hand, if you are a virus, then your number-one goal is to inhibit the formation of this type of eicosanoid. This is exactly what many viruses do by inhibiting the delta-6-desaturase enzyme. By doing so, the virus has devised an incredibly clever way to circumvent the body's primary anti-viral drug (i.e. PGA1).
The final factor that can decrease the activity of delta-6-desaturase is the presence of two types of fatty acids in your diet; trans fats and Omega-3 fats. Trans fatty acids don't exist naturally but are produced by food manufacturers. They are essential Omega-6 fatty acids that have been transformed by a commercial process (known as hydrogenation) into a new spatial configuration that is more stable to prevent oxidation.
The increased stability of these fatty acids makes them ideal for processed foods, but also makes trans fatty acids strong inhibitors of the delta-6-desaturase enzyme. Trans fatty acids occupy the active site of the delta-6-desaturase enzyme, thus preventing the formation of the activated essential fatty acids required for eicosanoid synthesis. In essence, trans fatty acids can be viewed as anti-essential fatty acids because of their inhibition of eicosanoid synthesis. This may be the reason why they are strongly implicated in the development of heart disease. How do you know if a food product you're consuming contains trans fatty acids?....."
"It wasn't that insulin was a cause, but that it drove the metabolism of essential fatty acids to make more arachidonic acid, and therefore more "bad" eicosanoids. The more "bad" eicosanoids you make, the more likely you will promote platelet aggregation and increased vasoconstriction, the underlying factors for a heart attack."
AGAIN EVIDENCE. METFORMIN WILL NOT CURE ESTROGEN DOMINANCE OR PCOS.
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
I have to pause right there. This is incredibly good information so far. Now we know that both PCOS and Endometriosis are both caused by Estrogen Dominance?
The progtaglandins' relationship with Progesterone is where it gets interesting.
We have concluded that the progressive decline in prostaglandin production and the rise in progesterone output from luteinizing human granulosa cells occur independently of each other.It was concluded that the co-operation of progesterone in the earlier stage and of prostaglandins in the later stage of the preovulatory interval is required to mediate the action of hCG on ovulation.hCG on ovulation. Oh my god!!! That's the release of the egg!That's fertility in Layman's terms.
That's a pleasant surprise. I'm not ready for a baby yet.
This study cites the excessive progtaglandins in endo patients who cannot conceive.
This is Greek to me.
"Based on our data and that of others, wehypothesize that these cAMP analogues act downstream of theEP2 receptor. Thus, in addition to a direct effect of GDF-9 onthe synthesis of hyaluronan synthase 2, GDF-9 appears tostimulate a Cox2yPGE2yEP2 pathway which in vivo is requiredfor optimal cumulus expansion. Furthermore, induction of thissame Cox2yPGE2yEP2 pathway by GDF-9 is also apparentlyimportant for progesterone synthesis by the cumulus granulosacells. Thus, at least two major functions of PGE2 signalingthrough EP2 in the periovulatory follicle appear to be enhancement of cumulus expansion and production of progesterone,both of which are necessary for efficient delivery of oocytes intothe oviduct, maintenance of oocyte function, and fertilization.Further studies are needed to determine which genes in theprogesterone synthetic pathway are directly induced by PGE2,whether StAR mRNA is stimulated indirectly by GDF-9 viainduction of the EP2 pathway, and which genes or gene productsin addition to Cox2 and EP2 are regulated by GDF-9 in thisprocess."
BACK TO THE ARTICLE:
http://basic-clinical-pharmacology.net/chapter%2018_%20the%20eicosanoids%20prostaglandins,%20thromboxanes,%20leukotrienes,%20&%20related%20compounds.htm
"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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"REPRODUCTIVE ORGANS"Animal studies demonstrate a role for Prostaglandin E2 and Prostaglandin F2
in early reproductive processes such as ovulation, luteolysis, and fertilization. Uterine muscle is contracted by Prostaglandin F2
F2
http://basic-clinical-pharmacology.net/chapter%2018_%20the%20eicosanoids%20prostaglandins,%20thromboxanes,%20leukotrienes,%20&%20related%20compounds.htm
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ReplyDeleteThanks for sharing such a great Blog. Women suffering from polycystic ovarian syndrome (PCOS) face many challenges. The biggest among them is the excessive gain of weight.
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Thank you. I'm nowhere close to being an expert, but grateful if this at least points people in the right direction.
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