- You and Your Hormones
- Alternative names for prostaglandins
- What are prostaglandins?
- How are prostaglandins controlled?
- What happens if my levels of prostaglandins are too high?
- What happens if my levels of prostaglandins are too low?
- What Are Prostaglandins?
- Prostaglandin Functions
- Beneficial Roles
- Negative Effects & Associated Conditions
- Factors That Decrease Prostaglandin Levels
- Low Prostaglandins Levels
- Factors That Increase Prostaglandins
- Prostaglandins and Reproduction
- Prostaglandins and Inflammation
- Prostaglandins and Other Conditions
- A Holistic Approach to Painful Menstrual Cycles
- Cannabinoids & Your Period
- Cannabinoids & Suppositories Help
- Your Uterus: Prepping for a Visit
- Goodbye, Progesterone
- Prostaglandins: Inflaming the Uterus
- NSAIDs Work, Sort Of
- CBD: a Better Alternative?
- Additional Cannabinoid Benefits
- Natural Remedies for Cramps
- Finding Relief With Cannabinoid Suppositories
- Lights and shadows of NSAIDs in bone healing: the role of prostaglandins in bone metabolism
You and Your Hormones
Alternative names for prostaglandins
Prostaglandin D2; prostaglandin E2; prostaglandin F2; prostaglandin I2 (which is also known as prostacyclin); a closely related lipid called thromboxane
What are prostaglandins?
Mechanism of action of the drug aspirin. Aspirin works by stopping prostaglandin being made: aspirin molecules (blue hexagons) enter the cell and chemically modify the cyclooxygenase enzyme (purple) to prevent prostaglandin being made.
Unlike most hormones, which are produced by glands and transported in the bloodstream to act on distant areas of the body, the prostaglandins are produced at the site where they are needed. Prostaglandins are produced in nearly all cells and are part of the body’s way of dealing with injury and illness.
Prostaglandins act as signals to control several different processes depending on the part of the body in which they are made. Prostaglandins are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process. When a blood vessel is injured, a prostaglandin called thromboxane stimulates the formation of a blood clot to try to heal the damage; it also causes the muscle in the blood vessel wall to contract (causing the blood vessel to narrow) to try to prevent blood loss. Another prostaglandin called prostacyclin has the opposite effect to thromboxane, reducing blood clotting and removing any clots that are no longer needed; it also causes the muscle in the blood vessel wall to relax, so that the vessel dilates. The opposing effects that thromboxane and prostacyclin have on the width of blood vessels can control the amount of blood flow and regulate response to injury and inflammation.
Prostaglandins are also involved in regulating the contraction and relaxation of the muscles in the gut and the airways.
Prostaglandins are known to regulate the female reproductive system, and are involved in the control of ovulation, the menstrual cycle and the induction of labour. Indeed, manufactured forms of prostaglandins – most commonly prostaglandin E2 – can be used to induce (kick-start) labour.
How are prostaglandins controlled?
The chemical reaction that makes the prostaglandins involves several steps; the first step is carried out by an enzyme called cyclooxygenase. There are two main types of this enzyme: cyclooxygenase-1 and cyclooxygenase-2. When the body is functioning normally, baseline levels of prostaglandins are produced by the action of cyclooxygenase-1. When the body is injured (or inflammation occurs in any area of the body), cyclooxygenase-2 is activated and produces extra prostaglandins, which help the body to respond to the injury.
Prostaglandins carry out their actions by acting on specific receptors; at least eight different prostaglandin receptors have been discovered. The presence of these receptors in different organs throughout the body allows the different actions of each prostaglandin to be carried out, depending on which receptor they interact with.
Prostaglandins are very short-lived and are broken down quickly by the body. They only carry out their actions in the immediate vicinity of where they are produced; this helps to regulate and limit their actions.
What happens if my levels of prostaglandins are too high?
High levels of prostaglandins are produced in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain and fever. This is an important part of the body’s normal healing process.
However, this natural response can sometimes lead to excess and chronic production of prostaglandins, which may contribute to several diseases by causing unwanted inflammation. This means that drugs, which specifically block cyclooxygenase-2, can be used to treat conditions such as arthritis, heavy menstrual bleeding and painful menstrual cramps. There is also evidence to suggest that these drugs may have a beneficial effect when treating certain types of cancer, including colon and breast cancer, however research in this area is still ongoing. New discoveries are being made about cyclooxygenases which suggest that cyclooxygenase-2 is not just responsible for disease but has other functions.
Anti-inflammatory drugs, such as aspirin and ibuprofen, work by blocking the action of the cyclooxygenase enzymes and so reduce prostaglandin levels. This is how these drugs work to relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and so can be used to prevent unwanted blood clotting in patients with heart disease.
What happens if my levels of prostaglandins are too low?
Manufactured prostaglandins can be used to increase prostaglandin levels in the body under certain circumstances. For example, administration of prostaglandins can induce labour at the end of pregnancy or abortion in the case of an unwanted pregnancy. They can also be used to treat stomach ulcers, glaucoma and congenital-heart-disease’>congenital heart disease in newborn babies. Further advances in understanding how prostaglandins work may lead to newer treatments for a number of conditions.
Last reviewed: Oct 2019
When you are injured, a complicated process of inflammation and blood clotting is triggered. Prostaglandins are a group of lipids that are part of this process. Problems with prostaglandins can limit the healing process, cause increased inflammation and pain, and impact your overall health.
Prostaglandins are hormones created during a chemical reaction at the site where an injury or other issue occurs. They are unique among hormones, because unlike most of the chemical messengers, they are not secreted from a gland. Instead, they are created at the time they are needed directly where the problem exists.
What does prostaglandins do?
Prostaglandins control several processes in the body, especially as it relates to the healing process. When tissue is damaged or infected, this group of hormones will create the reactions that cause pain, fever and inflammation, which sparks the healing process. Prostaglandins also stimulate the formation of a blood clot and the contraction of the blood vessel wall when your body is bleeding. Once blood clots are no longer needed and the injury begins to heal, another prostaglandin will stimulate the changes that allow the clots to dissipate and the blood vessel wall to relax.
In women, prostaglandins assist in regulating the reproductive system. They can start labor and control ovulation. Synthetic prostaglandins are sometimes used to induce labor for pregnant women.
Potential Problems with Prostaglandins
Problems with prostaglandins production can occur, leading to unwanted inflammation in the body. The prostaglandins are part of a natural response to stresses, but excessive prostaglandins production can cause chronic problems with pain. Painful menstruation, arthritis, heavy menstrual bleeding and some types of cancer are all connected to excessive prostaglandins levels. Some anti-inflammatory medications work by blocking the enzymes that cause these hormones’ production, thus reducing inflammation.
Sometimes, the body will not create enough prostaglandins to heal the injury or start labor. While this is not connected to any chronic health condition, artificial prostaglandins can help. In fact, prostaglandins are sometimes used to treat stomach ulcers and glaucoma as a result.
Questions to ask your doctor
If you are concerned that prostaglandins imbalance could be causing your physical symptoms, you need to discuss your concerns with an endocrinologist. You may wish to ask:
- How can I tell if I am producing enough prostaglandins?
- Could problems with prostaglandins be causing my symptoms?
- What can I do to improve prostaglandins levels?
If you do not have an endocrinologist, you can find one on our physician referral directory. With the help of the right doctor, you can take control of your health again.
Prostaglandins are powerful hormone-like substances that have diverse functions in the human body, most notably controlling the immune response and inflammation. Both high and low levels play roles in different chronic disorders, so it’s essential to keep them in check. Read on to learn what prostaglandins are, how they work, and how they affect your health.
What Are Prostaglandins?
Prostaglandins are hormone-like substances with diverse roles in the body, principally the acute immune reaction and inflammation .
Unlike typical hormones, prostaglandins are not made by glands and then released into the bloodstream. They are made in multiple different tissues and exert their effects locally. They have potent effects, but are short-lived and quickly cleared from the body .
Prostaglandins were first isolated from semen by Swedish pharmacologist Ulf Svante von Euler in 1935. The name prostaglandins is derived from the fact that they were originally thought to be produced by the prostate gland (they are actually produced in the seminal vesicles, among many other types of tissues).
Prostaglandins only affect the cells they are made by and the cells in the surrounding area. They have diverse effects on the body, including:
- increasing/decreasing inflammation, and contributing to the signs of acute inflammation, such as redness, heat, swelling, and pain
- constricting or dilating blood vessels
- inducing labor
- increasing the production of mucus
While the body produces many types of prostaglandins, there are four primary types:
|Type of Prostaglandin||Function|
|Prostaglandin E2 (PGE2)||
|Prostaglandin D2 (PGD2)||
|Prostaglandin F2α (PGF2α)||
Prostaglandins are made from a fatty acid called arachidonic acid. When this fatty acid is released from cells, it is converted into prostaglandin H2 (PGH2, the precursor to all four of the primary prostaglandins) by either one of two enzymes :
- cyclooxygenase-1 (COX-1). This enzyme maintains basal (minimal) levels of prostaglandins, that are needed for gut protection.
- cyclooxygenase-2 (COX-2) . This enzyme increases prostaglandin levels during acute inflammation such as infection or injury.
Prostaglandins help increase the concentration of cAMP, calcium ions, and activate G proteins inside the cells, all of which are involved in the transfer of energy and inflammatory signaling processes. These pathways are vital to initiate a defense response against foreign invaders that enter the body .
1) Protect the Gut and Help Against Ulcers
High levels of PGE2 and PGI2 are found in the gut, which protects the stomach and small intestine from damage .
Patients with ulcers have lower levels of PGE2 in their gut than healthy patients .
Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the production of prostaglandins and cause damage to the small intestine that can lead to ulcers .
In one study of 34 healthy volunteers, prostaglandin prevented NSAID-induced gut damage (measured as the number of small-intestinal lesions) in .
In a study of 11 patients with unmanageable ulcers, PGE2 administration completely healed the ulcers in seven patients within four to 14 weeks .
The NSAID indomethacin reduced ulcer healing in rats and mice with ulcers. Administering the synthetic prostaglandin 11-deoxy-PGE1 improved healing in these animals .
2) Protect the Heart
Studies indicate that estrogen, which is known to protect the heart, works by increasing COX-2 and prostaglandins, specifically PGI2 .
Estrogen significantly decreased infarct size in rabbits, but this positive effect was blocked with either a COX-2 or a PGI2 receptor inhibitor .
In a trial of 11 patients with heart failure, 4-week PGE1 therapy improved heart health compared to placebo .
In mice, PGD2 protected against heart injury by activating Nrf2, an important master-regulator of antioxidant enzymes .
3) Induce Labor
Prostaglandins induce uterine contractions and play a critical role in causing pregnant women to go into labor .
PGE2 vaginal gel and other delivery forms have been used to induce labor in pregnancy .
Prostaglandins given locally can also help with stillbirths and hemorrhages during pregnancy. C-sections for delivering stillborns or surgery to deal with postpartum hemorrhage may be avoided with the use of prostaglandins .
In a study involving 50 patients who had either a faulty abortion or had been diagnosed with fetal death, 47 of them were able to successfully expel the products of conception with PGE2 .
4) May Calm Allergies
In a study of 8 subjects with asthma, inhaling PGE2 decreased the response to allergens .
PGE2 also protected against allergic lung inflammation in mice. In another study, mice without PGD2 had more severe food allergies .
5) May Improve Sperm Function
When exposed to low levels of PGE2 and PGF2α, the motility and function of human sperm cells were improved .
Low doses of PGF2α at insemination improve conception rates in cattle .
Negative Effects & Associated Conditions
Prostaglandin levels are a marker of inflammation and overall health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
Additionally, there isn’t a definite conclusion about the exact role of prostaglandins in some of the conditions mentioned below. They might play a role in the development but also might increase in response to certain conditions as a protective mechanism.
Prostaglandins can both promote or suppress allergic inflammation, depending on many different factors.
For example, depending on the context, PGD2 can either increase or decrease inflammation in allergies .
In a study of 199 subjects, higher levels of PGD2 have been detected in those with severe asthma .
Similarly, levels of the PGD2 were higher in the urine in both humans and mice with food allergies .
Mice deficient for the PGI2 receptor have either a stronger or a weaker allergic response, depending on the experimental setting .
Administration of a synthetic prostaglandin increased Th17 cells in mice with allergic inflammation. Th17 cells are proinflammatory T- cells that are major contributors to allergic responses .
Prostaglandins can suppress the immune response. High levels of PGE2, in particular, have been linked to cancer in some studies.
One study found that PGE2 levels were significantly higher in esophageal cancer patients. Moreover, PGE2 levels were higher in tumor tissue compared to healthy tissue .
Similarly, higher levels of a PGE metabolite (an indicator of PGE production) were found in head and neck cancer patients whose disease progressed or spread after treatment .
In a population-based study, 153 gastric cancer patients had higher urinary PGE2 compared to 153 controls .
A high dose of prostaglandin PGE2 injected into rats decreased immune cell count and increased the spread of liver cancer .
In a cell study, abnormally high levels of PGE2 decreased the number of cancer-fighting immune cells (natural killer cells and lymphokine-activated killer cells) .
3) Migraines and Headaches
In two studies, the infusion of PGE2 and PGI2 caused immediate migraine-like attacks in 12 patients with migraines without aura .
In 11 healthy subjects, all subjects reported a headache after receiving PGE2 while no subjects reported a headache on placebo .
In 64 children with migraines, urinary PGF2a levels were significantly higher during a headache than during non-headache periods .
4) Menstrual Cramps
High levels of prostaglandins can cause intense period pain for menstruating women and also play a primary role in the mechanism of menstrual disorders, including abnormally heavy blood flow .
In a dose-escalating study with 24 women, higher doses of a PGF2a receptor blocker decreased menstrual pain .
5) Celiac Disease
Biopsies (surgical removal of tissue) of the gut of celiac disease patients revealed elevated PGE2 levels .
One study found that PGE2 levels were 2-10 times higher in amyotrophic lateral sclerosis (ALS) patients compared to controls .
7) Deformity of Nails and Fingers
Preliminary evidence suggests that PGE2 is involved in the deformity of the nails and fingers, referred to as nail clubbing or digital clubbing .
In a study of 29 lung cancer patients, higher PGE2 levels were seen in patients who developed nail clubbing compared to those who did not .
In a study of 30 depressed patients, all but one of them had increased PGE2 levels .
9) Alzheimer’s Disease
PGE2 levels were five times higher in the brains of seven Alzheimer’s patients compared to seven healthy individuals of the same age .
Another study found that PGE2 levels were higher in 33 patients with mild memory loss and Alzheimer’s disease compared to 35 healthy individuals .
Microglia are the main immune cells of the brain and their ability to clear amyloid-beta plaques becomes impaired in Alzheimer’s disease. In a mouse model of Alzheimer’s, mice whose microglia were missing PGE2 receptors had improved clearance of plaques, reduced brain inflammation, and fewer deficits in memory .
10) Kidney Failure
Higher PGD2 levels were found in 17 patients with kidney failure compared to 34 patients with healthy kidney function. Levels of an enzyme needed to make PGD2 (PGD synthase) were 35 times higher in kidney failure patients .
In 40 patients with schizophrenia, PGE2 levels were significantly higher than in 38 non-schizophrenic individuals. Schizophrenic patients with higher PGE2 levels had more feelings of guilt and hallucinatory behaviors .
Factors That Decrease Prostaglandin Levels
Prostaglandin levels are a marker of inflammation and overall health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it. Improving your prostaglandin levels won’t necessarily cause improvement in your health and inflammation, but it can be used as a biomarker.
The following is a list of factors that may balance high IgE levels. Though studies suggest various dietary and lifestyle factors may lower IgE levels, additional large-scale studies are needed. Remember to talk to your doctor before making any major changes to your day-to-day routine.
Drugs That Decrease Prostaglandins
1) Nonsteroidal Anti-Inflammatories (NSAIDs)
Nonsteroidal anti-inflammatory drugs (NSAIDs), are a popular choice for reducing prostaglandin production. Examples of popular NSAIDs include ibuprofen and aspirin. However, side effects can involve damage to the gut, high blood pressure, and excessive platelet production (this can increase blood clotting), which are all regulated by prostaglandins .
Selective COX-2 inhibitors (coxibs) are a new class of NSAIDs that only inhibit COX-2, unlike traditional NSAIDs that inhibit both COX-1 and COX-2 enzymes.
Since COX-1 produces prostaglandins that protect the gut, coxibs lower the risk of ulcers. Examples include etoricoxib and celecoxib. However, they are associated with an increased risk of heart damage, and some of them have been withdrawn from the market due to severe adverse effects .
Corticosteroids are steroids used to reduce inflammatory symptoms in a variety of conditions including asthma and arthritis. They have a wide range of anti-inflammatory effects, including the blockade of prostaglandin-related pathways .
3) Mepacrine (Quinacrine)
Mepacrine is a drug used to treat rheumatoid arthritis, giardiasis (infection with the protozoan giardia), and malaria.
Mepacrine prevents arachidonic acid from being released from the cells and converted to prostaglandins .
Herbs and Supplements
1) Green and Black Tea
A study involving 14 patients found that green tea reduced PGE2 levels four hours after consumption. Overall, 71% of the patients experienced decreased prostaglandin levels .
Another study found that 500 ml of black tea for one month decreased PGF2α levels in healthy volunteers .
Ginger is well-known for its anti-inflammatory effects that involve the suppression of prostaglandins .
In a cell study, certain compounds found in ginger, including -gingerol, blocked the production of prostaglandins .
Chamomile is another age-old complementary approach to reducing inflammation. Multiple experiments in test tubes have confirmed its ability to reduce prostaglandin levels .
Chamomile extract blocked the production of prostaglandin E2 in immune cells in response to bacterial toxins. Chamomile selectively blocks the COX-2 enzyme, which reduces the risk of ulcers .
5) Nettle Leaf
Nettle can combat different types of allergic reactions; according to preliminary research, its ability to suppress prostaglandins is likely responsible for this effect .
Nettle leaf (Urtica dioica) extract reduced COX-2 levels in dog cartilage cells .
Curcumin is among the best-researched natural anti-inflammatory compounds. Its mechanism of action includes the blockade of COX and other enzymes that produce prostaglandins .
Curcumin reduced an enzyme needed to make PGE2 in blood cells .
It also reduced COX-2 levels and blocked PGE2 production in the joint cells of rheumatoid arthritis patients .
7) White Willow Bark
White willow bark is a natural source of salicylic acid, which is used to produce aspirin. It inhibits COX-1 and COX-2, and prevents the production and activation of prostaglandins .
8) EPA and DHA (Omega 3s)
The fish oil omega 3s EPA and DHA have anti-inflammatory effects verified in multiple clinical trials. In one experiment, they decreased COX-2 levels, which decreased the production of the pro-inflammatory PGE2 in human melanoma (skin cancer) cells .
Low Prostaglandins Levels
Prostaglandin levels are a marker of inflammation and overall health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
1) Lower Inflammation
Because prostaglandins are produced in response to injury or infection in order to increase inflammatory immune response, low levels of prostaglandins are linked to lower inflammation in the body .
1) Gut Damage
Prostaglandins prevent excessive stomach acid secretion and increase mucus and bicarbonate secretion. Low levels of prostaglandins make the gut more vulnerable to damage from toxins and infections .
2) Heart Rhythm Disturbances
Low PGE2 and PGF2α levels caused irregularities in rat heart rhythms .
3) Diabetic Retinopathy and Neuropathy
Diabetic retinopathy is a condition in which high blood sugar levels damage the blood vessels in the retina.
Levels of PGE1, PGE2, and PGF2α were all lower in human retina cells from patients with diabetic retinopathy compared to retina cells from healthy patients .
Diabetic neuropathy is a group of nerve disorders caused by diabetes.
Ten days of daily PGE1 injections improved neuron function in 77 patients with diabetic neuropathy, compared to 42 controls .
Factors That Increase Prostaglandins
Prostaglandin levels are a marker of inflammation and overall health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it. Improving your prostaglandin levels won’t necessarily cause improvement in your health and inflammation, but it can be used as a biomarker.
The following is a list of factors that may balance low IgE levels. Though studies suggest various dietary and lifestyle factors may increase IgE levels, additional large-scale studies are needed. Remember to talk to your doctor before making any major changes to your day-to-day routine.
1) Gamma-linolenic Acid
Gamma-linolenic acid (GLA) is an anti-inflammatory omega-6 fatty acid found in borage oil and evening primrose oil. GLA increased the production of the anti-inflammatory PGE1 in rat aortas .
2) L. reuteri
The probiotic L. reuteri stimulated the production of PGE2 by the gingival (gum) cells. This may hasten the resolution of gum inflammation .
Estrogen increased PGI2 in rabbits, which protected their hearts against damage after a heart attack .
4) Sleep Loss (Not Recommended)
Three days of sleep deprivation increased PGE2 in 24 subjects. This was associated with more pain (e.g. headaches, stomach pain) and physical discomfort .
These natural chemicals in the body play a role in reproduction, as well as in promoting and resolving inflammation.
Prostaglandins are natural chemicals in the body with hormone-like qualities.
First discovered in semen, prostaglandins were later found in cells throughout the body, as well as in women’s menstrual fluid.
Prostaglandins affect reproductive processes and are also thought to play a major role in promoting and resolving inflammation in the body.
While most hormones are released by a gland and then carried throughout the body in the bloodstream, prostaglandins are not. Rather, they’re produced at the area of the body where they’re needed.
Prostaglandins and Reproduction
Although more research is needed to fully understand the role of prostaglandins in reproduction, it’s known that they’re present in the body throughout a woman’s menstrual cycle.
During your period, prostaglandins trigger muscles in your uterus to contract. These contractions help expel the uterus lining.
Higher levels of prostaglandins can cause more severe menstrual cramps, and severe contractions may constrict the blood vessels around the uterus.
When pregnant women go into labor, prostaglandins help cause the cervix to dilate and contractions to occur.
Your doctor may use prostaglandins to induce labor if it’s decided that you should give birth before labor naturally occurs.
Dinoprostone (Prepidil gel or Cervidil) inserts are used for this purpose.
The following risks and side effects are possible with induced labor:
- Uterine hyperstimulation, a serious complication that can cause injury and bleeding
Prostaglandins are also used to:
- Control excessive bleeding after giving birth
- Manage patent ductus arteriosus, a condition in which the ductus arteriosus (a blood vessel) doesn’t close in an infant after birth
- Terminate a pregnancy
Prostaglandins may also play a role in erections in men. Because of this role, they have been synthesized and used in injections to help men with erectile dysfunction (ED) obtain an erection.
ED occurs when a man consistently can’t get an erection or maintain one long enough to engage in sexual intercourse.
Prostaglandins and Inflammation
When part of your body is inflamed, it means that your immune system is responding to infection or injury.
Inflammation is a way for your body to try to heal damaged areas, but it can also get out of control and cause damage over time.
Inflammation has been shown to play a role in arthritis, lupus, cancer, and neurodegenerative and cardiovascular diseases.
Prostaglandins play a key role in inflammation by contributing to the development of redness, swelling, heat, and pain.
Excess production of prostaglandins due to inflammation may lead to:
- Heavy menstrual bleeding
- Painful menstrual cramps
While researchers understand prostaglandins well when it comes to promoting inflammation, they don’t understand how these chemicals help resolve inflammation.
Prostaglandins and Other Conditions
If your body doesn’t produce enough prostaglandins, your doctor may consider giving you prostaglandins to treat the following conditions:
- Stomach ulcers
- Congenital heart disease in newborn babies
Prostaglandins are a group of locally acting regulatory factors derived from arachidonic acid, a polyunsaturated fatty acid containing 20 carbon atoms. Arachidonic acid is an essential component of the phospholipids, which are building blocks of membrane structures in the cells; therefore it is present in every cell of the body. The normal metabolic turnover of the phospholipids involves the continuous release and reincorporation of the fatty acid components. This results in a small amount of free arachidonate being present in the cell all the time. However, not all the released arachidonate is incorporated back into lipids; a portion of it is acted upon by various enzymes. One such enzyme is cyclooxygenase, which attaches oxygen molecules to the fatty acid at specific positions. The resulting oxygenated derivatives are further modified by other enzymes in cascade-like sequences of reactions, giving rise to a host of products termed prostaglandins and thromboxanes, many of which have strong biological effects. Figure 5 shows the cascade leading to the formation of prostaglandins and thromboxanes. Some of the biologically active members of the group, such as prostacyclin and thromboxane A2 are chemically unstable; others are rapidly inactivated by enzymes. Because of the ubiquitous presence of their precursors, arachidonic acid and oxygen, and their instability, these compounds are ideally suited to their role, which is the short-term local regulation of a number of physiological functions. Among the varied roles of prostaglandins and thromboxanes are the control of vascular tone, hemostasis, cytoprotection, regulation of fetal sleep/wake states, kidney function, thermoregulation, inflammation, cell proliferation, and many others. An excellent overview of arachidonate release and metabolism to prostaglandins and thromboxanes has been published recently by Smith et al. (1991).
Figure 5. The conversion of arachidonic acid to prostaglandins and thromboxanes. Arachidonic acid is oxygenated to the prostaglandin endoperoxides prostaglandin G2 (PGG2) and prostaglandin H2 (PGH2) in sequential reactions by the enzyme cyclooxygenase (1). PGH2 is metabolized further to prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) by enzymes with PGD-synthase (2) and PGE-synthase (6) activities, respectively. Prostaglandin F2α (PGF2α) is formed from PGH2 by prostaglandin endoperoxide reductase (4). Prostacyclin (PGI2) and thromboxane A2 (TXA2) are generated from PGH2 by prostacyclin synthase (3) and thromboxane synthase (5), respectively. Non-enzymatic reactions (7) result in the formation of 6-ketoprostaglandin F1α (6-KPGF1α) from PGI2 and thromboxane B2 (TXB2) from TXA2. Boxes mark the compounds with biologic activities.
One of the earliest recognized effects of prostaglandins was the stimulation of myometrial contractions. This action, observed experimentally in animal models, was initially related to the fact that the semen contains exceedingly high levels of prostaglandins, and was thought to indicate a role of these compounds in fertility. Later studies revealed, however, that prostaglandins are powerful stimulators of the myometrium, and will terminate pregnancy in a number of species any time during gestation.
In humans, three lines of evidence suggest that prostaglandins are key physiological regulators of myometrial activity in late pregnancy and at parturition (Challis and Olson, 1988; Keirse, 1990). First, the administration of prostaglandin E2 or F2α to pregnant women induces labor. The prostaglandins not only stimulate the uterus to contract, but also cause the uterine cervix to soften and efface, a process essential for natural birth to take place. Second, prostaglandin E2 and F2α are synthesized by the intrauterine tissues, and this natural prostaglandin production is higher after the spontaneous onset of labor than before it. In agreement with this, prostaglandins and their precursor, arachidonic acid, accumulate in the amniotic fluid as labor progresses. The maternal plasma concentration and the urinary excretion of the metabolic product of prostaglandin F2α also increase at labor, indicating the enhanced production of the endogenous prostaglandins. Third, it was observed that the length of pregnancy as well as the duration of labor significantly increased in women who were treated with blockers of prostaglandin synthesis to alleviate the symptoms of chronic inflammatory diseases. Moreover, the administration of inhibitors of prostaglandin synthesis slowed down or stopped completely preterm labor. These findings firmly established prostaglandins as the principal factors controlling human birth.
Subsequent investigations were aimed at determining the exact mechanism of prostaglandin action in the pregnant uterus. Important questions were to be answered, such as: Which intrauterine tissues are the sources of the prostaglandins, and which are the targets? What are the primary actions of the prostaglandins in the target tissues? What are the factors which control the synthesis and regulate the inactivation of prostaglandins in the uterine compartment?
Research during recent years made significant progress toward answering these questions (see Olson et al., 1993 for review). The amnion was shown to produce copious amounts of prostaglandin E2, while the decidua was identified as the main uterine source of prostaglandin F2α. It was demonstrated that the amnion synthesizes significantly more prostaglandin E2 after labor than before the spontaneous onset of parturition. Also, a group of bone marrow-derived cells in the decidua carrying the CD45 surface antigen was shown to synthesize enhanced amounts of prostaglandins at labor. Interestingly, the proportion of these cells increases at term within the heterogeneous population of the decidual cells. At the same time, the chorion exhibits lower activity to synthesize prostanoids, but a very high capacity to inactivate them metabolically.
Administration of prostaglandins to pregnant women induces uterine contractions suggesting that the myometrium is a target of prostaglandin action. Studies with synthetic prostaglandin and thromboxane analogs revealed that the human myometrium contains at least seven types of prostanoid receptors. These receptors bind prostaglandin E2, F2α, D2, thromboxane A2, and prostacyclin with different affinities. The receptors are coupled to various signal transduction systems, and are capable of mediating the contraction as well as the relaxation of the tissue. Interestingly, isolated strips of pregnant human myometrium relax when exposed to prostaglandin E2. This indicates that, at least under in vitro conditions, the relaxing effects predominate. In vitro studies of prostaglandin transfer across the fetal membranes and the decidua have demonstrated that decidual prostaglandins have unimpeded access to the myometrium because of the anatomical proximity of the two tissues. However, more than 90% of the amniotic prostaglandin E2 is inactivated in the chorion before reaching the myometrium, suggesting that the primary target of the prostaglandins produced by the amnion membrane is not the myometrium (Olson et al., 1993). Because of these observations, there is a growing consensus among investigators that the traditional view, that labor is initiated by a rise in intrauterine prostaglandin levels which directly stimulate uterine contractions, is too simplistic. It is more likely that prostaglandins act indirectly, or in concert with other agonists to stimulate the uterus to contract. Although the myometrium is undoubtedly one of the chief targets of intrauterine prostaglandins, the regulation of its contractile activity is complex, and not well understood.
The uterine cervix and the amnion membrane are other likely targets of prostaglandins. Both of these structures undergo changes at parturition which result in cervical softening and membrane rupture, respectively. The cervical changes include the remodeling of the collagen and glycosaminoglycan components of the extracellular matrix. This process is influenced by prostaglandins, especially prostaglandin E2 (Challis and Olson, 1988; Huszar and Walsh, 1991). The mechanism of prostaglandin action in these tissues is obscure, but it probably involves a local reaction resembling inflammation.
Various in vitro studies with perfused placentas, placental explants, cells, or homogenates have shown that the placenta produces measurable amounts of all major products of the prostanoid synthetic pathway (Figure 5; Myatt, 1990). The majority of these compounds are most likely released from the cells of the placental vasculature and participate in the regulation of fetal placental blood flow. The placental trophoblasts are very rich in prostaglandin inactivating enzymes. Similar to the chorion, this high metabolic activity effectively separates the maternal and fetal prostanoid pools.
The regulation of prostaglandin synthesis in human gestational tissues has been extensively studied because of its potential significance in the control of birth. Most of these studies, reviewed recently by Olson et al. (1993), comprised in vitro treatments of cells or tissues with agonists, followed by the determination of prostaglandin output or other relevant parameters of prostanoid biosynthesis such as enzyme levels or arachidonate depletion. A variety of natural and synthetic agonists have been found to modulate prostaglandin synthesis in these experiments. Among the steroids, cortisol was demonstrated to inhibit the prostaglandin output of amnion and placental explants, while progesterone or estrogens were not reported to affect prostaglandin production in term human gestational tissues. Oxytocin was shown to stimulate the prostaglandin production of decidual tissue and cultured amnion cells, however, these observations were not confirmed independently (Hirst et al., 1993). ACTH and CRH (corticotropin releasing hormone) increased the prostaglandin output of amnion, chorion, decidua, and placenta at term pregnancy, while GnRH (gonadotropin releasing hormone) stimulated the prostaglandin production of placental explants. Several cytokines, growth factors, and second messenger analogs also affect gestational tissue prostaglandin output; some of these will be discussed in more detail in later sections of this chapter.
Despite the wealth of information concerning the in vitro regulation of prostaglandin biosynthesis in the fetal membranes, placenta, and the decidua, little is known about the factors and mechanisms which control intrauterine prostaglandin production in vivo. Mechanical stimulation appears to play a role, because artificial rupture of the membranes or distension of the cervix lead to increased prostaglandin levels in the maternal circulation and in the amniotic fluid. However, none of the hormones or paracrine factors which affect the prostanoid output of the gestational tissues in vitro have been shown unequivocally to be the physiological regulator(s) of the increasing intrauterine prostaglandin levels observed at labor in women. The criteria to be satisfied by such regulator(s) include: (1) the changing endogenous production preceding or concomitant with the increase of intrauterine prostaglandin levels; (2) the ability to modulate prostaglandin levels upon exogenous administration; and (3) the blockade of the in vivo changes of prostaglandin synthesis by antagonists and/or synthesis inhibitors. Additionally, it is necessary to demonstrate that the agonist(s) gain access to the target tissues, the amnion and the decidua, without metabolic inactivation.
These criteria are difficult to establish through experimentation because ethical considerations and technical difficulties often limit the scope of research involving human subjects. Nevertheless, recent data suggest that a group of regulatory substances called inflammatory cytokines may indeed increase prostaglandin levels in the pregnant uterus, at least in certain pathological situations.
A Holistic Approach to Painful Menstrual Cycles
“Can you help me with my unbearable period cramps?”
As a nurse practitioner, I get this question all the time from young women. It’s a common problem. But the common “solution” of automatically putting girls on the pill isn’t always best for them. I have had great success with several healthy and holistic options to make those few uncomfortable days much more comfortable.
I first help these women understand what is causing such bad cramping. During a woman’s period, the body is essentially shedding off the inner lining of the uterus, to start the cycle over. The lining would have been what nourished the baby, had a pregnancy resulted that cycle. But since it did not, the body is having menses in order to start the cycle over. This process can only happen by the production of inflammatory chemicals called prostaglandins. Prostaglandins are hormone-like chemicals that cause mini-uterine contractions that expel the tissue from the uterus. Ideally the contractions are small enough that the process isn’t very painful. But for some women it becomes extremely unpleasant due to increased amounts of prostaglandins or increased sensitivity to them. This results in painful menstrual cycles, a condition clinically called dysmenorrhea. Dysmenorrhea can effect anywhere from 20-90% of women of reproductive age; 20% having symptoms on such a severe level that they significantly impact their quality of life.
Dysmenorrhea not only causes cramping, it can lead to other unpleasant symptoms like low back pain, bloating, nausea, leg pain, diarrhea and fatigue. When severe, these symptoms certainly make a woman want to crawl back into bed with a heating pad instead of jumping into a productive day at work, school, or home.
One of the most common conventional treatments offered to women for painful periods is birth control pills. Birth control helps with painful periods only through a mechanism of action that is actually shutting down the primary function of our reproductive system. The synthetic hormones in birth control suppress the normal menstrual cycle and overlay it with a pseudo-cycle created by the artificial hormones being ingested in the body. Although this is considered an effective way to manage pain with the menstrual flow, it is also ridden with side effects, including nausea, weight gain, abnormal bleeding, irritability and breast tenderness. Even if one is willing to overlook these nuisance side effects, artificial hormones in birth control also lead to increased risk of blood clots, stroke, and heart attack, as well as increased breast and cervical cancer. For these reasons, many women do not want to use this treatment to treat their painful periods.
Instead of suppressing a normally functioning system of the body, treatment for menstrual cramps should focus on the actual cause of the cramps, which is inflammation. The goal of treatment should be to tame or quiet the inflammatory response caused by the inflammatory prostaglandins being produced by the body.
The easiest and sometimes most effective conventional treatment is using non-steroid anti-inflammatory medicines. I like ibuprofen since it is readily available over the counter and works very well. In order to really get on top of the pain, women need to understand how to take ibuprofen effectively to reduce pain and bleeding. Indeed, not only can ibuprofen decrease cramps, but, if taken correctly, can reduce the heaviness of her menstrual flow by 20-30%, which women are also very grateful for. But women must take ibuprofen at a higher dose, more frequently, and more consistently to receive these benefits. I tell my patients to take either 600 (3 tablets) or 800 mg (4 tablets) every 6 to 8 hours around the clock as soon as their cramps start or when the flow starts to pick up, whichever comes first. If you take the ibuprofen, without missing doses, for that first day or two of the worst part of the period, you have essentially tamed the prostaglandins and decreased inflammation, making your period much happier to live with. Remember that you should check with your doctor if you have any concerns about taking ibuprofen, such as when you are a small-framed and maybe can’t handle that higher dosage.
If you do not like the idea of using ibuprofen, or need additional support on top of the medicine, there are other more natural options to reduce inflammation. For example, in some studies, fish oil taken by women on their period had a powerful effect similar to ibuprofen. Fish oil is also an anti-inflammatory and is tolerated very well. You can take one 1000-1200 mg fish oil capsule three times a day starting right at the very beginning of the period all the way through the few days of full bleeding.
I often use other supplements that are very beneficial to cramps, as well as those earlier PMS symptoms like fatigue, bloating, and headaches. Magnesium glycinate at 400 mg if very helpful for all these symptoms and can be taken once to twice daily starting several days before the period starts all the way through the period. Vitamin E is also found to be effective for relieving breast tenderness and period discomfort. I recommend 400 units two to three times a day starting a week before your period and continuing through the heavier days of your period can make a significant improvement.
Another supplement I recommend for both PMS and period pain is Iron. Studies show that getting at least 18-20 mg of Iron daily was found to lead to less PMS symptoms overall.
This amount of iron is what is in prenatal vitamins, so taking a good quality prenatal vitamin, even if you are not trying to get pregnant, can help with period symptoms. As an additional option instead of a prenatal vitamin, I also like the multivitamin called optivite-PMT. It was formulated for PMS and it has healthy amounts of magnesium, vitamin A and B vitamins, and was found to decrease PMS up to 50% in clinical trials.
DIET AND EXCERCISE
Another natural solution to reducing pain with menstrual cramps is to adopt an anti-inflammatory diet. If a woman rids her diet of prostaglandin promoting foods, you can reduce inflammation and essentially have a pain-free period. This will also lesson PMS and help women feel great in so many other ways too!
There are different recommended diets which you can research online, but I tell my patients to reduce sugar, carbohydrates from foods like bread and pasta, dairy products, and processed foods. Eat lots of healthy fats such as olive oil, avocadoes, coconut oil, and grass-fed butter. Try adding raw ground flax, walnuts, and pumpkin seeds to salads, snacks, or entrées. Eat more cold-water fish like wild-caught salmon. Get anti-inflammatory nutrients from vegetables like carrots, sweet potatoes, and dark leafy greens and fruits such as apples, coconuts, citrus fruits, berries, beans, artichokes, asparagus, and broccoli.
Exercise can also be a beneficial way to reduce the discomfort with your period. A recent study found that core strengthening exercises and stretching significantly reduced duration of pain and the intensity of pain with the period. We know that exercise not only increases blood flow throughout the body, but it also release endorphins, which are positive immune system chemicals, also called neurotransmitters. Endorphins can affect the way the brain perceives pain by interacting with the brain’s opiate receptors. The higher the endorphins or “feel good hormones” the less pain we feel.
STRESS AND MORE
Stress can also cause inflammation. Let’s not forget how important sleep is in keeping our stress levels in check. This can be difficult since for women, who are often busy caring for others and forget to take care of themselves. But if a woman is suffering from stress and the resulting inflammation and possible period pain, she needs a full night of sleep, meaning at least 7-8 hours, and she needs to spend intentional time each day relaxing and restoring her mental health. I recommend prayer as one great way to reconnect us with the spiritual aspects of our health. By adding just 10-15 minutes of daily prayer, you can significantly decrease stress and improve your overall health through the mind-body connection.
Lastly, I want to mention acupuncture as an alternative therapy to improve menstrual cramping. Studies have shown a significant reduction in pain using acupuncture therapy. This treatment could be particularly beneficial for women who do not prefer the use of traditional medical treatments. This should only be utilized by a trained acupuncturist.
WHEN TO SEE A DOCTOR
There are several holistic and effective ways to make your cramps and the whole menstrual period experience much more comfortable, without resorting to birth control right away. But remember that it is not normal to have very severe cramping. Those who would describe their pain as severe or almost unbearable, want advice on these various options, or have tried these approaches without success, really need to be evaluated by a healthcare professional. Pro Women’s Healthcare Centers offer trained professionals to help you find answers about any serious underlying women’s healthcare issue that may be contributing to their problems, such as PCOS or Endometriosis. There are cures for these conditions and I urge women to take their health seriously and get the help they need.
Clinical Evidence Handbook; Dysmenorrhea PALLAVI LATTHE, B February 15, 2012 ◆ Volume 85, Number 4 www.aafp.org/afp American Family Physician
Rebecca Peck & Charles Norris (2012) Significant Risks of Oral Contraceptives(OCPs): Why This Drug Class Should Not Be Included in a Preventive Care Mandate, The Linacre Quarterly, 79:1, 41-56
Saleh HS, Mowafy HE, El Hameid AA (2016) Stretching or Core Strengthening Exercises for Managing Primary Dysmenorrhea. J Women’s Health Care 5:295.
A Holistic Approach to Painful Menstrual Cycles was last modified: March 26th, 2019 by
Most women will experience some level of discomfort associated with their monthly menstrual cycle. For some women the discomfort will be mild, while for others the distress can undermine their ability to go about their daily life for a day, or two or perhaps more. The medical term for menstrual cramps is dysmenorrhea. There are two kind of dysmenorrheal – primary and secondary.
Primary dysmenorrheal refers to cramping that does not involve any underlying gynecological problem. Primary dysmenorrhea is associated with the onset of ovulation and since many young girls will begin to menstruate prior to beginning to ovulate, often these cramps will not set in until months after menstruation has begun.
Secondary dysmenorrhea means that some underlying abnormal condition (most often involving the reproductive system) is contributing to a woman’s menstrual pain. More often than not, these conditions do not occur at the onset of menarche, but manifest later.
Each month, the inner lining of the uterus builds up to prepare for a potential pregnancy. When the egg is not fertilized during ovulation, there is no pregnancy and this built up lining in the uterus is no longer needed. A woman’s estrogen and progesterone levels decline and eventually the lining of the uterus is shed in the menstrual flow, to be replaced by a new lining in the next monthly cycle.
When the lining of the uterus begins to break down, prostaglandins are released. These are compounds that cause the uterine muscles to contract, constricting blood supply to the tissue of the endometrium (lining the uterus). This causes the tissue to die and the contractions squeeze the old tissue out through the cervix and vagina and out of the body. In addition to the prostaglandins, substances called leukotrienes, which are chemicals that are related to the body’s inflammatory response are elevated, and it may be that elevated levels of prostaglandin and leukotrienes in a woman’s body play a key role in the severity of cramping she may experience.
How to Find Relief
If you are experiencing cramps during your menstrual cycle that have increased in their level of discomfort the first thing you should do is talk with your AOA healthcare provider so that we can determine if there are any underlying conditions that should be addressed.
If there are no abnormalities, there are some steps you can take to find relief. First and foremost, be sure that you are getting adequate rest, sleep AND exercise. Walking is particularly beneficial. The application of warmth in the form of a hot water bottle or heating pad to the abdomen can also help. Additionally, there is an array of nonprescription pain relievers available that may help control mild menstrual pain, including aspirin and various kinds of acetaminophen. It should be noted that these medications have a limited effect in curbing the production of prostaglandin, so they may not do the job if your cramping is severe.
If you have stronger cramping, some nonsteroidal anti-imiflammatory drugs such as Advil, Midol, Motrin and Aleve do lower the production of prostaglandin and can provide some relief. If you regularly have more painful cramping, you may want to start taking one of these medications a day or two before your period is scheduled to begin, just to get a running jump on the pain.
If the cramps you are experiencing are severe and debilitating, there are medical procedures that can provide temporary relief, including a dilation and curettage procedure to remove some of the lining of the uterus. This procedure is primarily used as a diagnostic measure to detect cancer or precancerous conditions.
A more common solution these days to severe menstrual cramping is a procedure called an endometrial ablation. If you are absolutely sure that you never want to have children, or if you’ve already given birth to your family and you want to stop your heavy periods and cramping, you can talk with your AOA physician about an endometrial ablation procedure. It is a simple, one-time, five-minute procedure that does not use hormones and does not require a hysterectomy. It can be done in our AOA offices and most women report little or no pain and resume normal activities within a day or two.
Talk with your AOA doctor if you’re experiencing painful periods that are cramping your style. We can help you find the right solution to reduce your pain and get you back into the swing of things.
Learn more about how to deal with painful menstrual cramps:
- Menstrual Cramps – Dysmenorrhea
- Is NovaSure Endometrial Ablation right for me?
- Painful Menstrual Periods
- Dysmenorrhea – ACOG
Cannabinoids & Your Period
- Should I take CBD oil for period cramps?
- How do CBD and ibuprofen compare?
- How can I get the best benefits from CBD oil for my period?
It’s that time of the month again — time to call in sick, cancel plans, curl up in bed with a hot water bottle, and try to distract yourself with a non-stop stream of movies and TV.
If this sounds like your monthly ritual, you are not alone. Up to 90% of reproductive-age women suffer from painful periods — the medical term for it is “dysmenorrhea” — and it can completely derail your daily life.
Cannabinoids & Suppositories Help
More and more women are reporting that CBD and THC products are the best tools they have for treating painful periods. But how do they stack up when compared to NSAIDs like Ibuprofen?
Quite well, it turns out, but it’s worth a deeper look at why they work — exactly how cannabinoids’ anti-inflammatory, pain-relieving, muscle-relaxing effects interact with your period.
This touches on the actual causes of pain & discomfort during your period, and how additional natural remedies can help combat these symptoms.
Move over NSAIDs and heating pads! Read on to discover why cannabinoids might become your new favorite companion when your period comes to town…
Your Uterus: Prepping for a Visit
In people who have periods, the uterus diligently prepares itself all month.
First, your body’s increasing estrogen told your uterus to build up its endometrial tissue. Then, after you ovulated, and the boost of progesterone helped plump up that tissue with arteries and blood — prepping to give a warm welcome to an incoming embryo … or in this case to prepare for menstruation.
Once your body discovers it won’t be hosting a guest, your progesterone levels decline — telling your uterus to roll up the welcome mat.
Your body takes back what it can from the endometrium, shrinking the tissue and cutting off blood flow to its spiral-shaped arteries. Without a proper blood supply, your endometrial tissue prepares to shed, and you likely begin experiencing pangs of pain.
Without progesterone, the endometrium loses its protection – creating a domino effect, and the perfect conditions for inflammation.
Prostaglandins: Inflaming the Uterus
While your progesterone was declining, inflammatory chemicals called prostaglandins were increasing. Prostaglandins (particularly one called PGF2⍺) peak during menstruation, creating the following effects:
- Inflammation: certain prostaglandins trigger an inflammatory response, which leads to more pain.
- Pain sensitization: prostaglandins and other inflammatory compounds can actually prime pain-perceiving nerves to become more sensitive.
- Vasoconstriction: the prostaglandins rampant during menstruation cause blood vessels to constrict, inhibiting blood flow to the endometrial tissue.
- Uterine contractions: People with higher prostaglandin levels have stronger, more painful contractions and doctors are finally acknowledging that this pain can be as intense as heart attack pain.
- Heavy bleeding: Unusually heavy periods could result from excessive inflammation, which increases tissue damage. People with heavy bleeding have higher levels of the enzyme the produces prostaglandins (COX-2), and medications to combat this process can decrease menstruation.
- Diarrhea: In addition to uterus contractions, prostaglandins also trigger smooth muscle contractions in the digestive tract — which might push your last few meals out a bit too soon.
(Note: some people claim that having sex helps to jump-start their periods — scientists believe that the prostaglandins in semen could contribute to this effect.)
We’re not trying to say that prostaglandins are all bad. They’re essential for a healthy, functioning menstrual cycle.
However, numerous studies indicate that women with higher levels of prostaglandins also have more painful or heavier periods — and treatments that lower prostaglandin levels can be highly effective.
NSAIDs Work, Sort Of
When their periods kick in, most women reach for an Ibuprofen or similar NSAID (Non Steroidal Anti-Inflammatory Drug). Why are NSAIDs the most frequently-prescribed treatment for menstrual pain?
NSAIDs work by inhibiting the enzyme responsible for producing prostaglandins (COX-2). This means that NSAIDs could potentially decrease all the symptoms aggravated by prostaglandins — including inflammation, contractions and pain.
Unfortunately, NSAIDs can also have unpleasant gastrointestinal side effects, because they inhibit another enzyme (COX-1). For this reason, NSAIDs should be used with moderation, and people with certain digestive issues might want to avoid them entirely.
CBD: a Better Alternative?
Recently, scientists discovered that — similar to NSAIDs — CBD also inhibits the prostaglandin-producing enzyme. However — unlike NSAIDs — CBD preferentially inhibits COX-2 over COX-1, which means its anti-inflammatory benefits come without the gastrointestinal side effects.
Added bonus: Not only does CBD inhibit the COX-2 enzyme, but both CBD and THC physically stop your DNA from producing so much of this enzyme in the first place (via the PPARγ receptor).
Additional Cannabinoid Benefits
By decreasing prostaglandin levels during your period, you can reduce inflammation, pain and cramps. However, you cannot entirely eliminate prostaglandins.
This means that you could benefit from combining a prostaglandin-reducing treatment with other treatments that target the discomforts caused by prostaglandins.
CBD and other cannabinoids can also treat painful menstrual cramps in the following ways:
- Anti-inflammatory: Cannabinoids have many anti-inflammatory activities beyond reducing production of inflammatory prostaglandins. For instance, THC activates endocannabinoid receptors (CB2) located on your immune system’s killer cells (macrophages). When these receptors are activated, they prevent macrophages from releasing inflammatory proteins (cytokines).
- Pain-relieving: Although prostaglandins and other inflammatory molecules can make pain-perceiving nerves more sensitive, cannabinoids fight back by desensitizing these nerves. Both CBD and THC target nerve receptors that help decrease the sensation of pain (TRPV1 and CB1, respectively). Additionally, not only does CBD desensitize TRPV1, but those soothing effects can spread to neighboring pain receptors.
- Muscle-relaxing: Menstrual cramps are exacerbated by contractions of the smooth muscle lining the uterus — and cannabinoids are widely recognized to relax smooth muscles. THC and CBD both target different receptors embedded in the muscle tissue to relax contractions.
- Vascular-relaxing: Blood vessels are also lined with smooth muscle, and when cannabinoids trigger this smooth muscle to relax, blood flow increases. Increased blood flow could help provide relief to oxygen-starved tissues, further decreasing painful cramps.
Natural Remedies for Cramps
- Apply heat: Hot water bottles may seem old-fashioned, but they can bring as much relief from menstrual cramps as NSAIDs — and oftentimes much faster. Heat increases blood flow to the area, which soothes the overworked muscles and delivers oxygen to oxygen-starved tissues. Some scientists also think that heat desensitizes the same pain receptors that CBD works on.
- Fish oil: Interestingly enough, multiple studies have demonstrated that daily fish oil supplements decrease pain and reliance on NSAIDs during periods. It turns out that prostaglandins are synthesized from omega fatty acids, and a diet high in omega-3 fatty acids could shift your body away from producing inflammatory prostaglandins.
- Magnesium: Do you ever crave chocolate around this time of the month? Women who take magnesium supplements during their periods have reduced pain and reduced inflammatory prostaglandin levels. Foods like chocolate, lentils and avocados are high in magnesium — so go ahead and feed the craving.
- Treat early: Many doctors suggest that it’s best to start taking painkillers an hour or more before the cramps start. This is true whether you’re using NSAIDs, CBD, or other cannabinoid blends. If you hold off treatment until you’re in excruciating pain, the prostaglandins will already be in full demolition mode and harder to bring under control.
- Discuss your treatment plan with a doctor: Sometimes painful cramps and/or heavy bleeding can be a symptom of an underlying problem like endometriosis (another painful condition that can be soothed by cannabinoids). We encourage you to talk with your doctor about your symptoms and treatment plan in order to rule out other health problems, particularly if your symptoms don’t improve with standard treatments. Your doctor can help you determine if there are surgical or hormonal treatments that could be more effective.
Finding Relief With Cannabinoid Suppositories
Many women are shocked and surprised to experience how effective cannabinoids are at relieving menstrual cramps (especially cannabinoid suppositories).
But the science is pretty clear about why: CBD targets the cause — inflammatory prostaglandins — while also relieving the symptoms (especially with help from a little THC).
Perhaps this is why women and people who bleed have been using cannabis to treat period pain for millennia. Though there are increasing numbers of doctors and scientists who know why cannabinoids work to relieve menstrual cramps, many more of them are only just beginning to hear from their female patients about how well cannabinoids work for their periods.
If you’re considering treating your menstrual cramps with cannabinoids for the first time, we encourage you to read testimonials from other customers. You may also be curious to know how cannabinoids help to soothe endometriosis.
And if “weed tampons” aren’t available in your city or state, try our CBD Suppositories which are now available online and ship world-wide.
More articles by: Genevieve R. Moore PhD
Identification and understanding of the various processes which may underlie the pathogenesis of functional bowel diseases are complex. Apart from the possible contributions of misperception or error, there seem to be four major types of processes potentially involved, namely: (a) motor or secretomotor abnormalities; (b) enteric nervous dysfunction; (c) abnormal sensation; and (d) abnormal central responses to sensory input from peripheral sensations, leading to abnormal responses of efferent autonomic, endocrine, or behavioural activities. In this brief review I will focus on (c) and (d).
Unknown at the present time are: (i) the extent to which visceral pain emanates from hypersensitivity to mechanical, chemical, or other stimuli and (ii) the ways in which learning, conditioning, habituation, long term and short term memory, and explicit or implicit memory or neuronal potentiation, participate in these processes, including the possibility that plastic “memory” (for want of a better word) in peripheral cells and their components (dendrites, nuclei, or axons) or connections (synapses, ganglia, neural networks) is involved in ways in which early or repetitive traumatic life events might act to condition patients to have abnormal sensory responses to normal stimuli at a later stage. My particular inquiries have principally explored the answers to two questions: (1) Are prostaglandins (PGs) involved in these processes? (2) Is PG production from arachidonic acid, the action of cyclooxygenase 2 (COX-2), most relevant to functional bowel disease?
Various types of eicosanoids are made by a variety of cells of the nervous system including neurones (benign and neoplastic) in cell culture, nerve cells in brain, spinal cord, autonomic nerves, and peripheral ganglia, and also in juxtaneuronal cells (astroglia and capillary endothelia) in various sites: products include those of both the cyclooxygenase and lipoxygenase pathways.1 While much is known about their localisation, regulation, and functional roles in central sites, less is known about these in spinal, autonomic, and enteric nervous systems but it is now emerging that many mechanisms elucidated centrally may also apply peripherally.1
What is known is that there are high concentrations of PGs in all nervous tissue thus far explored. In brain, both COX-1 and COX-2 are expressed constitutively and are probably both inducible, although induction applies mainly to COX-2. In whole brain, there are approximately equal amounts of the messenger RNAs for both COX-1 and COX-2 but the enzymes are found in different loci. COX-1 occurs mainly in forebrain, in areas concerned with consciousness and sensory processing. COX-2 is also expressed and regulated in forebrain (allocortex) but even more so in the hippocampus, amygdala, anteroventral region around the third ventricle, and in discrete brain stem loci.1 2 Exhaustive analysis by Brederet al of the distribution and activation of COX-2 has strongly suggested that PGs derived intracellularly from COX-2, in the absence of any inflammatory processes, are induced physiologically and involved in the activation of autonomic, endocrine, and behavioural responses to visceral and special sensory input.2
COX-2 expression in brain, and presumably synthesis of PGs in brain, seems to depend closely on synaptic activity.3 4 Basal levels are higher in awake animals and fall to low levels preceding or during sleep. Much of the activation is dependent on release of glutamate by presynaptic axons. In some synapses, release of an endogenous N-methyl-d-aspartate (NMDA) receptor agonist is produced by the action of 5-hydoxytryptamine or opioids on peripheral nerves; such stimuli seem to modify postsynaptic activity-dependent neuroplasticity. Expression of COX-2 is also stimulated by nerve growth factor (NGF) but rapidly reduced by glucocorticoids or deafferentation. NGF increases the incorporation of arachidonic acid into PGs, the rise in PG synthesis always being accompanied by increases in c-fos, c-jun, or other immediate early genes (IEGs) and their products.
The processes of neuronal learning, conditioning, and both explicit and implicit memory must involve neural plasticity (in addition to other processes). The neural changes which contribute to plasticity include elimination of neurones by apoptosis, growth or proliferation of neurones, or of the synaptic connections on or between neurones, alteration in the configuration of neural networks, changes in dominant pathways, or modifications in the group of neurones affected by a particular signal. This fine tuning, based on use, goes on throughout life although it is much greater during development and within the “critical period”. Ultimately, the actual structure of neurones must change as their functions change. Exactly how this occurs has not been elucidated but it is clear that PGs are involved.1
The sequence of events involves, in brain and spinal cord, release from glutaminergic nerves of neurotransmitter which then binds to NMDA receptors on postsynaptic dendrites, causing calcium to enter cells. This activates phospholipase A2 and releases arachidonic acid substrate for COX-2 and lipoxygenase (fig 1). Arachidonic acid can also be released by the action of phospholipase C. These phospholipases and COX-2 are located in the endoplasmic reticulum and perinuclear envelope, and result in generation of PG products which then bind to PG receptors within the nucleus, activating a variety of genes, but particularly IEGs such as fos and jun, which are responsive to cyclic nucleotides. Depending on the circumstances, this activation results in a variety of effects such as signalling, mitosis, altered cell shape, apoptosis, etc. Related to neural plasticity, COX-2 products are involved in rapid depolymerisation of actin filaments, followed by a slower repolymerisation that is thought to be stimulated by leukotrienes generated during the same burst of arachidonic acid release: this sequence permits cellular remodelling.
Outside of inflammation, PG production by COX-1 and COX-2 increases rapidly following ischaemia and the products are involved in apoptosis, neuronal elimination, and remodelling of neural connections. COX-2 expression and PG production increase rapidly following convulsions, including electroconvulsive therapy. The PGs produced result in three effects: (1) they are anticonvulsive, (2) they erase memories or change preferred pathways, and (3) they stimulate long term potentiation of newer synaptic connections.
COX-2 expression in brain increases rapidly with stress (for example, cold, swimming, etc) and brief non-injurious electrical stimulation, the effects of brief stresses persisting for long periods (months).
Finally, we come to the possible involvement of PGs, principally of COX-2 origin, in the genesis of pain and perhaps visceral hypersensitivity. These effects of PGs can occur at many sites (table1). Firstly, they can act peripherally, such as in the gut, where PG and lipoxygenase products such as leukotrienes can stimulate smooth muscle contractions and activate their sensors leading to afferent traffic: this is little studied. In peripheral nerves, PGs sensitise C fibres to painful stimuli. In animal pain models, intravenous administration of antiprostaglandin antibodies which do not cross the blood-brain barrier greatly reduces or abolishes pain behaviour. At the level of the spinal cord, induction of inflammation and pain at a peripheral site (for example, paw) induces spinal activation of NMDA receptors, and release of COX-2 mRNA and PGs at the relevant level of the cord. Exposing the spinal cord to PGs induces hyperalgesia and allodynia. Notably, intrathecal non-steroidal anti-inflammatory agents, at doses <1% of those needed for a systemic response, abolish the local production of inflammatory mediators and pain in some models.5 Finally, many sensory stimuli upregulate COX-2 and COX-1 in various areas of brain known to be involved with pain perception and responses. For all of these reasons, PGs are thought to be important in modifying how pain is perceived and acted upon.
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Prostaglandins and pain—sites of action
However, recent evidence suggests that the effects of COX-2 on pain may not be mediated solely via PGs, but rather by destruction of endogenous cannabinoids by the enzyme, diminishing the normal analgesic tone in tissues.5 These molecules include arachidonyl ethanolamide and palmitylethanolamide which respectively bind to CB-1 and CB-2 receptors, relieving pain. These appear to be metabolised to PGs by COX-2 but not by COX-1. Intrathecal injection of glutamate leads to hyperalgesia, probably in this way. Intrathecal injection of SR141716A, a CB-1 antagonist, increases NMDA receptor induced hyperalgesia, an effect blocked dose dependently by the NMDA receptor antagonists DAP5 and MK-801.6 These observations suggest that the analgesic effects of selective COX-2 inhibitor non-steroidal anti-inflammatory agents may be mediated by maintaining high tissue levels of endogenous cannabinoids involved in the normal damping down of painful stimuli. However, these cannabinoids are degraded in the presence of inflammation, or other inducers of COX-2, leading to pain (table 2). This may be prevented by drugs which inhibit COX-2, regardless of their selectivity. The study of PGs in the enteric nervous system seems to be a fruitful area for further research.
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COX-2: role in pain
- Kaufmann WE,
- Andreasson KI,
- Isakson PC,
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(1997) Cyclooxygenase and the central nervous system. Prostaglandins 54:601–624.
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(1995) Characterisation of inducible cyclooxygenase in rat brain. J Comp Neurol 355:296–315.
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Lights and shadows of NSAIDs in bone healing: the role of prostaglandins in bone metabolism
Barbara Lisowska,1 Dariusz Kosson,2 Karolina Domaracka3
1Department of Anesthesiology and Intensive Care, John Paul II Western Hospital in Grodzisk Mazowiecki, Grodzisk Mazowiecki, Poland; 2Division of Teaching, Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland; 3Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
Abstract: In this review, we discuss the current data about the anatomy and function of bone tissue with particular regard to influence of prostaglandins. Bone tissue dynamics are characterized by a constant remodeling process that involves all bone tissue cells. The communication between bone component cells and other organs is necessary for bone remodeling equilibrium and confirms the dynamic character of bone tissue. Remodeling is also a vital element of healing processes and in adapting bone tissue to stress responses. Therefore, in our review we present the role and significance of bone cells and signaling pathways enabling maintenance of bone homeostasis and remodeling process stability. Cyclooxygenase (COX) is a crucial enzyme in the production of prostaglandins and thromboxane. We focus on the role of COX isoenzymes with highlighting their connection with bone formation, resorption and repair. Prostaglandins are known as arachidonic acid metabolites acting through specific membrane receptors and play an important role in the regulation of osteoblast and osteoclast functions. Prostaglandin PGE2 with its four defined receptors (EP1R, EP2R, EP3R and EP4R) is crucial to maintain balanced bone turnover. Their stimulatory or inhibitory effects appear to depend on different structure-activity relations and signaling pathways. We have described the role of these receptors in bone metabolism and healing. We conclude that the activity of prostaglandins in bone tissue is defined by maintaining bone remodeling balance and its reactions to humoral mediators and mechanical stress. Most data confirm that among prostaglandins, PGE2 takes part in all processes of trauma response, including homeostasis, inflammation and healing, and plays a key role in bone physiology.
Keywords: bone cells and metabolism, COX, prostaglandins