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Causes of Endometriosis and Complications – Can it be cured?

Endometriosis affects 6-10% of women of reproductive age worldwide. Symptoms can vary from mild irritation to severe pelvic pain. Endometriosis can cause pain and infertility. Normally women tend to have pain and mild cramps during menstruation. In case they have intense pain and it hinders them from participating in day-to-day life activities, it may indicate that they suffer from endometriosis.

Causes of Endometriosis
The exact cause of endometriosis is not fully understood. Some of the possible explanations given are mentioned below:

Retrograde menstrual flow  
It has been proposed that menstrual blood enters the fallopian tubes and the pelvis instead of leaving the body as menstrual flow. This retrograde flow, along with potential hematogenous or lymphatic circulation, may result in the seeding of endometrial tissue in ectopic sites.

Embryonic cell transformation 
Another theory states that embryonic cells may develop into endometrial tissue within the abdomen and pelvis. 

Surgical scar implantation 
During surgery involving reproductive organs (hysterectomy or caesarian section), endometrial cells may be displaced. Endometrial cells may attach to a surgical incision.

Endometrial cell transport 
Endometrial cells could be transported to other parts by the lymphatic system. 

Risk factors 
Early menarche, shorter menstrual length is associated with a higher risk of endometriosis.

Complications of endometriosis
Ø Infertility 
Ø Internal scarring 
Ø Adhesions 
Ø Cysts – Pelvic cysts and chocolate cysts of ovaries
Ø Intestinal (Faecal) and urinary obstruction 

Endometriosis can lead to problems and complications like infertility due to damage to fallopian tubes and ovaries. Peritoneal inflammation causes harm to the sperm and the fertilized egg and also decreases uterine receptivity. Other complications are ovarian cysts and adhesions.

Ovarian endometriosis typically presents as an ovarian cyst containing old blood; usually called a chocolate cyst or an endometriotic cyst. Cysts are diagnosed in about 17 – 44% of women with endometriosis. These cysts have shown to have a damaging effect on ovarian physiology. Studies show that there is a decrease in the number of ovarian follicles in patients with endometriotic cyst and there appears to be increased intracellular reactive oxygen species generation contributing to oxidative stress. These cysts lead to Oocytes having a higher chance of failing in vitro maturation and showing altered morphology. Fluid-filled ovarian cysts can become large and painful and require surgical management. If endometriosis affects bladder and bowel, major surgery may be needed. 

Treatment of endometriosis
The treatment of endometriosis is initiated with medical management. Symptomatic treatment involves drugs that inhibit ovulation. Treatment is started with combined oral contraceptives and progestogens which provide pain relief. Danazol has been used in the past. Newer drugs used are the GnRH (gonadotropin-releasing hormone) agonists, GnRH antagonists (Elagolix) and hormonal receptor modulators (such as ulipristal). Each of these drugs has their specific side effects and cannot be used for a long time. 

Surgery and assisted reproductive techniques are useful in patients with infertility. Surgery is not the solution in all patients as it can lead to other adverse effects and cannot be performed on women who have not completed their family

Also, complementary treatment options are being looked at with keen hope and interest. Evidence-based highly-researched nutrition derived supplements are being developed to manage the conditions better. These treatment options ensure that the progression of endometriosis is kept in check. Data suggest that women who are treated using complementary options are able to manage their conditions better.None of the therapies are curative and can’t be used as a long term treatment due to the side effects.

Oxidative stress and inflammation 
Reactive oxygen species have an important role in conditions such as endometriosis and infertility. Oxidative stress has been implicated in the pathophysiology of endometriosis which may result in a general inflammatory response in the peritoneal cavity. It has been reported that increased numbers of activated macrophages, cytokines, angiogenic factors, and growth factors have been identified in the peritoneal fluid of patients with endometriosis.

Looking beyond hormonal treatment – How complementary treatment options help with Oxidative stress and Inflammation.

Curcumin 
Curcumin has been used in the prevention and treatment of many diseases since ancient times. Curcumin is the active constituent in Turmeric. Evidence exists for the anti-inflammatory, antioxidant, anti-tumor, anti-angiogenesis, and anti-metastatic activities of curcumin. Curcumin has the ability to inhibit endometriosis in vivo and may help in the management of endometriosis by reducing estradiol production. It has also been found to inhibit the migration and invasion of endometrial carcinoma cells.

Standard curcumin products that are available have challenges such as poor bioavailability and low aqueous solubility. Ultrasol, a novel, patented and sophisticated molecular dispersion process enhances the bioavailability of curcumin by 46 times as compared to the standard curcumin. Curcumin obtained from Ultrasol technology exerts much better anti-inflammatory and anti-oxidative properties. Curcumin starts altering the endometriotic cell morphology in 48 hours of administration.

Resveratrol
A natural drug, induces apoptosis in endometrial stromal cells and has shown promising results. Resveratrol is a phytochemical found in high concentrations in grapes, wine, tea, peanuts, and berries. It has demonstrated anti-inflammatory, anti-oxidative, anti-microbial, anti-atherogenic and anti-angiogenic properties. It has anti-oxidant properties that can be used to combat and manage the effects of oxidative stress in endometriosis. It is a safe and effective choice in the effective treatment and management of the condition. When resveratrol is used in combination with curcumin, the combination shows a 4 fold increase in its anti-oxidant activity. Resveratrol limits the invasiveness of the endometriotic stromal cells and also ensures that the number and volume of endometriosis implants are reduced.

N-acetylcysteine
NAC is the acetylated form of the amino acid cysteine naturally present in some substances like garlic. It has demonstrated anti-antiproliferative action on cells of epithelial origin like endometrial cells in addition to anti-inflammatory and anti-oxidant action. It has been found to be effective in treating ovarian endometriosis.These agents will be useful for the prevention and management of endometriosis. Being natural products, there is no risk of adverse effects and hence they can be used for longer periods of time.

References

https://www.hindawi.com/journals/omcl/2017/7265238/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480968/.

https://www.nhs.uk/conditions/endometriosis/complications/

https://www.ncbi.nlm.nih.gov/pubmed/29080464

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662115/

https://link.springer.com/article/10.1007/s13669-011-0002-3