Endometriosis and Antioxidant Therapies - A Review of Current Research

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Endometriosis is a chronic pain condition, which in 2009 was estimated to impact more than 344,000 women in Canada. ^[1] This number of cases was reflective only of surgically confirmed cases, and many more women experience the condition without a formal diagnosis. The condition can have dramatic impacts on quality of life, as women experience symptoms including severe menstrual bleeding and pain. Based on the prevalence of the condition, the cost of endometriosis to Canadian society has been estimated to be roughly 1.8 billion dollars per year (when accounting for health-care costs as well as the added losses associated with missed work and productivity). ^[1]

What Is Endometriosis?

The endometrium is the uterine lining which is shed each month during a woman’s menstrual period. In endometriosis, this uterine lining is found in areas throughout the body and not restricted to the uterus itself. ^[2] Most often, endometrial tissue will be found in areas immediately around the uterus in the pelvic cavity (such as adhesions on the bladder, colon, or outside of the ovaries) but can also be found on structures as far-reaching as the diaphragm. ^[3] During the menstrual period, changes in hormone levels causes these endometrial tissue adhesions to behave similarly to the uterine lining, and they bleed and break down, causing irritation, pain, and inflammation, as the endometrial tissue has no way to leave the body. ^[4] Unfortunately, this inflammation leads to the formation of further scar tissue and adhesions, which can over time cause additional pain. ^[4] This condition can present at any age but will generally present during the reproductive years of women (from first menstrual period to menopause) and can have long term impacts on fertility. ^[4]

Symptoms of Endometriosis

The symptoms of endometriosis are wide-ranging, but the condition can cause symptoms, including: ^[3]

• Pain (dependent on location of endometrial implants) is typically pelvic or abdominal and related to the menstrual cycle though may be felt throughout the cycle as well. Often patients will have pain for the two weeks prior to menses.
• Painful sex: Will felt deep internally.
• Bladder symptoms: Pain with urination, blood in the urine, urgency to urinate.
• Bowel symptoms: Constipation is common, as well as bloating.
• Changes to vaginal bleeding: Bleeding may be heavier than normal.

Diagnosing Endometriosis

The gold standard for diagnosis of endometriosis involves imaging using internal laparoscopy of the pelvic area. ^[5] This involves the surgical insertion of a small camera through the abdominal wall to visually examine organs and abdominal cavity for endometrial lesions. Unfortunately, as a result of performing a laparoscopy, there can be increased risk for additional scar-tissue formation. As a result, women are often diagnosed without imaging; however, to get a conclusive diagnosis of endometriosis, laparoscopy is required.

Potential Causes of Endometriosis

Unfortunately, at this point, there is no consensus regarding the cause of endometriosis. We do know that there are genetic linkages in the inheritance of endometriosis. Women are up to seven times more likely to have endometriosis if they have another family member with endometriosis. ^[1] Other than genetic factors, some of the potential theories behind why endometriosis happens in the first place include:

• Retrograde menstruation: During menstruation, there may be blood which instead of exiting the uterus through the cervix, moves backwards and exits via the fallopian tubes, implanting elsewhere in the pelvis.[5]
• Potential movement of endometrial cells through the bloodstream that implant elsewhere inappropriately.[5]
• Changes in hormone levels due to inappropriate exposure to chemicals/estrogenic compounds.[5]
• Elevated levels of inflammation and immune dysregulation contributing to endometrial pelvic lesion formation as well as worsening the symptoms of the condition.[6]

Antioxidants

Our bodies are consistently exposed to chemicals, pollution, toxins, and environmental factors which induce damage through the process of oxidation. Antioxidants are either naturally occurring or synthetic compounds which have been shown to reduce the impacts of this oxidative damage on our cells. ^[7] A couple of common examples of sources of oxidative damage might be things like cigarette smoking or sun exposure. At this point, there is mixed evidence about the clinical benefits of taking antioxidant compounds on overall health; however, eating foods with high antioxidant levels, such as fruits and vegetables, has been shown to be helpful for various health conditions.

Endometriosis and Antioxidant Therapies

At this point, several antioxidant substances have been identified as being helpful in the management of endometriosis in both animal and human studies. While these substances may have alternate mechanisms of action, they all also serve to reduce oxidative damage on cells, thereby potentially reducing inflammation throughout the whole body in patients with endometriosis. ^[6] The following list of antioxidant therapies is not exhaustive, but these are the primary natural antioxidant therapies that have evidentiary support for endometriosis management.

Vitamins C and E

Vitamins C and E are both considered dietary antioxidants and are a relatively cheap intervention in care. A 2013 study compared placebo to the administration of 1200 IU vitamin E and 1000 mg vitamin C in 59 reproductive-aged women with endometriosis for two months. ^[8] They evaluated pain scales for chronic daily pain, pain during menses (dysmenorrhea), and pain during sex (dyspareunia). ^[8] Before and after therapy, they also completed peritoneal fluid measures of inflammatory markers. ^[8] Though in a small population group, the patients who received combined vitamin E and C therapy demonstrated improvements in chronic daily pain (43% of patients), dysmenorrhea (37% of patients), and dyspareunia (24% of patients), while there were minimal changes in patients receiving placebo. ^[8] The study also demonstrated reductions in inflammatory markers in the peritoneal fluid overall with therapy. ^[8]

N-Acetylcysteine (NAC)

NAC is an amino acid naturally present in foods including garlic which has been shown to mitigate the impacts of oxidative damage, and which has a number of other antiproliferative effects. ^[9] A 2013 study over three months of 92 women demonstrated reduction in the size of ovarian endometrioma growth. ^[9] Women received NAC, 1.8 g/d for three consecutive days a week for three months. ^[9] Those who received NAC therapy had a reduction in endometrioma size by −1.5 mm when compared with those individuals who were controls, who demonstrated an increase in size of +6 mm. ^[9] Some patients also had a reduction in pain and patients had no compromise in fertility when compared with controls. ^[9] This requires further evaluation as an intervention, as there hasn’t been a placebo-controlled trial completed as of yet; however, this may be a cost-effective therapy with limited side effects which can improve the reduction of endometrial implants and endometriomas.

Melatonin

Melatonin is an antioxidant chemical that the brain naturally produces to help in regulating the sleep-wake cycle. It also has numerous other health benefits including potential benefits for immune health, cancer adjunctive care, and insomnia. Synthetically developed products are readily available and fairly low-cost. A small placebo-controlled trial was completed in 40 reproductive-aged women looking at the effectiveness of melatonin in endometriosis patients. ^[10] Women received either placebo or 10 mg/d of melatonin. The study looked at factors including severity of pain, dyspareunia, and analgesic use. ^[11] When compared with placebo, patients who received the melatonin had reductions in pain during menses, pain during sexual activity, pain during urination and defecation, and general pelvic pain overall (they saw approximately a 35% reduction in pain). ^[11] Patients also reported using 80% less analgesics overall. ^[11] Further larger studies are needed to evaluate this intervention properly, but these initial results are highly optimistic in the supportive effect of melatonin in endometriosis management.

Conclusion

Preliminary research regarding the use of antioxidant therapies in the management of endometriosis appears to be positive. These therapies likely help to reduce generalized inflammation and oxidative damage, and therefore mitigate some of the formation of new endometrial implants and reduce pain overall. While studies are only preliminary and small, and further evaluation of these therapies will have to be done in the future, this positive evidence may make these cost-effective and generally well-tolerated therapies a good support in the care of patients with endometriosis going forward.