Women's Health: Endometriosis

Endometriosis is a common disease affecting approximately 10-15% of women of reproductive age both in the UK and worldwide. The name of this condition comes from the word "endometrium," which is the tissue that lines the uterus. Endometriosis is characterised by the growth of endometrial-like tissue outside of the uterus, and this tissue behaves as though it was normal uterine tissue within the uterus i.e. thickening and shedding in line with the menstrual cycle.

During a woman's regular menstrual cycle, endometrial tissue builds up and is shed if pregnancy does not occur. Women with endometriosis develop tissue that looks and acts like endometrial tissue outside of the uterus, usually on other reproductive organs inside the pelvis such as the fallopian tubes, ovaries and vagina, or in the abdominal cavity involving organs such as the bladder, intestines and rectum. Each month, this misplaced tissue responds to the hormonal changes of the menstrual cycle by building up and breaking down just as the endometrium does. This causes small bleeding inside the pelvis, which leads to inflammation, swelling and scarring of the normal tissue surrounding the misplaced endometriosis implants.

When the ovary is involved, blood can become embedded in the normal ovarian tissue, forming a "blood blister" surrounded by a fibrous cyst, called an endometrioma.

Lesions can range between superficial implants, deep infiltrating, peritoneal lesions or ovarian cysts. Common sites for these endometrial lesions include the fallopian tubes, pelvic peritoneum, ovaries and uterosacral ligaments, however the urinary tract, gastrointestinal tract, chest and soft tissues can also be affected. In some cases, endometriosis can be asymptomatic, often only being diagnosed when investigating infertility, however symptoms are often felt, and these can be severe and significantly impact the quality of life for the individual.

The reported prevalence of endometriosis varies but is thought to be about;

  • 6 to 10% in all women

  • 25 to 50% in infertile women

  • 75 to 80% in women with chronic pelvic pain

The average age at diagnosis is 27 years old, and the condition can also occur among adolescents.

Aetiology & Pathophysiology

The pathophysiology of endometriosis is widely debated and numerous hypothesises exist. As research progresses it is being increasingly recognised as a disease that is highly complex and multifactorial, with both environmental and genetic influences playing a role in its pathogenesis. In reality, it is likely to be a result of an interplay between multiple theories.

The current postulated theories include:

1. Immune Dysfunction - This theory focusses on endometrial tissue evading attack by the immune system, which would otherwise prevent their ability to implant outside of the uterus. Women with endometriosis have been shown to have eutopic endometrial cells which have an increased capacity for proliferation, as well as an increased resistance to cell mediated immune attack. For translocated endometrial tissue to attach to the surface of the peritoneal cavity and form a lesion, it must evade immune defences. Eutopic endometrium in women with endometriosis demonstrates resistance to natural killer cells, and as such, immune surveillance dysfunction is likely to be a contributing factor.

2. Inflammation & Oxidative Stress - DNA damage of endometrial cells that may be driven by lipid peroxidation caused by reactive oxygen species (ROS), has been observed in endometriosis. In addition, iron overload in the peritoneal cavity occurs from haemoglobin breakdown, leading to redox reactions. ROS leads to inflammation including recruitment of macrophages and lymphocytes and the production of cytokines, which leads to the promotion of endothelial cell growth.

3. Bacterial Contamination - A recent theory involving microorganisms from the lower genital tract migrating and infecting the upper genital tract, contaminating menstrual blood / peritoneal fluid. The subsequent release of lipopolysaccharide (LPS) from the bacteria then causes pelvic inflammation and promotes growth of endometrial lesions via the LPS / toll-like receptor 4 cascade. It has also been observed that estradiol (an oestrogen) may have an additive pro-inflammatory response with LPS.

4. Retrograde Menstrual Flow - This is the oldest theory, which suggests that during menstruation, some of the endometrial tissue which should be exiting the female reproductive tract instead travels in reverse up through the fallopian tubes into the abdomen, in "reverse menstruation", where it attaches and grows into endometrial lesions. However retrograde menstruation is considered to occur in about 75-90% of women and only approximately 10% develop endometriosis. This theory also does not account for endometriosis occurring in newborn babies, males or pre-pubescent girls.

5. Coelomic Metaplasia - A theory centring on the idea that cells in any location may transform into endometrial cells. This theory suggests that endometriosis is driven by hormonal and/or immunological factors, and develops from the metaplasia of certain cells in the mesothelial lining of the abdominal and visceral peritoneum. The regular peritoneal cells and tissue therefore transform into endometrium-like tissue. It also postulates that a contributing factor in this transformation of cells are endocrine disrupting chemicals (EDCs) such as BPAs, PCBS, pesticides and phthalates.

6. Embryonic Remnants - This suggests that in response to oestrogen, residual embryonic cells in the Mullerian ducts develop into endometriotic lesions. However this theory does not account for endometriosis developing outside of these Mullerian ducts.

7. Lymphatic Dissemination – A theory suggesting that endometrial tissue may travel and implant via blood or lymphatic channels, similar to the way cancer cells spread around the body. This theory may explain the formation of lesions in less common or distant locations, involving endometrial tissue travelling via the lymphatic system to implant and form lesions in other parts of the body.

Figure 1 | The interrelationship between different factors involved in pathogenesis of superficial and deep endometriosis

Key Risk Factors for Endometriosis:

  • Family history of endometriosis

  • Heavy alcohol use

  • Early age of menarche (beginning of periods)

  • Low body weight

  • Shorter menstrual length (less than 27 days)

  • Abnormal uterus shape

  • High caffeine intake

  • Infant exposure to soy formula

  • Prenatal exposure to oestrogens

  • Prenatal and adult exposure to estrogenic endocrine-disrupting compounds e.g. Bisphenols (e.g. BPA), phthalates, organochlorine pesticides

Potential Protective Factors:

  • Multiple births

  • Prolonged breastfeeding

  • Late age of menarche

  • Regular exercise (especially if begun before the age of 15, for > 4 hours/week, or both)

Stages of Endometriosis:

I Minimal: A few superficial implants

II Mild: More and slightly deeper implants

III Moderate: Many deep implants, small endometriomas on one or both ovaries, some filmy adhesions

IV Severe: Many deep implants, large endometriomas on one or both ovaries, and many dense adhesions, sometimes with the rectum adhering to the back of the uterus

Signs & Symptoms:

These vary depending on the location of the lesions (i.e. fallopian tubes, ovaries, vagina, bladder, intestines, rectum) and include the following:

  • Dysmenorrhea (painful periods)

  • Dyspareunia (pain on intercourse)

  • Dysuria (painful urination)

  • Pelvic or abdominal pain

  • Pain on defaecation

  • Abdominal bloating

  • Rectal bleeding during monthly periods

  • Diarrhoea or constipation

  • Increased urinary frequency

  • Urinary urge incontinence

  • Fatigue

  • Nausea

  • Pain on and around ovulation

  • Infertility

  • Irregular menstruation

  • Menorrhagia (heavy periods)

  • Anaemia (from either menorrhagia or inflammation)

It is important to note that the amount of pain a woman experiences is not necessarily related to the severity of the disease. Some women with severe endometriosis experience no pain at all, while others with a milder form of the disease may have severe pain and/or other debilitating symptoms.

Endometriosis & Infertility

Endometriosis is one of the 3 major causes of female infertility, considered to be found in between 25 to 50% of women who experience infertility. In mild to moderate cases, the infertility is often temporary and effective treatment to remove adhesions, cysts and scar tissue can restore fertility. In a small number of cases however, women may remain infertile.

The exact mechanism behind this close association is not well understood, however it might relate to scar tissue from the endometrial lesions impairing the release of the egg from the ovary and fallopian tube or changes in the pelvic environment that results in impaired implantation of the fertilized egg such as from hormonal imbalances or bacterial infection.

Diagnosis & Tests:

Diagnosis is usually obtained by the use of laparoscopy and biopsy. A diagnosis requires the presence of 2 or more of the following: endometrial epithelium, stroma, glands and hemosiderin-ladin macrophages. Deep infiltrating endometriosis is hard to detect however and therefore can be missed.

Laparoscopy: This is a minor surgical procedure in which a laparoscope, a thin tube with a camera at the end, is inserted into the abdomen through a small incision. Laparoscopy is also used to determine the location, extent and size of the endometrial growths.

Biopsy: A small tissue sample is taken from the lining of the uterus (endometrium) to be studied under a microscope to look for abnormal cells.

Other examinations that may be used in the diagnosis of endometriosis include:

Ultrasound: A diagnostic imaging technique that uses high-frequency sound waves to create an image of the internal organs offers a limited ability to diagnose endometriosis, however it can show the presence of large lesions. The transvaginal ultrasound can also detect lesions on the bladder and deep nodules in the rectovaginal septum.

CT scan: A non-invasive diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce horizontal, or axial, images of the body to detect any abnormalities that may not show up on an ordinary X-ray.

MRI scan: A non-invasive procedure that produces a two-dimensional view of an internal organ or structure.

Blood test CA125: This can be positive in cases of endometriosis however it is generally associated with more advanced stage endometriosis. This is also a marker of reproductive inflammation or serious carcinoma and can therefore be associated with other reproductive pathologies.

Conventional Treatment:

In general, conventional medical treatment for endometriosis may include:

  • “Watchful waiting” to observe the course of the disease

  • Pain medication: nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen

  • Hormone therapy, including:

- Oral contraceptives, with combined oestrogen and progestin (a synthetic form of progesterone) hormones to prevent ovulation and reduce menstrual flow;

- Progestins alone;

- Gonadotropin-releasing hormone agonist, which stops ovarian hormone production, creating a “medical menopause”;

- Danazol, a synthetic derivative of testosterone (a male hormone)

Surgical techniques that may be used to treat endometriosis include:

  • Laparoscopy (also used to diagnose endometriosis): A minor surgical procedure in which a laparoscope, a thin tube with a lens and a light, is inserted into an incision in the abdominal wall. Some endometrial growths might be able to be removed in the process.

  • Laparotomy: A more extensive surgery to remove as much of the displaced endometrium as possible without damaging healthy tissue

  • Hysterectomy: Surgery to remove the whole uterus and possibly the ovaries

Naturopathic Treatment:

Naturopathic treatment focusses on identifying each individual's specific form of the disease via a thorough health assessment and relevant testing, with subsequent treatment directed at resolving those particular underlying causes. Treatment considerations typically involve the following:

  • Down-regulate inflammation

  • Reduce pain levels

  • Improve antioxidant status

  • Reduce pelvic congestion & improve circulation

  • Address menorrhagia (heavy bleeding) if relevant

  • Rebalance hormones; increase progesterone and/or reduce oestrogen

  • Support optimal gut microbiota & address stealth pathogens, gut integrity, reduce LPS

  • Support immune surveillance and modulate the immune system

  • Support liver function/phase 2 liver detoxification (hormone/toxin clearance)

Herbal medicine offers an extremely useful avenue of support for all women's health conditions, being both gentle and highly effective. Useful herbs for the treatment of endometriosis include Turmeric, Boswellia, Green Tea, Cinnamon, Rosemary, St Mary's Thistle and Chaste Tree. The exact combination of herbal medicines indicated will depend on the mechanisms underlying each particular individual's course of disease.