The endometrium is the lining of the uterus that is usually sloughed off every month in the form of menstruation. Endometriosis is the growth of the uterine lining known as endometrium outside of the uterus, and the endometrial tissue that grows ectopically is known as the endometrial implant.
In endometriosis, endometrial implants are usually found on ovaries, fallopian tubes, and over the uterus. They rarely are found out of the pelvic region. It usually affects women in the third or fourth decade of their life but can also affect prepubescent girls.
Inflammation of the endometrial implants in response to the monthly hormonal changes leads to irritation and excruciating pain. It also shares most of its symptoms with other diseases like Pelvic inflammatory disease (PID), which causes common misdiagnosis of endometriosis.
Endometriosis is a very common gynecological condition, affecting 1 in 10 women and 176 million women worldwide.
Etiology & Risk Factors of Endometriosis
Exact etiology of Endometriosis is not known. However, studies have found a genetic component to the development of this disorder. Researchers believe that endometriosis develops as a result of multiple hits to target genes resulting in altered gene expression. They linked mutations in CA-125, WNT4, CDKN2BAS, VEZT, and many other genes with endometriosis. Furthermore, they suspect these altered gene expressions to be both; inherited and the result of environmental toxins.
Environmental toxins associated with endometriosis is estrogen. Prolonged exposure to estrogen, as in early menarche and late menopause, has been associated with endometriosis and many other gynecological conditions.
Many hypotheses have been proposed to explain the etiology of endometriosis and the only conclusion that can be made from these is that Endometriosis is a multifactorial disease.
Some of the hypotheses are mentioned below:
- Retrograde Menstruation Hypothesis: Also known as the implantation theory or transplantation theory, this theory is one of the widely accepted theories. First proposed by John A, Sampson, this theory suggests the cause of endometriosis to be a backward flow of menstrual blood through the fallopian tubes into the peritoneal cavity. This blood contains endometrial cells, which can then transform into endometrial implants in the pelvic region.
- Hormone induced transfer: Many researchers believe in this theory that hormonal imbalance causes the transformation of cells in the pelvic region into endometrial cells. These transformed cells act as endometrial implants
- Metaplasia: It is believed that endometriosis can occur if certain parts of abdominal tissue undergo metaplastic change into endometrial tissue.
- Mullerian theory: This theory came into existence after a fetal autopsy showed cells with the potential to become endometrial cells. It is believed that these cells separate from the Mullerian tract during development and act as seeds implanted outside of the uterus. These ‘seeds’ can become endometrial implants and cause endometriosis in adulthood.
Many other theories exist, none of them explaining every aspect of endometriosis. It is important to note that accepting one of these doesn’t reject the others.
Stages of Endometriosis
The staging of endometriosis is done based on location, depth of implants, number, and size of lesions. There are four stages:
- Minimal: Small lesions or wounds accompanied by shallow endometrial implants on ovaries. Few filmy adhesions may be seen.
- Mild: Light lesions and shallow endometrial implants on ovaries and the pelvic lining.
- Moderate: Deep implants and numerous lesions on ovaries and the pelvic lining. Endometriomas (chocolate cysts) are present in this stage.
- Severe: Deep implants on ovaries and pelvic lining accompanied by lesions on fallopian tubes and even, bowel. Plus massive endometriomas and extensive adhesions are seen.
Symptoms of Endometriosis
Around 20-25% of affected females are asymptomatic. The rest may present with pelvic pain and infertility as major symptoms.
- Pelvic pain: Pain felt by women can range from mild to extreme, stabbing & cramping pain that radiates to the back and legs. Also, this pain is associated with stages of endometriosis. Monthly menstrual hormonal changes can make the pain even worse. Symptoms of pelvic pain are:
1. Dysmenorrhea: cramping pain with menstruation
2. Chronic pelvic pain with lower back pain
3. Dyspareunia: pain associated with sexual intercourse
4. Dysuria with urgency and frequency.
5. Mittelschmerz: pain associated with ovulation
6. Discomfort with voiding and bowel movements
- Infertility: Depending on the stages of endometriosis, affected females may present with fertility problems
- Low-grade fever
- Heavy menstruation
- Chronic fatigue
These symptoms present due to irritation, adhesions, and scar formation of endometrial implants entrapped in the pelvic region. Sometimes, endometrial implants can travel all the way to the thorax and cause thoracic endometriosis, which is endometrial implants around lung pleura. The symptoms of this include hemoptysis, bleeding into pleural space, or even lung collapse.
The diagnosis of endometriosis starts with suspicion for endometriosis based on personal health history and clinical symptoms. After that, either of the following modalities may be used to diagnose the patient, with the gold standard being diagnostic laparoscopy:
- Pelvic USG: This modality helps view large endometrial cysts, however, smaller ones may be difficult to visualize with USG.
- Vaginal USG: Using this, even small endometriomas can be visualized.
- Laparoscopy: Diagnostic laparoscopy, as mentioned above is the gold standard for diagnosis. It helps visualize lesions that may appear dark blue, powder-burn black, red, white, yellow, brown, or non-pigmented. Also, if visible lesions do not seem conclusively endometriosis associate, biopsy should be taken for further evaluation
- Use of CA-125 marker: As mentioned above, the CA-125 gene is mutated in certain cases of endometriosis, and levels of this can be used to support the diagnosis of endometriosis
Differential Diagnosis of Endometriosis
Endometriosis has symptoms similar to various other gynecological disorders, and it is important to exclude these disorders or find conclusive lesions for endometriosis diagnosis to be made. The following disorders may present similarly as endometriosis:
- pelvic adhesions
- pelvic inflammatory disease
- congenital anomalies of the reproductive system
Treatment of Endometriosis
Unfortunately, endometriosis has no cure. However, the management of pain and infertility is possible. Interventions for endometriosis can also be divided into medical and surgical interventions. Medical Interventions are further divided into hormonal and other pain-management medications.
- Hormonal, oral contraceptives: Birth control pills have been known to reduce the risk of ovarian and endometrial cancer development, along with reducing menstrual pain.
- Progesterone: Progesterone inhibits estrogen and hence, estrogen-induced endometrial growth.
- Danazol: Suppressive steroid with androgenic activity. Can help with endometriosis-related pain but can cause virilization.
- GnRH Modulators: These include both GnRH agonists and antagonists and provide pain relief through decreasing estrogen levels.
Other Pain Management Interventions
These help with general pain and do not play an active role in stopping/slowing the progression of endometriosis
Surgical interventions are of two types; conservative surgery and hysterectomy. Conservative surgery is a laparoscopic surgery, which destroys and removes endometrial growths in patients with no response to hormonal therapy. This type of surgery is preferred for women who wish to get pregnant as it does not affect any reproductive organs. Hysterectomy is the last resort treatment if no other treatment modalities work. It is important to note that this is not a cure for endometriosis, rather a radical treatment of pain.
Complications of Endometriosis
Endometriosis is associated with an increased risk for ovarian and/or endometrial cancer. It can also lead to endometriosis-associated infertility due to scarring. It can also result in chocolate cysts, adhesions, fibrotic scars, and pain.
Thoracic endometriosis can be complicated by catamenial hemothorax, which is the result of cyclic menstrual bleeding of thoracic endometrial implants.
Endometriosis can be fatal if not treated in time due to the high risk of developing ovarian and/or endometrial cancer. Therefore, severe menstrual cramps that are worse than normal or are of new-onset need to be examined by a gynecologist to rule out endometriosis. The choice of treatment, whether conservative or invasive will be decided by the gynecologist based on the patient’s response to hormonal therapy.
Endometriosis is a very common gynecological disorder that warrants urgent treatment. An accurate diagnosis is necessary and sometimes, difficult due to overlapping of symptoms with other gynecological disorders. Furthermore, the stigma associated with women visiting their gynecologists for cramps, like that in endometriosis can result in women choosing not to get diagnosed. All of this only increases the risk of complications associated with endometriosis.
Awareness about what endometriosis is also vital for timely diagnosis. Many women may themselves brush off the pain as severe period cramps, delaying the diagnosis and treatment.