Endometriosis

Endometriosis (endo meaning "inside" and metra, “womb”) is a common cause of menstrual-related pelvic pain and pain with intercourse impacting up to 10 percent of reproductive-age women. The uterine cavity is lined by endometrial cells, which are influenced by the reproductive hormone estrogen and progesterone, which change throughout the menstrual cycle. Endometrial cells deposited in areas outside the uterus are also influenced by these hormonal changes and respond similarly as do those cells found inside the uterus.

Symptoms often are worse in time with the menstrual cycle.  Treatments are both medical and/or surgical. Symptoms depend on the site of implantation. Its main but not universal symptom is pelvic pain in various forms.  Endometriosis is common in women with infertility.

Diagnosis

Endometriosis is a cause of pelvic pain or dyspareunia (painful sex with intercourse) mainly in pre menopausal women. About 60% of women with endometriosis have the onset of their symptoms before 20 years of age. Ninety percent or more of women with pelvic pain and endometriosis have a history of dysmenorrhea (a medical condition characterized by severe   pain during menstruation so severe it limits normal activities, or requires medication).  

A common complaint, dyspareunia occurs with deep penetration and not with initial entry. Dyspareunia occurs in up to 60% of patients with pain symptoms. Rarely is dyspareunia an isolated pain symptom of endometriosis. Deep dyspareunia is most often associated with the uterosacral ligaments (the uterosacral ligaments belongs to the major ligaments of uterus. and/or rectovaginal fold which contain a considerable amount of fibrous tissue and muscle), which are attached to the front of the sacrum.

PHYSICAL EXAMINATION: Physical examination findings in women with endometriosis are often negative. Many women only have tenderness during menses and sometimes repeating the exam at this time can be useful. Other women with endometriosis have persistent areas of tenderness that overlay endometriosis  areas, whether or not they are menstruating. In women whose primary complaint is deep dyspareunia, localized tenderness of the cervix, cul de sac, or a fixed, and retroverted uterus may be found at the time of examination. 

IMAGING STUDIES: Radiologic studies can be useful in the preoperative evaluation and surgical planning in a patient with suspected endometriosis, but are not sensitive or specific for diagnostic purposes. Magnetic resonance imaging has also been described to identify endometriosis lesions, particularly in unusual locations, such as with rectal, nervous system, or thoracic involvement. 

LAPAROSCOPY: Laparoscopy is a surgery that uses a thin, lighted tube put through a tiny cut (it is sometimes called “band-aide” surgery) that can look at pelvic organs. Laparoscopy is used to help in the diagnosis of endometriosis Tissues samples can be taken for a biopsy as well. .The diagnosis of endometriosis is based on positive histology (the study of the microscopic anatomy of cells and tissues), and should not be based solely on a visual diagnosis made at the time of laparoscopy. Histologic diagnosis is important because endometriosis lesions can have many different appearances, from the “classic” powder burn lesions (black, brown, or gray) to the “atypical” lesions which can be clear, red, yellow, or white.

Also, many other lesions can look like endometriosis, such as hemangiomas, old suture, ovarian carcinoma, residual carbon deposits from prior surgery, and even normal peritoneum. When the diagnosis is based only on the visual appearance, the diagnosis is incorrect about half the time.  Conversely, relying only on visual diagnosis can lead to under-diagnosis or under-staging, as many atypical lesions are actually endometriosis.   

Laparoscopy is the ideal diagnostic tool, with histologic sampling for reasons outlined above. Compared with laparotomy, laparoscopy allows for magnification of lesions and results in easier identification of microscopic endometriosis, particularly in the setting of “atypical” lesions. Many women with endometriosis will likely undergo more than one operation, and laparoscopy results in less adhesive disease, shorter hospital stay, and a better cosmetic result. 

Now the Details

Endometriosis encompasses a wide spectrum of presentations ranging from disease found incidentally during laparoscopy to extensive, seemingly malignant disease that can spread outside of the pelvis and into the upper abdomen. The severity of symptoms also varies greatly and does not always correlate with the amount of endometriosis.

Classically, endometriosis appears with one or more of the following:

  • an adnexal mass: a lump in tissue near the uterus, usually in the ovary or fallopian tube. Adnexal masses include ovarian cysts, ectopic (tubal) pregnancies, and benign (noncancerous) or malignant (cancerous) tumors.)  
  • infertility
  • pelvic pain

Up to 70% of women with endometriosis have some type of pain symptoms, most commonly dysmenorrhea, non-cyclic pelvic pain, or deep-pain with intercourse. A total of 60-79% of patients undergoing surgery for endometriosis and have been affected by deep pain with intercourse. 

This in itself results in a negative attitude towards sexuality, anxiety toward and avoidance of intercourse, lower levels of desire and arousal, and fewer orgasms. Women with uterosacral ligament endometriosis in particular have the most severe impairment of sexual function, higher intensity of pain, and less satisfying orgasms The most common site for endometriosis is on the uterosacral ligaments behind the uterine cervix. 

The Causes And Effect

 The two causal aspects of endometriosis of importance to the doctor are the cause of the disease and the cause of symptoms of pelvic pain and infertility. Neither is completely understood.

The etiology (cause or causes) of endometriosis is complex. Both genetic and environmental factors are important. There are several general theories regarding the etiology of endometriosis. None of these theories is sufficient to explain the protean manifestations (very changeable; readily taking on different shapes and forms) and locations of endometriosis, or the predilection of some women, but not others, to develop endometriosis.

The theory of retrograde menstruation (backflow of menstrual fluid, epithelial cells, and debris through the uterine tubes and into the peritoneal cavity.) leading to the implantation of endometrial cells in the peritoneal cavity (also known as Sampson’s theory) is supported by observational data. 

Adolescents with obstructive reproductive tract malformations and adult women with cervical stenosis (a narrowing or a constriction) both have high rates of endometriosis. However, most, if not all, women experience some form of retrograde menstruation, so retrograde menstruation is not the sole source of endometriosis. There must be other factors that allow implantation, invasion, and proliferation of ectopic endometrium in some, but not all, women.

More Theories

Other theories include immune system defects, and lymphatic spread of disease. Recently, research has focused on environmental factors and on the unique attributes of the endometrial cells of endometriosis. Environmental pollutants such as polychlorinated biphenyls (PCBs) and dioxin have been associated with an increased risk of confirmed endometriosis among women undergoing laparoscopy.

Endometriotic cells have the ability to produce enzymes such as aromatase, an enzyme that is not present in normal endometrium and is integral to the conversion of androstenedione and testosterone to estrogen, a conversion usually done only in the ovary.

The ability to produce estrogen locally may lead to auto-stimulation of endometriotic lesions. Not only do endometriotic lesions show high levels of estradiol biosynthesis, they also show low estradiol inactivation compared to normal endometrium. Additionally, there is some evidence that alterations in progesterone receptors in endometriosis may play a role in the development or progression of endometriotic lesions.

The Pain Issues

The etiology of pain symptoms with endometriosis is less well understood, although there is ample epidemiological evidence of the relationship of endometriosis and pelvic pain symptoms. Since endometriosis is most commonly a disease of pelvic organs and visceral peritoneum, (visceral peritoneum is a complete covering for the stomach, spleen, liver, intestines from the distal duodenum to the upper end of the rectum, uterus, and ovaries; it also partially covers some other abdominal organs) endometriosis pain is usually visceral (from viscera-- the organs in the cavities of the body, especially. those in the abdominal cavity) in origin.

Visceral pain (pain sensation of the internal organs) has a number of characteristics that are important to any understanding of endometriosis-associated pain:  not all internal organs are sources of pain, possibly due to lack of sensory neurons.  In addition, visceral pain frequently results in referred pain,  because the nerve of the internal organs enter the spinal cord at the at the same level as the nerve ending of external structures. For example- and injury to the liver “feels” like an injury to the shoulder.    

A number of studies have shown that endometriotic lesions produce and release inflammatory mediators, particularly certain prostaglandins that are potent mediators of the inflammatory response. In addition to directly causing visceral pain, inflammation induced by endometriosis may also enhance pain sensitivity. The presence of inflammation tends to significantly enhance both the sensitivity and the severity of visceral pain. This characteristic of visceral pain may be relevant in patients with endometriosis, because in the presence of local inflammation, visceral afferents may develop peripheral hyper sensitization and start to respond to previously innocuous physiological stimuli.

In addition to nociceptive pain, neuropathic pain may also be a significant factor in endometriosis-associated pelvic pain. For example, there are significant differences in the uterine nerve supply of women with endometriosis and chronic pelvic pain compared to those without pelvic pain. Women with endometriosis and chronic pelvic pain have an increase in nerve fibers and nerve proliferation in their uteri. These neural changes may be a cause of both dysmenorrhea and chronic pelvic pain.

Finally, referred visceral pain with hyperalgesia (increased pain sensitivity) may be an important mechanism in endometriosis-associated pain. Referral of pain with hyperalgesia of somatic tissue is a well-known characteristic of visceral pain. In the case of endometriosis, there are both animal experimental and human clinical evidence of hyperalgesia of the vagina, abdominal wall, and lumbosacral back. Referred pain with hyperalgesia may be an important mechanism in the generation of dyspareunia in women with endometriosis.

Remember, endometriosis is estimated to be present in 1-7% of the general population, although the true prevalence is unknown. In women undergoing laparoscopy for pelvic pain and infertility, for example, endometriosis lesions are present 33% and 40% of the time, respectively.

Treatment

Treatment of endometriosis may be surgical, medical, or both. Many factors must be considered in planning treatment and the patient needs to be actively involved in treatment decisions. Her understanding of the disease and her unique needs and problems will influence her decisions about treatment. From my, the location and extent of endometriosis, the severity of symptoms, and any other pelvic pathology will influence recommendations. The patient’s age, reproductive plans, duration of pain or infertility, and attitude toward surgery or toward hormonal medications may be vital components of treatment planning. Treatment may need to be modified, based on the tolerance of the therapy or the persistence or worsening of symptoms.


MEDICAL TREATMENT: 
 Most medical therapies for endometriosis work by decreasing estrogen levels. For the majority of the commonly used medical treatments there is good evidence supporting their efficacy for symptomatic relief of pain. Danazol (a 17-ethinyl-testosterone derivative) is an oral medication, which stops menses and lowers estrogen levels by directly inhibiting steroidogenesis at the ovarian and adrenal levels. This induces atrophic changes in the endometrium and endometriosis. It was the first drug approved by the FDA for the treatment of endometriosis, and at one time was considered the gold-standard in medical treatment of endometriosis.
       
However, the extensive side effect profile which includes acne, edema, weight gain, hirsutism, voice changes, hot flushes, abnormal uterine bleeding, decreased breast size, decreased libido, vaginal dryness, nausea, weakness, and muscle cramps, makes it difficult for many patients to tolerate and limits its effectiveness as a treatment option.

An early, uncontrolled study showed that about 75% of patients had relief of either pelvic pain or dysmenorrhea, and about 60% had relief of dyspareunia. Gonadotropin releasing hormone agonists (GnRHa) are analogues of naturally occurring gonadotropin-releasing hormone that shut down production and release LH and FSH, thereby dramatically reducing estradiol levels. This induces a pseudomenopausal state. Clinical trials show that efficacy is comparable to Danazol, with side effects of hot flushes, vaginal dryness, decreased libido, emotional lability, and decreased bone density. Loss of lumbar spinal bone density averages 3.2% at 6 months and 6.3% at 12 months. Add-back therapy with the progestin norethindrone acetate, with or without estrogen, reduces the loss of bone density and decreases other side effects without loss of efficacy. The GnRH agonists currently available for use in the United States are nafarelin, leuprolide, and goserelin.
       
Combined oral contraceptives (COCs) are widely used to treat endometriosis associated pelvic pain. COCs inhibit ovulation, decrease gonadotropin levels, and decrease menstrual flow. At least one randomized clinical trial suggests that COCs are almost as effective as GnRH agonists for the treatment of pelvic pain and dyspareunia.. Both COCs and GnRH agonists decreased pelvic pain, but the GnRH agonist was somewhat more effective in relief of dysmenorrhea and dyspareunia. Side effects of COCs include nausea, headache, abnormal uterine bleeding, thrombophlebitis and thromboembolism.


SURGICAL TREATMENT:
 Although many patients with suspected endometriosis based upon history and physical exam findings are treated successfully with medical therapy, diagnostic laparoscopy is still recommended for diagnosis. Treatment can be combined with diagnosis. Excision, coagulation, and vaporization with various energy sources have been described as appropriate treatment options for the conservative surgical management of endometriosis, both for pelvic pain and for infertility. Regardless of energy source, care should be taken to treat all lesions identified and to remove or ablate each lesion in its entirety. This is especially important for deeply infiltrating lesions like those commonly present in the uterosacral ligaments or in the rectovaginal septum.

There are two randomized clinical trials showing the effectiveness of laparoscopic surgical treatment of endometriosis. The first used laser energy to destroy the lesions. At six months postoperatively, 23% of the placebo group showed decreased pain and 62% of the surgically treated group showed decreased pain. Over the subsequent six to 12 months, 16% of the surgically treated patients required repeat surgery compared to 52% of the control group. In a study of   excision of endometriotic lesions, there was improvement of symptoms in 80% of the treated group versus 32% of the control group. Additionally, observational studies suggest that dyspareunia improves in 70-80% after conservative surgical treatment.

The second study also showed slight improvements in dyspareunia and non-menstrual pelvic pain with presacral neurectomy. Long-term complications of presacral neurectomy include constipation and urinary urgency. Two randomized clinical trials of with endometriosis surgery have shown that uteroscral neurectomy does not improve dysmenorrhea, dyspareunia, or non-menstrual pelvic pain over that obtained solely with excision or ablation of endometriosis. For women who are not interested in future childbearing, hysterectomy with or without removal of the ovaries is also an option for treatment. There is no consensus regarding the necessity of removal of ovaries with endometriosis, although one study reported 62% recurrence of pain when one or both ovaries were retained, compared to 10% after both were removed.   

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