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Introduction to Endometriosis

Endometriosis is an enigmatic condition which is extremely common. Those with access to the internet will find many sites discussing severe disease but the vast majority is of a much more minor nature. The condition was first described in 1869 but even now it is poorly understood.

Endometriosis is a condition where tissue just like the endometrium or lining of the womb, is found outside the cavity of the womb. The old term, endometriosis interna, meaning endometriosis within the muscle of the womb, is now called adenomyosis and may cause problems similar to the problems of fibroids. What we now call endometriosis used to be called endometriosis externa, being endometrium outside the womb altogether. It is most usually found on structures close to the womb but may be found in very distant parts of the body. In some women endometriosis causes no problems at all and in others there may be intense pain.

Epidemiology and Diagnosis


Who gets endometriosis?

Endometriosis is found almost exclusively in women of reproductive age though it has been seen in young girls and women past the menopause. No-one knows how many women have the condition as it can only be diagnosed conclusively by surgical intervention (this is usually laparoscopy). We seem to be finding endometriosis more and more frequently and it is suggested that this is related to higher living standards. However, it could just as easily be because we are performing more and more laparoscopies.
The prevalence of endometriosis in certain groups of women has been estimated. It has been found in 2% of women undergoing tubal sterilization (1), 7% of women with an affected first degree relative (2). It is found quite frequently in women undergoing investigation for infertility, about 15-25% overall but where there is no other obvious reason for the infertility it may be at 70 or 80% (3).


How does endometriosis develop?

This question is, as yet, unanswered. We know that growth and spread of endometriosis is dependent upon the female hormones produced during the menstrual cycle. Many theories have been advanced about how endometriosis develops but none completely explains all the possibilities.

  1. Menstrual regurgitation and implantation.   Sampson in 1927 suggested that endometriosis develops as a result of tiny pieces of endometrium which during menstruation pass along the fallopian tube into the pelvis rather than through the cervix to the outside. In the pelvis, he proposed that they would in some way be able to gain a foothold and grow behaving as if they were still inside the womb. This theory is supported by experimental evidence as endometriosis has been produced in animals by placing menstrual fluid or endometrial tissue in the peritoneal cavity. Retrograde menstruation appears to be very common as it is usually seen at laparoscopy during the time of the period but it does not seem to produce endometriosis in the majority of women.
  2. Spread through blood vessels is proposed to explain the occasional finding of endometriosis in distant sites from the pelvis such as the lung but it is difficult to envisage how lymphatic or blood vessels could carry fragments of endometrium from the womb to some of the sites in which it is seen such as joints or the navel.
  3. Direct surgical implantation.   At the time of caesarean section relatively large quantities of the lining of the womb may come out through the surgical incision. Fragments of viable (living) endometrium could be deposited in the wound. In future menstrual cycles the endometrium grows and then breaks down with some bleeding and shows up as pain in the wound at the time of periods and possibly swelling and redness.
  4. Cellular transformation.         Every cell in our bodies has the same chromosome content and therefore the information to actually be any other sort of cell in the body. It is proposed by some that for some, as yet, unknown reason, cells of the peritoneum (the lining of the cavity of the pelvis and belly) or synovium (the lining of joints) or other tissues might be caused to change into endometrial tissue.
  5. Other genetic and immunological factors.    The relatively high incidence of endometriosis in women with first degree relatives with the disease suggests some genetic factor. It is also suggested that there are racial differences with an increased prevalence amongst oriental women and a lower prevalence in patients of negroid origin compared with the caucasian.
  6. Environmental factors:          Links between endometriosis and chemical substances present in everyday life have been shown. Many industrial chemicals, agricultural pesticides and their metabolites have oestrogenic activity when chlorinated (eg tetrachlorodibenzo-p-dioxin).  However the link to clinical findings is tenuous.

Symptoms

Endometriosis results in an extremely variable set of symptoms and the intensity of symptoms bears little or no relationship to the severity of the disease. As the ectopic endometrium behaves in a similar fashion to the endometrium within the uterus, one experiences some pain and bleeding associated with menstrual cycles.

This pain and bleeding may result in painful periods (dysmenorrhoea) or rectal bleeding if the endometriotic deposits are in the rectum. Coughing up blood (haemoptysis) has been reported where there is lung endometriosis and implantation endometriosis in scars has been mentioned above. The swellings and release of prostaglandins may result in further symptoms such as diarrhoea or spasm of the anal sphincter. There may also be tenderness at the top of the vagina which is painful at intercourse. As the disease process produces more scarring lower abdominal and pelvic pain may extend throughout the cycle. Others may suffer the problems associated with an ovarian cyst such as rupture or torsion.


Infertility

The symptom of infertility is frequently associated with endometriosis. In many cases a few small deposits of endometriosis which have resulted in no other symptoms may be found at laparoscopy and it is difficult to be sure of the relationship between this finding and the symptom. However, advanced disease may produce obvious anatomical distortion blocking tubes. Several mechanisms by which endometriosis could possibly produce infertility have been suggested but none proven beyond doubt.

Symptom

Likely frequency

Dysmenorrhoea (painful periods)

 60-80%

Pelvic pain

30-50%

Infertility

30-40%

Dyspareunia (painful intercourse)

25-40%

Menstrual irregularities

10-20%

Cyclical dysuria/haematuria

1-2%

Constipation (cyclic)

1-2%

Rectal bleeding (cyclic)

<1%

Diagnosis


Blood tests

There are no blood tests which will diagnose endometriosis nor predict one's susceptibility to the condition. A substance which is present in all people's blood stream (Ca125) is frequently slightly raised by many conditions affecting the pelvis such as fibroids or ovarian cysts and, of course, endometriosis. As it is raised by many conditions, it is not diagnostic but is frequently used as an indicator of the success of treatment once the diagnosis is made. Ca125 is also a tumour marker, raised to much higher levels where there is cancer of the ovary. A slight rise does not indicate cancer.

Ultrasound
Most deposits of endometriosis are not visible on ultrasound. However, if it arises in an ovarian cyst, the cyst may well be visible. Ultrasound reports may suggest the possibility when the density of the fluid in the cyst is such that it suggests blood rather than the clear fluid of a simple cyst but cannot make the diagnosis.


Magnetic resonance imaging (MRI), computerised tomography (CT)

These investigations cannot make the diagnosis of endometriosis but are sometimes used to delineate the extent of lesions in complex cases.


Laparoscopy

Most endometriosis is diagnosed at laparoscopy. The visual appearance of deposits is usually considered sufficient to make the diagnosis. Sometimes a biopsy is taken for confirmation by histology but this can sometimes be inconclusive.


Laparotomy

Where a large mass is present, an open operation may be used to remove the mass. The nature of this mass (being endometriosis) may be apparent at the time of operation or on subsequent histological examination.

Treatment of Endometriosis

Hormonal therapy has been the mainstay of medical treatment for endometriosis for more than half a century. In the 1940s and 1950s diethylstilboestrol and methyltestosterone were used but were abandoned because of the side effects being too great. Today, the techniques divide into 3 groups:
It is known that endometriosis tends to clear up during pregnancy. We therefore attempt to produce a pseudopregnancy for some women. Anti-oestrogen drugs or androgenic hormones (masculine hormones) cause the endometrium to shrivel away and have been the mainstay of therapy for many years. It is also noticed that endometriosis will resolve after the menopause and so a temporary artificial menopause is used.


Pseudopregnancy

In 1959 Kistner reported the use of Enovid (a contraceptive pill) in 58 women with pelvic endometriosis. More modern contraceptive pills may be used these days and if used continuously without allowing the monthly bleed, may be effective.
The major hormonal difference in pregnancy is a huge rise in the level of progesterone in the woman's blood stream. This is produced by the placenta (afterbirth). A wide variety of progestogens have been used to mimic this effect including oral medroxyprogesterone acetate or injectable medroxyprogesterone acetate. However, the side effects are similar to those of pregnancy with weight gain, fluid retention, breast tenderness, mood changes and also include irregular vaginal bleeding. This irregular vaginal bleeding does not necessarily mean that it has not been successful in reducing the endometriosis.


Anti-oestrogen or Androgen-type drugs

Danazol has been the mainstay of treatment for many years until quite recently. It is a synthetic relation to testosterone, the male hormone and is taken by tablets. A peak blood level is reached about 2 hours after the tablet is taken and it is undetectable after 8 hours. Quite high doses may be required to suppress menstruation and therefore side effects are not uncommon. Less commonly they are related to the androgenic state with weight gain, oily skin, acne, hirsutism. Very occasionally there is deepening of the voice and when this rarely occurs it is irreversible. Side effects due to the lowered oestrogen state such as hot flushes, night sweats, sleep disturbance and decreased breast size may sometimes occur.

Danazol should not be used for long periods of time because of changes in cholesterol metabolism. It is metabolised in the liver so those with liver disease should mention this to their doctors. It is also inadvisable to conceive whilst taking the drug and therefore barrier methods of contraception should be used.
Gestrinone is a progesterone agonist or antagonist. This is a much longer half-life after the tablet is taken, enabling one to take a tablet twice a week. It has fewer androgenic symptoms and metabolic effects compared with Danazol and fewer side effects due to lowering of oestrogens. Again, it is inadvisable to become pregnant and barrier methods of contraception should be used.


Pseudomenopause

The ovaries are stimulated by hormones (follicle stimulating hormone and luteinizing hormone) produced by the pituitary gland in the base of the brain. This gland is in turn stimulated to produce these hormones by gonadotrophin-releasing hormone (GnRH). The gland keeps only small supplies of these hormones and therefore if constantly stimulated by GnRH, runs out of its stock and can no longer stimulate the ovary. One can therefore use GnRH agonists (that is drugs which act in the same way as the real hormone (to shut-off the pituitary gland and produce a temporary artificial menopause). There are a number of preparations which may be administered as a nasal spray, a sub-cutaneous pellet or a depot injection. All can be very successful at reducing the pain of endometriosis and reducing the amount of disease. However, the side effects are those of the menopause and lack of oestrogen. I therefore, use the GnRH agonists, almost invariably with "add-back therapy" of a form of HRT which is known to have minimal chance of stimulating any endometrial tissue and most commonly use Tibolone (Livial) which is a synthetic molecule with some androgenic and some progestogenic activity (see above) as well as the oestrogen effect. This may allow more prolonged therapy by reducing symptoms and also by preventing the development of osteoporosis which is a risk of natural or pseudomenopause.


Surgical Treatment

The mainstay of diagnostics and treatment is laparoscopy. Small deposits of endometriosis may be destroyed (or ablated) by diathermy, a miniature spark generator (Helica) or laser energy. Adhesions may be divided laparoscopically. Ovarian cysts containing old blood due to the monthly release from endometriosis (endometriomas) may also be successfully removed laparoscopically and the originating endometriosis destroyed. However, such ovarian cysts are almost always stuck to other tissues and may sometimes require open surgery.


More Radical Surgery

In the early days, surgical removal of the uterus was the sole treatment for endometriosis. However, nowadays it is generally reserved for those who have completed their family and in whom conservative treatment has failed. Nevertheless, 10% or more of patients with endometriosis do require hysterectomy. However, even after hysterectomy, if the ovaries remain there is a chance of recurrence of the endometriosis and so one must consider removing the ovaries at the same time. If the ovaries are removed, I will generally use Tibolone or a combined continuous oestrogen progestogen HRT, both of which have minimal effects on endometrium and are valuable in preventing the long term problems of the post-menopausal state such as osteoporosis. This is particularly important for a woman whose ovaries have been removed some years before the expected time of her menopause.


Other procedures for pelvic pain

Uterine suspension or ventrosuspension: As the ovaries lie to either side of the uterus and slightly behind it, they may become tethered close to the top of the vagina. This can allow them to be squeezed during intercourse with associated severe pain. Pulling the womb forwards and anchoring the round ligaments to the anterior abdominal wall can pull the ovaries up out of the way. This operation can be performed laparoscopically.

Laparoscopic uterosacral nerve ablation (LUNA): Where the woman suffers central pain, rather than pain to one side or the other, it is likely that the nerves carrying these impulses travel along the uterosacral ligaments. These nerves may be divided laparoscopically and 50-70% of women in these circumstances can expect relief of pain. It is, however, also possible that pain derives from other structures such as the bowel which have become irritated and adherent to endometriosis. The nervous pathways for that sort of pain will, of course, be different.

Presacral neurectomy: This is a similar operation which can be performed in the traditional open method or laparoscopically where nerves are divided on the front of the sacral bone rather than on the back of the uterus.


References or Further Reading
  1. Strathy J H, Molegaard GA, Coulam CB and Molton LJ (1982). Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril 38 667.
  2. Simpson JL, Elias S, Malinak LR and Buttram VC (1980). Heritable aspects of endometriosis. Am J Obstet Gynecol 137 327.
  3. Kistner RW (1977) Endometriosis. In Sciarra J (ed) Gynecology and Obstetrics Vol 1 (Hagerstown, New York, London: Harper And Row)
  4. Shaw RW (1993). Atlas of Endometriosis - (Encyclopedia of Visual Medicine Series) (UK & Europe, Parthenon Publishing Group)

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