Current Thinking on Endometriosis
Current thinking on endometriosis
Endometriosis is a poorly understood disease, traditionally defined as the presence of endometrium (the lining of the uterus shed at periods) outside the uterus. The disease appears to have a familial component and current estimates are that it effects some 10 to 15% of the female population (ie probably more prevalent than diabetes and asthma). The average time to diagnosis has been estimated at more than 10 years.
Several theories exist as to the cause
Exciting new evidence reveals that the underlying problem may lie within the uterus in the zone between the endometrium (which is shed at menstruation) and the myometrium (the muscle of the uterus). Our research team at Sydney University have demonstrated the striking finding that patients with endometriosis have nerve fibers in the lining of their uterus (ie the “normal” endometrium) whilst those without the disease do not have these nerve fibers. (Al-Jefout et al. 2009) This allows for the dramatic possibility of diagnosing endometriosis without an invasive laparoscopy.
Others have shown the possibility that stem cells in this region are implicated in the development of endometriosis. (Sasson and Taylor 2008) Endometriosis might thus be the first stem cell disease described.
Why do people get endometriosis?
Anecdotally, endometriosis appears to be getting more common and possibly more severe. There must be some reason in nature for this. New, somewhat controversial evidence, suggests that endometriosis may decrease the chance of pre-eclampsia (fitting and high blood pressure) in pregnancy. (Brosens et al. 2007) Thus it might actually be that endometriosis is protective for pregnancies, particularly if you are very young, but becomes a problem if you defer pregnancy or get a bigger “dose” of endometriosis. (Brosens et al. 2010)
Our new endometrial biopsy test and possible other non-invasive tests will dramatically alter the management of the disease in years to come. The cornerstone of diagnosis has been a good clinical history. Premenstrual spotting and cyclical symptoms, particularly pain, are good indicators. Examination is usually normal, although at times nodules can be felt on vaginal examination in the region of the uterosacral ligaments. Imaging modalities such as CT and MRI are of limited value. The only real role of ultrasound is to exclude ovarian endometriomas. CA125 testing is of minimal value.
We know that pregnancy appears to decrease the severity of the disease and may even clear it. The contraceptive pill is also useful. Medical therapy has a role in maintenance but unfortunately does not result in longstanding regression or cure. All agents are contraceptive and there is no data to suggest an improvement in fertility rates. Unfortunately many have significant side effects.
In most cases the areas containing endometriosis are reasonably superficial but they can at times be deeply invasive and cause significant scarring and fibrosis not unlike a malignant process. Surgery is thus often necessary.
The surgical philosophy in recent times has moved towards an excisional approach rather than simple diathermy techniques. (Garry 1997, Redwine 1991) To a certain extent endometriosis may be likened to an iceberg and diathermy may result in residual disease. Diathermy is also unsuitable for many situations with disease adjacent to bowel or ureters. Excisional surgery results in a 70 to 80% chance of substantial ongoing pain relief with an increase also in fertility rates. (Marcoux, Maheux and Berube 1997) The best results paradoxically occur in those with the most severe disease (such as illustrated). Most of these procedures can be done via laparoscopy. Our data and audits are in accord with these results and show low complication rates. (Kaloo, Cooper and Reid 2006)
Combined treatment approaches
Given the findings we have demonstrated in the uterus of people with endometriosis I have been recommending most patients either try and get pregnant following surgery or contemplate placing a Mirena device which secretes a progestogen and “mimics” pregnancy. This appears the best method of decreasing the risk of recurrence whilst maintaining fertility.
IVF or surgery for endometriosis?
This is a controversial area and management needs to be individualised. In general terms, IVF success rates are lower if you have endometriosis and there is the possibility of making symptoms worse, so removing the disease before starting IVF is appropriate.
Cancer and endometriosis
In many respects endometriosis is similar to malignancy. There appears to be an increased risk of progression to frank cancer, particularly for those patients who have large ovarian endometriomas. Worryingly it also appears that in some cases endometriosis is capable of producing it’s own estrogen thus enabling it to be sustained even after castration.
Figure 1. Significant endometriosis with bowel involvement and cul de sac obliteration
Figure 2. Post excision of endometriosis and bowel resection. The cul de sac is now clear.
Al-Jefout, M., G. Dezarnaulds, M. Cooper, N. Tokushige, G. M. Luscombe, R. Markham & I. S. Fraser (2009) Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study. Hum Reprod, 24, 3019-24.
Brosens, I., I. Derwig, J. Brosens, L. Fusi, G. Benagiano & R. Pijnenborg (2010) The enigmatic uterine junctional zone: the missing link between reproductive disorders and major obstetrical disorders? Hum Reprod, 25, 569-74.
Brosens, I. A., P. De Sutter, T. Hamerlynck, L. Imeraj, Z. Yao, B. Cloke, J. J. Brosens & M. Dhont (2007) Endometriosis is associated with a decreased risk of pre-eclampsia. Hum Reprod, 22, 1725-9.
Garry, R. (1997) Laparoscopic excision of endometriosis: the treatment of choice? British Journal of Obstetrics & Gynaecology, 104, 513-515.
Kaloo, P. D., M. J. Cooper & G. Reid (2006) A prospective multi-centre study of major complications experienced during excisional laparoscopic surgery for endometriosis. Eur.J Obstet Gynecol Reprod.Biol., 124, 98-100.
Marcoux, S., R. Maheux & S. Berube (1997) Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis New England Journal of Medicine, 337, 217-222.
Redwine, D. B. (1991) Conservative laparoscopic excision of endometriosis by sharp dissection: life table analysis of reoperation and persistent or recurrent disease. Fertility & Sterility, 56, 628-634.
Sasson, I. E. & H. S. Taylor (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci, 1127, 106-15.