Adenomyosis

I have no qualms about insisting that most of the information the general public will “google” about Adenomyosis, is outdated, obviously written with information extracted from literature searches alone and little from experience gained at the coal face.  That is not to say that other doctors have not got an interest in adenomyosis and its  diagnosis! But I am particularly interested in it. 

I recently read a “Literature Review” on Adenomyosis – the type of article a young inspiring gynaecologist might go to when preparing for his/her specialist exam. Adenomyosis is still quoted as “only diagnosed at hysterectomy and rare in young women” – Read, less than 25! Case reports of Adolescent Adenomyosis are few in number, with authors profoundly stating that their collection of 1, 2 or 3 cases, written up often in prestigious medical journals , is something rare and startling. This really bothers me because I personally have over 35 young women of my own, aged 19 or less (youngest 13) with MRI proven adenomyosis.  

Perhaps I should not be too critical, when my data is as yet unpublished. I became particularly interested in adenomyosis in teenagers, when I read an article in the Australian & New Zealand Journal of Obstetrics and Gynaecology (Ref 2011, 51; 280-283, by Kelton Tremellen & Peter Russell). What caught my eye was an image very similar to the image (left).

The laparoscopic image in the journal showed what I had been personally observing for some years – an instrument pushed gently against the posterior surface of a uterus.  In this particular photo, the uterus is indeed “bulky” as was quite correctly been taught to me as a registrar in Australia in the early 1980’s.

However, if one presumes that at every laparoscopy undertaken with the intent of diagnosing and treating Endometriosis, that one is also looking for Adenomyosis, there are several “other findings that increase my suspicion of Adenomyosis (other than the soft looking uterus)(.24 )

 This uterus, from a patient with no endometriosis, shows what I call ‘bumpiness’.

I have trade marked the sign Tronc’s Tubal Sign (TTSTM)to describe what is depicted in this image – a bulky uterus, where the tubes take on a whiteish appearance where they join the uterus. It is a strong indication of adenomyosis.

Longitudinal grooves seen at the fundus, at hysteroscopy, are called lacunae by the radiologists and are another moderately strong sign that adenomyosis will be found. 

Firstly, my choice of scanning techniques for the confirmation of Adenomyosis is the MRI scan, not the ultrasound scan (USS).  That is not to say that an USS is totally useless.  For example, if a patient presents not having a laparoscopy yet, but does have a scan report, suggesting “heterogeneity” of the myometrium, this will suffice, at least, in making the diagnosis of Adenomyosis. However, there is no Medicare rebate for an MRI when looking for adenomyosis. But there is a rebate for an ultrasound scan.

Generally speaking, however, I would not recommend the “generalist suburban scanner” which perhaps less experience with Adenomyosis to perform an ultrasound scan to confirm the diagnosis. 

Reports from tertiary, high quality scanning centres using a good machine and reported on by an experienced gynaecological scanner (preferably a scanner who is also a gynaecologist) are, however, useful at least, to make the diagnosis.

Unless the radiologist is experienced in the diagnosis of early adenomyosis, an ultrasound scan may not give me the quality report I need to properly treat my patient. Here, knowledge is certainly power. 

In 80% of cases with histological Adenomyosis (hysterectomy specimens), the junctional zone can be seen to be enlarged or thickened.  

 The Junctional Zone is the junction between the Endometrium (the bit that builds up and sheds cyclically) and the Myometrium (the muscle that contracts with periods and in labour).

 The French pioneered the measurement of the junctional zone for use in infertility 

(Maubon A, Faury A, Kapella M et al. Uterine junctional zone at magnetic resonance imaging: a predictor of in vitro fertilization implantation failure. J Obstet Gynaecol Res 2010; 36 (3); 611-618

In order to get the most accurate diagnosis of Adenomyosis, I ask my patients to try to have the test performed in the “late proliferative” phase.  I tell them that is usually on days 10 to 13 of a 28 day cycle).  If someone is on the OCP (Oral Contraceptive Pill), it seems not to matter when it is done.  Similarly, if I have recently operated on the patient, I try to leave the test a month or so, so that any minor surgical disruption of the endometrium does not interfere with the image quality obtained at MRI or USS.

 In my practice I do see many patients for second opinions, who already have a Mirena device in, and that does not preclude me ordering an MRI.  In fact, patients often present with ongoing bleeding (with a Mirena device in) simply because there was a failure to diagnose the Adenomyosis in the first place.  What I mean by that is that the Mirena was put in to treat a condition that had not actually been diagnosed and thus the hormone in one Mirena is not enough to stop menstruation. Only by stopping menstruation will adenomyosis be supressed, and pain begin to be controlled.

A Normal uterus the junctional zone is less than 5mm (as measured on MRI scan).

Diagnosis is unclear when the junctional zone measures between 6 and 12mm.  This could, perhaps represent developing adenomyosis not yet reaching diagnostic criteria.

Proven adenomyosis has a junctional zone of more than 12mm.

Personally, I tell my patients who have laparoscopic signs suggestive of developing adenomyosis (6-12mm group), that we should repeat the test in 12 months, meanwhile treating their symptoms  eg. a mirena and the pill.

Another important clue to the diagnosis of adenomyosis, especially in the younger (smaller) uterus, is the ratio of the junctional zone to the myometrium.

In normal (no Adenomyosis) women this ratio is less than .4 (40%).  Greater than 40% is usually, but not always, also found where the junctional zone thickness is more than 12mm.  However, in teenage patients with Adenomyosis (I have found over 35 in my practice in 10 years) and the number increases every year 

Because the uterus is not yet matured, if their junctional zone is in the 5 to 12mm range (strictly not diagnostic), but the ratio of the junctional zone to the myometrium is greater than 40% (in a small uterus), I treat them “as if” they have Adenomyosis.  This is not forgetting that the patient has presented with the symptoms of Endometriosis and this is especially pertinent if, after my very diligent look at all peritoneal surfaces for early bubble type endometriosis, none is found.  This is particularly important in a teenager where symptoms of endometriosis have led to a laparoscopy, but as above stated, no endometriosis was found. What I am getting at here, is something must be causing their symptoms, and it is usually adenomyosis.

At the Wesley Hospital in Brisbane, Australia, where I work, I was some years ago, ordering MRI and receiving reports, which I personally described as “radiology speak”.  By that I mean a fairly long description full of radiological terms and measurements and descriptions only radiologists could interpret.  (I exaggerate slightly here).

 So, to try and simplify the reporting I met with three of the Radiologists from the Wesley Hospital who had shown interest in Adenomyosis and together we sat down to discuss the drawing up of a table.  I showed them many of my laparoscopic findings indicating what I was looking for from an MRI report by way of pictures and came up with the table below.

The table has saved me an enormous amount of time in reading reports fully.  I glance down the table and look specifically at whether the junctional zone is more than 12mm and whether there is an associated increase in the percentage thickness of the junctional zone amongst other features.

So, what does it mean when the Junctional Zone is thickened?  Well, it may not mean anything other than the patient has Adenomyosis.  Not all patients with Adenomyosis will find it impossible to achieve a pregnancy. 

However, in the junctional zone there are spiral arteries.  In Adenomyosis, these arteries have been well documented by Brosens of Belgium. These arteries which supply the endometrium and hence the embryo and later the developing foetus, can be constricted.  The worse the Adenomyosis, the worse the constriction of these vessels.  

This is of major importance in female subfertility and is thought to contribute to either/or some of;

• Not getting pregnant at all

• Recurrent miscarriages – note of course, there are other causes for miscarriage.

• Small for gestational age babies (their growth is restricted) because of the suboptimal blood supply.

• Premature rupture of the membranes and therefore premature labour.

• (Possibly) pregnancy induced hypertension.

 What can be done about the Constricted Spiral Arteries, secondary to Adenomyosis and severe Endometriosis when a woman wishes to conceive?

Luckily, because the Endometrium is oestrogen sensitive, by switching off/or blocking oestrogen receptors, the narrowing of the spinal arteries is reversible (at least long enough for conception to occur).

The Role of Macrophages

I often describe Macrophages (large cells of the immune system) as like “pac-man” scavenger cells. Macrophages are part of the cellular immune system that circulate in the body, mopping up and engulfing foreign particles, bacteria and unwanted cells.  Put simply, in Adenomyosis there is an increased number of foreign cells in the muscle (myometrium) of the uterus, and they should not be there.  These cells are of course, the endometrial cells that have invaded the muscle. Macrophages respond to try to get rid of the muscle of these Endometrial like cells.

However, when other foreign cells, like a very small embryo is trying to embed itself into the endometrium, these “other” foreign cells, (being foreign because they are 50% derived from the father) are in effect consumed when excess macrophages are present.  This is of course a simplistic view of the whole process.

We, as Endometriosis Specialists, Obstetricians and IVF Doctors, and I am all 3, try to counter that immune response by adding in Prednisolone 15mg a day in the morning from day 7 of the natural cycle or day 7 of the IVF treatment cycle.  I continue this Prednisolone until 15 weeks’ gestation if the patient conceives.

Before pregnancy occurs, I have my patients taking Vit E 1000 i/u a day, and I also check their Vit D, which is often low and I also give them Vit C if their Vit C is low.  Vitamin C is important for maintaining the integrity of the blood vessels where Vitamin E is important for keeping the blood vessels open.

Personally, I also use progesterone pessaries or a progesterone gel delivered to the vagina twice a day from the time of ovulation until 12 weeks in that group of patients who is known to have had adenomyosis.  I keep this going until the patient is 12 weeks pregnant.  Similarly, I use aspirin (baby aspirin) from conception until 20 weeks of pregnancy.  Again, this ensures adequate placentation (invasion of the placenta into the uterus) and allows normal growth of the baby and decreases the risks of pregnancy induced hypertension.

Many of my obstetric patients have had adenomyosis.  It is my practice to advise my patients to consider booking in for the placement of a Mirena device at about 12 weeks post-delivery.  Why do I choose 12 weeks?  Firstly, the uterus is smaller by then.  (We don’t want them coming out).  Secondly, the uterus is firmer by then and this avoids the possibility of perforation at insertion.  Thirdly, unless they have elected not to breastfeed, they still have not had a period by this stage.  No period means no bleeding into the Adenomyosis itself, and no retrograde menstruation either. Here  we are trying to suppress whatever caused their pain, period problems, painful intercourse and painful bowel motions, namely adenomyosis and endometriosis. 

I personally, almost always, insist that the Mirena is placed under a brief general anaesthetic in a hospital (Wesley Hospital in Brisbane) in my case.    The cavity of the uterus is inspected at the same time, and there is an opportunity to remove any residual placental tissue or membranes that may still be present.  It often surprises me that even at 4 months there is still some placental tissue present when the placenta had been apparently removed intact and completely.  But most importantly, I can check the Mirena is correctly placed by using the hysteroscope after they had been placed as well.

 Adenomyosis in a woman who has definitely finished having children

What do we do here?  The literature about Adenomyosis still abounds with the “treatment is (read must be) hysterectomy”.  

However, there are other options:

 Firstly, if the adenomyosis is not too severe, I will often suggest drug treatment ie. a Mirena.  This often suits the woman who does not want to have a hysterectomy. 

A good alternative treatment, in a woman who is either not desirous of children or has finished her family, is to perform a Hysteroscopic Endometrial Resection (described in detail elsewhere) with the placement of a Mirena, depending on the severity of the disease, but in combination with a laparoscopic resection of any pelvic endometriosis not previously diagnosed or considered.  Note I say resection here NOT ablation, which gives suboptimal results. 

When I first started performing hysteroscopic endometrial resections in England in 1989, we did not routinely combine this with a laparoscopy.  I think this was a mistake, because if the endometrium is removed from the uterus, the ovaries still produce oestrogen, instead of acting on the target tissue of Endometrium it acts fully on any pelvic endometriosis,  thus making the pelvic endometriosis worse.  Hence it is important to laparoscopically remove any visible endometriosis at the time.

Of course, some of my patients do ask me, after being offered the alternatives, if I would still do a hysterectomy and the answer, of course, is Yes!  They want to be 100% certain of never having a period again.  Such is the demon that Adenomyosis is!

Having looked at Endometriosis sufferers for three decades, I am convinced that stress has an impact on the two diseases.

Part of my history has always involved the question of whether or not they have recently suffered such diseases as glandular fever, Ross River Virus (common in my region); or have had recent stressors such as break ups, marriage break ups, financial troubles, the loss of a loved one or pet, or some other calamitous event in their life (eg.  I had a patient whose house burnt down who suffered a flare up of her endometriosis shortly afterwards).

Indeed, to make matters worse, women and teenagers with diagnosed Endometriosis and Adenomyosis report the endometriosis symptoms themselves cause a high level of stress.  Work stress, martial relationship problems and infertility, all combine to increase the stress levels in Endometriosis sufferers. 

The following paragraphs are quoted from a reproductive scientist’s article (Aug 2012).

Stress stimulates the hypothalamus to manufacture and release CRF (corticotrophin-releasing factor) , causing the pituitary gland to produce and release corticosteroids (primarily cortisol in humans and corticosterone in rodents) into the body. In addition to its effects on the brain, cortisol/corticosterone also affects the immune system. Acute stressors are associated with an upregulation of the immune system, while prolonged increase in cortisol levels has been shown to depress immunologic function. The physiological mechanisms activated by stress are likely an adaptation to help cope with the threat at hand; the transformation of these stress responses into physiological illness depends upon the severity and persistence of the stress response.

It is now widely accepted that stressful life events can impact the health of an individual, including immunological health. Endometriosis is associated with increased secretion of proinflammatory cytokines and impaired function of cell-mediated natural immunity. This network of locally produced cytokines modulates the growth of ectopic endometrial implants, and involvement of these inflammatory mechanisms has been demonstrated previously in the rat model. In humans, ectopic endometrial tissue is surrounded by abundant fibrotic tissue and inflammatory infiltrate, including mast cells, but the triggering factors for these processes are not yet understood. These infiltrating mast cells exhibit degranulation and scattered granules, suggesting that an abnormal immune response, specifically a hypersensitivity reaction, is strongly related to endometriosis. Anaf et al demonstrated that in deeply infiltrating endometriosis lesions (the most painful type), there was an increase in both activated and degranulating mast cells, and a close histological relationship with nerves possibly contributing to the associated pain.  Specific nerve fibers have been found in endometriotic tissues.

In addition, there is ample evidence from qualitative and quantitative studies that document the significant negative impact on quality of life in patients with endometriosis. Taken together, data from both animal models and human studies strongly suggest that stress does play a role in endometriosis. Whether stress is a causal or exacerbating factor in disease is still unknown. Our data support this hypothesis and provide evidence for the role of neuroinflammatory mechanisms in this disease. 

The importance of future research in this area to lead to a better understanding of this disease and the importance of the “brain–body–brain cross talk.”