Endometriosis is normal endometrial glands and stroma found outside the uterus. Adenomyosis is normal endometrial glands and stroma found embedded deep inside the myometrium of the uterus.
AdenoMYOsis is in the MYOmetrium
First a few definitions (because I had no idea what these words meant before I looked them up) …
Parenchyma refers to the functional tissue of an organ. Stroma is all the other tissue in the organ including connective tissue, blood vessels, nerves etc.
The endometrium lines the inside of the uterus and is comprised of 3 layers. There is a single top layer of columnar epithelial cells which is usually ignored by everyone and lumped in with the layer underneath. This layer underneath is the functionalis layer and is the one which is sloughed during menstruation. It is made up of stroma and traversed by uterine glands. The layer beneath (the one in contact with the myometrium) is the basalis layer from which the functionalis is regenerated each cycle. The uterine glands run from the bottom of the basalis up through to the surface. Blood supply comes through the myometrium up through the basalis and into the functionalis supplying the tissue and glands.
Endometriosis is the condition where some endometrial tissue (stroma and glands) is found outside the uterus. Adenomyosis is the same idea except the location of the diseased tissue is deep inside the myometrium. Adenomyosis was formerly called endometriosis interna. Both endometriosis and adenomyosis can present with chronic pelvic pain, dysmenorrhea (pelvic pain during menstruation i.e. cyclic pain), vaginal bleeding (chronic or heavy menstrual bleeding i.e. menorrhagia), and dyspareunia (pain during intercourse). With either condition it is very common to be asymptomatic. Only a third of women with adenomyosis are symptomatic. It’s difficult to make an estimate in endometriosis, but it’s likely a similar rate. One important thing to note is that in both conditions, the tissue that wanders off can behave differently than expected in terms of immune response, prostaglandin production, etc. It may be that all of the woman’s endometrial tissue behaves differently, but the impact is especially problematic because the disease tissue is in the wrong spot.
The reason these two have been broken into separate conditions is due in large part to the epidemiology. Endometriosis is often found in younger women whereas adenomyosis usually develops in the 40’s and 50’s. Having babies is a risk factor for adenomyosis whereas infertility can be a presenting symptom in endometriosis.
In women with pelvic pain, 40-50% are eventually found to have endometriosis. In infertile women, 20-50% have endometriosis. The etiology remains unclear. There appears to be a genetic component as the condition can run in families, although simple Mendelian inheritance doesn’t explain it. Early menarche, short menstrual cycles (i.e. cycling more frequently), menorrhagia, anatomic variants which obstruct reproductive tract outflow, delayed childbearing, having few children, or even exposure to dioxins may all increase risk. How the tissue gets into the wrong place is debatable. Lymphatic spread, errors during embryogenesis, metaplasia (transformation of one tissue type into another), or retrograde menstruation have been proposed. Many theories involve the idea that viable endometrial tissue is sloughed during menstruation and somehow migrates towards more dependent portions of the pelvis (ovaries, rectouterine pouch, etc.) and attaches there rather than passing out normally. This is reasonable given that even after surgical tissue resection, endometriosis can recur. It’s also supported by the fact that women with impeded outflow tracts are at higher risk since this would increase incidence of retrograde menstruation.
Pelvic pain or vaginal bleeding are the most common presenting complaints (also infertility). Depending on the area of involvement there could also be dyschezia or hematochezia (pain/bleeding with defacation), dysuria/hematuria (pain/bleeding with urination), etc. Note that these symptoms may be cyclic and reflect the menstrual cycle. The most common sites of involvement are ovaries, rectouterine pouch (Pouch of Douglas) and uterine ligaments (broad, utero-sacral, etc.). Wandering tissue can even turn up on surgical scars (e.g. C-section scars). There are women that bleed out of their old surgery scars each month!
Pain and bleeding can be the result of the tissue responding to circulating hormones and following the normal menstrual cycle. For example, improperly located endometrial tissue in the rectouterine pouch may shed blood into the peritoneal cavity during menstruation. As blood is an irritant it will cause inflammation and pain. If the tissue is near a nerve there can be pain. If ligaments are affected there will be pain with movement of those tissues. Again, the tissue is not necessarily normal endometrial tissue so there may be chronic pain from abnormal prostaglandin release fueling chronic inflammation, etc. Some endometriotic tissues have even been found to express aromatase so they are capable of producing their own estrogen (estrogen thickens endometrial tissue). Systemic changes in the immune systems of symptomatic women have been noted too leading some to believe there is an auto-immune component to the disease. Related to all this is the observation that there is a lower rate of natural pregnancy success and even IVF success in women with endometriosis.
The gold standard of diagnosis is laparotomy. Imaging has been used increasingly, but actually opening things up and taking a look is the best. CA 125 (cancer antigen) is a serum biomarker that has been used with some success as well as it is elevated in endometriosis.
Treatment will be different depending on the complaint (pain/infertility/bleeding). Usual treatment involves NSAIDs which reduce prostaglandin production and inflammation, OCPs (oral contraceptive pills) to thin the endometrium and reduce menstrual flow (progestins), GnRH analogues for the same reason, and the weak androgen Danazol. Danazol supresses the midcycle LH surge thus preventing ovulation (and lowering estrogen production). It also occupies a binding site on SHBG (sex hormone binding globulin) which usually binds testosterone, thus free circulating levels of testosterone increase. The drop in estrogen and rise in testosterone thins the endometrium. Danazol has lots of bad side effects though, not the least of which is virilization (masculinization). Surgical intervention is also possible. Laprascopic surgery can identify extra-uterine endometrial tissue and remove it. Nerve tissue can be removed to reduce pain. Ovarian tissue can be removed leaving just enough behind to provide estrogen (90% of the ovary can be removed). Hysterectomy is an option, as is radical removal of uterus, salpinx and ovaries. Any combination of therapies can be used depending on the situation. Even after laparoscopy though, 30% of women were found to have progression of disease.
It turns out it’s rather difficult to find a lot of information on adenomyosis. I had to look in Williams Gynecology to get a decent overview (by the way I highly recommend Williams Obstetrics and Williams Gynecology for Ob/Gyn rotations). Anyhow, adenomyosis is the presence of endometrial glands and stroma deep within the myometrium. It can be diffuse or focal and the mechanism is widely thought to be downward invasion of the endometrium into the myometrium. It turns out that it’s fairly common to see superficial invasion of the myometrium by endometrial tissue, so adenomyosis is the unique condition where the tissue is deep into the myometrium. Since it’s the basalis layer doing the invasion, and the basalis doesn’t slough during periods, bleeding from the wayfaring tissue is minimal during menstruation. In some cases there is significant bleeding though and it’s thought to be a result of increased vascularization around the tissue. Pain is thought to come from increased prostaglandin production from the tissue which causes dyspareunia too.
Why the tissue decides to invade is a mystery. Since age and parity (having babies) are the most significant risk factors for adenomyosis (80% of cases occur in the 40s and 50s, 90% of cases are in parous women), the weakening of the uterus from multiple pregnancies, and the cumulative effects of progesterone and estrogen are thought to contribute to development of the disease. Hormone involvement is supported since apparently the condition regresses after menopause. Alternatively, pluripotent Mullerian remnants have been suggested as a cause for adenomyosis.
Diagnosis used to be on biopsy of hysterectomy samples, but lately there has been some effort in using MRI or ultrasound to make the diagnosis. The uterus can be enlarged (up to the size of a 12 week pregnant uterus). Medscape and Radiopedia have great articles on the subject.
Treatment is usually NSAIDs and certain types of OCPs which cause endometrial thinning and decrease prostaglandin production. Lesser used agents are danazol and GnRH agonists. Of course, hysterectomy is the definitive treatment.
Medscape’s chronic pelvic pain article
Medscape’s Endometriosis article
Wikipedia’s page on Endometriosis
Wikipedia’s page on Adenomyosis
SOGC Guidelines on Endometriosis
SOGC Guidelines on chronic pelvic pain
Williams Gynecology 2008 (my supervisor had the book on her desk)