Q&A on adenomyosis

Adenomyosis is commonly considered a disease with an older age of symptom onset than endometriosis, and which typically affects women aged 30 and above, especially those who have already been pregnant.

What is adenomyosis?
Adenomyosis refers to glandular tissue within the muscle wall of the uterus where it doesn't belong. The glandular tissue resembles the glandular tissue lining the endometrium (the uterine cavity). We don't know what the glands secrete, but presumably the secretions are irritative similar to the secretions of glands in endometriosis. Adenomyosis can be diffuse, like termites in a wall, or it can be found in a more discrete nodule called an adenomyoma. This is shown on the attached photomicrograph. The Latin plural of adenomyoma is adenomyomata.

Figure 1. Diffuse adenomyoma of the posterior uterine wall.

What are the symptoms of adenomyosis?
Since adenomyosis is a disease process involving the muscular wall of the uterus, the main symptom of adenomyosis is uterine cramping, especially with the menstrual flow. Some women with adenomyosis may have cramping all month long, although still aggravated during menses. When the uterus hurts, it can radiate pain to the lower back, up to the belly-button and down the front of the legs. On pelvic exam, the uterus may be tender to palpation, especially when the symptoms of adenomyosis are severe. If palpation of the uterus reproduces some component of a woman's pelvic pain, then this points a finger at the uterus as the source of at least some of the pain and adenomyosis would be a main contender. Since the uterus gets hit during intercourse, some women with adenomyosis can have painful intercourse due to adenomyosis. A tender uterus involved by adenomyosis also gets rearranged with filling or emptying of the bladder or rectum, so painful urination and painful bowel movements can be symptoms of adenomyosis. Thus, adenomyosis shares several of the same symptoms with endometriosis and this can confuse the clinical diagnosis. One of the features of adenomyosis that differs from endometriosis is that adenomyosis can sometimes be a cause of irregular or heavy menstrual flows. Endometriosis would rarely cause derangement of the menstrual flow.

Why do you think the symptom onset in adenomyosis is later than in endometriosis and is this always the case?
Since uterine cramping is the classic symptom of adenomyosis, and since many women with endometriosis may have pain with the menstrual flow even in early teenage years, there is overlap of this symptom of adenomyosis with endometriosis which makes it difficult to know exactly when adenomyosis might start to develop. On the other hand, it is clear that endometriosis can be diagnosed by laparoscopy in early teens (or even the fetus by Signorile's work), while the diagnosis of adenomyosis by MRI (the earliest way to diagnose the disease without doing a hysterectomy) would be uncommon before the age of 20 and becomes more common thereafter. So there is some evidence that adenomyosis does become manifest later in life than endometriosis, but is that simply because very early (and therefore very tiny) adenomyosis can't be seen on a scan because it's too small? Although adenomyosis is typically diagnosed later in life than is endometriosis, this does not necessarily mean it begins later in life than does endometriosis. Since adenomyosis most commonly requires hysterectomy for its diagnosis, this requirement means the diagnosis will commonly be delayed by two things: 1. until childbearing is completed; 2. after all conservative surgical or medical forms of treatment have been unsuccessful. And since the symptoms of adenomyosis are somewhat similar to endometriosis, are some of the symptoms of adenomyosis overshadowed by the symptoms of endometriosis which gets more attention because it is easier to diagnose?

Should adenomyosis still be considered as a possible source of pain in younger patients presenting with uterine pain, including teenagers?
Yes, although there is little that can typically be done because teens have not usually completed their childbearing and may not have exhausted all forms of conservative treatment.

Do you think the association between adenomyosis and previous pregnancy/later age of symptom onset is accurate or rather a function of sampling bias (i.e. women who are older and who have completed their families are more likely to opt for a hysterectomy and therefore receive a biopsy-confirmed diagnosis)?
I favor sampling bias. One thing I was taught in medical school and specialty training was that adenomyosis is more common in women who have had kids, but since the diagnosis usually requires hysterectomy, that will push the diagnosis into the older age groups.

What in your view is the cause of adenomyosis? Is adenomyosis developmental in origin or could it also plausibly be an acquired condition, such as in the case of symptom onset following pregnancy?
I think adenomyosis is developmental, in the same way endometriosis appears to be developmental. In fact, Mülleriosis, the single best-fit model of origin of endometriosis, is actually an overarching concept that can include adenomyosis as a cousin of endometriosis (see Mülleriosis: The best-fit theory of the origin of endometriosis).

Do you think the host tissue (uterine muscle) and site of disease could have anything to do with the later onset of pain compared to endometriosis?
That is a good question. Endometriosis begins on the peritoneum, which is very thin and has a reasonably good nerve supply. Adenomyosis begins within the uterine muscle near the endometrium, the uterine lining. The uterine muscle is thicker but also has nerves. So one might think that a glandular disease like endometriosis secreting some irritative substance onto the peritoneum might cause pain earlier than tiny glands beginning to form within the muscular wall of the uterus. But then we get back to the earlier questions above - does adenomyosis begin at the same time as endometriosis, cause similar symptoms, but is more difficult to diagnose and so gives the appearance of becoming symptomatic later?

Does adenomyosis likely compromise fertility?
Adenomyosis has been linked to infertility in baboons, so it may compromise fertility in humans. Some women with adenomyosis and infertility may conceive if the bulk of their adenomyosis is removed.

In the management of adenomyosis hormone therapies or hysterectomy are often offered. Obviously, not all patients with debilitating symptoms will be ready to opt for removal of the uterus and hormone therapies are not well tolerated by many and not suitable for those trying to conceive. Are there other surgical treatments available for the management of symptomatic adenomyosis?
There are several conservative procedures which can be performed in an effort to retain the uterus and to reduce the pain associated with adenomyosis. An isolated adenomyoma can be removed surgically, similar to how a fibroid tumor is removed. The main difference between removing an adenomyoma compared to a fibroid is that the fibroid peels out easily, like a marble being peeled out of gelatin. An adenomyoma is not so well-demarcated and can invade the surrounding muscle so it is more difficult to remove because the tendrils of tissue mix into the surrounding muscle tissue. One problem with removing an adenomyoma is that there frequently may be more diffuse adenomyosis present elsewhere in the uterus, and that residual disease may cause continuing symptoms. To surmount this problem, Osada developed a procedure for removal of more uterine tissue throughout the uterus. This is done at laparotomy and further information about this procedure, including surgical footage and a patient interview, can be viewed at www.infertile.com. Another procedure which may be of some benefit is a presacral neurectomy (PSN) in which the nerves carrying the sensation of uterine cramping out of the uterus are cut. This is a simple procedure which can be done laparoscopically. While its efficacy has been shown by a randomized controlled trial, it works less well in women who have adenomyosis as the cause of their uterine pain. The reason this is known is that if a PSN is unsuccessful in relieving uterine pain, and if the patient undergoes a hysterectomy later, there is a high prevalence of adenomyosis in the uterus when looked at under the microscope. One possible reason PSN may fail is that the uterus involved by adenomyosis may also be releasing inflammatory chemicals. These chemicals can irritate the pelvic and abdominal cavities resulting in IBS-type symptoms, as well as be carried throughout the body where more widespread symptoms might occur such as fatigue, low-grade fever, and aches and pains of the muscles and joints.

To what extent are adenomyosis and endometriosis related? At what rate did they co-occur in your series of patients? Is there a specific link between adenomyosis and invasive endometriosis?
Adenomyosis and endometriosis are both related to aberrant differentiation and migration of the Müllerian ducts. The Müllerian ducts are the fetal anlage of the internal female genital organs. A problem of differentiation and migration of the Müllerian ducts during embryonic formation could be the cause of both disease. It is difficult to know what the rate of co-occurrence is because most of the patients I operated on for endometriosis did not want a hysterectomy, so I had no way to know the true incidence of adenomyosis in women with endometriosis. In women who didn't respond to conservative surgery and in whom a hysterectomy was eventually done, adenomyosis was probably present in over 50% of cases. There may be a link between extensive endometriosis and extensive adenomyosis, because I encountered that combination every so often. In fact, deep invasive endometriosis used to be called adenomyoma because invasive endometriosis resembles adenomyosis when looked at under the microscope.

Are adenomyosis and endometriosis essentially the same condition only with a different location of disease or are they also histologically and morphologically different?
This question is truly Zen-like. I think they are so closely related that they could be considered identical other than location. This is especially apparent when invasive endometriosis and severe adenomyosis are considered. Invasive endometriosis and severe adenomyosis look virtually identical under the microscope and both can appear similar to the naked eye.

When a woman undergoes a hysterectomy for suspected adenomyosis yet her post-operative biopsies are negative for disease, what would be the likely explanation?
Even a 'normal' uterus can cause pain for reasons we don't fully understand, in which cases all biopsies would be negative for adenomyosis even though the patient displayed classic symptoms. Also, if a biopsy of the outer or inner surface of the uterus is obtained in an effort to diagnose adenomyosis, the biopsy may miss disease hidden somewhere within the muscular wall of the uterus. If there is an obvious bulge of the uterus or hemorrhagic discoloration of its surface, the biopsy may return with adenomyosis. But in many cases of adenomyosis, the surface of the uterus looks normal and the biopsy may be too shallow to have a chance of returning with a correct diagnosis. When the uterus has been removed, the pathologist has a lot of tissue to work with. The normal procedure is for the pathologist to take many samples of the entire thickness of the uterine wall from several areas of the uterus, as well as samples from obvious lumps, bumps, or discolored areas. These areas are inspected under the microscope for the presence of adenomyosis. If they are negative, the surgeon may sometimes request that even more tissue be removed from the uterus for further microscopic study. These steps greatly reduce the chance that adenomyosis would be missed.

Is the muscular layer of the walls of the uterus uniformly susceptible to developing adenomyosis or does the disease tend to be located in a specific portion of the muscle? If so, why might this be?
The posterior wall of the uterus is more commonly involved, so the distribution of adenomyosis is not random. Involvement of the posterior wall would be explained by problems of differentiation and migration of the Müllerian ducts down and across the posterior pelvis, laying down endometriosis most commonly in the cul-de-sac and adenomyosis most commonly right next door in the posterior cervix. Cuthbert Lockyer illustrated this in a publication almost a century ago:

Figure 2. Adenomyoma (adenomyosis and invasive endometriosis) of the recto-vaginal space. Microscopic view of the sagittal section.

This is a drawing of a surgical specimen - the uterus has been removed along with a segment of bowel attached to it. The specimen has been cut in half and represents what is called a sagittal section. In this drawing, we can see the uterus as the white organ to the left and the rectum as the hollow structure on the right. Between the uterus and rectum is an area of deeply invasive endometriosis which has resulted in complete obliteration of the cul-de-sac. The rectum is involved by a rectal nodule which is shown as a somewhat round white tumor. Notice that tendrils of tissue extend from the endometriosis into the posterior cervix and up the posterior wall of the uterus. This represents adenomyosis of the posterior uterine wall. Notice also that Lockyer was using the term du jour - adenomyoma - for what many surgeons would now call deep invasive endometriosis.

What is the difference between focal adenomyosis (adenomyoma) and diffuse adenomyosis? Which variant is more common? Are these two variants treated in the same way?
Focal adenomyosis or adenomyoma is less common than diffuse adenomyosis. The two types of adenomyosis are illustrated above. Focal adenomyomas can be removed surgically as previously discussed. Diffuse adenomyosis may be removed by the Osada procedure or by hysterectomy. There is no medicine that eradicates adenomyosis, although suppression of estrogen production by the ovaries may reduce symptoms while the patient is on the medicine.

Why is adenomyosis often not detected by an ultrasound or mri?
For something to show up on a scan, it has to have either a sufficient volume or sufficient difference in density from surrounding tissue. The smaller something is, the less likely a scan will detect it. Scans have difficulty detecting things smaller than about 0.5 cm. The density of a disease compared to the surrounding tissue is also important. For example, a small marble suspended in lemon gelatin will show up better than a small bit of raspberry gelatin suspended in lemon gelatin.

Should physicians withhold the option of hysterectomy to younger patients with uterine pain?
If all conservative medical and surgical treatments have been tried, or explained and rejected, then in my opinion there is no reason to withhold the option of hysterectomy from a woman of any age whose life is made miserable by suspected uterine symptoms, whether due to adenomyosis or something else. The youngest patient I performed hysterectomy on was 21. In America it is against federal law to discriminate on the basis of age.

Is there, in your opinion and experience, such a thing as "too young to have a hysterectomy"?
Saying someone is "too young" for a hysterectomy is patronizing, limits the therapeutic options available to the patient, and reduces the patient to a child. Physicians do not need to assume the in loco parentis role when dealing with their patients. The main role of the uterus is to maintain a pregnancy. Women who have had a hysterectomy but who still have at least one ovary can still donate an egg which can be fertilized with their partner's sperm and the resulting pregnancy carried by a surrogate mother. The availability of advanced reproductive technology has mitigated the effects of hysterectomy and therefore reduced the concern that a patient is "too young".

Is there a role for GnRH agonists, such as lupron, in the management of symptomatic adenomyosis?
Lupron has been shown to reduce symptoms of adenomyosis and reduce the size of the uterus a bit if it is enlarged by adenomyosis. When the medicine is stopped, the uterus can regain its normal size and symptomatology very quickly. It can be a very expensive and very symptomatic waste of time.

With regard to hysterectomy as a definitive treatment of adenomyosis, does a hysterectomy have any adverse effects on sexual pleasure and the ability to have intercourse?
Studies have shown that after hysterectomy, women have more frequent intercourse, more enjoyable intercourse, more frequent orgasm, and more pleasurable orgasm. This is because hysterectomy is done primarily for uterine symptoms such as pain or bleeding. These symptoms have typically been vexing the patient for months or years, interfering with daily life as well as sexual life. When the cause of these problems is removed, patients improve in all aspects. Women can be multi-orgasmic after hysterectomy. If, prior to hysterectomy, a woman had pleasurable sensations of uterine contraction with orgasm, then that sensation will be gone. However, many women report painful uterine contractions with orgasm, so the presence of the uterus is a liability for such patients. There are many other abdominal and pelvic muscles than the uterus involved in orgasm, as well as sympathetic discharge, so female orgasm does not necessarily have to be uterocentric.

Is there any rationale for performing a supracervical hysterectomy in these patients (leaving the cervix behind)?
Studies have shown that for whatever reason supracervical hysterectomy is done, it has no advantage over complete hysterectomy (where the entire uterus including the cervix are removed) in regards to pelvic support or female sexual function. The retained cervix can cause problems and may need to be removed later. I had to remove many retained cervices over the years for pain, persistent endometriosis, scar tissue, and bowel obstruction related to adhesions binding the bowel to the cervix.

What are the possible short- and long-term complications of hysterectomy?
Hysterectomy refers to removal of the uterus. The ovaries are not removed when only a hysterectomy is done. When the proper patient is selected on the basis of symptoms and receives the proper surgical treatment, there are no short- or long-term adverse effects of hysterectomy unless there is a surgical complication. Surgical complications are possible with any surgery and fall into three main categories: bleeding, infection, and damage to other organs. Bleeding is a part of any surgery and surgeons know how to control bleeding during surgery. Post-op bleeding is fortunately rare and may stop on its own or require reoperation to stop it. Most post-op bleeding occurs within the first day or two after surgery, although I had one patient who had a significant post-op bleed two weeks after a hysterectomy. Infection is also rare. Bacteria like warm, dark, moist places and grow well in blood. I would always leave a drain in after a hysterectomy to drain out any bloody fluid and this greatly reduced the risk of infection. My infection rate among hysterectomy patients was less than 0.5%. Studies in older men with other diseases have found that pre-op antibiotics may reduce the surgical infection rate to 5%, so the federal government decided that they would give hospitals more money if all patients of any age or either sex received antibiotics before surgery. This has resulted in hospitals requiring all patients to receive antibiotics before surgery whether the surgeon thought antibiotics were indicated or not. A fourth category of complication could be said to be pain occurring after surgical healing has been completed. Such pain might be due to scar tissue, or to the persistence of a non-uterine cause of pain such as conditions involving the bowel, bladder, or musculoskeletal system.

What is the best surgical strategy when performing hysterectomy in women with suspected adenomyosis with and without concurrent endometriosis?
The best surgical strategy for performing hysterectomy in any patient with uterine symptoms is to do it in a way which minimizes post-op pain, hospital stay, and subsequent recovery as well as enhancing cosmetic appearance of the abdominal wall. This means laparoscopic hysterectomy is preferred over hysterectomy performed by laparotomy. Robotic hysterectomy has been shown to be no better in outcome than non-robotic hysterectomy, although robotic hysterectomy takes longer, uses more incisions which are larger and more obvious, and adds expense. If there is no endometriosis in the pelvis and if the patient has only uterine symptoms, then removal of the uterus is sufficient. Removal of the uterus does not make endometriosis go away since endometriosis rarely involves the uterus. Therefore, hysterectomy is not rational treatment for endometriosis. Hysterectomy should be done for uterine symptoms which are interfering with the patient's life. If endometriosis is present, it should always be removed by excision when hysterectomy is done. Otherwise, the patient will be left with a disease which is known to be a common cause of pelvic pain and may require surgery later. It usually is not necessary to remove the ovaries when performing a hysterectomy in a woman with endometriosis, so post-op hormone therapy can be avoided for most (until their ovaries begin to drop in function later in life).

Questions by Libby Hopton and answers by Dr. David Redwine