Adenomyosis: Causes, Diagnosis and Therapy as well as Differentiation from Endometriosis
Adenomyosis: For a long time, this condition was considered a subtype of endometriosis. In adenomyosis, changes occur in the muscular layer of the uterus that cause pain and can lead to infertility or miscarriage. Similar to endometriosis, the causes of adenomyosis are not yet clear. Therefore, the disease cannot be prevented.
However, there are now several therapeutic approaches, both medicinal and surgical. Contrary to what was assumed for a long time, adenomyosis does not only affect women at the end of the reproductive phase or after menopause, but also younger women [1].
Definition: What is adenomyosis?
Adenomyosis is a gynecological disease that has long been considered a subtype of endometriosis. Adenomyosis is characterized by the invasion of endometrial-like tissue into the muscular layer of the uterus. The ingrowths consist of glands as well as stroma. In addition, there may be enlargement of the entire uterus. In addition, there may be disturbances in the junctional zone, which is located between the uterine muscle and the endometrium. Adenomyosis can be localized, as in fibroids, or diffuse throughout the muscle of the uterus. Finally, there is a mixed form in which both diffuse and localized ingrowths are present [2, 3].
To date, there are few reliable figures on how many women are affected by adenomyosis. The numbers vary between five and 70 percent. There are several reasons for this inaccuracy: Differentiating adenomyosis from endometriosis and, in some cases, from fibroids (benign growths) is not always easy. In addition, the figures are partly based on results of examinations after (partial) removal of the uterus. This is usually done at the end or after the reproductive phase and only when symptoms are very severe [4].
Adenomyosis and Endometriosis
A Comparison under the Microscope
Adenomyosis:
Endometriosis:
Symptoms: What symptoms does adenomyosis cause?
The leading symptom triggered by the ingrowths is chronic pain in the lower abdomen. In addition, some of those affected experience severe pain during menstruation or sexual intercourse, as well as bleeding disorders. In addition, women with adenomyosis increasingly experience so-called retrograde menstruation. This leads not only to bleeding into the abdomen during the period, but also to a more difficult path for the egg when the movement of the fallopian tubes favors its transport into the abdomen instead of the uterus [9]. As a result of adenomyosis, infertility as well as miscarriages also occur more frequently due to mucosal changes [5].
Nevertheless, women with adenomyosis can also become pregnant and, according to current research, around 30 percent of affected women are spared symptoms [6].
Differentiation: What are the similarities and differences between endometriosis and adenomyosis?
The name “endometriosis” is derived from “endometrium”, the technical term for the lining of the uterus. It results in the formation of so-called endometriosis foci, cell clusters that resemble the uterine lining, outside the uterus. The foci consist of glands, stromal cells and smooth muscle and are supplied by nerves, lymphatic and blood vessels [7].
The most common symptoms of endometriosis include chronic abdominal pain, which may increase, especially around menstruation. Bleeding disorders, pain during sexual intercourse, and an unfulfilled desire to have children are also among the symptoms. In addition, other symptoms may occur. However, the leading symptoms are almost identical to those caused by adenomyosis.
Due to the almost identical symptoms and insufficient diagnostic means, it was assumed for a long time that adenomyosis is a subtype of endometriosis. The following distinction was made according to the localization of the disease:
- If the endometriosis is located inside the uterus, it is called endometriosis genitalis interna, also known as adenomyosis.
- Localization outside the uterus, then it is called endometriosis genitalis externa.
- Localization outside the pelvis, then it is endometriosis extragenitalis.
Even if there are similarities between the two diseases, so many differences can be demonstrated today. These differences are particularly those at the molecular and epigenetic levels. And there are also differences in the risk factors that may favor the development of the two diseases. Therefore, adenomyosis is no longer considered a subtype of endometriosis. The term endometriosis genitalis interna has therefore been abandoned, but can still be found in some books or articles [8].
However, it is now known that up to 22 percent of affected women suffer from both endometriosis and adenomyosis. The extent to which the two diseases promote or trigger each other or have common causes has not yet been clarified [1].
Causes: How does adenomyosis develop?
What causes the development of adenomyosis has not yet been conclusively clarified. There are several explanations, which are presented below. In addition, some risk factors have been identified that are associated with the occurrence of adenomyosis.
One theory is that mucosal cells from the uterus migrate into the muscular layer of the uterus when the so-called junctional zone (intermediate layer between the endometrium and the muscular layer) is disturbed. This may be the case, for example, if it is injured by surgery or scraping (after abortions or miscarriages) [10].
According to another theory, degenerated tissue or stem cells in the muscle layer of the uterine wall lead to the development of adenomyosis [11].
A more recent theory is that strong contractions of the uterus cause minute tears in the layer between the mucosa and the muscle layer. The injury results in increased estrogen release and allows cell ingrowth into the muscle layer. Tissue-injury-and-repar (TIAR) is recognized, especially in adenomyosis, but like all other theories has not yet been definitively proven.
Risk factors that are considered responsible for the development of adenomyosis are:
- operations on the uterus
- multiple pregnancies
- advanced age
- early first menstruation (at age 10 or younger)
- short cycles (24 days or less)
- obesity [12]
Diagnosis: How can adenomyosis be diagnosed?
Strictly speaking, the diagnosis of adenomyosis can only be clearly established by histology, i.e. the examination of a tissue sample [9]. However, other non-invasive methods are now also used for diagnosis.
Non-invasive diagnostic procedures
- Sonography
When diagnosing by means of sonography, a distinction is made between conventional 2D ultrasound and the newer elastrography ultrasound, which is also called 3D ultrasound. Both ultrasound procedures are performed using a vaginal probe. In clinical practice, 2D ultrasound is usually used. Both methods are used to determine the thickness of certain areas as well as their structure. 3D ultrasound can additionally be used to determine the elasticity of tissue. Therefore, a combination of 2D and 3D ultrasound allows a better assessment of whether changes in the uterine muscles are adenomyosis [13]. According to the guideline program for the diagnosis and treatment of endometriosis (and adenomyosis), the suspected diagnosis of “adenomyosis” should first be clarified by ultrasound.
- Magnetic resonance imaging
Magnetic resonance imaging is also an imaging procedure. It has comparable results to sonography in terms of thickness and structure of the junctional zone. However, the results are more reproducible. According to the guideline program, magnetic resonance imaging is considered a second-line diagnostic procedure. However, if it is performed by an experienced radiologist, it is very well suited for the differentiation of fibroids as well as prior to surgical interventions in fertility patients (fertility patients).
Invasive procedures for diagnostics
- Hysteroscopy
Hysteroscopy is a mirror examination of the uterus. An endoscope is inserted into the uterus through the vagina, through which the inside of the uterus can be viewed. Adenomyosis cannot be directly visualized during this examination, as only the very top layer of the uterine lining is viewed. However, clues, such as severely dilated vessels, can be seen that indicate adenomyosis. In addition, tissue samples can be taken during a hysteroscopy for later examination. However, these tissue samples provide only limited conclusive results, as they are usually obtained too superficially.
- Laparoscopy
During laparoscopy, the endoscope is inserted into the abdomen through a small incision. Working instruments can be introduced into the abdominal cavity through a second small incision. In this way, tissue samples can be taken in a targeted manner. By means of laparoscopy, the position and size of the uterus can be easily estimated, which gives conclusions about the existence of adenomyosis, since the uterus may be enlarged in this case. However, adenomyosis is often difficult to localize externally during laparoscopy, making sampling difficult and almost never performed outside of therapeutic surgery.According to the guideline program, biopsies should not be used as part of the diagnosis of adenomyosis.
Therapy: How is adenomyosis treated?
Since the causes of the disease are not yet clear, it is not yet possible to treat and cure adenomyosis causally. However, there are several therapeutic approaches, both drug and non-drug. Which form of therapy is used depends on the specific individual case. In particular, the patient’s age and whether she wishes to have children are taken into account.
Drug therapy approaches for adenomyosis
Due to the proximity of adenomyosis to endometriosis, drug treatment concepts are often based on experience in the therapy of endometriosis. All drug treatments that can be used so far show their effect only as long as the treatment itself lasts. A significant proportion of women (the proportion varies greatly depending on the study) do not respond at all to the drug treatment approaches or continue to struggle with residual symptoms.
The main drug therapy concepts are:
- Hormonal treatment approaches
Different substances can be used as part of hormonal therapy. In addition to progestins, these include GnRH analogs, aromatase inhibitors, and levonorgestrel IUDs. Hormonal therapeutics can be administered in a variety of ways: The agents can be applied locally, such as by hormonal coil. Alternatively, they can be administered by injection into the subfatty tissue (subcutaneous) or into the muscle tissue (intramuscular). - Non-hormonal therapy approaches
Furthermore, based on experience in the treatment of endometriosis, non-steroidal anti-inflammatory drugs (= painkillers) are used, since pain is the main symptom in adenomyosis. - Integrative medicinal therapy approaches
According to the guideline program, treatment approaches from traditional Chinese medicine, especially the use of San Jie Zhen Tong capsules in particular, have not yet been found to have any clear positive effects.
Surgical treatment options for adenomyosis
The main surgical treatment options are:
- Hysterectomy
Hysterectomy is a hysterectomy or the removal of parts of the uterus. Despite the fact that in adenomyosis the ingrowths are found exclusively in the uterus, the pain associated with the condition cannot always be completely eliminated. Hysterectomy can lead to other complications and is not suitable for women who wish to have children. - Resection
Here, the parts of the uterus affected by adenomyosis are removed in one operation. The uterus as a whole organ remains intact. After the operation, individual recommendations usually apply to births, e.g. the performance of a planned caesarean section. - Embolization
During embolization or endometrial ablation, the growths are removed or cut off from the supply of nutrients through the blood vessels. These procedures are only suitable for women who have completed their pregnancy or do not wish to have children. According to the guideline program, these procedures should only be used in the context of studies.
Because of the prolonged occurrence of pain, women with adenomyosis should consider multimodal pain management to additionally improve their quality of life.
Summary:
Adenomyosis uteri or adenomyosis is a disease of the uterus. Here, there is growth of endometriosis tissue into the muscular layer of the uterus. These foci resemble the endometriosis foci outside the uterus. The symptoms triggered by adenomyosis are also largely identical to those of endometriosis. These are, in particular, abdominal pain, bleeding disorders and subfertility.
For a long time, adenomyosis was considered a subtype of endometriosis. Today, however, it is classified as a disease in its own right. However, there appears to be a link between adenomyosis and endometriosis, as there are many affected individuals who suffer from both conditions. The connection has not yet been conclusively clarified.
Depending on the findings and the situation of the affected person, treatment is carried out with medication or with surgery. Additional measures of multimodal pain therapy are recommended.
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References
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- Benagiano G, Brosens I, Habiba M.: Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update. 2014; 20(3): 386-402.
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- Uduwela AS, Perera MA, Aiqing L, Fraser IS: Endometrial-myometrial interface: relationship to adenomyosis and changes in pregnancy. Obstet Gynecol Surv. 2000; 55(6): 390-400.
- Vannuccini S, Tosti C, Carmona F, et al: Pathogenesis of adenomyosis: an update on molecular mechanisms.
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