Adenomyosis

 

Adenomyosis is a gynecologic medical condition characterized by the abnormal presence of endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). In contrast, when endometrial tissue is present entirely outside the uterus, it represents a similar but distinct medical condition called endometriosis. The two conditions are found together in many cases, but often occur independently. Before being recognized as its own condition, adenomyosis used to be called endometriosis interna. Additionally, the less-commonly used term “adenomyometritis” is a more specific name for the condition, specifying involvement of the uterus.

The condition is typically found in women between the ages of 35 and 50 but can also be present in younger women. Patients with adenomyosis often present with painful and/or profuse menses (dysmenorrhea & menorrhagia, respectively). Other possible symptoms are pain during sexual intercourse, chronic pelvic pain and irritation of the urinary bladder.

In adenomyosis, basal endometrium penetrates into hyperplastic myometrial fibers. Therefore, unlike functional layer, basal layer does not undergo typical cyclic changes with menstrual cycle.

Adenomyosis may involve the uterus focally, creating an adenomyoma. With diffuse involvement, the uterus becomes bulky and heavier.

Signs and symptoms
Adenomyosis can vary widely in the type and severity of symptoms that it causes, ranging from being entirely asymptomatic 33% of the time to being a severe and debilitating condition in some cases. Women with adenomyosis typically first report symptoms when they are between 40 and 50, but symptoms can occur in younger women.

Symptoms and the estimated percent affected may include:

Chronic pelvic pain (77%)
Heavy menstrual bleeding (40-60%), which is more common with in women with deeper adenomyosis. Blood loss may be significant enough to cause anemia, with associated symptoms of fatigue, dizziness, and moodiness.
Abnormal uterine bleeding
Painful cramping menstruation (15-30%)
Painful vaginal intercourse (7%)
A ‘bearing’ down feeling
Pressure on bladder
Dragging sensation down thighs and legs
Clinical signs of adenomyosis may include:

Uterine enlargement (30%), which in turn can lead to symptoms of pelvic fullness.
Tender uterus
Infertility or sub-fertility (11-12%) – In addition, adenomyosis is associated with an increased incidence of preterm labour and premature rupture of membranes. Women with adenomyosis are also more likely to have other uterine conditions, including:

Uterine fibroids (50%)
Endometriosis (11%)
Endometrial polyp (7%)

Causes
The cause of adenomyosis is unknown, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, known as the junctional zone, such as a caesarean section, surgical pregnancy termination, and any pregnancy. It can be linked with endometriosis, but studies looking into similarities and differences between these two conditions have conflicting results.

The pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone (JZ), is believed to play a major role in the development of adenomyosis. It is also a matter of discussion whether the link between reproductive disorders and major obstetrical disorders also lies here. Parity, age, and previous uterine abrasion increase the risk of adenomyosis. Hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors. As both the myometrium and stroma in an adenomyosis affected uterus show significant differences from those of a non-affected uterus, a complex origin that includes multifactorial changes on both genetic and biochemical levels is likely.

The tissue injury and repair (TIAR) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (EMI) region. That again leads to elevation of local estrogen in order to heal the damage. At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. Iatrogenic injury of the junctional zone or physiological damages due to placental implantation most likely results in the same pathological cascade. This also explains that adenomyosis often gets more severe after each pregnancy and childbirth, while endometriosis will ameliorate.

Treatment
Adenomyosis can only be cured definitively with surgical removal of the uterus. As adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. In women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding.

Medications
NSAIDs: Nonsterioidal anti-inflammatory drugs, such as ibuprofen and naproxen, are commonly used in conjunction with other therapies for pain relief. NSAIDs inhibit the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase. Prostaglandins have been shown to be primarily responsible for dysmenorrhea or the cramping pelvic pain associated with menses.
Hormones and hormone modulators
Levonorgestrel-releasing intrauterine devices or hormonal IUDs, such as the Mirena, are an effective treatment for adenomyosis. They reduce symptoms by causing decidualization of the endometrium, reducing or eliminating menstrual flow. Additionally, by helping downregulate estrogen receptors, hormonal IUDs shrink the clusters of endometrial tissue within the myometrium. This leads to reduced menstrual blood flow, helps the uterus contract more properly, and helps to reduce the menstrual pain. The use of hormonal IUDs in patients with adenomyosis have been proven to reduce menstrual bleeding, improve anemia and iron levels, reduce pain, and even result in an improvement of adenomyosis with a smaller uterus on medical imaging. At least in the short term, patients who can tolerate hormonal IUDs for the treatment of adenomyosis result in equivalent improvement of symptoms and better quality-of-life and social well-being as compared to women who undergo a hysterectomy. Hormonal IUDs are particularly well suited for individuals needing effective treatment of their adenomyosis while still maintaining future fertility potential. The most common negative side-effect of hormonal IUDs is irregular menstrual bleeding or spotting.
Oral contraceptives reduce the menstrual pain and bleeding associated with adenomyosis. This may require taking continuous hormone therapy to reducing or eliminating menstrual flow. Oral contraceptives may even lead to short-term regression of adenomyosis.
Progesterone or Progestins: Progesterone counteracts estrogen and inhibits the growth of endometrial tissue. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.
Gonadotropin-releasing hormone (GnRH) agonists and danazol have been tried in order to relieve adenomyosis related symptoms and show some effect, but the studies are few in number, mainly with a retrospective study design and have small sample sizes. Long-time use of GnRH-analogues is often associated with heavy side effects, loss of bone density and increased risk of cardiovascular events, and therefore not feasible for young women. Furthermore, all present treatment options are irrelevant options for women trying to conceive. Exogenous progestogenic treatments have been found to be ineffective. In IVF-settings long down-regulation prior to IVF might have a positive effect on pregnancy rates.
Surgery
Broadly speaking, surgical management of adenomyosis is split into two categories: uterine-sparing and non-uterine-sparing procedures. Uterine-sparing procedures are surgical operations that do not include surgical removal of the uterus. Some uterine-sparing procedures have the benefit of improving fertility or retaining the ability to carry a pregnancy to term. In contrast, some uterine-sparing procedures worsen fertility or even result in complete sterility. The impact of each procedure on a woman’s fertility is of particular concern and typically guides the selection. Non-uterine-sparing procedures, by definition, include surgical removal of the uterus and consequently they will all result in complete sterility.

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