Practice Essentials
Adenomyosis is a common, but poorly understood condition that affects women of all age groups. It is defined as the presence of ectopic nests of endometrial glands and stroma within the myometrium, surrounded by reactive smooth muscle hyperplasia. (See the image below.) Adenomyosis is a common cause of dysmenorrhea, menorrhagia, and chronic pelvic pain but is often underdiagnosed.
Signs and symptoms
Patients with adenomyosis commonly report the following symptoms:
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Menorrhagia
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Dysmenorrhea
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Metrorrhagia
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Chronic pelvic pain
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Dyspareunia
On physical examination, a diffusely enlarged, tender, “boggy” uterus is suggestive of adenomyosis.
See Presentation for more detail.
Diagnosis
Ultrasound is the most common imaging modality used to evaluate gynecologic symptoms. Currently, adenomyosis remains a largely clinical diagnosis. Definitive diagnosis requires histologic examination of uterine tissue.
See Workup for more detail.
Management
The only definitive treatment for symptoms associated with adenomyosis is hysterectomy; however, this is not an option for patients who desire future fertility and may not be an option for patients who are poor surgical candidates.
The medications most commonly used to treat symptoms of adenomyosis are anti-inflammatory drugs and hormonal therapies.
See Treatment and Medication for more detail.
Pathophysiology
In a normal uterus, the uterine corpus is composed of a muscular myometrial layer, a smooth outer serosal layer, and an inner endometrial layer which lines the uterine cavity. The endometrium is composed of two layers. The basalis endometria is a thin, deep layer bordering the myometrium, consisting of ample stroma but rare glands. Overlying this is the functional layer, or functionalis endometria, consisting of abundant glands with less stromal tissue. During a woman’s reproductive years, the functionalis endometria responds to cyclic changes in progesterone and estrogen levels with resulting monthly menses. [1]
Adenomyosis is defined as the presence of ectopic nests of endometrial glands and stroma throughout the myometrium, surrounded by reactive hypertrophic smooth muscle cells. [2] The pathophysiology of adenomyosis development remains poorly understood. Adenomyosis may be present either as diffuse, scattered individual glands, or focal collections of glandular tissue. [3] The most widely accepted theory for the origin of adenomyosis is an abnormal invagination of the basalis layer of the endometrium into the adjacent myometrial layer. The endometrial-myometrial interface is composed of the basalis endometria and the subendometrial myometrium, also known as the myometrial junctional zone. [4] There is no intervening layer between myometrium and endometrium. The absence of any discrete transitional layer is thought to permit abnormal invagination of the basalis endometria directly into the myometrium when endometrial invasion is provoked. [4]
Multiple hypotheses exist regarding the causal factors of endometrial invagination. Likely factors may include mechanical disruption of the endometrial-myometrial interface, hormonal imbalance, and impaired immunity. [4, 5]
Mechanical disruption of the endometrial-myometrial interface has long been thought to predispose women to adenomyosis. This hypothesis is supported by the association of adenomyosis with multiparity and any history of uterine trauma, such as uterine curettage and cesarean section. [5] More recently, the theory of dysfunctional uterine contractility has become popular. This proposes that disordered hyperperistalsis of the uterus can cause mechanical auto-trauma to the endometrial-myometrial junction, causing aberrant dislocation of the basalis endometria into the myometrial layer. [6]
Some studies have suggested that elevated levels of estrogen are necessary for development and maintenance of adenomyosis, just as they are required for ectopic endometrial proliferation and proliferation of endometriotic implants. [7, 4, 5] Some studies have noted elevated estradiol levels in the menstrual blood of women with endometriosis and adenomyosis, and other studies have noted elevated levels of aromatase enzymes in the endometrium of adenomyotic tissue, suggesting elevated estradiol levels are necessary to maintain active adenomyosis. [6, 7] Additionally, symptoms of adenomyosis have been strongly linked to the menstrual cycle. Often, patients will report severely increased abdominal pain during menses. As adenomyotic tissue responds to hormonal changes within the myometrium, it may cause reactive inflammation in the surrounding tissue, with resultant severe menstrual cramping and pain. [8] Supporting this hypothesis is the observation that estrogenic suppression with danazol induces involution of ectopic endometrium and causes remission of symptoms such as dysmenorrhea and menorrhagia. [7, 5]
Etiology
Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. [9, 10]
Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades [8, 11] , likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development.
Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. As pregnancy progresses, mechanical weakening of the myometrium may occur as the uterus becomes distended, with further resultant infiltration of the endometria basalis. Finally, the tremendous hormonal fluctuations which occur throughout pregnancy may facilitate development of adenomyotic foci. [12, 9]
There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. [5, 12] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated. [13, 14, 9]
Epidemiology
Despite advances in imaging studies, definitive diagnosis still relies on a histologic examination of a surgical specimen, typically at the time of hysterectomy. Prevalence of adenomyosis at the time of hysterectomy has been estimated anywhere between 14% and 66%, dependent upon the pathologist’s diagnostic criteria. [10] A mean frequency of 20-30% has been reported [15, 8] and has been extrapolated to suggest the same incidence in the general population [8] . Risk factors include increased parity, spontaneous abortions, uterine surgery, and middle age.
Prognosis
Natural history of adenomyosis is difficult to chart. Typically, patients seek treatment shortly after presentation. Definitive treatment with hysterectomy then precludes any further observation or understanding of symptomatic adenomyosis. However, the presence of adenomyosis has been well documented as an incidental finding in postmenopausal women at time of autopsy, and as an incidental finding at time of hysterectomy. [11] Symptoms of adenomyosis are rarely reported in women older than 60 years, however, presumably due to a postmenopausal hypoestrogenic state. [2]
Some studies suggest that adenomyosis has a negative impact on fertility outcomes; however, limited data exist. [16] A meta-analysis by Cozzolino et al showed that infertile women with adenomyosis who underwent in vitro fertilization (IVF) had a lower live birth rate, clinical pregnancy rate, and ongoing pregnancy rate than did women without adenomyosis. Additionally, the rate of miscarriage was higher in women who had adenomyosis. [17] Furthermore, a meta-analysis by Wang et al found that symptomatic and diffuse adenomyosis, but not asymptomatic adenomyosis, was associated with worse IVF outcomes, including live birth and clinical pregnancy rates. [18]
Patient Education
The symptoms of adenomyosis are very common among other gynecologic diseases. During the initial workup, it is important to counsel patients about the diagnostic process, including tests and imaging to rule out malignancy. If adenomyosis is suspected or the diagnosis of adenomyosis is made, discussing the pathophysiology and natural history of the disease should be considered to allow the patient to understand her prognosis and the mechanism of possible treatment.
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MRI of fundal adenomyoma.
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Photo of an adenomyoma dissecting through the uterine wall.
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Ultrasound of an adenomyoma dissecting through the anterior uterine wall separate from the endometrial cavity.
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Adenomyosis noted within thickened myometrium.
