Adenomyosis is a benign condition characterized by the invasion of endometrial glands and stroma into the myometrium. It is most commonly observed in multiparous women aged 30–50 years. Approximately 15% of patients with adenomyosis also have endometriosis, and nearly half of the patients exhibit coexisting uterine fibroids. Histological examination of serial sections from autopsied uteri or uteri removed due to disease reveals that 10%–47% of the myometrium contains endometrial tissues; however, 35% of such cases present without clinical symptoms. While adenomyosis and endometriosis have different underlying causes, both are influenced by estrogen.
Related Factors in Pathogenesis
The exact cause of adenomyosis remains unknown. Some researchers propose that adenomyosis results from the invasion and growth of basal endometrium into the myometrium. This is supported by findings in serial histological sections of uteri with adenomyosis, which show that endometrial lesions in the myometrium are directly connected to the uterine cavity. The lack of a submucosal layer in the endometrial basal layer, which allows the endometrial tissue to come into direct contact with the myometrium, may provide an anatomical basis for invasion. Factors such as repeated pregnancies, childbirth, surgical abortions, and chronic endometritis, which can damage the basal endometrium, are closely associated with the development of adenomyosis.
Adenomyosis frequently coexists with uterine fibroids and endometrial hyperplasia, suggesting that elevated levels of estrogen and progesterone may promote the growth of endometrial tissue into the myometrium. Other theories include Müllerian remnant metaplasia, differentiation of somatic stem cells, inflammatory stimulation, genetic predisposition, epithelial-mesenchymal transition, and immune dysfunction.
Pathology
Adenomyosis can be classified into two types: diffuse and focal.
Diffuse Type
This is characterized by the diffuse growth of ectopic endometrium within the myometrium, predominantly involving the posterior wall. The uterus becomes uniformly enlarged with a notably increased anteroposterior diameter, often resembling a spherical shape, and typically does not exceed the size of a 12-week pregnant uterus. On cross-section, the myometrium appears significantly thickened and firm, lacking the whorled appearance seen in fibroids. Bands of thickened muscle fibers and microcysts containing old blood may be observed within the myometrial walls.
Focal Type
In some cases, adenomyotic lesions grow as localized nodules or masses, resembling intramural fibroids, and are referred to as adenomyomas. Repeated local bleeding may result in fibrosis of the surrounding tissue, making the boundaries with normal myometrium indistinct and challenging to excise during surgery. Microscopically, the hallmark feature is the presence of ectopic endometrial glands and stroma in an island-like distribution within the myometrium, surrounded by varying degrees of smooth muscle hyperplasia.
Characteristic islands of adenomyosis consist of typical endometrial glands and stroma, originating from the immature basal layer of the endometrium. The ectopic endometrium exhibits responsiveness to estrogen but is insensitive or minimally responsive to progesterone. Consequently, the ectopic glands often show proliferation-phase changes, with occasional areas displaying secretory-phase characteristics.
Clinical Manifestations
Symptoms of adenomyosis vary, and 35% of patients have no typical symptoms. The main clinical features include heavy menstrual bleeding, prolonged menstrual periods, progressively worsening secondary dysmenorrhea, and infertility.
Heavy Menstrual Bleeding
This occurs in 40%–50% of adenomyosis cases and is characterized by an increase in menstrual volume over consecutive cycles, generally exceeding 80 ml. This can negatively impact physical, psychological, social, and economic aspects of a patient’s quality of life. Primary factors contributing to heavy menstrual bleeding include increased endometrial surface area, impaired myometrial contractility caused by adenomyotic lesions, and endometrial hyperplasia.
Dysmenorrhea
Secondary dysmenorrhea affects approximately 30%–40% of adenomyosis patients. Pain is typically localized in the central lower abdomen and begins about one week prior to menstruation, persisting until menstrual bleeding ceases.
Infertility
Approximately 20% of patients with adenomyosis experience infertility. Those who conceive face an elevated risk of miscarriage, preterm delivery, and postpartum hemorrhage.
Physical examination often reveals a uniformly enlarged uterus or localized nodular prominence, with the uterus feeling firm and tender to palpation, especially during menstruation. Asymptomatic cases may be difficult to distinguish from uterine fibroids during examination.
Diagnosis
A preliminary diagnosis can be considered based on a history of progressively worsening secondary dysmenorrhea and heavy menstrual bleeding, combined with findings of a uniformly enlarged uterus or localized nodular prominence, firm texture, and tenderness on gynecological examination. However, the "gold standard" for a definitive diagnosis is histopathological confirmation.
Imaging techniques, including ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT), can provide diagnostic assistance and may be utilized as appropriate. Elevated serum CA125 levels may also be observed.
Differential Diagnosis
Adenomyosis should be differentiated from the following conditions:
Uterine Fibroids
Typically asymptomatic, although submucosal fibroids may cause increased menstrual volume. Dysmenorrhea is uncommon. Imaging studies usually reveal well-demarcated masses, and serum CA125 levels are not significantly elevated.
Endometrial Cancer
This often presents with abnormal vaginal bleeding as the main symptom. Gynecological examination may show a full and tender uterus. Serum tumor markers are markedly elevated. Endometrial biopsy via hysteroscopy can aid in differentiation.
Uterine Sarcoma
Ultrasound findings often show an ill-defined mass with unusually rich vascularity. Magnetic resonance imaging (MRI) can aid in preliminary assessment. If necessary, transvaginal ultrasound-guided biopsy can assist in the diagnosis.
Treatment
Treatment should be tailored based on the patient's symptoms, age, and fertility aspirations. There are currently no definitive curative medications for adenomyosis. Mild symptoms, fertility requirements, and perimenopausal status may warrant the use of nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, oral progestins, gonadotropin-releasing hormone agonists (GnRH-a), or levonorgestrel-releasing intrauterine systems (LNG-IUS). These options can alleviate symptoms, although their side effects must be monitored, and symptoms may recur after discontinuation. Bone loss should be noted during GnRH-a treatment, with concurrent add-back therapy and calcium supplementation when needed.
Young patients or those wishing to preserve fertility may consider lesion excision, but a risk of recurrence exists post-surgery. For those with severe symptoms, no fertility requirement, or failure of medical treatment, total hysterectomy may be performed. The decision to preserve the ovaries should depend on the presence of ovarian pathology and the patient's age.
For patients with a strong desire to preserve the uterus, poor adherence to medication, unwillingness to undergo surgery, and no suspicion of malignancy, interventional treatments may be considered. Options include high-intensity focused ultrasound (HIFU) ablation and uterine artery embolization (UAE). These methods can reduce lesion size and improve symptoms in the short term, but they do not remove the lesions or provide pathological tissue for analysis. Therefore, the indications for these treatments should be carefully evaluated.