Adenomyosis

Adenomyosis occurs when endometrial tissue is found within the myometrial, or muscular, layer of the uterine walls, resulting in growth, or hyperplasia, of the surrounding myometrium.  

There are three different layers of tissue in the wall of the uterus. The innermost layer is termed the endometrium, which contains endometrial glands, columnar epithelium, and endometrial stroma. The middle layer is referred to as the myometrium and consists mainly of uterine muscle. The outermost layer is a thin layer of tissue called the perimetrium. Adenomyosis occurs when ectopic, or abnormally positioned, endometrial tissue is found within the myometrium. This occurrence can be classified into either diffuse or focal. Diffuse adenomyosis is characterized by endometrial tissue scattered diffusely within the myometrium. Conversely, focal adenomyosis occurs when the endometrial tissue is only found in a localized area of the myometrium. The ectopic endometrial tissue induces growth within the surrounding myometrium, which causes enlargement of the uterus. Adenomyosis is a common condition among individuals who have given birth. 

Adenomyosis is caused by the invasion of the endometrial basal layer into the myometrium, likely triggered by mechanisms involving tissue injury and repair at the junctional zone between these layers. There are two layers of endometrial tissue: the basal layer and the functional layer. The basal layer, or deepest portion of tissue that connects to the myometrium, is responsible for regeneration after menstruation. This layer does not shed during menstruation. In contrast, the functional layer is the layer of tissue that lines the uterus. The functional layer proliferates throughout the menstrual cycle and then sheds during menstruation if the egg is not fertilized. 

Several factors have been studied that may increase the likelihood of developing adenomyosis. Although the mechanism is unknown, it’s thought that estrogen, progesterone, and prior uterine surgery may contribute to the development of adenomyosis. It has also been linked to elevated aromatase levels, an enzyme responsible for synthesizing estrogen. Additionally, studies have indicated that age and parity may play a role. The risk of adenomyosis has been found to decrease after menopause, likely due to change in the levels of various hormones, such as progesterone, estrogen, prolactin, and follicle stimulating hormone (FSH). 

Diagnosis of adenomyosis begins with a thorough review of symptoms and medical history. A physical exam may also reveal an enlarged and tender uterus. Imaging tests may also be used while diagnosing adenomyosis. Most commonly, a transvaginal ultrasound can reveal an enlarged, round uterus, with myometrial thickening, diverse myometrial texture, cystic glands within the myometrium, and projections from endometrium into the myometrium with increased vascularity. A transabdominal ultrasound may also be performed that show signs of changes to the myometrium. If leiomyomas, or uterine fibroids, are suspected, an MRI may be performed to distinguish between adenomyosis and leiomyomas. A definitive diagnosis can be made through a needle biopsy of the myometrial layer. However, due to the invasive nature of biopsies, they are rarely performed in cases of adenomyosis. 

Additional lab work may be used to rule out other possible diagnoses. If the individual is of childbearing age, a pregnancy test should also be performed. 

Treatment of adenomyosis is primarily focused on relieving the individual's symptoms, which may include pain and irregular menstruation. Non-steroidal anti-inflammatory medications (NSAIDs), such as ibuprofen, may be recommended for pain relief, while hormonal treatment options may be used to prevent irregular bleeding. Studies have shown that combined oral contraceptives, which include both estrogen and progesterone, as well as progestin-only medications, may be used to promote a regular menstrual cycle. In some cases, gonadotropin-releasing hormone (GnRH) agonists may also be used to prevent excess estrogen production. 

If necessary, other treatment options, such as endometrial ablation or resection, may be used to remove the endometrium. Emerging treatments for adenomyosis focus on addressing underlying molecular mechanisms with a particular emphasis on targeting epigenetic modifications that regulate gene expression involved in the disease’s progression, without altering the DNA sequence. Definitive treatment would require a hysterectomy (i.e., removal of the uterus), but this is primarily reserved for individuals who are no longer of childbearing age. 

If necessary, other treatment options, such as endometrial ablation or resection, may be used to remove the endometrium. Definitive treatment would require a hysterectomy (i.e., removal of the uterus), but this is primarily reserved for individuals who are no longer of childbearing age.