Adenomyosis Symptoms, Causes & Treatment
Learn about adenomyosis types, theories, symptoms, causes, risk factors, diagnosis methods, and treatment options.
ADENOMYOSIS
Adenomyosis is non-cancerous condition of uterus in women, which is very common during childbearing women. In adenomyosis, endometrial glands are found in the myometrium of the uterus. This is associated with hyperplasia that causes the uterus to enlarge and become bulky.
Adenomyosis is classified as diffuse or focal based on how it is distributed within the uterine muscle (myometrium).
Diffuse adenomyosis
In diffuse adenomyosis, multiple endometrial glands and stroma are scattered throughout large areas of the myometrium, leading to a uniformly enlarged and often “boggy” uterus.
Focal adenomyosis
Focal adenomyosis is characterized by localized, well-defined nodules composed of hypertrophied (thickened) myometrium containing ectopic (outside) endometrial tissue. These focal lesions are sometimes referred to as adenomyomas because they resemble fibroids but contain endometrial elements.
Related article:
Endometriosis: Symptoms, diagnosis and treatments
Estrogen Balance: The Secret Behind Energy, Mood, and Glow
THEORIES PROPOSED FOR THE DEVELOPMENT OF ADENOMYSOSIS
The invagination hypothesis
The invagination hypothesis suggests that adenomyosis develops because of excessive uterine contractions (uterine hyperperistalsis).
Strong and repeated contractions of the uterine muscle (myometrium) can cause small injuries at the boundary between the endometrium (uterine lining) and the myometrium. This boundary is called the junctional zone. Due to repeated trauma, the basal layer of the endometrium may push or grow inward (invaginate) into the myometrium, leading to adenomyosis.
The metaplasia theory
The metaplasia theory suggests that adenomyosis develops from special stem or primitive cells located within the uterine muscle (myometrium).
The outside-to-inside theory
The “outside-to-inside” theory proposes that adenomyosis develops when endometrial cells penetrate the uterine wall from the outer surface. According to this hypothesis, during retrograde menstruation, menstrual blood containing viable endometrial cells flows backward into the pelvic cavity. These ectopic endometrial cells, especially those associated with endometriosis lesions, may migrate and invade the myometrium from the outside of the uterus, leading to focal adenomyotic lesions.
The strong association between posterior focal adenomyosis and deep infiltrating endometriosis (Endometriois POST) in the posterior pelvic compartment supports this theory. This suggests that, in some cases, adenomyosis may result from the direct extension or implantation of endometriotic tissue into the uterine muscle.
IMPACT OF HORMONAL IMBALANCE IN ADENOMYOSIS
Hormonal imbalance plays an important role in the development of adenomyosis.
Specifically, an excess of estrogen activity combined with reduced progesterone response promotes the disease. This imbalance occurs due to increased estrogen receptor-beta activity and higher local estrogen production within the uterus (because of increased aromatase enzyme activity), even though blood estrogen levels may remain normal. At the same time, progesterone receptor activity especially type B progesterone receptors is decreased, leading to progesterone resistance.
The increased estrogen effect stimulates excessive cell proliferation and reduces apoptosis (normal cell death) in the basalis layer of the endometrium. This anti-apoptotic and proliferative environment promotes the invagination of endometrial tissue into the myometrium and supports the progression and “spreading” of adenomyotic lesions within the uterine muscle. (Estrogen Balance POST)
ADENOMYOSIS SYMPTOMS
Adenomyosis does not have specific characteristic symptoms, and approximately one-third of patients are asymptomatic.
Symptoms of adenomyosis typically begin to appear between 40 and 50 years of age.
Common symptoms
Adenomyosis causes abnormal uterine bleeding and dysmenorrhea (painful menstruation). It may also lead to an enlarged uterus, uterine tenderness (pain on examination), a soft or “boggy” consistency of the uterus, and infertility. However, an enlarged uterus is not always due to adenomyosis alone. Other conditions, such as leiomyomas (uterine fibroids), can also cause uterine enlargement.
In fact, up to 50% of patients with adenomyosis also have leiomyomas (fibroids, Read Fibrois POST). About 11% of patients have endometriosis along with adenomyosis.
Less common symptoms
Adenomyosis causes dyspareunia and chronic pelvic pain.
Menorrhagia
Approximately 40–60% of patients experience menorrhagia (heavy menstrual bleeding), which is mainly caused by an increased surface area and total volume of the endometrium and endometrial glands, as well as increased blood vessel formation (vascularization) in the uterine lining.
Dysmenorrhea
Approximately 15–30% of patients experience dysmenorrhea (painful menstrual bleeding). It is believed that the pain is due to increased number of oxytocin receptors in the endometrium (uterine lining) and increase production of prostaglandins.
Both oxytocin and prostaglandins stimulate uterine contractions. Stronger and more frequent contractions lead to menstrual pain (dysmenorrhea).
ADENOMYOSIS RISK FACTORS
Multiple pregnancies (multiparity)
Having multiple pregnancies (multiparity) increases the risk of adenomyosis. This may happen because during pregnancy, hormonal changes (especially high estrogen levels) may affect the uterine lining. The mechanical stress of childbirth may push endometrial tissue into the uterine muscle (myometrium).
Miscarriages
Women who have had one or more miscarriages may have a higher risk of adenomyosis. Uterine surgical procedures (such as curettage or cesarean section) are also considered risk factors, likely because they may disrupt the boundary between the endometrium and myometrium.
Smoking
Interestingly, the incidence of adenomyosis is lower in women who smoke daily. This is thought to be due to lower estrogen levels in smokers. Since adenomyosis is estrogen-dependent, reduced estrogen exposure may decrease risk.
Estrogen
Prolonged exposure to estrogen may lead to adenomyosis in older women.
Age factor
Earlier, it was believed that adenomyosis mainly affect women in their 40s and 50s. However, with improved diagnostic techniques, it is now increasingly being diagnosed in younger women who present with pelvic pain, abnormal uterine bleeding, or infertility.
ADENOMYOSIS DIAGNOSIS
For many years, adenomyosis could only be definitively diagnosed after hysterectomy (surgical removal of the uterus). The diagnosis was confirmed by examining the uterine tissue under a microscope (histology). The main types identified were focal, diffuse, cystic, and adenomyoma forms of adenomyotic lesions.
However, this situation has changed significantly with advances in imaging technology. Modern techniques such as transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) now allow doctors to diagnose adenomyosis non-invasively.
ADENOMYOSIS TREATMENT
MEDICAL THERAPIES
Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for patients with adenomyosis who experience dysmenorrhea (painful menstruation). NSAIDs help reduce pain by inhibiting prostaglandin production.
Levonorgestrel-releasing intrauterine system (LNG-IUS)
LNG-IUS is used to treat dysmenorrhea and menorrhagia (heavy menstrual bleeding). It helps reduce uterine volume, pain, and abnormal uterine bleeding (AUB).
In patients with mild forms of adenomyosis, LNG-IUS significantly improves quality of life by controlling pain and heavy bleeding. It also helps improve hemoglobin levels by reducing blood loss.
Combined oral contraceptive pill (COC)
The combined oral contraceptive pill is effective in managing abnormal uterine bleeding, dysmenorrhea (painful menstruation), and chronic pelvic pain. It works by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby inhibiting ovulation.
Dienogest
Dienogest is a synthetic oral progestin that helps reduce dysmenorrhea (painful menstruation), chronic pelvic pain, and dyspareunia in patients with adenomyosis.
It is generally not considered highly effective in reducing uterine size or adenomyotic lesions. However, some studies suggest that long-term use of dienogest may significantly reduce uterine volume.
Gonadotropin-releasing hormone (GnRH) analogs
Gonadotropin-releasing hormone (GnRH) analogs (both agonists and antagonists) work by suppressing the release of reproductive hormones FSH and LH, which leads to a reduction in estrogen levels in the body. The decreased estrogen levels cause shrinkage of the uterus and help relieve pain.
1. GnRH agonists
GnRH agonists, such as leuprolide acetate, can help shrink adenomyotic lesions and reduce chronic pelvic pain. This means they are effective in improving symptoms of adenomyosis.
However, in women with adenomyosis who are undergoing In vitro fertilization (IVF), treatment with GnRH agonists does not appear to significantly improve IVF outcomes (such as pregnancy or implantation rates), even though it may improve symptoms.
2. GnRH antagonists
GnRH antagonists such as linzagolix and elagolix, directly block the GnRH receptors in the pituitary gland. This immediately reduces the release of FSH and LH, without causing the initial “flare-up” effect (temporary worsening of symptoms) that occurs with GnRH agonists.
By lowering FSH and LH, further leads to decrease in estrogen levels, which helps reduce uterine size and improve symptoms such as pain and heavy bleeding.
One possible advantage of GnRH antagonists over agonists is that they can maintain moderate (controlled) estradiol levels. This may help reduce side effects like bone loss and other low-estrogen symptoms such as hot flashes.
Selective progesterone receptor modulators (SPRMs)
Selective progesterone receptor modulators (SPRMs) are synthetic steroid drugs derived from norethindrone. They are designed to act specifically on progesterone receptors, where they can either activate or block gene activity depending on the tissue.
SPRMs such as Ulipristal acetate (UPA) and Mifepristone have been shown to reduce the size of uterine fibroids, stop or significantly reduce endometrial (uterine) bleeding.
SURGICAL CONSERVATIVE THERAPY
Uterine Artery Embolization (UAE)
Uterine artery embolization (UAE) is a minimally invasive procedure in which small particles (embolic agents) are injected into the uterine arteries to block blood flow. Blocking the blood supply leads to reduced oxygen delivery (hypoxia), ischemia (restricted blood flow), and tissue necrosis of adenomyotic lesions, with minimal impact on surrounding healthy tissue. Studies suggest that UAE improves dysmenorrhea, menorrhagia, and reduces uterine size.
UAE is generally recommended for patients who have completed childbearing and wish to preserve their uterus. However, it is not typically recommended for women who desire future pregnancies.
Radiofrequency Ablation (RFA)
Radiofrequency ablation (RFA) is an emerging uterus-preserving treatment for adenomyosis. In this procedure, a thin electrode is inserted into the adenomyotic lesion under imaging guidance. The electrode generates heat, which destroys the abnormal tissue. The heat induces thermal damage and coagulative necrosis (controlled tissue destruction).
Studies have shown that RFA significantly improves dysmenorrhea and reduces abnormal uterine bleeding (AUB).
High-Intensity Focused Ultrasound (HIFU)
High-intensity focused ultrasound (HIFU) is a non-surgical treatment for adenomyosis. It uses focused ultrasound waves to generate heat within adenomyotic tissue. This heat induces coagulative necrosis (controlled tissue death), which helps shrink the lesions.
Studies have shown that HIFU helps relieve dysmenorrhea (menstrual pain) and menorrhagia (heavy menstrual bleeding). It significantly reduces uterine size and decreases the volume of adenomyotic lesions (both focal and diffuse types) without adversely affecting ovarian function.
HIFU appears to be more effective for adenomyotic tissue located in the anterior uterine wall than in the posterior wall. This is because ultrasound waves have limited penetration depth, making treatment less effective for deeply situated lesions.
Compared to laparoscopic excision surgery, HIFU has demonstrated higher pregnancy rates in some studies. Additionally, it may be associated with a lower risk of uterine rupture and abnormal placentation in future pregnancies compared to myomectomy or cesarean section; however, further research is needed.
Read article:
