Adenomyosis is not classified as an autoimmune disease. It is a benign uterine condition in which tissue that normally lines the inside of the uterus grows into the muscular wall. However, the relationship between adenomyosis and the immune system is more complex than that simple answer suggests. The condition involves significant immune dysfunction, shares some features with autoimmune diseases, and appears alongside autoimmune conditions more often than expected.
What Adenomyosis Actually Is
Adenomyosis occurs when endometrial glands, the tissue that builds up and sheds during your period, push at least 2.5 mm into the surrounding muscle layer of the uterus. This displaced tissue continues to respond to hormonal signals each cycle, thickening, breaking down, and bleeding inside the muscle wall. The result is an enlarged, often painful uterus.
The global prevalence in the general population is roughly 1%, but that figure is misleadingly low because many cases go undiagnosed. Among women with pelvic pain, nearly half (49%) have adenomyosis. Among those with abnormal uterine bleeding, about 42% do. Women who have given birth are more likely to develop it (38%) compared to those who haven’t (28%), and among women experiencing infertility, the prevalence jumps to around 31%.
There is no universally accepted classification system for adenomyosis. Diagnosis still relies on imaging or, historically, on examining uterine tissue after hysterectomy. Several classification systems have been proposed, but none has been adopted into widespread clinical practice, which makes both research and treatment planning more difficult than it should be.
Why People Suspect an Autoimmune Connection
Autoimmune diseases happen when the immune system mistakenly attacks the body’s own tissue. Adenomyosis doesn’t fit that definition neatly, but it does share some hallmarks. Women with adenomyosis produce autoantibodies, particularly against phospholipids, at higher rates than women without the condition. In one study of 234 patients, about 3.8% tested positive for autoantibodies to a specific protein called calreticulin, with one case showing levels roughly eight times the average of other positive samples. These antibodies are a signature of immune systems that have started reacting to the body’s own cells, a core feature of autoimmune disease.
Still, the presence of autoantibodies alone doesn’t make something autoimmune. Many chronic inflammatory conditions produce autoantibodies as a byproduct of ongoing tissue damage. The current medical consensus treats adenomyosis as a hormonally driven, inflammatory condition rather than a true autoimmune one.
The Immune System’s Role in Adenomyosis
Even though adenomyosis isn’t autoimmune, the immune system plays a central role in how the disease develops and progresses. Women with adenomyosis show clear changes in both their innate immune response (the body’s first line of defense) and adaptive immune response (the more targeted, learned response) compared to women without the condition.
Several inflammatory signaling molecules are elevated in the uterine tissue of women with adenomyosis. These include IL-6, IL-1β, and TNF-alpha, all of which drive inflammation and tissue damage. When immune cells called macrophages interact with the displaced endometrial tissue, they ramp up IL-6 production significantly. This creates a self-reinforcing cycle: the displaced tissue triggers inflammation, and the inflammation helps the displaced tissue survive and spread deeper into the muscle wall.
The type of immune cells present also shifts. Women with adenomyosis have increased numbers of a specific macrophage subtype (M2) in their uterine lining, particularly in severe cases. These M2 macrophages are typically involved in tissue repair and immune suppression, which may help explain why the body fails to clear the misplaced tissue. The condition also shows elevated Th17 cells, which promote persistent inflammation, and reduced levels of regulatory T cells (Foxp3+), which normally keep immune responses in check. This imbalance between inflammation-promoting and inflammation-suppressing cells worsens with disease severity and correlates directly with how painful periods are.
How It Differs From Endometriosis
Adenomyosis and endometriosis are closely related. Both involve endometrial tissue growing where it shouldn’t, and one prominent theory proposes they are actually the same disease at different locations. The Tissue Injury and Repair (TIAR) theory, developed by researcher Leyendecker and colleagues starting in 2009, argues that both conditions originate from the same disruption within the uterus, coining the term “archimetrosis” to describe them as a unified disease. About 42% of women with endometriosis also have adenomyosis.
Despite this overlap, the two conditions create different immune environments. Endometriosis is dominated by pro-inflammatory M1 macrophages, while adenomyosis leans toward M2 macrophages that suppress normal immune surveillance. Natural killer cell behavior also differs: endometriosis significantly reduces NK cell activity, while adenomyosis only affects NK cell numbers in severe cases. These distinctions matter because they suggest the two conditions may eventually require different treatment approaches, even if they share an origin.
Adenomyosis and Autoimmune Comorbidities
Women with adenomyosis do develop autoimmune conditions at notable rates, but the picture depends heavily on whether endometriosis is also present. In a study of nearly 700 patients, 14% of women with adenomyosis alone had an autoimmune-related disorder (including conditions like Hashimoto’s thyroiditis, celiac disease, inflammatory bowel disease, and connective tissue diseases). That number jumped to nearly 24% in women who had both adenomyosis and endometriosis. For women over 35 with adenomyosis alone, the autoimmune comorbidity rate dropped further to about 6%, compared to roughly 13% in those with both conditions.
This pattern suggests that endometriosis, rather than adenomyosis itself, may be the stronger driver of autoimmune overlap. But the fact that adenomyosis alone still carries a measurable rate of autoimmune comorbidity points to shared biological pathways between the conditions.
Treatment Approaches That Target Inflammation
Because adenomyosis isn’t classified as autoimmune, standard treatment doesn’t involve the immune-suppressing drugs used for conditions like lupus or rheumatoid arthritis. Instead, treatment primarily targets the hormonal drivers of the disease, using medications that reduce estrogen’s effects on the displaced tissue or manage pain and bleeding symptoms.
That said, some treatments do affect the immune component. Mifepristone, for example, has been shown to lower IL-6 and TNF-alpha levels in endometrial tissue, reduce the infiltration of mast cells (immune cells that amplify inflammation), and decrease nerve fiber density in the affected tissue. More recent research has found that mifepristone also works by dialing down immune checkpoint proteins that are abnormally elevated in adenomyosis tissue. These effects are secondary to the drug’s hormonal action, but they highlight how tightly the hormonal and immune aspects of the disease are intertwined.
The immune involvement in adenomyosis is real, measurable, and clinically significant. But the disease is best understood as an inflammatory, hormonally driven condition with immune features, not as a true autoimmune disease where the immune system has fundamentally turned against the body’s own tissue.