Adenomyosis: What it is, what causes it, and how it is treated

Adenomyosis is a benign uterine condition characterized by the presence of endometrial glands and stroma within the myometrium (the muscular wall of the uterus). This ectopic endometrial tissue induces a locally reactive hypertrophy and hyperplasia of adjacent myometrium, leading to uterine enlargement, menstrual bleeding abnormalities, and pelvic pain. Although historically diagnosed only after hysterectomy by histologic examination, improvements in imaging have made non‑invasive diagnosis increasingly common. This article reviews the anatomy, pathophysiology, clinical presentation, diagnostic approach, and evidence‑based management strategies for adenomyosis, with attention to fertility implications and patient counseling.

Anatomy and basic definitions

To understand adenomyosis, it helps to recall uterine structure:

Endometrium: the inner mucosal lining that proliferates and sheds during the menstrual cycle.
Myometrium: the muscular layer responsible for uterine contraction.
Junctional zone: the interface between endometrium and myometrium; on MRI this is a distinct low‑signal band whose integrity is important diagnostically.

Adenomyosis is defined by the presence of endometrial glands and stroma deeper than the normal endometrial–myometrial interface, typically producing a thickened and irregular junctional zone. When a localized mass of adenomyotic tissue forms, it is sometimes called an adenomyoma.

(For clinical summaries see ACOG, Mayo Clinic, Cleveland Clinic; for reviews and imaging criteria see NIH/NCBI.)

Epidemiology

Reported prevalence of adenomyosis varies widely because of differences in diagnostic criteria and the historical reliance on hysterectomy specimens. Estimates range from approximately 5% to over 30% in surgical series. It is most commonly diagnosed in women in their late reproductive years (commonly ages 35–50), although adenomyosis can occur in younger women as well. Many patients have coexisting uterine leiomyomas (fibroids) or endometriosis. Risk factors that have been associated with adenomyosis include prior uterine surgery (such as cesarean delivery or dilation and curettage), multiparity, and prolonged exposure to estrogen, although causation is not definitively established (ACOG, Mayo Clinic, NCBI).

Pathophysiology and proposed mechanisms

The exact cause of adenomyosis is unknown, but several hypotheses exist:

Invagination theory: repeated cycles of injury and repair at the endometrial–myometrial interface lead to downward invagination of basalis endometrium into the myometrium. Uterine trauma (surgical procedures, childbirth) may facilitate this process.
Metaplasia theory: multipotential Müllerian remnants or stem cells within the myometrium undergo metaplastic transformation into endometrial tissue.
Developmental origin: aberrant development of endometrium during embryogenesis results in heterotopic endometrial tissue.
Hormonal and inflammatory influences: local hyperestrogenism, increased aromatase activity, and inflammatory mediators may promote glandular proliferation and adjacent myometrial hypertrophy.

These processes result in functional endometrial tissue within the myometrium that responds to cyclical hormones, leading to bleeding, myometrial irritation, and uterine enlargement. The reactive myometrial hypertrophy and increased uterine contractility contribute to dysmenorrhea and pelvic pain (NCBI, ACOG).

Classification and gross patterns

Adenomyosis can be categorized by distribution:

Diffuse adenomyosis: widespread involvement of the myometrium leading to overall uterine enlargement and a uniformly thickened junctional zone.
Focal adenomyosis (adenomyoma): a localized area of adenomyotic tissue that may mimic a fibroid on examination or imaging.

Histologically, diagnosis is established by identification of endometrial glands and stroma within the myometrium, usually extending a minimum depth (criteria vary) below the endometrial–myometrial interface.

Clinical presentation

Symptoms are variable and include:

Heavy menstrual bleeding (menorrhagia): prolonged or heavy menstrual periods are common due to bleeding from ectopic endometrial tissue and impaired uterine contractility.
Painful menses (dysmenorrhea): often severe and progressive; pain may begin earlier and last longer than typical menstruation‑related pain.
Chronic pelvic pain: many patients report persistent lower pelvic or low back discomfort outside menses.
Dyspareunia (pain with intercourse): can occur, generally described as deep pelvic pain.
Enlarged, tender uterus: on pelvic examination, the uterus may be uniformly enlarged, soft, and tender.
Anemia: heavy bleeding can result in iron deficiency anemia and associated fatigue.
Infertility or subfertility: associations between adenomyosis and reduced fecundity or recurrent pregnancy loss have been reported (Mayo Clinic, NCBI, Cleveland Clinic).

Importantly, symptoms are not specific to adenomyosis and may overlap with uterine fibroids, endometriosis, endometrial hyperplasia, or malignancy; careful evaluation is required.

Diagnostic evaluation

Diagnosis integrates clinical assessment with imaging. Historically definitive diagnosis required hysterectomy and histologic confirmation, but modern imaging affords high accuracy.

Clinical history and examination

Detailed menstrual and obstetric history, prior uterine surgery.
Assessment of bleeding patterns, pain characteristics, impact on quality of life, and fertility desires.
Pelvic examination for uterine size, contour, and tenderness; focal masses may suggest fibroids.

Laboratory tests

Complete blood count (CBC): evaluate for anemia in the setting of heavy bleeding.
Iron studies: assess for iron deficiency.
Pregnancy test in reproductive‑age women with abnormal bleeding.
Tumor markers (e.g., CA‑125) are nonspecific and not diagnostic; CA‑125 can be elevated in adenomyosis but also in endometriosis and ovarian pathology.

Imaging

Transvaginal ultrasound (TVUS): often the first‑line imaging modality. Sonographic features suggesting adenomyosis include an enlarged globular uterus, asymmetrical myometrial thickening, heterogeneous myometrial echotexture, myometrial cysts or hypoechoic microcysts, and indistinct endometrial–myometrial junction. Sensitivity and specificity vary with operator experience (Mayo Clinic, Cleveland Clinic).
Magnetic resonance imaging (MRI): the most accurate noninvasive test. MRI criteria include thickening of the junctional zone (commonly >12 mm is used as a threshold), a poorly defined junctional zone, high-signal intensity foci within the myometrium on T2 or T1 sequences (reflecting glands or hemorrhagic foci), and diffuse or focal myometrial involvement. MRI is particularly helpful when ultrasound is inconclusive or when planning conservative surgery (NCBI, ACOG summaries).
Hysteroscopy and endometrial sampling: may help exclude other causes of abnormal uterine bleeding but typically do not diagnose adenomyosis unless adenomyotic tissue communicates with the endometrial cavity. Endometrial biopsy may be normal despite adenomyosis.
Definitive diagnosis: histologic identification of endometrial glands and stroma within myometrium on hysterectomy specimen remains the gold standard.

Differential diagnosis

Uterine leiomyomas (fibroids): can cause similar bleeding and enlargement; imaging helps distinguish fibroids from adenomyomas.
Endometriosis: presence of ectopic endometrial tissue outside the uterus; may coexist.
Endometrial hyperplasia or carcinoma: must be excluded in abnormal bleeding.
Pelvic inflammatory disease, ovarian pathology, or gastrointestinal conditions that cause pelvic pain.

Management overview: goals and individualized care

Management is individualized and depends on symptom severity, age, desire for fertility, uterine size and extent of disease, and patient preferences. Primary goals are control of bleeding and pain, treatment of anemia, improvement in quality of life, and preservation of fertility when desired.

Therapeutic options include medical management, minimally invasive or image‑guided procedures, and surgical approaches. Many therapies provide symptom relief but are not curative except hysterectomy.

(Recommendations from ACOG and major specialty centers emphasize shared decision‑making and a stepwise approach.)

Medical management

Medical therapy aims to suppress ectopic endometrial activity, reduce bleeding and pain, and improve anemia.

Nonsteroidal anti‑inflammatory drugs (NSAIDs)

NSAIDs (ibuprofen, naproxen, others) are effective first‑line agents for dysmenorrhea and pelvic pain, reducing prostaglandin‑mediated uterine contractility.
They do not treat heavy bleeding as effectively as hormonal therapies but are often used adjunctively (ACOG patient resources).

Hormonal therapies

Hormonal suppression is central to medical management.

Combined oral contraceptives (estrogen‑progestin): cyclic or extended‑cycle regimens can reduce menstrual blood loss and dysmenorrhea in many patients. They regulate endometrial proliferation and reduce bleeding episodes.
Continuous progestin therapy: oral progestins (e.g., norethindrone, medroxyprogesterone acetate) may reduce bleeding and pain by inducing endometrial decidualization and atrophy of ectopic glands.
Levonorgestrel‑releasing intrauterine device (LNG‑IUD): substantial evidence supports the LNG‑IUD as an effective, uterus‑sparing option for reducing heavy menstrual bleeding and improving pain scores in adenomyosis. It delivers localized progestin, reducing uterine bleeding and often producing amenorrhea. Multiple studies and guideline statements identify the LNG‑IUD as a highly effective conservative treatment for symptomatic adenomyosis (Cleveland Clinic, Mayo Clinic).
Progestin implants or depot medroxyprogesterone acetate: alternative systemic progestin options with variable efficacy.
Dienogest: an oral progestin used in some countries with data for endometriosis and emerging evidence for adenomyosis symptom control.
Gonadotropin‑releasing hormone (GnRH) agonists: downregulate the pituitary–ovarian axis, inducing a hypoestrogenic state and reducing bleeding and pain. They are effective for symptom control but associated with menopausal‑like side effects (hot flashes, bone mineral density loss) and are generally used short‑term or as preoperative therapy. Add‑back therapy (low‑dose estrogen/progestin or progestin alone) reduces side effects.
GnRH antagonists and novel oral agents: new oral GnRH antagonists (e.g., relugolix, elagolix in other indications) have shown promise for uterine bleeding and pain associated with uterine disorders; their role in adenomyosis is under investigation.
Aromatase inhibitors: used off‑label in refractory cases to reduce local estrogen production; evidence is limited and side effects significant.

Choice of hormonal therapy depends on patient tolerance, desire for contraception, side effect profile, and fertility desires.

Antifibrinolytics

Tranexamic acid: effective for heavy menstrual bleeding by reducing fibrinolysis. It can be used during menses to reduce blood loss but does not address dysmenorrhea outcomes and may not be suitable for all patients (contraindicated in some thrombotic disorders).

Minimally invasive and image‑guided procedures

For patients who do not respond to medical therapy, desire uterine preservation, or are poor surgical candidates, several interventional options exist.

Uterine artery embolization (UAE)

UAE reduces uterine blood flow by embolizing the uterine arteries, leading to ischemic reduction of adenomyotic tissue. Some studies report improvement in bleeding and pain, but efficacy may be less durable compared with treatment of fibroids. UAE is not universally effective for diffuse adenomyosis, and fertility outcomes after UAE are of concern; therefore, it is generally offered to patients not desiring future fertility (Cleveland Clinic, Mayo Clinic).

Magnetic resonance‑guided focused ultrasound (MRgFUS) and high‑intensity focused ultrasound (HIFU)

MRgFUS and HIFU use focused ultrasound energy to thermally ablate adenomyotic tissue under image guidance. Early and mid‑term results show symptom improvement in selected patients, particularly with focal disease. Availability is limited, and long‑term data and comparative trials are ongoing.

Endometrial ablation

Endometrial ablation techniques are effective for some causes of heavy menstrual bleeding but are typically not recommended for adenomyosis when deep myometrial involvement is present, since these procedures treat only the endometrium and may not reach intramyometrial adenomyotic foci. Recurrence of bleeding and persistent pain is common. Endometrial ablation should be avoided in patients desiring future fertility.

Surgical management

Surgery provides definitive or symptomatic relief depending on the procedure.

Adenomyomectomy (focal excision)

For focal adenomyosis (adenomyoma) and selected diffuse cases, surgical excision of adenomyotic tissue with uterine reconstruction may relieve symptoms while preserving the uterus and fertility potential. The procedure is technically demanding due to ill‑defined tissue planes and risk of uterine rupture in future pregnancy if myometrial closure is inadequate. It is typically performed in specialized centers.

Hysterectomy

Total hysterectomy (removal of the uterus) is the only definitive cure for adenomyosis and is indicated for women with severe symptoms who have completed childbearing and have failed or declined conservative therapy. Hysterectomy reliably resolves bleeding and dysmenorrhea attributable to adenomyosis. Decisions about concurrent bilateral oophorectomy (removal of ovaries) depend on age, ovarian status, and risk factors for ovarian pathology; removal of ovaries induces surgical menopause and requires counseling regarding risks and benefits (ACOG guidance on hysterectomy indications).

Surgical approach (vaginal, laparoscopic, robotic, or open) depends on uterine size, coexisting conditions, surgeon skill, and patient preference.

Fertility and pregnancy considerations

Adenomyosis has been associated with impaired fertility and adverse pregnancy outcomes in some studies:

Associations include decreased implantation rates, increased miscarriage rates, preterm birth, preeclampsia, and increased cesarean delivery rates. The strength of these associations varies across studies, and confounding factors (such as coexisting endometriosis or fibroids) complicate interpretation (NCBI reviews).
For women desiring pregnancy, management emphasizes symptom control while attempting to preserve fertility. Options may include LNG‑IUD replacement after fertility treatment, short‑term suppression before assisted reproductive technologies (ART), or adenomyomectomy for focal lesions. IVF outcomes in women with adenomyosis may be improved by pre‑treatment with GnRH agonists in some studies, but data are heterogeneous.
Consultation with a reproductive endocrinologist is advised for individualized planning.

Counseling, quality of life, and supportive care

Adenomyosis can have substantial effects on physical functioning, emotional well‑being, sexual health, and work productivity. Clinicians should:

Screen for anemia and treat iron deficiency.
Provide clear information about diagnosis, expected benefits and limitations of therapies, and potential side effects.
Discuss fertility desires early and involve fertility specialists when appropriate.
Offer referral to pelvic pain specialists, pain management, pelvic physical therapy, or mental health services for chronic pain and quality‑of‑life concerns.
Encourage shared decision‑making when selecting conservative versus definitive therapy.

Prognosis and follow‑up

Medical therapies can provide meaningful symptom relief, but recurrence of symptoms may occur when therapy is discontinued. LNG‑IUD and continuous hormonal therapies often provide sustained control while in place.
Hysterectomy provides definitive resolution of uterine‑related bleeding and pain attributable to adenomyosis.
Regular follow‑up should monitor symptom control, side effects of therapy, and hematologic status.

Special situations and emerging therapies

Research continues into targeted therapies that modulate local estrogen production (aromatase inhibitors), novel oral GnRH antagonists, and minimally invasive ablative techniques. Longitudinal and randomized studies are needed to clarify long‑term efficacy and fertility outcomes.
In women with coexisting fibroids or endometriosis, management strategies often need to address multiple pathologies.

Practical approach algorithm (summary)

Clinical evaluation: history, pelvic exam, CBC.
Imaging: begin with transvaginal ultrasound; perform pelvic MRI if ultrasound inconclusive or if surgical planning is anticipated.
Initial management: for mild symptoms, NSAIDs and hormonal therapy (combined OCPs or progestin). For heavy bleeding, consider LNG‑IUD or tranexamic acid (during menses).
Reassess after an adequate trial (3–6 months). If symptoms persist and fertility preservation is desired, refer to reproductive specialist and consider conservative surgical options for focal disease. If fertility is not desired and symptoms are refractory, discuss hysterectomy.
Consider interventional radiology (UAE) or focused ultrasound in selected cases when surgery is contraindicated or undesired.

Key takeaways

Adenomyosis is a benign but potentially symptomatic condition in which endometrial tissue exists within the myometrium, producing uterine enlargement, heavy menstrual bleeding, and pelvic pain.
Diagnosis combines clinical assessment with imaging; MRI is the most accurate noninvasive test.
Management is individualized: medical therapies (NSAIDs, hormonal suppression, LNG‑IUD) are first‑line for many patients; minimally invasive procedures and surgery (adenomyomectomy or hysterectomy) are options for refractory disease or when definitive cure is required.
Fertility implications should be discussed; hysterectomy is contraindicated for women desiring future pregnancy.
Shared decision‑making, correction of anemia, and attention to quality of life are central to comprehensive care.

References and further reading

American College of Obstetricians and Gynecologists (ACOG). Patient education materials and committee opinions on abnormal uterine bleeding and hysterectomy indications. ACOG Practice Resources.
National Institutes of Health (NIH) / National Library of Medicine (NCBI). Review articles on adenomyosis: pathophysiology, diagnosis, and management in Obstetrics & Gynecology literature.
Mayo Clinic. Adenomyosis overview: symptoms, causes, diagnosis, and treatment. Mayo Clinic patient information.
Cleveland Clinic. Adenomyosis: causes, symptoms, diagnosis, and treatment options.

(For clinician‑level guidance and up‑to‑date evidence, consult specialty society guidelines, recent systematic reviews and randomized controlled trials comparing medical and interventional approaches.)