Approach

Key Points

Consider the possibility of adenomyosis if a woman presents with dysmenorrhea, menorrhagia, dyspareunia, and/or chronic pelvic pain.[2][11][49] Also be alert to the diagnosis in patients with unexplained subfertility, infertility, and/or adverse pregnancy outcomes and who may be otherwise asymptomatic.[2]

Be aware that adenomyosis is one of multiple differential diagnoses to consider if a woman presents with abnormal uterine bleeding (AUB), such as endometriosis, leiomyoma (uterine fibroids), polyps, endometrial hyperplasia, and malignancy.[3][49][50]

Obtain a detailed history in any patient with suspected adenomyosis, covering symptomatology, menstrual history, gynecologic history, obstetric history, and family history.[3][50]

Perform a pelvic examination, including speculum and bimanual examination; a mobile, diffusely enlarged, bulky, and tender uterus is highly suggestive of adenomyosis.[3][50]

Offer transvaginal ultrasound (TVUS) as the first-line investigation in all patients presenting with signs and symptoms suggestive of adenomyosis.[2][3][49][50][51] In adolescents, or if an adult patient declines TVUS, a transabdominal ultrasound or magnetic resonance imaging may be offered as an alternative.[3][50]

Definitive diagnosis generally only happens following hysterectomy and requires histopathologic confirmation of endometrial stroma and glandular tissue in the smooth muscle of the myometrium.

General principles

Adenomyosis is a noncancerous (benign) gynecologic condition characterized by the existence of endometrial-like tissue within the uterine myometrium.[2]

  • It is most commonly definitively diagnosed via histopathology in women between 35 years of age and menopause. Approximately 70% to 80% of women who undergo hysterectomy for adenomyosis are in the fourth or fifth decade of life.[9]

  • However, studies using magnetic resonance imaging (MRI)-based diagnostic criteria highlight that adenomyosis can be a cause of dysmenorrhea and chronic pelvic pain in women of all ages, including adolescents.[10][11]

  • After menopause, estrogen deficiency may decrease both symptoms and prevalence of adenomyosis; in one study, premenopausal and perimenopausal women had an increased prevalence of surgically confirmed adenomyosis at baseline compared with postmenopausal women not using hormone therapy (prevalence odds ratio [POR] 4.72, 95% CI 3.22 to 6.91 and 3.40, 95% CI 2.10 to 5.51, respectively).[12]

Consider the possibility of adenomyosis if a woman presents with dysmenorrhea, menorrhagia, dyspareunia, and/or chronic pelvic pain.[2][11][49]

  • Note, however, that around 30% of patients are asymptomatic and may be diagnosed incidentally following hysterectomy or in women with a history of subfertility and/or adverse pregnancy outcomes.[2][8]

Be aware that adenomyosis is one of multiple differential diagnoses to consider if a woman presents with abnormal uterine bleeding (AUB), such as endometriosis, leiomyoma (uterine fibroids), polyps, endometrial hyperplasia, and malignancy.[3][49][50]

The diagnosis of adenomyosis has traditionally relied on histopathologic examination (usually following hysterectomy), but recent interest has shifted toward using transvaginal ultrasound (TVUS) or MRI to make a diagnosis.[2][49] However, universally recognized diagnostic criteria are lacking for all modalities.

History

Patients with symptomatic adenomyosis may present with:

  • Dysmenorrhea (present in a reported 95% of cases).[2][17]

  • Abnormal uterine bleeding (AUB).

    • Approximately 65% of patients with adenomyosis experience menorrhagia.[2][17] Menorrhagia is defined based on the patient's perception of excessive blood loss that is heavy enough to interfere with quality of life (physically, socially, emotionally, and/or materially).[3][49][50]

    • Menstruation lasting >8 days is also defined as AUB by the International Federation of Gynecology and Obstetrics (FIGO).[49]

  • Dyspareunia (reported by 60%).[2][17]

  • Chronic pelvic pain (reported by 50% to 90%).[2][11][52]

  • Pressure symptoms (genitourinary or gastrointestinal).[3] In one cross-sectional study of 31 women with adenomyosis, 26% reported abdominal pressure symptoms.[53]

Be alert to the possibility of adenomyosis in patients who present with unexplained subfertility, infertility, and/or adverse pregnancy outcomes and who may be otherwise asymptomatic.[2]

  • In one study of 1015 patients undergoing assisted reproduction techniques following a history of infertility, pregnancy loss, or recurrent implantation failure, 24.4% were found to have sonographic signs of adenomyosis.[54]

  • One systematic review and meta-analysis found that adenomyosis was associated with a higher risk of adverse pregnancy outcomes including preterm delivery (odds ratio [OR] 2.65), preeclampsia (OR 4.32), pregnancy-induced hypertension (OR 3.11), cesarean section (OR 2.48), fetal malpresentation (OR 3.05), small for gestational age (OR 2.86), intrauterine growth restriction (OR 3.4), postpartum hemorrhage (OR 2.90), and placental malposition (OR 4.94).[55]

  • One literature review and meta-analysis assessing IVF/intracytoplasmic sperm injection (ICSI) outcomes found that women with adenomyosis had a reduced likelihood of clinical pregnancy compared with women without adenomyosis (clinical pregnancy rate of 41% in women with adenomyosis vs. 50% in those without).[56] The same study found that miscarriage occurred in 32% of women with adenomyosis compared with 14% of those without adenomyosis.[56]

Obtain a detailed history in any patient with suspected adenomyosis.[3][50] Ensure this covers:

  • Symptoms. Enquire about the presence and duration of each presenting symptom, including age of onset, frequency of symptom occurrence, and impact on quality of life. Ask in particular about pelvic pain and/or pressure symptoms.[3]

    • Dysmenorrhea, dyspareunia, and chronic pelvic pain are cardinal symptoms of both adenomyosis and endometriosis.[11] In one case-control study comparing symptoms among 255 women undergoing hysterectomy, pain symptoms predicted a higher likelihood of both adenomyosis and fibroids rather than fibroids alone being found on histology.[41]

  • Menstrual history. Obtain a full menstrual history, including age of menarche, menstrual bleeding pattern and severity (e.g., clots or flooding), and pain associated with bleeding.[50]

    • Early menarche may be a risk factor for the development of adenomyosis. In one large cohort study of 80,000 women, menarche at or before age 10 was associated with a 59% increase in prevalence of surgically confirmed adenomyosis compared with later age of menarche (prevalence odds ratio [POR] 1.59, 95% CI 1.26 to 2.01).[12]

    • The relationship between menstrual cycle length and the risk of adenomyosis remains inconclusive, although some studies suggest that shorter menstrual cycles may be associated with a higher risk.[12][39][43]

  • Gynecologic history, including any past history of endometriosis or uterine leiomyomas (fibroids).[50]

    • Adenomyosis shares key pathologic traits with endometriosis and has been shown to be present in approximately 65% of women with histologically proven endometriosis.[17][38]

    • Adenomyosis often occurs alongside leiomyomas; in women with leiomyomas who undergo hysterectomy, the prevalence of adenomyosis in the specimens ranges between 15% and 57%.[39][40][41]

    • A strong correlation has also been found between adenomyosis and endometrial hyperplasia.[4][39]

  • Obstetric history. Ask about any previous pregnancies and outcomes, as well as any history of miscarriage, ectopic pregnancy, pregnancy complications, and infertility (including assisted reproductive treatments and outcomes). Enquire about any previous cesarean sections.

    • While some studies have reported an association between parity and adenomyosis in hysterectomy patients, results have been inconsistent.[37] One study of 985 women undergoing TVUS revealed a positive correlation between the number of pregnancies and the risk of adenomyosis.[6]

    • Some studies have reported an association between spontaneous and induced abortions and an increased risk of adenomyosis, although the evidence is inconsistent.[39][40] Spontaneous and induced abortions may cause disruption of the endometrial-myometrial border if the pregnancy lasts longer than 9 weeks, due to peak trophoblast invasion during this time.[39][40]

    • Note that among parous women, those who have breastfed have been shown in some studies to have a decreased incidence of surgically confirmed adenomyosis compared with those who have never breastfed (POR 0.74, 95% CI 0.62 to 0.88).[12]

  • History of uterine surgery. Data from two studies conducted among hysterectomy patients suggested a positive association between past uterine surgery and adenomyosis.[9][43][44] Most studies have found no association between previous cesarean delivery and risk of adenomyosis, although one study did report a modest association.[4][5][43][45]

  • Family history of AUB, uterine conditions, and bleeding disorders.

Enquire about drugs taken, including herbal remedies and supplements.[50] Use of tamoxifen has been associated with a higher incidence of adenomyosis.[18][19] Note that use of certain drugs or herbal remedies can cause AUB, including:[50]

  • Anticoagulants (e.g., heparin, warfarin)

  • Hormonal contraceptives

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • Ginkgo

  • Ginseng

  • Motherwort.

Note that some studies have reported an increased prevalence of adenomyosis in Latina women compared with white women and in black women compared with Hispanic individuals.[12][42]

Physical exam

Perform a general physical exam in all patients with suspected adenomyosis, with a focus on excluding other potential causes of AUB. Note:

  • Body mass index (BMI). Obesity may be a pointer to anovulatory AUB. Evidence is inconsistent on whether a BMI ≥30 kg/m² is associated with a higher risk of adenomyosis.[12][43][45][48]

  • Signs of polycystic ovary syndrome (PCOS) (e.g., hirsutism and acne).

  • Signs of thyroid disease (e.g., thyroid nodule).

  • Signs of insulin resistance (e.g., acanthosis nigricans).

  • Findings suggestive of a bleeding disorder such as petechiae, ecchymoses, skin pallor, or swollen joints.

Perform a pelvic exam, including:[50]

  • External exam ± speculum exam (perform in all consenting adults and consider in consenting adolescents who are sexually active): inspect for visual abnormalities and to help exclude other pathologies that may be a cause of pelvic pain or bleeding symptoms, such as infection, vaginal lesions, or cervical lesions.

  • Bimanual exam (perform in all consenting adults and consider in consenting adolescents who are sexually active): a mobile, diffusely enlarged, bulky, and tender uterus is highly suggestive of adenomyosis.[3]

Differential diagnosis

The differential diagnosis of adenomyosis is extensive and often presents a clinical challenge. Many manifestations of adenomyosis, including AUB, dysmenorrhea, and infertility, can result from either adenomyosis alone or other commonly concurrent pathologies.

  • In patients with suspected adenomyosis, consider significant differentials based on the patient's age and presenting signs and symptoms.

Bear in mind that adenomyosis commonly co-occurs with other causes of AUB, such as endometriosis, uterine leiomyomas, and endometrial hyperplasia.[4][9][17][38][39]

  • For patients with AUB, the FIGO classification system employs the PALM-COEIN mnemonic to categorize potential causes for, or contributors to, a patient's symptoms, dividing them into structural factors (Polyp, Adenomyosis, Leiomyomas, Malignancy) and nonstructural factors (Coagulation, Ovulation, Endometrial, Iatrogenic), as well as a category for potential factors not otherwise classified (N).[49][57]

  • Adenomyosis is most commonly confirmed histopathologically in women ages 35 years to menopause. In this age group, anovulatory cycles are a common etiology of AUB (reflecting the normal physiologic decline in ovarian function). Other differentials to consider in this age group include endometrial hyperplasia, cancer, endometrial atrophy, or leiomyomas.[50]

Consider hysteroscopy and concomitant histopathologic analysis via endometrial biopsy to rule out malignancy in patients with AUB who are at high risk of endometrial pathology.[3][50]

See Evaluation of abnormal uterine bleeding.

Initial tests

The definitive method for diagnosing adenomyosis is via histopathologic exam.[50] However, in most cases, this only allows for retrospective diagnosis following hysterectomy. TVUS or MRI are now commonly used to make a clinical diagnosis of adenomyosis.[2][11][50]​ These imaging techniques are noninvasive and provide valuable information about the extent and location of adenomyotic lesions.

Note that there is still a lack of standardized diagnostic criteria for both imaging and histopathologic modalities.[2] Improved standardization and training are needed to enhance the accuracy of adenomyosis diagnosis.

Transvaginal ultrasound (TVUS)

Offer TVUS as the first-line investigation in all patients presenting with signs and symptoms suggestive of adenomyosis (in particular, significant dysmenorrhea and/or menorrhagia and/or a diffusely enlarged, bulky, tender, globular uterus on clinical exam).[2][3][49][50][51] Ultrasound is widely available and is generally well tolerated.[58]

  • Two-dimensional (2D) TVUS is the most commonly used imaging modality for diagnosing adenomyosis. Three-dimensional (3D) TVUS allows for better visualization of the junctional zone; one systematic review of the effectiveness of various nonsurgical methods for the diagnosis of adenomyosis found that combining 2D TVUS with 3D TVUS improved specificity from 64% with 2D TVUS alone to 81% when combined with 3D TVUS, without a significant difference in sensitivity (85% compared with 84%).[59]

  • TVUS is preferred over transabdominal ultrasound due to superior imaging capabilities, including higher resolution and better image quality, achieved through the utilization of higher transducer frequencies and the elimination of beam deformation caused by the ventral abdomen.[60]

    • In adolescents, or if an adult patient declines TVUS, a transabdominal ultrasound or MRI may be offered as an alternative.[3][50]

TVUS should be used to assess for direct and indirect features of adenomyosis.[61][62] Note that the presence of indirect features in the absence of direct features is not conclusive for the presence of adenomyosis.[62]

  • Direct features of adenomyosis are:

    • Cysts within the myometrium. If present, cysts may measure between 1 mm and 5 mm. These are a specific ultrasound finding for adenomyosis.[63][64]

    • Hyperechogenic islands.

    • Echogenic subendometrial lines or buds - indicate the existence of ectopic endometrial glands and stroma beyond the subendometrial layer.

  • Indirect features are:

    • Globular uterus. Note that this may also be seen if leiomyomas are present.

    • Asymmetric myometrial thickening.

    • Fan-shaped shadowing. The "Venetian blind" appearance with fan-shaped shadowing is a posterior acoustic artifact that can be caused by echogenic heterotopic myometrial tissue. Note that this finding can also be seen in women with leiomyoma.[65]

    • Translesional vascularity.

    • Ill-defined endomyometrial junction or irregular junctional zone. Considered suggestive of adenomyosis if junctional zone is poorly defined, irregular, or interrupted.

TVUS may also be used to assess for:[2][49]

  • Extent of disease, classified as mild (<25% of myometrium), moderate (25% to 50% of myometrium), or severe (>50% of myometrium).

  • Location of disease (anterior wall, posterior wall, left lateral, right lateral, fundus).

  • Size of the largest lesion or affected area.

  • Focal versus diffuse disease.

    • In focal disease, nodular aggregates of endometrial glands and stroma are surrounded by normal myometrium, whereas in diffuse disease there are endometrial glands and stroma distributed throughout the myometrium.[1] One group has proposed that an adenomyotic lesion should be classified as focal if >25% of the lesion is surrounded by normal myometrium and as diffuse if <25% is surrounded by normal myometrium.[1] If there is difficulty distinguishing focal from diffuse disease, the adenomyosis should be classified as diffuse.[1]

  • Uterine layer involvement (junctional zone, middle myometrium, or outer myometrium).

The limitations of ultrasound as a diagnostic test include the field of view and interobserver variability, which can affect its generalizability.[58]

MRI

Do not use MRI as a routine investigation for suspected adenomyosis.[51] MRI may be appropriate, where available:

  • for surgical or interventional treatment planning[2][50]

  • following TVUS if there is inconclusive sonographic evaluation of adenomyosis or if there is suspicion of significant coexisting pelvic pathology[2][51]

  • for women who decline TVUS or for whom it is unsuitable (e.g., adolescents).[3][49]

MRI has lower false-positive rates and reduced interobserver variability when compared with TVUS.[2]

  • MRI has a similar sensitivity to TVUS (reported range: 77% to 78%), but its specificity is higher (reported range: 88% to 93%).[66][67][68]

  • The positive likelihood ratio for adenomyosis (the probability that a positive test would be expected in a patient with the condition divided by the probability that a positive test would be expected in a patient without the condition) is higher with MRI compared with TVUS (11.98 vs. 4.93, respectively).[67]

  • MRI is better able than TVUS to differentiate between adenomyosis and leiomyomas (uterine fibroids).[49][68]

MRI can be used to diagnose adenomyosis by evaluating the thickness of the junctional zone, which appears as a distinct T2 hypointense band separating the T2-hyperintense endometrium and the intermediate-intensity myometrium.[69]

  • T2 hypointense junctional zone thickness >12 mm is indicative of adenomyosis (with a sensitivity of 72% and specificity of 86%), while a thickness <8 mm excludes the disease.[70]

  • T2 hyperintense foci can be observed, representing cystic dilation of the endometrial glands. These are similar to anechoic myometrial cysts seen on TVUS.[63][71]

  • T1 signal hyperintensity can be seen if hemorrhage occurs in these foci. This is highly specific (up to 95%) for adenomyosis.[63][71]

Direct features of adenomyosis that may be seen on MRI include:

  • myometrial cysts (sensitivity of 60% and specificity of 96%)[72]

  • adenomyoma (a myometrial mass that does not involve the uterine serosa or junctional zone)[73]

  • external adenomyosis (involvement of the serosa but not the junctional zone).[73]

Diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) images are beneficial.[58] DWI can be helpful in differentiating between benign and malignant neoplasms when characterizing lesions.[74][75] DCE is useful to distinguish endometrial pathology, such as polyps and tumors, from myometrial lesions such as fibroids, as myometrial lesions are typically hypovascular.[76]

Note that MRI should not be performed during menstruation or the early proliferative phase to avoid pseudo-widening of the junctional zone, which can occur due to decreased signal intensity of the myometrium.[72]

There is limited research associating specific features of adenomyosis on MRI with clinical symptoms and symptom severity.[77]

[Figure caption and citation for the preceding image starts]: Sagittal MRI of a woman's pelvis showing a uterus with adenomyosis in the posterior wall. Gross enlargement of the posterior wall is noted, with many foci of hyperintensityCase courtesy of Dr Varun Babu, Radiopaedia.org. From the case rID: 43504; reproduced under the Creative Commons CC BY-SA 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/) [Citation ends].com.bmj.content.model.Caption@62a1a1d1

Other tests

Histologic diagnosis of adenomyosis following hysterectomy

Histopathologic diagnosis (usually following hysterectomy) is considered the definitive method for confirming adenomyosis; this involves identifying the presence of endometrial stroma and glandular tissue within the smooth muscle of the myometrium.[78]

  • This can provide a definitive diagnosis in women who have no wish for future fertility and in whom hysterectomy is considered the most appropriate option for managing adenomyosis.[2]

  • In women who desire future fertility, or when hysterectomy is not feasible or not acceptable to the patient, imaging remains the most appropriate modality to make a clinical diagnosis.[16]

Note that there are no universally accepted histologic criteria for diagnosing adenomyosis, and the accuracy of diagnosis can be influenced by several factors including:[2]

  • Variability in the depth of myometrial invasion, which plays a crucial role in categorizing the pathology as adenomyosis.[16]

  • Extent of uterine sectioning during tissue sampling.[79]

  • Interobserver variability.[79]

Hysterosalpingography (HSG)

Note that although HSG is not typically used to diagnose adenomyosis, it is often performed on patients with infertility who may also have adenomyosis; as a result, adenomyosis may be incidentally detected during an HSG exam.[80]

  • Adenomyosis is characterized by heterotopic endometrial foci that extend into the myometrium, which also fills with contrast. As a result, patients with adenomyosis often exhibit a distinct appearance of contrast outpouching into the myometrium at the margins of the endometrial cavity.[80]

Tissue-sampling techniques

Fertility-sparing tissue-sampling techniques are under investigation for their potential to obtain diagnostic samples while preserving reproductive potential.[2] Directed tissue-sampling techniques are reserved for specific scenarios in which confirmatory diagnosis may be of benefit.[2] If laparoscopy is performed for other fertility-sparing reasons and there is a preliminary suspicion of adenomyosis, such biopsy techniques may have a role in providing a confirmatory diagnosis and guiding future surgical treatment recommendations for these patients.[81]

These techniques can be performed either through intrauterine tissue sampling using a hysteroscopic approach or via extrauterine sampling, where a myometrial biopsy is obtained through ultrasound or laparoscopy guidance.[81]

The sensitivity of these tissue-sampling techniques varies significantly, ranging from 22.3% to 97.8%, with the highest sensitivity being reported for laparoscopic-guided uterine biopsy with a 14-gauge needle.[82] The variation in sensitivity may be influenced by factors such as the number and location of biopsies, as well as the technique employed for biopsy collection.[81] The specificity of these techniques is generally higher, ranging from 78.5% to 100%.[81]

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