Adenomyosis

Adenomyosis is a benign, estrogen-dependent condition defined by the presence of endometrial glands and stroma within the myometrium, surrounded by hypertrophic and hyperplastic smooth muscle.^[1] It is a genuinely distinct diagnosis from endometriosis — where similar endometrium-like tissue implants outside the uterus altogether — even though the two conditions share much of the same hormonal biology, share several of the same treatments, and are frequently found together in the same patient (see Assessment & Diagnosis).^[2] Roughly a third of patients are asymptomatic, with the disease found incidentally on imaging performed for another reason.^[2] A major point of diagnostic uncertainty runs through this entire chapter: adenomyosis was traditionally a diagnosis of exclusion confirmed only by histologic examination of a hysterectomy specimen, and more than 80% of women with the disease historically ended up undergoing hysterectomy.^[2] Current Canadian guidance supports a non-invasive diagnostic approach using transvaginal ultrasound and MRI, and empiric medical therapy started on that basis, without requiring surgical or histologic confirmation first — but pharmacists should understand that neither imaging modality is perfectly sensitive or specific, so a degree of diagnostic uncertainty is inherent to this disease in a way it is not for many other conditions in this library.^[1] This chapter deliberately does not re-teach the full hormonal-therapy ladders already owned by the Dysmenorrhea, Heavy Menstrual Bleeding, and Endometriosis chapters — see those chapters for shared content, cross-referenced throughout below.

The 3 cardinal symptoms are heavy menstrual bleeding (reported in 40-60% of symptomatic patients), dysmenorrhea (15-30%), and chronic pelvic pain, with deep dyspareunia also reported; any combination — or none of these, given how often the disease is asymptomatic — can occur.^[2] Symptom severity does not reliably track with the extent of myometrial involvement seen on imaging.

Examination

The classic finding is a diffusely, symmetrically enlarged, soft ("boggy"), and tender uterus, with tenderness often most pronounced just before or during menses — this symmetric, globular enlargement is a useful bedside clue that distinguishes adenomyosis from the irregular, asymmetric enlargement typical of uterine fibroids (see the comparison table in Assessment & Diagnosis). A normal pelvic examination does not exclude the diagnosis, particularly for focal disease.

• Any prior uterine surgery or instrumentation that disrupts the endometrial-myometrial junction — Cesarean delivery, dilation and curettage, myomectomy, or other uterine instrumentation.
• Multiparity.
• Advancing reproductive age — adenomyosis is most often diagnosed in the 4th and 5th decades of life, though it is increasingly recognized in younger and infertile patients as imaging quality and clinician familiarity with its ultrasound features improve.
• Coexisting uterine leiomyoma (fibroids) — roughly half of patients with adenomyosis also have fibroids, and each condition independently raises the likelihood the other is also present.^[2]
• Coexisting endometriosis — the reverse association also holds; see Assessment & Diagnosis for how often the two conditions are found together.
• Early age at menarche has been proposed as a risk factor, though the supporting evidence is weaker and less consistent than for endometriosis.

History and examination

Characterize the bleeding pattern, dysmenorrhea, and any chronic pelvic pain or dyspareunia; ask specifically about prior Cesarean delivery, dilation and curettage, or other uterine instrumentation, and about fertility goals, which materially change the management approach (see Choose Initial Treatment and Special Populations). On bimanual examination, a symmetrically enlarged, soft, tender ("boggy") uterus supports the diagnosis, though a normal examination does not exclude it.

Imaging — the primary diagnostic tools, and their real limitations

Transvaginal ultrasound (TVUS) is the first-line investigation given its accessibility and lower cost. Consensus (MUSA-style) sonographic features fall into 2 groups: direct signs — myometrial cysts, hyperechoic islands, echogenic subendometrial buds/lines, and translesional vascularity on Doppler — and indirect signs — asymmetric myometrial thickening, globular uterine enlargement, fan-shaped shadowing, and an irregular or interrupted junctional zone. A junctional-zone maximum thickness of 8 mm or more on TVUS, fan-shaped striations, and the so-called "question mark" sign are among the more specific individual findings. Reported diagnostic accuracy varies widely by study and by which specific features are used, averaging around 78-85% sensitivity and 64-71% specificity in recent pooled data — meaningfully imperfect, and highly operator-dependent.^[3]

MRI trades sensitivity for specificity relative to TVUS (pooled figures of roughly 65-77% sensitivity but 87-89% specificity) and is the more useful confirmatory or problem-solving test — particularly when TVUS is equivocal, when a focal lesion needs to be distinguished from a fibroid before planning a fertility-sparing procedure, or when coexisting deep infiltrating endometriosis is also suspected (see the Endometriosis chapter). Key MRI features include a widened junctional zone (generally 12 mm or more), hyperintense myometrial foci and linear striations on T2-weighted sequences (representing ectopic endometrial glands and hemorrhage), and, for focal disease, an ill-defined T2-hypointense mass without the well-circumscribed pseudocapsule typical of a fibroid.^[3]

No blood test or tumour marker reliably diagnoses adenomyosis — none is part of routine workup for this indication.

Adenomyosis, fibroids, and endometriosis: distinguishing and overlapping features

Adenomyosis is the "A" in the FIGO PALM-COEIN classification of structural causes of abnormal uterine bleeding used throughout this platform (see the Heavy Menstrual Bleeding chapter for the full framework).^[5] Identifying adenomyosis on imaging does not exclude a second, concurrent PALM-COEIN cause — the same structural workup described in that chapter (pelvic ultrasound, and endometrial biopsy when age or risk factors warrant it) still applies whenever adenomyosis is found.

• Reduce menstrual blood loss and relieve dysmenorrhea/chronic pelvic pain to a degree that no longer interferes with the patient's quality of life.
• Identify and directly correct any resulting iron-deficiency anemia — see the Heavy Menstrual Bleeding chapter for anemia workup and treatment, which applies identically here.
• Avoid unnecessary hysterectomy where a fertility-sparing or uterus-sparing medical or procedural option can achieve adequate symptom control, while still identifying the patients who genuinely need definitive surgery.
• Preserve fertility potential and, where pregnancy is being actively pursued, address adenomyosis's own independent negative effect on IVF/ICSI success (see Special Populations) rather than treating it as identical to a fertility-neutral diagnosis.
• Minimize treatment-related adverse effects, particularly the bone mineral density loss associated with prolonged hypoestrogenic GnRH-agonist therapy.

• Have the patient track bleeding and pain using the same pad/tampon-diary approach described in the Heavy Menstrual Bleeding chapter — it both quantifies baseline severity and gives an objective way to judge whether treatment is working.
• Iron-rich dietary counselling for a patient with or at risk of iron-deficiency anemia, alongside — not instead of — oral iron supplementation when indicated.
• Before LNG-IUS insertion, counsel that irregular spotting is expected for the first 3-6 months and does not mean the device has failed; advise waiting at least 6 cycles before judging its effect on bleeding and pain.

Pregnancy

No ovarian-suppressing hormonal therapy (CHC, dienogest or another progestin used for suppression, LNG-IUS insertion, or a GnRH agonist) is started or continued once a patient is pregnant. Manage breakthrough pain with acetaminophen first; avoid NSAIDs from around 20 weeks gestation onward given the risk of fetal renal impairment and premature closure of the ductus arteriosus with later use — the same caution that applies in the Endometriosis chapter. Some observational studies have reported an association between adenomyosis and adverse pregnancy outcomes, including preterm birth, preeclampsia, and postpartum hemorrhage, though the evidence is heterogeneous and adenomyosis is not itself an indication for any specific antenatal intervention beyond standard risk-based obstetric care.

Breastfeeding

Progestin-only options (the LNG-IUS, oral dienogest, or another oral progestin) are generally preferred over an estrogen-containing option if suppressive therapy is needed while breastfeeding, consistent with the Dysmenorrhea and Endometriosis chapters.

Adolescents

Adenomyosis is diagnosed far less often in adolescents than in patients in their 40s, but consider it in an adolescent with heavy bleeding and/or dysmenorrhea that does not respond to an adequate NSAID and hormonal-contraceptive trial, alongside the broader differential covered in the Heavy Menstrual Bleeding chapter (a bleeding disorder, in particular, needs to be excluded first in this age group). First-line hormonal options remain the same as in adults; use a GnRH agonist more cautiously given ongoing bone mass accrual through adolescence, reserved for severe, refractory disease with mandatory add-back therapy.

Perimenopausal patients

Because adenomyosis is estrogen-dependent, symptoms characteristically improve and the disease itself regresses after natural menopause. For a perimenopausal patient with tolerable symptoms, this makes a time-limited medical "bridge" (hormonal or non-hormonal therapy, reassessed periodically as menopause approaches) a reasonable alternative to proceeding straight to hysterectomy, and this expectation is worth discussing explicitly when the patient is weighing definitive surgery against continued medical management. Any bleeding occurring after actual menopause is a red flag requiring its own workup, never attributed to a prior adenomyosis diagnosis (see Red Flags & Refer).

Patients desiring pregnancy (fertility considerations)

Adenomyosis carries its own independent negative association with IVF/ICSI outcomes, distinct from — and in addition to — any effect from coexisting endometriosis; meta-analytic data have reported a meaningfully decreased probability of clinical pregnancy with adenomyosis present.^[2] Ovarian-suppressing hormonal therapy is not used to manage adenomyosis-related infertility, since it prevents pregnancy; for a patient with pain who is not yet ready to conceive, NSAIDs alone are the appropriate pharmacologic option while a fertility-focused plan is developed. Refer to a fertility specialist for assessment — a time-limited course of GnRH-agonist down-regulation before a planned IVF/ICSI cycle is one strategy that has been studied specifically in adenomyosis with the aim of improving implantation outcomes, and should be considered as part of a specialist-directed fertility plan rather than routine adenomyosis management.^[1]

Reassess bleeding and pain severity after an adequate trial of any new therapy — generally 3-6 months, allowing for the LNG-IUS's expected early irregular-spotting phase — before judging it a failure and switching. Recheck CBC (and ferritin if previously low) to confirm anemia is resolving on the chosen regimen plus iron repletion, per the Heavy Menstrual Bleeding chapter. For a patient on a GnRH agonist beyond 6 months, follow the same bone-health monitoring and add-back-therapy reinforcement described in the Endometriosis chapter. Do not repeat imaging routinely in a patient whose symptoms are adequately controlled — reserve repeat ultrasound or MRI for a change in the bleeding or pain pattern, a new red-flag symptom, or specific pre-procedural planning. For a perimenopausal patient on a medical bridge, periodically reassess whether continued treatment is still needed as natural menopausal symptom resolution approaches.

1. Confirm correct use and that a genuinely adequate trial has elapsed (generally 3-6 months, allowing for the LNG-IUS's expected early irregular-bleeding phase) before calling any therapy a failure.
2. Reassess the diagnosis — re-image if the bleeding or pain pattern has changed since the original workup, and specifically look for coexisting endometriosis, a fibroid, an endometrial pathology, or an undiagnosed bleeding disorder that was not part of the original assessment.
3. If only 1 first-line hormonal option has been tried (for example, the LNG-IUS alone), switch to a different first-line class — continuous CHC or oral dienogest — before escalating further.
4. If a hormonal option alone gives incomplete relief, add tranexamic acid and/or an NSAID rather than assuming the hormonal option has entirely failed.
5. If first-line hormonal options have genuinely failed an adequate trial, or are contraindicated, consider a time-limited GnRH-agonist trial with mandatory add-back therapy — particularly useful as a bridge before a planned uterine-sparing procedure.
6. Refer for gynecologic surgical evaluation once medical therapy is genuinely exhausted: a uterine-sparing option if fertility or the uterus itself is to be preserved (setting realistic expectations given the more limited evidence base for these procedures), or hysterectomy if childbearing is complete and the patient wants definitive treatment.

• Requiring histologic or hysterectomy-based confirmation before starting empiric medical therapy in a patient with a classic history and a supportive imaging pattern.
• Treating a positive ultrasound or MRI finding as a certain diagnosis, or a negative/equivocal one as fully excluding adenomyosis — both modalities are meaningfully imperfect against the traditional histologic reference standard.
• Attributing new postmenopausal bleeding to a previously known adenomyosis diagnosis instead of investigating it as postmenopausal bleeding.
• Missing a coexisting fibroid, endometriosis, or bleeding disorder because the adenomyosis finding on imaging was assumed to fully explain the presentation.
• Using any ovarian-suppressing hormonal therapy, or an NSAID beyond about 20 weeks gestation, in a pregnant patient.
• Prescribing dienogest or the LNG-IUS for adenomyosis without counselling the patient that this use is off-label in Canada (dienogest is labelled for endometriosis-associated pain; the LNG-IUS is labelled for idiopathic menorrhagia).
• Continuing a GnRH agonist beyond 6 months without adding estrogen-progestogen add-back therapy.
• Recommending endometrial ablation without counselling that deep myometrial involvement lowers the chance of durable symptom relief.
• Prescribing tranexamic acid without checking for a personal/family thrombosis history, or before the cause of irregular bleeding has been established, per the same caution that applies in the Heavy Menstrual Bleeding chapter.
• Applying the same fertility-preservation reasoning used for endometriosis without recognizing that adenomyosis has its own independent, additional negative association with IVF/ICSI success.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Non-Hormonal Options

Antifibrinolytic and NSAIDs

Taken only on heavy-flow days, exactly as described in the Heavy Menstrual Bleeding chapter. Listed here only to show typical adult dosing for a patient presenting with adenomyosis-associated bleeding; see that chapter for the complete class detail, contraindications, and renal adjustment.

Hormonal Therapy

Levonorgestrel-releasing intrauterine system

The single most effective medical option for adenomyosis-associated bleeding and pain, and simultaneously long-acting contraception. Full device detail (insertion, approved durations, and the distinction between its contraception-only and menorrhagia-treatment approved durations) is in the Heavy Menstrual Bleeding chapter.

Oral progestin

Dienogest has the strongest dedicated randomized, placebo-controlled trial evidence specifically in adenomyosis of any oral hormonal agent — a 16-week trial found significant reductions in adenomyosis-associated pain versus placebo.

Combined hormonal contraceptive (continuous)

An alternative when the LNG-IUS is declined or unsuitable and the patient prefers an estrogen-containing option. Confirm no CHC contraindication first — see the Dysmenorrhea or Endometriosis chapter for the full contraindication list and ACHES counselling.

2nd-Line and Refractory-Disease Options

A time-limited GnRH agonist with mandatory add-back hormone therapy — the identical regimen and dosing already detailed in the Endometriosis chapter's Drug Tables (leuprolide acetate, goserelin, triptorelin, or nafarelin, each requiring add-back for any course beyond a brief initial trial) — is used for adenomyosis refractory to first-line therapy, or as a pre-procedural bridge to reduce uterine/lesion volume before a planned uterine-sparing procedure.^[1] GnRH antagonists (elagolix, or the relugolix/estradiol/norethindrone acetate combination) are Health Canada-approved only for endometriosis-associated pain — using either for adenomyosis specifically is off-label and should be reserved for specialist-directed refractory cases; see the Endometriosis chapter's Drug Tables for their full dosing and contraindications.