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Top 15 Differential Diagnoses

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🔴 HIGH PRIORITY (Most Likely)

1. Endometriosis

• Why: The #1 cause of severe dysmenorrhoea in adolescents. Ectopic endometrial glands/stroma implant on pelvic peritoneum, ovaries, or bowel — causing cyclic inflammatory pain, heavy bleeding, and secondary iron-deficiency anaemia. Can cause apparent endometrial thickening on ultrasound due to adenomyosis-like changes.
• Typical/Atypical features: Cyclic pelvic pain, dyspareunia, dyschezia; atypically may present as non-cyclic chronic pain. Often under-diagnosed by years in teenagers.
• — Tintinalli's Emergency Medicine, Table 38-4: "Endometrial glands and stroma outside of the normal location... dysmenorrhea or pain"

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2. Anovulatory Dysfunctional Uterine Bleeding (DUB) with Iron-Deficiency Anaemia

• Why: Unopposed oestrogen from anovulatory cycles leads to continuous endometrial proliferation → thickened endometrium → irregular, prolonged, heavy bleeding → iron-deficiency anaemia. Extremely common in the first 1–3 years post-menarche while the hypothalamic-pituitary-ovarian axis matures.
• Atypical feature: Pain may be from endometrial cramping rather than structural cause.
• — Textbook of Family Medicine 9e: "It is normal for menstrual cycles to be anovulatory for an average of 18 months after menarche… menorrhagia is most often caused by anovulation"

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3. Polycystic Ovary Syndrome (PCOS)

• Why: PCOS-related anovulation causes unopposed oestrogen → endometrial hyperplasia/thickening → heavy/irregular bleeding → anaemia. Dysmenorrhoea occurs when bleeding is eventually heavy. One of the most common causes of anovulatory bleeding in adolescents.
• Key features: Irregular cycles, hyperandrogenism (acne, hirsutism), polycystic ovaries on USS.
• — Textbook of Family Medicine 9e: "The majority of anovulation is related to hypothalamic abnormalities or polycystic ovarian syndrome (PCOS)"

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4. Endometrial Polyp

• Why: Polyps cause abnormal uterine bleeding (AUM — PALM-COEIN classification: Polyp), thickened or irregular endometrial echo on USS, and painful cramping as the uterus tries to expel the polyp. Can cause significant blood loss → anaemia.
• Atypical feature: May be asymptomatic or mistaken for endometrial hyperplasia on USS.
• — Textbook of Family Medicine 9e, PALM-COEIN classification: Polyp listed as structural cause

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5. Von Willebrand Disease (vWD) / Coagulopathy

• Why: Up to 24% of adolescents presenting with menorrhagia have an undiagnosed bleeding disorder. vWD is the most common; others include platelet function disorders. Heavy bleeding → anaemia. Pain from large clots passed.
• Key features: Mucocutaneous bleeding (epistaxis, easy bruising), family history of bleeding.
• — Textbook of Family Medicine 9e: "Up to 24% of adolescents with menorrhagia may have an undiagnosed bleeding disorder (Strickland, 2004)"
• — The Washington Manual: "Clinical findings consist of mucocutaneous bleeding (epistaxis, menorrhagia, GI bleeding), easy bruising"

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🟠 MODERATE PRIORITY

6. Adenomyosis

• Why: Endometrial glands invade the myometrium → bulky uterus, thickened endometrium, severe dysmenorrhoea, and heavy bleeding. Classically a disease of older parous women but increasingly recognised in adolescents, especially those with endometriosis.
• PALM-COEIN: Adenomyosis (structural cause).

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7. Uterine Leiomyoma (Fibroids)

• Why: While rare in teenagers, submucosal fibroids cause heavy bleeding, thickened/distorted endometrium, and severe dysmenorrhoea → iron-deficiency anaemia. PALM-COEIN: Leiomyoma.
• Atypical feature: In adolescents, associated with genetic predisposition or hereditary leiomyomatosis.

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8. Endometrial Hyperplasia

• Why: Prolonged oestrogen stimulation (from anovulation, PCOS, obesity) → endometrial gland proliferation → thick endometrium → menorrhagia and pain. Risk of progression to malignancy with atypia, though rare in this age group.
• PALM-COEIN: Malignancy and Hyperplasia (structural).

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9. Hypothyroidism

• Why: Thyroid hormone deficiency → menorrhagia via multiple mechanisms (anovulation, coagulopathy — decreased vWF and factor VIII), secondary anaemia, and dysmenorrhoea. Also causes endometrial build-up due to prolonged anovulatory cycles.
• Key features: Fatigue, cold intolerance, weight gain, constipation, dry skin — easily missed in teens.
• — Rosen's Emergency Medicine: Oligomenorrhea and menorrhagia listed under reproductive effects of thyroid dysfunction

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10. Iron-Deficiency Anaemia (Primary / Nutritional)

• Why: In a teenage girl, dietary inadequacy combined with menstrual loss may cause anaemia independently, which also worsens menorrhagia (by impairing platelet function and uterine contractility), creating a feedback cycle that intensifies pain from a hypoxic, contracting uterus.
• Atypical feature: May present before any underlying gynaecological cause is identified.

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11. Pelvic Inflammatory Disease (PID)

• Why: Ascending infection (chlamydia, gonorrhoea, anaerobes) → endometritis → thickened, inflamed endometrium → pelvic pain and abnormal bleeding. Anaemia from chronic inflammation (anaemia of chronic disease).
• Key features: Cervical motion tenderness, mucopurulent discharge, fever — though atypical/subclinical PID in teens can be subtle.

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🟡 LOWER PRIORITY (Must Not Miss)

12. Ovarian Cyst / Haemorrhagic Ovarian Cyst

• Why: Functional or haemorrhagic ovarian cysts can cause pelvic pain mimicking dysmenorrhoea, distort the adnexa/endometrium on ultrasound, and bleed sufficiently to cause anaemia. Endometriomas ("chocolate cysts") directly cause endometriosis.
• Atypical feature: Acute rupture causes sudden severe pain and haemoperitoneum.

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13. Cervical Stenosis / Outflow Obstruction (e.g. Imperforate Hymen, Haematometra)

• Why: Partial or complete outflow obstruction → retrograde menstruation → haematometra (blood-filled uterus = apparent endometrial thickening), severe dysmenorrhoea, and secondary anaemia.
• Key features: Primary or secondary amenorrhoea with cyclic pain, absent flow, bulging hymen.
• — Textbook of Family Medicine 9e: "Structural abnormalities (e.g., transverse vaginal septum or imperforate hymen)" listed in primary amenorrhoea causes

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14. Leukaemia / Haematological Malignancy

• Why: Bone marrow infiltration → thrombocytopenia + anaemia → menorrhagia and systemic anaemia. The uterus may show thickening from endometritis or coagulopathic congestion.
• Must not miss: Acute leukaemia in adolescents can present as heavy abnormal uterine bleeding.
• Key features: Fatigue, pallor, lymphadenopathy, hepatosplenomegaly, petechiae, recurrent infections.

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15. Endometrial/Cervical Malignancy (rare) or Hereditary Gynaecological Cancer Syndrome

• Why: Extremely rare in a 16-year-old but must be considered if symptoms are refractory, endometrial biopsy shows atypia, or there is a family history (e.g., Lynch syndrome → endometrial cancer risk). Thickened endometrium with abnormal bleeding is the hallmark presentation.
• PALM-COEIN: Malignancy (structural).

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Summary Table

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Recommended Initial Workup

• FBC + film (anaemia type, blasts for leukaemia)
• Coagulation screen + vWF antigen/activity (exclude bleeding disorder)
• Thyroid function tests (TSH, free T4)
• Pelvic ultrasound (endometrial thickness, ovarian morphology, structural lesions)
• Iron studies (ferritin, serum iron, TIBC)
• Hormonal profile (LH, FSH, prolactin, androgens — PCOS workup)
• STI screen (chlamydia, gonorrhoea — if sexually active, for PID)
• Laparoscopy if endometriosis/adenomyosis strongly suspected and ultrasound inconclusive