dysfunctional uterine bleeding
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"dysfunctional uterine bleeding" OR "abnormal uterine bleeding"
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Dysfunctional Uterine Bleeding (DUB)
Definition and Modern Terminology
Dysfunctional uterine bleeding (DUB) refers to uterine bleeding that lacks an underlying structural abnormality - it is a diagnosis of exclusion. The bleeding stems primarily from hormonal disturbances rather than from organic pathology such as polyps, fibroids, endometritis, or neoplasms.
Note on current nomenclature: The term "dysfunctional uterine bleeding" has been largely replaced in modern gynecology by the broader term Abnormal Uterine Bleeding (AUB), with the FIGO classification system using the PALM-COEIN acronym to categorize causes (see below). However, DUB remains in widespread clinical and pathology use, particularly in reference to anovulatory and ovulatory hormonal causes without structural lesions.
- Tintinalli's Emergency Medicine, p. 649
Pathophysiology
Normal menstruation requires the finely-timed, cyclical interplay of the hypothalamic-pituitary-ovarian (HPO) axis. Any disruption produces DUB. There are two main mechanisms:
1. Anovulatory DUB (Most Common)
The most frequent cause of DUB is failure to ovulate. Without ovulation:
- No corpus luteum forms
- Progesterone is absent
- Estrogen stimulates the endometrium unopposed, causing continuous proliferation
- The endometrium becomes thickened and eventually sheds irregularly, producing unpredictable, often heavy bleeding
- Bleeding tends to occur at less frequent intervals than organic causes
This is most common at two extremes:
- Menarche: Immaturity of the HPO axis
- Perimenopause: Incipient ovarian failure
Robbins & Kumar Basic Pathology, p. 595; Goldman-Cecil Medicine, p. 2555
2. Ovulatory DUB (Luteal Phase Defect)
Less common. Results from an inadequate luteal phase - insufficient progesterone production by the corpus luteum - leading to early endometrial breakdown.
Causes of Anovulation
| Category | Examples |
|---|---|
| Physiological | Perimenarchal, perimenopausal fluctuations in HPO axis |
| Endocrine disorders | Thyroid disease (hypo/hyperthyroidism), adrenal disease, Cushing syndrome, pituitary prolactinoma (elevates prolactin, suppresses GnRH → reduced LH/FSH) |
| Ovarian lesions | Polycystic ovary syndrome (PCOS), granulosa cell tumors |
| Metabolic disturbances | Obesity, malnutrition, chronic systemic diseases, eating disorders, excessive exercise |
| Other | Liver disease (impairs estrogen metabolism), renal disease, stress |
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 927; Tintinalli's, p. 651
Causes of AUB by Age Group (PALM-COEIN Framework)
The modern PALM-COEIN classification distinguishes:
- Structural (PALM): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia
- Non-structural (COEIN): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not otherwise classified
| Age Group | Common Causes |
|---|---|
| Prepuberty | Precocious puberty (hypothalamic, pituitary, or ovarian origin) |
| Adolescence | Anovulatory cycle, coagulation disorders (von Willebrand disease most common - up to 20% of heavy bleeders) |
| Reproductive age | Pregnancy complications (ectopic, miscarriage), leiomyomas, adenomyosis, polyps, endometrial hyperplasia, anovulatory/ovulatory DUB, oral contraceptive use |
| Perimenopausal | Anovulatory DUB, anatomic lesions (carcinoma, hyperplasia, polyps) |
| Postmenopausal | Endometrial atrophy (most common), anatomic lesions (carcinoma, hyperplasia, polyps) |
Robbins & Kumar Basic Pathology (Table 17.2); Goldman-Cecil Medicine, p. 2555
Histopathology
Fig. 22.20 - Robbins, Cotran & Kumar: Common causes of abnormal uterine bleeding. (C) shows the hallmark of anovulatory DUB - proliferative endometrial glands with stromal breakdown in the absence of secretory transformation.
In anovulatory DUB, the endometrium shows:
- Proliferative phase glands (no secretory transformation because progesterone is absent)
- Stromal breakdown and areas of irregular shedding
- No predecidual change
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 927
Clinical Features
- Normal menstrual blood loss: ≤30 mL per cycle; >80 mL is abnormal
- Normal cycle: 4.5-8 days duration, 24-38 day interval
- DUB is typically painless, in contrast to dysmenorrhea associated with endometriosis or fibroids
- Anovulatory DUB: irregular, unpredictable, often heavy; prolonged amenorrhea followed by heavy bleeding
- Signs of anemia in severe/chronic cases
- Hirsutism, obesity, galactorrhea may point toward endocrinologic causes (PCOS, hyperprolactinemia)
Tintinalli's Emergency Medicine, p. 649; Goldman-Cecil Medicine, p. 2555
Diagnosis (Exclusion-Based)
DUB is a diagnosis of exclusion. Always rule out:
Step 1 - History: Bleeding pattern (duration, frequency, amount), family history of bleeding disorders, medications (OCP, anticoagulants, SSRIs, tamoxifen, herbal supplements like ginseng), sexual history
Step 2 - Exclude pregnancy (urine/serum hCG - mandatory)
Step 3 - Physical examination: Hemodynamic stability, pelvic exam, speculum exam to exclude cervical/vaginal causes
Step 4 - Laboratory tests:
- Complete blood count, platelets
- Coagulation studies (including von Willebrand disease screen: heavy menses since menarche, postpartum hemorrhage, surgery/dental bleeding, bruising)
- Thyroid function tests (TSH)
- Fasting glucose
- Serum prolactin if suspected
Step 5 - Endometrial sampling (biopsy or D&C):
- All women >35 years with abnormal bleeding
- Any patient with risk factors for endometrial carcinoma (prolonged anovulatory bleeding, obesity, diabetes, unopposed estrogen)
Step 6 - Imaging: Transvaginal ultrasound or sonohysterography to exclude polyps, fibroids, and structural lesions
Goldman-Cecil Medicine, p. 2556; Tintinalli's, p. 649
Treatment
Management depends on acuity, age, and desire for fertility.
A. Acute / Massive Bleeding (ED Setting)
| Agent | Dose | Notes |
|---|---|---|
| Conjugated equine estrogen (IV) | 25 mg IV every 4-6 hours (up to 3 doses) | Stops bleeding within hours; give antiemetics; contraindicated if VTE, thrombophilia, vascular disease, or malignancy |
| Combined OCP | 1 pill every 6 hours x 5-7 days (off-label) | Bleeding should cease within 24 hours; warn patient of withdrawal bleed 2-4 days after stopping |
| Tranexamic acid | As per local protocol | Antifibrinolytic; useful in ovulatory heavy bleeding |
| Blood transfusion | If anemia is profound | |
| Curettage (D&C) | If bleeding continues despite hormonal therapy | Diagnostic and temporarily therapeutic |
Goldman-Cecil Medicine, p. 2556; Tintinalli's, p. 651
B. Chronic / Non-Acute Management
Medical (first-line):
- Combined oral contraceptives (cyclic): If pregnancy not desired - regulates cycle, reduces blood loss
- Progestin therapy: Medroxyprogesterone acetate 5-10 mg orally for 10 days/month; or norethindrone 5 mg daily
- Levonorgestrel-IUD (Mirena): Highly effective for ovulatory AUB and heavy menstrual bleeding
- NSAIDs: Effective for ovulatory heavy bleeding (reduce prostaglandin-mediated blood loss)
- GnRH agonists/antagonists (e.g., elagolix 300 mg BD, relugolix 40 mg/day): For uterine fibroids causing AUB
If pregnancy desired:
- Induce ovulation (clomiphene citrate or gonadotropins)
Surgical (second-line / when medical therapy fails):
- Endometrial ablation: Effective but not 100%; ~29% of patients may require hysterectomy by 5 years
- Uterine artery embolization: For fibroid-related bleeding; ~31% ultimately require hysterectomy
- Hysterectomy: Reserved for refractory cases or malignancy; definitive treatment
Berek & Novak's Gynecology, p. 1411; Goldman-Cecil Medicine, p. 2556; Sabiston Textbook of Surgery, p. 1411
Key Risk: Endometrial Hyperplasia and Carcinoma
Prolonged anovulatory bleeding results in unopposed estrogen stimulation of the endometrium. This can progress:
Anovulatory DUB → Endometrial Hyperplasia → Endometrial Carcinoma
Risk factors that increase this progression:
- Obesity (adipose tissue converts androgens to estrogens)
- PCOS
- Prolonged use of exogenous estrogens without progesterone
- Estrogen-producing ovarian tumors (granulosa-theca cell tumors)
This is why endometrial sampling is mandatory in women >35 years or with prolonged anovulatory bleeding before initiating hormonal treatment.
Robbins & Kumar Basic Pathology, p. 611
Summary Table
| Feature | Anovulatory DUB | Ovulatory DUB |
|---|---|---|
| Mechanism | No ovulation → no progesterone | Luteal phase defect |
| Pattern | Irregular, unpredictable, heavy | Regular intervals, but heavy |
| BBT chart | Monophasic | Biphasic but shortened luteal phase |
| Endometrium | Proliferative glands, stromal breakdown | May show secretory changes |
| Age group | Perimenarche, perimenopause, PCOS | Reproductive age |
| Malignancy risk | Elevated (unopposed estrogen) | Low |
Recent evidence note: A 2025 systematic review (PMID 39617186) on etiology and diagnosis of heavy menstrual bleeding in adolescents and adults highlights that coagulation disorders (particularly von Willebrand disease) are substantially underdiagnosed as a cause - reinforcing the importance of screening all patients with heavy bleeding since menarche, especially adolescents.
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