What are the causes of heavy menstrual bleeding (menorrhagia)?

Causes of Heavy Menstrual Bleeding (Menorrhagia)

Heavy menstrual bleeding results from structural abnormalities (polyps, adenomyosis, leiomyomas, malignancy) or nonstructural causes (coagulopathy, ovulatory dysfunction, endometrial disorders, iatrogenic factors), systematically classified by the PALM-COEIN framework developed by ACOG. 1

Structural Causes (PALM)

Polyps

• Endometrial polyps are among the three most common structural causes in premenopausal women, particularly in those over 40 years of age 2, 3
• These benign growths project into the uterine cavity and cause irregular or heavy bleeding 1

Adenomyosis

• Adenomyosis frequently coexists with fibroids and presents with heavy menstrual bleeding, dysmenorrhea, and dyspareunia 2
• Most commonly affects women in their 40s and represents endometrial tissue growing into the myometrium 2

Leiomyomas (Fibroids)

• Uterine fibroids are the most common structural cause in women under 40 years of age 2, 3
• Submucosal fibroids (those projecting into the uterine cavity) are particularly associated with heavy bleeding 1
• Physical examination typically reveals an enlarged, irregular uterus on palpation 2

Malignancy and Hyperplasia

• Endometrial hyperplasia and malignancy must be excluded, especially in postmenopausal women where endometrial cancer is the most serious etiology 1, 2
• Women 35 years or older with recurrent anovulation require endometrial biopsy 4
• Women younger than 35 with risk factors for endometrial cancer also require tissue sampling 4

Nonstructural Causes (COEIN)

Coagulopathy

• Coagulation disorders are more common than many physicians realize and should be suspected in specific populations 5
• Von Willebrand disease is the most common inherited bleeding disorder causing menorrhagia 4
• Up to 20% of women with heavy menstrual bleeding have an underlying inherited bleeding disorder 6
• All adolescents with menorrhagia should be screened for coagulopathy until proved otherwise 5
• Women on anticoagulation, particularly NOACs like rivaroxaban, have significantly increased risk (27% vs 8.3% with warfarin) 2

Ovulatory Dysfunction

• Chronic anovulation leads to irregular bleeding and prolonged unopposed estrogen stimulation of the endometrium 4
• Specific causes include:
  • Polycystic ovary syndrome (PCOS): affects 4-6% of women, characterized by hyperandrogenic chronic anovulation with low mid-luteal phase progesterone levels 2
  • Hypothalamic amenorrhea: causes oligomenorrhea without hyperandrogenemia, associated with disturbed pituitary gonadotropin secretion 2
  • Thyroid dysfunction: both hypothyroidism and hyperthyroidism cause menstrual irregularities; evaluate with TSH levels 1, 2, 4
  • Hyperprolactinemia: results from pituitary adenomas, hypothyroidism, or medications (antipsychotics, antiepileptics); requires prolactin measurement 1, 2
  • Adolescence, perimenopause, lactation, pregnancy, premature ovarian failure 1

Endometrial Disorders

• Primary endometrial disorders involve molecular deficiencies in the regulation of endometrial hemostasis 1
• These represent intrinsic abnormalities of the endometrium itself rather than hormonal or structural causes 1

Iatrogenic Causes

• Progestin-only contraceptives (pills, DMPA, implants) frequently induce irregular bleeding patterns, especially during the first 3-6 months, though this may persist longer with implants 2
• Antiepileptic drugs (carbamazepine, phenobarbital, phenytoin) induce hepatic cytochrome P450-dependent steroid hormone breakdown, reducing biologically active sex hormone concentrations 2
• Intrauterine contraceptive devices can cause abnormal bleeding 5
• Other medications include hypothalamic depressants, digitalis, and anticoagulants 5

Not Yet Classified

• This category includes causes that don't fit into other classifications 1

Critical Diagnostic Approach

Initial Assessment

• Rule out pregnancy first in all reproductive-age women with abnormal bleeding 1, 5
• Obtain complete blood count to assess for anemia 7, 3
• Measure TSH and prolactin levels to evaluate for thyroid dysfunction and hyperprolactinemia 1

Risk-Stratified Endometrial Sampling

• Women ≥35 years with recurrent anovulation require endometrial biopsy 4
• Women <35 years with risk factors for endometrial cancer require endometrial biopsy 4
• Women with excessive bleeding unresponsive to medical therapy require endometrial biopsy 4

Imaging Evaluation

• Transvaginal ultrasonography is the first-line imaging modality 1, 4
• Saline infusion sonohysterography or hysteroscopy provides superior diagnosis of endometrial polyps and fibroids compared to standard ultrasound 1, 3
• Hysteroscopy allows direct visualization of the endometrial cavity and can diagnose focal lesions missed by endometrial sampling 1

Common Pitfalls to Avoid

• Never assume dysfunctional uterine bleeding until organic causes are excluded through appropriate evaluation 7, 5
• Do not perform digital pelvic examination in pregnant women with vaginal bleeding until placenta previa and vasa previa are excluded 1
• Unexplained vaginal bleeding suspicious for serious conditions requires complete evaluation before initiating treatment, as hormonal therapies might mask symptoms of underlying malignancy 2
• Cyclic progestogens do not significantly reduce menstrual bleeding in women who ovulate, contrary to common practice 3
• Screen for coagulopathy in all adolescents with menorrhagia, women with anovulatory bleeding who fail therapy, and women with ovulatory bleeding without anatomic lesions 5