What are the possible causes of vaginal bleeding in women of different ages and reproductive stages?

Causes of Vaginal Bleeding

Vaginal bleeding causes vary dramatically by reproductive stage, with pregnancy complications being the most critical to exclude in women of childbearing age, followed by structural lesions in reproductive years, and malignancy in postmenopausal women. 1

By Age and Reproductive Stage

Premenarchal Girls

• Any bleeding is abnormal and requires immediate evaluation for trauma, foreign bodies, infection, or precocious puberty 2

Reproductive Age Women (Non-Pregnant)

Anovulatory Bleeding Causes

• Polycystic ovary syndrome is the most common cause of chronic anovulation leading to irregular bleeding and unopposed estrogen stimulation 3
• Thyroid dysfunction (both hypothyroidism and hyperthyroidism) disrupts normal menstrual patterns 3, 1
• Hyperprolactinemia from pituitary adenomas or medications (antipsychotics, antiepileptics) causes anovulation 3
• Uncontrolled diabetes mellitus contributes to menstrual irregularity through metabolic disruption 3

Ovulatory Bleeding (Menorrhagia) Causes

• Coagulation disorders, particularly von Willebrand disease, are more common than typically recognized and should be screened in all adolescents with menorrhagia 1, 4
• Submucosal uterine fibroids distort the endometrial cavity and increase menstrual flow 3, 5
• Endometrial polyps cause irregular or heavy bleeding, well-visualized on transvaginal ultrasound 3, 5
• Adenomyosis results in heavy, painful periods in women typically over 35 years 3, 5

Structural and Infectious Causes

• Cervical lesions including polyps, erosion, cervicitis, and ectropion cause intermenstrual or postcoital bleeding 1, 2
• Endometritis and pelvic inflammatory disease present with irregular bleeding and pelvic pain 1
• Endometriosis causes cyclic pelvic pain with abnormal bleeding patterns 5

Iatrogenic Causes

• Hormonal contraceptives commonly cause irregular bleeding patterns, particularly with progestin-only methods (DMPA, implants, POPs) 6, 7
• Intrauterine devices (both copper and levonorgestrel) can cause irregular or heavy bleeding, especially during initial months 6, 1
• Anticoagulants (warfarin, heparin, DOACs) increase menstrual flow 1
• Anticonvulsants and certain antidepressants may disrupt normal menstrual patterns 3

Pregnant Women

First Trimester (0-13 weeks)

• Threatened abortion with viable intrauterine pregnancy confirmed by ultrasound showing fetal cardiac activity 8, 9
• Ectopic pregnancy must be excluded immediately, as 7-20% of pregnancies of unknown location will be ectopic 8, 9
• Missed or incomplete abortion diagnosed by absent fetal cardiac activity or retained products 8, 1
• Gestational trophoblastic disease including molar pregnancy presents with bleeding and abnormally elevated beta-hCG 6, 1
• Subchorionic hemorrhage is a common finding on ultrasound in viable pregnancies with bleeding 8

Second and Third Trimester (>13 weeks)

• Placenta previa is the most common diagnosis in late pregnancy bleeding, affecting 1 in 200 pregnancies at delivery 8, 10
• Placental abruption affects approximately 1% of pregnancies but ultrasound misses up to 50% of cases initially 8, 10
• Vasa previa carries risk of fetal exsanguination and requires Doppler evaluation 8
• Cervical change with preterm labor causes bleeding that may be accompanied by contractions 8
• "Bloody show" in term labor is normal physiologic bleeding characterized as pink or brown-tinged mucus, minimal in volume 8, 10

Postpartum Period

• Retained products of conception cause persistent or heavy bleeding after delivery 8
• Uterine atony results in excessive bleeding from inadequate uterine contraction 8
• Genital tract lacerations from delivery trauma 8
• Subinvolution of placental site causes delayed postpartum hemorrhage 1

Perimenopausal and Postmenopausal Women

Malignant Causes (Must Exclude First)

• Endometrial cancer should be assumed in any postmenopausal bleeding until proven otherwise 1
• Cervical cancer requires evaluation with speculum examination and biopsy 6, 1
• Vaginal and vulvar malignancies are less common but must be considered 1
• Ovarian granulosa-theca cell tumors produce estrogen causing endometrial stimulation 1

Benign Causes

• Atrophic vaginitis and endometrium from estrogen deficiency is common in postmenopausal women 5
• Endometrial hyperplasia (with or without atypia) from unopposed estrogen exposure 3, 1
• Hormone replacement therapy causes predictable withdrawal bleeding or breakthrough bleeding 2
• Endometrial or cervical polyps remain common in this age group 1, 5

Systemic Disease Causes (All Ages)

• Liver cirrhosis impairs estrogen metabolism and coagulation factor production 1
• Chronic kidney disease causes platelet dysfunction and uremic bleeding 1
• Coagulation disorders beyond von Willebrand disease include factor deficiencies and platelet disorders 1, 4

Critical Clinical Pitfalls

• Never perform digital pelvic examination before ultrasound in pregnant women with bleeding, as this can precipitate catastrophic hemorrhage with undiagnosed placenta previa or vasa previa 8, 9, 10
• Assume pregnancy complications first in reproductive-age women until pregnancy is definitively excluded with negative beta-hCG 1, 2
• Assume malignancy in perimenopausal/postmenopausal bleeding until endometrial sampling proves otherwise 1
• Screen for coagulation disorders in adolescents with menorrhagia, as von Willebrand disease affects up to 13% of women with heavy menstrual bleeding 1, 4
• Recognize that 50% of abnormal uterine bleeding cases have no identifiable organic cause (dysfunctional uterine bleeding), but this is a diagnosis of exclusion 3, 2