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Vaginal bleeding

Vaginal bleeding refers to any discharge of blood from the vagina, which is a normal physiological process during menstruation but can also signal abnormal conditions when it occurs outside of expected menstrual cycles.^[1] In reproductive-age individuals, normal vaginal bleeding typically occurs as part of the menstrual cycle every 21 to 35 days, lasting from a few days to a week, and involves the shedding of the uterine lining.^[2] Abnormal vaginal bleeding, often termed irregular or unexpected bleeding, includes spotting between periods, excessively heavy flow (such as soaking a pad or tampon every hour for several hours), bleeding after menopause, bleeding during pregnancy, or any vaginal blood loss in prepubescent children.^[2]^[1] This condition affects individuals across all ages with female anatomy and can stem from a wide array of causes, categorized under frameworks like PALM-COEIN, which includes structural issues (polyps, adenomyosis, leiomyomas/malignancy) and non-structural factors (coagulopathy, ovulatory dysfunction, endometrial disorders, iatrogenic, or not otherwise classified).^[3] Common etiologies encompass hormonal imbalances, such as those from polycystic ovary syndrome or perimenopause; infections like cervicitis or pelvic inflammatory disease; pregnancy-related complications including ectopic pregnancy or miscarriage; noncancerous growths like uterine fibroids or polyps; and systemic conditions such as thyroid disorders or bleeding coagulopathies like von Willebrand disease.^[4]^[3] More serious causes may involve cancers of the cervix, endometrium, or ovaries, underscoring the need for prompt evaluation.^[4] Epidemiologically, abnormal vaginal bleeding is prevalent; in reproductive-age women, it accounts for up to 30% of outpatient gynecology visits and affects approximately one third during their reproductive years. It occurs in up to 25% of first-trimester pregnancies and in 5-10% of postmenopausal individuals, with higher risks shortly after menopause onset.^[3]^[5] Diagnosis often involves a thorough history, physical examination, pregnancy testing, blood work, ultrasound, and potentially endometrial biopsy to identify the underlying cause, particularly to rule out malignancy in older adults or those with persistent symptoms.^[1]^[3] Medical attention is essential for any abnormal bleeding, especially if it is heavy (soaking a pad hourly for 2-3 hours), lasts longer than a week, occurs during pregnancy or after menopause, or is accompanied by severe pain, dizziness, or fever; immediate care is recommended for pregnant individuals or postmenopausal bleeding to prevent complications.^[6]^[1] Treatment varies by cause and may include hormonal therapies, medications like tranexamic acid, or surgical interventions such as dilation and curettage or hysterectomy in severe cases.^[3]

Overview

Definition and Classification

Vaginal bleeding refers to any blood loss originating from the vagina, which may arise from the uterus, cervix, vagina, vulva, or adnexa.^[3] It encompasses a spectrum from light spotting, characterized by small amounts of blood that do not typically require a pad or tampon, to heavy bleeding, defined as soaking through a sanitary pad or tampon every hour for several consecutive hours.^[2]^[7] Abnormal uterine bleeding (AUB), a subset of vaginal bleeding, is classified by the International Federation of Gynecology and Obstetrics (FIGO) as bleeding from the uterine corpus that is abnormal in volume, regularity, frequency, or duration outside of pregnancy.^[8] Basic etiologic classification distinguishes structural causes, such as polyps or leiomyomas (fibroids), from non-structural causes, including hormonal imbalances like ovulatory dysfunction.^[9]^[10] Traditional terms include menorrhagia for heavy menstrual bleeding exceeding 80 mL per cycle and metrorrhagia for bleeding occurring between menstrual cycles.^[11]^[12] The modern FIGO framework, introduced in 2011 and revised in 2018, replaced outdated terminology like dysfunctional uterine bleeding (DUB)—a diagnosis of exclusion from the 1930s—with the structured PALM-COEIN system to better categorize AUB causes and patterns, emphasizing heavy, prolonged, or irregular bleeding. The 2018 revisions included reclassifying certain iatrogenic causes, such as anticoagulants, from other categories to iatrogenic (I).^[13]^[14]^[15] This evolution facilitates more precise clinical assessment across reproductive life stages.^[16]

Normal Versus Abnormal Bleeding

Normal menstrual bleeding, also known as menses, typically occurs as part of the menstrual cycle in individuals of reproductive age, characterized by a cycle length of 24 to 38 days, a duration of 4.5 to 8 days, and a blood volume ranging from 5 to 80 mL per cycle.^[17]^[18]^[19] These patterns are influenced by the onset of puberty, which begins with breast development (thelarche) between ages 8 and 13 in girls, leading to menarche around age 12.4 on average, and by menopause, which occurs at an average age of 51 years, marking the end of cyclical bleeding.^[20]^[21]^[22] Variations in normal bleeding can occur across life stages; for instance, adolescents often experience heavier flow due to anovulatory cycles stemming from the immaturity of the hypothalamic-pituitary-ovarian axis in the first few years post-menarche.^[23] In perimenopause, bleeding patterns may become irregular, with flow that is lighter, heavier, or of varying duration as hormonal fluctuations intensify.^[24] Abnormal bleeding is distinguished from normal patterns by specific criteria, including intermenstrual bleeding (spotting between periods), postcoital bleeding (after intercourse), or prolonged duration exceeding 7 to 8 days.^[25]^[26] The severity of heaviness can be quantified using the Pictorial Blood Assessment Chart (PBAC), a semi-quantitative tool where a score greater than 100 correlates with menorrhagia, typically indicating blood loss over 80 mL.^[27] Even within the spectrum of normal but heavy bleeding, there is a risk of iron deficiency anemia, particularly in susceptible individuals with chronic blood loss, leading to symptoms such as fatigue and reduced quality of life.^[28]

Causes by Life Stage

Prepubertal Causes

Vaginal bleeding in prepubertal girls, typically those under 8 years of age, is a rare occurrence that requires prompt medical evaluation, as it often signals an underlying pathology rather than normal physiological development.^[29] Unlike in older females, prepubertal girls lack the hormonal fluctuations of menstrual cycles, making any bleeding abnormal and potentially indicative of endocrine, infectious, traumatic, or neoplastic conditions.^[30] The evaluation prioritizes ruling out serious etiologies, with studies reporting that local causes predominate but systemic issues must be excluded.^[31] Precocious puberty represents a key endocrine cause of vaginal bleeding in this age group, characterized by the early activation of the hypothalamic-pituitary-gonadal axis or peripheral hormone production leading to secondary sexual characteristics and menstrual-like bleeding before age 8.^[30] Central precocious puberty (CPP), which is gonadotropin-releasing hormone (GnRH)-dependent, arises from premature hypothalamic-pituitary stimulation and is often idiopathic in girls, though it may stem from central nervous system lesions such as hypothalamic tumors or hamartomas.^[32] In contrast, peripheral precocious puberty is GnRH-independent and results from exogenous or endogenous estrogen sources, such as ovarian cysts, tumors, or adrenal disorders, leading to endometrial stimulation and breakthrough bleeding without central axis activation.^[33] The incidence of precocious puberty is estimated at 1 in 5,000 to 10,000 girls, with a female predominance and higher rates observed in certain populations due to environmental or genetic factors.^[34] Trauma and foreign bodies account for a significant proportion of local causes, often presenting with spotting or overt bleeding accompanied by foul-smelling discharge or pain.^[35] Trauma may result from accidental injury, straddle falls, or non-accidental causes such as sexual abuse, which can lead to vaginal lacerations or hematomas in the fragile, estrogen-deficient prepubertal mucosa.^[36] Foreign bodies, including toilet paper, small toys, or hygiene products, are frequently inserted unintentionally and cause chronic irritation, inflammation, and secondary bleeding; they are identified in up to 12.7% of cases of persistent vaginal bleeding via vaginoscopy.^[37] Infections, particularly vulvovaginitis, are among the most common infectious etiologies, affecting the thin, non-estrogenized vaginal epithelium that is susceptible to poor hygiene, irritants, or pathogens.^[38] Nonspecific vulvovaginitis from bacterial overgrowth or poor perineal hygiene leads to friable mucosa and spotting in 5-10% of cases, while specific infections like group A Streptococcus or Shigella species can cause more pronounced hemorrhagic discharge.^[39] These infections are responsible for approximately 7% of evaluated bleeding episodes and often resolve with targeted hygiene measures or antibiotics, but they mimic more serious conditions.^[37] Neoplasms are rare but critical to consider, comprising less than 5% of cases yet carrying high morbidity if undiagnosed.^[37] The most notorious is embryonal rhabdomyosarcoma (sarcoma botryoides), a soft tissue malignancy that typically presents in girls under 5 years with a grape-like polypoid vaginal mass protruding from the introitus, accompanied by bleeding and discharge.^[36] This botryoid variant arises from the submucosal connective tissue and requires multidisciplinary management, including imaging and biopsy for confirmation.^[40] Other benign tumors, such as Müllerian papillomas, may also cause intermittent bleeding but are far less aggressive.^[37] Endocrine disorders beyond precocious puberty include exogenous estrogen exposure, which can induce endometrial proliferation and withdrawal bleeding mimicking menses.^[41] Sources such as estrogen-containing cosmetics, creams, or inadvertent ingestion lead to transient elevated estradiol levels (>100 pg/mL) and spotting, resolving upon removal of exposure; this is distinct from endogenous overproduction and affects a small subset of cases with environmental risk factors.^[42]

Reproductive-Age Causes

In women of reproductive age, abnormal vaginal bleeding often stems from disruptions in the normal menstrual cycle, categorized under the FIGO PALM-COEIN system into structural and nonstructural etiologies.^[16] Hormonal imbalances, structural abnormalities, coagulopathies, iatrogenic factors, and malignancies represent the primary causes, with ovulatory dysfunction being the most prevalent nonstructural contributor.^[10] Hormonal imbalances frequently lead to anovulation, resulting in irregular, heavy, or prolonged bleeding due to unopposed estrogen stimulating endometrial proliferation without progesterone counterbalance. Polycystic ovary syndrome (PCOS), affecting approximately 5-10% of reproductive-age women, is a leading cause of anovulatory bleeding through chronic anovulation and hyperandrogenism.^[16] Thyroid disorders, including hypothyroidism and hyperthyroidism, which impact 1-2% of menstruating women, disrupt the hypothalamic-pituitary-ovarian axis and cause irregular cycles.^[10] Similarly, obesity contributes via excess estrogen production from adipose tissue aromatization, exacerbating unopposed estrogen effects and ovulatory dysfunction.^[16] Structural issues account for a significant portion of cases, often distorting the endometrial cavity or increasing vascularity. Uterine fibroids (leiomyomas), benign smooth muscle tumors affecting 70-80% of women by age 50, commonly cause heavy menstrual bleeding by enlarging the endometrial surface area and compressing venous drainage.^[10] Endometrial polyps, benign overgrowths of endometrial tissue with a prevalence of 7-10%, typically present with intermenstrual spotting or irregular bleeding due to fragile surface vessels.^[16] Coagulopathies impair hemostasis and manifest as heavy menstrual bleeding, particularly in adolescents and young women. Von Willebrand disease, the most common inherited bleeding disorder with a general prevalence of about 1% but accounting for up to 13% of cases of heavy menstrual bleeding, reduces platelet adhesion and factor VIII stability, often remaining undiagnosed until gynecologic evaluation.^[9] Platelet function disorders, though less prevalent, similarly contribute by hindering clot formation during menses.^[16] Iatrogenic causes arise from medical interventions that alter endometrial stability or vascular integrity. Intrauterine devices (IUDs), particularly copper-based ones, increase spotting or irregular bleeding in 10-20% of users by inducing local inflammation and endometrial disruption.^[10] Hormonal contraceptives, including combined oral pills or progestin-only methods, can disrupt cycles and cause breakthrough bleeding in the initial months of use due to fluctuating hormone levels affecting endometrial shedding.^[16] Malignancies, though rare in reproductive-age women (affecting less than 5%), warrant consideration, especially with risk factors like unopposed estrogen exposure. Endometrial hyperplasia, a precursor to cancer, and endometrial cancer itself present with unpredictable bleeding from abnormal tissue proliferation; the risk rises with prolonged anovulation or obesity, though malignancy rates remain low under age 45.^[10]

Pregnancy-Associated Causes

Vaginal bleeding during pregnancy can arise from various physiological and pathological processes, ranging from benign implantation to life-threatening obstetric emergencies that endanger both maternal and fetal health. These causes are distinct from non-pregnant vaginal bleeding and often require urgent evaluation to prevent complications such as hemorrhage, preterm delivery, or maternal mortality. Common presentations include spotting in early gestation and heavier bleeding later on, influenced by gestational age and underlying placental or uterine abnormalities.^[43] In early pregnancy, implantation bleeding occurs as the fertilized egg attaches to the uterine lining, typically 1 to 2 weeks after conception, manifesting as light spotting that lasts a few hours to days and affects approximately 25% of pregnancies. This event is generally harmless and resolves without intervention, though it may mimic early miscarriage symptoms. Another critical early cause is ectopic pregnancy, where the embryo implants outside the uterus, most commonly in the fallopian tube, with an incidence of 1% to 2% of all pregnancies; it carries a significant risk of rupture, leading to severe intra-abdominal bleeding and accounting for a substantial portion of first-trimester maternal deaths if undiagnosed.^[44]^[45]^[45] During the mid-trimester, placenta previa emerges as a key etiology, characterized by the placenta partially or completely covering the cervical os, which occurs in about 0.5% of viable pregnancies and predisposes to painless, bright red bleeding due to cervical-vascular interactions as the lower uterine segment stretches. In contrast, placental abruption involves premature separation of the normally implanted placenta from the uterine wall, affecting roughly 1% of pregnancies and presenting with painful bleeding, uterine hypertonus, and potential fetal distress; risk factors include hypertension, trauma, and smoking.^[46]^[47]^[47] In late pregnancy and the postpartum period, variants of placental abruption may persist or recur, exacerbating bleeding risks near term, while retained placenta—failure of complete placental expulsion after delivery—can lead to secondary postpartum hemorrhage through subinvolution of the placental site or infection, contributing to up to 20% of severe cases.^[48] Gestational trophoblastic disease, particularly complete molar pregnancy, arises from abnormal fertilization leading to trophoblastic proliferation without a viable fetus, with an incidence of 1 in 1,000 pregnancies; it often causes irregular bleeding in the first trimester and may be accompanied by hyperthyroid symptoms such as tachycardia, tremors, and heat intolerance due to elevated human chorionic gonadotropin stimulating thyroid activity.^[49]^[50]^[51] Coagulopathy in pregnancy, notably disseminated intravascular coagulation (DIC), can trigger profound vaginal bleeding as a complication of amniotic fluid embolism, a rare event with an incidence of approximately 1 in 40,000 deliveries where amniotic fluid enters the maternal circulation, causing anaphylactoid reactions, cardiovascular collapse, and widespread clotting dysregulation. This condition underscores the need for rapid multidisciplinary intervention to mitigate maternal hemorrhage and multiorgan failure.^[52]

Perimenopausal Causes

Perimenopausal vaginal bleeding, often manifesting as irregular, heavy, or prolonged menstrual cycles, arises primarily from the hormonal instability characteristic of the menopausal transition. This phase, typically beginning in the mid-40s and lasting an average of four years (though it can extend up to eight years), involves fluctuating levels of estrogen and progesterone due to declining ovarian function.^[53] These changes disrupt the normal ovulatory process, leading to anovulatory cycles where ovulation fails to occur regularly. In anovulatory cycles, erratic elevations in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) prevent consistent corpus luteum formation, resulting in unopposed estrogen exposure to the endometrium and subsequent irregular, heavy bleeding. Such patterns affect over 90% of women during this transition, often with multiple episodes of abnormal bleeding.^[54] Endometrial changes during perimenopause further contribute to bleeding risks, particularly through hyperplasia induced by prolonged unopposed estrogen stimulation in anovulatory states. Endometrial hyperplasia involves excessive proliferation of the uterine lining, which can lead to heavy or irregular bleeding; atypical forms carry a markedly elevated cancer risk, with progression to endometrial carcinoma occurring in approximately 20-50% of cases compared to less than 5% in non-atypical hyperplasia. This heightened risk underscores the need for evaluation, as unopposed estrogen exposure during the transition amplifies endometrial vulnerability.^[24]^[55] Structural abnormalities also play a significant role in perimenopausal bleeding. Adenomyosis, characterized by the invasion of endometrial tissue into the myometrium, has a prevalence of 20-35% in women of reproductive age, often becoming symptomatic during perimenopause with heavy, painful bleeding. Similarly, uterine fibroids (leiomyomas) may undergo degeneration in this phase due to hormonal shifts, exacerbating bleeding; fibroids are present in up to 80% of women by age 50, though symptomatic degeneration is more common during the transition.^[56]^[24] Medications, particularly hormone replacement therapy (HRT), can induce breakthrough bleeding in perimenopausal women. In users of combined estrogen-progestin HRT, unscheduled bleeding occurs in 10-20% after the initial months, often due to endometrial response to progestin withdrawal or imbalance, though rates vary by regimen (e.g., higher in sequential HRT at 8-40%).^[57] Lifestyle factors influence the severity and timing of perimenopausal bleeding. Smoking accelerates the menopausal transition by 1-2 years through direct ovarian toxicity and anti-estrogenic effects, thereby increasing the duration and irregularity of bleeding episodes.^[58]

Postmenopausal Causes

Postmenopausal vaginal bleeding, defined as any bleeding occurring 12 months or more after the cessation of menses, carries a significant risk of underlying malignancy, with approximately 9-10% of cases linked to endometrial cancer, necessitating urgent clinical evaluation.^[59]^[60] The most frequent cause is endometrial atrophy, resulting from diminished estrogen levels that lead to thinning of the uterine lining and increased fragility of superficial blood vessels, often manifesting as spotting or light bleeding; this condition accounts for 60-80% of postmenopausal bleeding episodes.^[61]^[62] Endometrial cancer represents a critical etiology, with about 90% of postmenopausal women diagnosed with this malignancy presenting with vaginal bleeding as the initial symptom; the age-adjusted incidence rate is 28.3 new cases per 100,000 women annually, predominantly affecting those over age 50.^[59]^[63] Among other malignancies, cervical cancer, frequently associated with human papillomavirus (HPV) infection, can contribute to postmenopausal bleeding due to neoplastic involvement, while vaginal cancer remains exceedingly rare, comprising less than 1% of instances and typically occurring in older postmenopausal women.^[62]^[64] Atrophic vaginitis, stemming from estrogen deficiency, causes inflammation and friability of the vaginal and cervical epithelium, leading to bleeding upon contact or spontaneously; it affects up to 50% of postmenopausal women and is a common benign contributor to bleeding.^[65]^[66] Trauma or iatrogenic factors, such as bleeding following endometrial biopsy, cervical procedures, or radiation therapy in patients with prior gynecologic malignancies, can also provoke postmenopausal bleeding, particularly in those undergoing active treatment or surveillance.^[62]

Diagnostic Approach

History and Physical Examination

The initial evaluation of vaginal bleeding begins with a detailed history to characterize the bleeding pattern, which includes assessing frequency (e.g., frequent if less than 24 days between episodes, normal if 24-38 days, or infrequent if more than 38 days), regularity (regular if variation is within 2-7 days or irregular if more than 20 days), duration (prolonged if exceeding 8 days), and volume (heavy if greater than 80 mL per cycle, often indicated by frequent changes of sanitary products, passage of clots, or flooding).^[16] Patients are encouraged to use a menstrual calendar or validated tools such as the Menstrual Distress Questionnaire (MEDI-Q) to track these details accurately over time.^[16] Associated symptoms should be explored, including pelvic pain, unintended weight loss, abnormal discharge, fatigue, or signs of anemia, as these may point to underlying conditions.^[67] Risk factors are also elicited, such as smoking, use of hormone replacement therapy (HRT), family history of gynecologic cancers or bleeding disorders, and exposure to unopposed estrogen, which can influence the likelihood of structural or hormonal etiologies.^[16] A screening for coagulopathies is essential, including history of heavy bleeding since menarche, postpartum hemorrhage, frequent bruising or epistaxis, or family history of bleeding tendencies, as up to 20% of women with heavy menstrual bleeding may have an underlying coagulation disorder.^[9] Reproductive history is critical and includes the date of the last menstrual period, parity, current contraception methods, and any recent changes in fertility desires or sexual activity; a pregnancy test is indicated in reproductive-age patients to rule out pregnancy-related causes.^[67] Additionally, details on age at menarche, history of sexually transmitted infections, and compliance with cervical cancer screening (e.g., Pap smears) help contextualize the bleeding within the patient's gynecologic profile.^[16] The physical examination starts with vital signs to detect hemodynamic instability, such as tachycardia, hypotension, or orthostatic changes, which signal significant blood loss and require urgent stabilization.^[9] A speculum examination is performed to visualize the vagina and cervix, identifying the bleeding source (e.g., cervical versus vaginal origin), lesions, polyps, or abnormal discharge, while a bimanual examination assesses uterine size, tenderness, or palpable masses suggestive of enlargement.^[67] In adolescents, Tanner staging may be included to evaluate pubertal development.^[16] Red flags in the history and examination include heavy bleeding accompanied by dizziness or syncope, indicating hypovolemia, and postcoital bleeding, which raises concern for cervical pathology such as infection or malignancy.^[68] Persistent or unremitting bleeding, especially in patients aged 45 years or older, warrants prompt further evaluation.^[16] Cultural and patient-centered considerations are integral, as discussions of vaginal bleeding may cause discomfort due to stigma; clinicians should foster a supportive environment by explaining procedures clearly, offering chaperone options, and using appropriately sized speculums to enhance comfort during the pelvic exam.^[67] Validated menstrual history questionnaires can standardize data collection while respecting patient privacy.^[16]

Laboratory and Imaging Investigations

Laboratory investigations for vaginal bleeding begin with blood tests to evaluate for anemia, coagulopathies, endocrine disorders, and pregnancy. A complete blood count (CBC) is routinely performed to assess hemoglobin levels, with anemia indicated by hemoglobin below 12 g/dL in nonpregnant women, signaling potential iron deficiency from chronic blood loss.^[69] Coagulation studies, including prothrombin time (PT) and partial thromboplastin time (PTT), are recommended if a bleeding disorder such as von Willebrand disease is suspected, particularly in adolescents or those with heavy flow lasting 7 or more days.^[16] Hormone assays, such as thyroid-stimulating hormone (TSH) for hypothyroidism and prolactin for hyperprolactinemia, help identify endocrine causes of ovulatory dysfunction.^[70] A beta-human chorionic gonadotropin (beta-hCG) test is essential in all reproductive-age patients to exclude pregnancy-related bleeding.^[71] Endometrial sampling via Pipelle biopsy is an office-based procedure used to detect hyperplasia or malignancy, offering approximately 90% sensitivity for endometrial cancer and 82% for atypical hyperplasia in postmenopausal women.^[72] It is indicated for women over 45 years with abnormal bleeding or those under 45 with risk factors such as obesity, unopposed estrogen exposure, or persistent symptoms despite treatment.^[9] Imaging starts with transvaginal ultrasound (TVUS) as the first-line modality due to its cost-effectiveness and good sensitivity for detecting structural lesions like polyps or fibroids, as recommended by ACOG.^[73] In postmenopausal women, an endometrial thickness greater than 4 mm on TVUS is suspicious and warrants further evaluation.^[74] Saline infusion sonography enhances visualization of intracavitary lesions such as polyps, while hysteroscopy provides direct endometrial assessment for definitive diagnosis.^[16] Advanced imaging with magnetic resonance imaging (MRI) is reserved for evaluating deep or intramural fibroids when TVUS is inconclusive, and computed tomography (CT) may be used if malignancy is suspected beyond the uterus.^[70]

FIGO PALM-COEIN Classification

The FIGO PALM-COEIN classification system, established in 2011 by the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group, offers a structured etiology-based categorization for abnormal uterine bleeding (AUB) in nongravid women of reproductive age. This system replaces outdated and imprecise terminologies, such as "dysfunctional uterine bleeding," with nine distinct categories organized under the acronym PALM-COEIN, distinguishing structural pathologies (PALM) from non-structural or systemic factors (COEIN). It promotes consistent terminology to enhance clinical communication, research comparability, and patient management across diverse resource settings. The PALM components address structural uterine abnormalities identifiable through imaging, hysteroscopy, or biopsy. Polyp (AUB-P) refers to benign endometrial or endocervical polyps, which are often friable and contribute to irregular bleeding. Adenomyosis (AUB-A) involves ectopic endometrial tissue within the myometrium, leading to heavy or painful bleeding and diagnosed primarily via transvaginal ultrasound or MRI. Leiomyoma (AUB-L) encompasses uterine fibroids, subclassified by location (e.g., submucosal L_{SM} for those distorting the endometrial cavity, which are most likely to cause bleeding), with prevalence up to 80% in reproductive-age women. Malignancy and hyperplasia (AUB-M) includes endometrial or cervical cancers and atypical hyperplasia, necessitating urgent histopathological evaluation per WHO and FIGO staging criteria. In contrast, the COEIN elements focus on non-structural etiologies, often requiring laboratory or hormonal assessments rather than invasive procedures. Coagulopathy (AUB-C) involves inherited or acquired bleeding disorders, such as von Willebrand disease, accounting for approximately 13% of heavy menstrual bleeding cases. Ovulatory dysfunction (AUB-O) arises from anovulation or irregular cycles, commonly linked to conditions like polycystic ovary syndrome during adolescence or perimenopause. Endometrial (AUB-E) denotes primary endometrial defects in local hemostasis, typically diagnosed by exclusion after ruling out other causes. Iatrogenic (AUB-I) stems from medications or devices, including anticoagulants, intrauterine systems, or hormonal therapies. Not yet classified (AUB-N) captures uncommon or emerging causes, such as vascular anomalies, pending further research. Application of the PALM-COEIN system guides diagnostic prioritization: structural PALM causes typically warrant imaging (e.g., ultrasound) or biopsy for confirmation, while COEIN evaluation emphasizes hematological tests, hormonal profiles, and medication reviews. Multiple etiologies may coexist, denoted by a notation system (e.g., AUB-L_{SM}C0O1 for present submucosal leiomyoma and ovulatory dysfunction), allowing tailored treatment strategies like polypectomy for AUB-P or hormonal therapy for AUB-O. In 2018, FIGO refined the system through further expert consensus, incorporating intermenstrual bleeding into the symptom nomenclature, adopting "heavy menstrual bleeding" over "menorrhagia," and expanding categories to include "polypoid" variants under AUB-P and cervical etiologies under AUB-M for greater precision. These updates particularly highlight the need to prioritize coagulopathy screening (AUB-C) in adolescents, where structural causes are rare (<10%) and bleeding disorders may affect up to 20% of heavy cases, improving early detection in this group.^[16] A key limitation remains the system's exclusion of pregnancy-associated bleeding, which requires separate evaluation to avoid misclassification. Overall, PALM-COEIN enhances prior systems by providing actionable, etiology-specific categories that support evidence-based care.

Management and Treatment

Initial Management and Complications

The initial management of vaginal bleeding prioritizes hemodynamic stabilization and rapid control of hemorrhage to prevent complications. Patients presenting with signs of instability, such as systolic blood pressure below 90 mmHg, tachycardia exceeding 110 beats per minute, or heavy ongoing blood loss, require immediate intravenous fluid resuscitation to restore circulating volume.^[75] In cases of severe blood loss leading to hemoglobin levels below 7-8 g/dL or ongoing instability, blood transfusion is indicated to correct anemia and support organ perfusion.^[3] For acute heavy bleeding in nonpregnant reproductive-aged women, medical interventions form the cornerstone of initial therapy. High-dose conjugated equine estrogen (25 mg intravenously every 4-6 hours for up to 24 hours) is often used to promote endometrial stabilization and reduce bleeding, followed by transition to oral progestins.^[76] Tranexamic acid, administered orally (1-1.5 g every 6-8 hours) or intravenously, provides effective nonsurgical control by inhibiting fibrinolysis; recent guidelines emphasize its role, noting a 40-50% reduction in blood loss per menstrual cycle.^[9]^[77] Short-term complications of unmanaged acute vaginal bleeding include acute anemia from significant blood loss, resulting in symptoms such as fatigue, pallor, and tachycardia, with hemoglobin potentially dropping below 10 g/dL.^[70] In severe instances, hypovolemic shock may develop, characterized by hypotension, oliguria, and altered mental status, which can progress to multiorgan failure if not addressed promptly; however, with timely intervention, mortality remains low in resource-available settings.^[3]^[78] Retained products of conception, if present, increase the risk of infection such as endometritis, manifesting as fever, leukocytosis, and purulent discharge.^[79] Emergency indicators necessitating immediate care include blood loss exceeding 500 mL in pregnant or postpartum patients, which signals potential hemorrhage requiring urgent evaluation and intervention.^[80] Similarly, persistent heavy flow—defined as soaking a pad hourly for more than 2-3 hours—unresponsive to initial medical measures demands expedited assessment to avert decompensation. Post-acute follow-up emphasizes anemia prevention and patient education. Serum ferritin should be measured, with iron supplementation recommended if levels fall below 30 ng/mL to restore stores and mitigate fatigue.^[81] Counseling should cover warning signs for emergency return, including dizziness, rapid heartbeat, or bleeding that soaks more than one pad per hour, ensuring timely recognition of recurrent instability.^[82]

Medical Treatments

Medical treatments for vaginal bleeding primarily involve pharmacological interventions aimed at reducing blood loss, stabilizing the endometrium, and addressing underlying etiologies such as ovulatory dysfunction or coagulopathies. Selection of therapy is guided by the FIGO PALM-COEIN classification to target specific causes like polyps, fibroids, or coagulopathies.^[9] These options are typically non-invasive and focus on hormonal regulation or antifibrinolytic mechanisms. Hormonal therapies form the cornerstone for managing abnormal uterine bleeding in reproductive-age women by suppressing ovulation and inducing endometrial atrophy. Combined oral contraceptives (COCs), containing estrogen and progestin, reduce menstrual blood loss by 40-60% through ovulation inhibition and thinner endometrial shedding.^[83] Progestins, such as medroxyprogesterone acetate at 10 mg daily for 10 days per cycle, provide effective control for dysfunctional bleeding by promoting endometrial stabilization, with rapid saturation leading to significant reduction in excessive flow.^[84] Non-hormonal options offer alternatives for patients intolerant to hormonal agents or with contraindications. Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen at 600 mg three times daily during menses, decrease prostaglandin-mediated bleeding by 30-50%, thereby alleviating heavy menstrual flow without affecting the reproductive axis.^[85] Tranexamic acid, an antifibrinolytic agent dosed at 1.3 g three times daily during menstruation, reduces blood loss by 26-60% by inhibiting fibrinolysis in the endometrium.^[86] For specific causes, targeted therapies enhance efficacy. The levonorgestrel-releasing intrauterine device (IUD), such as Mirena, delivers localized progestin and achieves over 90% reduction in menorrhagia within 6 months, with sustained benefits up to 5 years by atrophying the endometrium.^[87] In cases of von Willebrand disease contributing to bleeding, desmopressin increases factor VIII and von Willebrand factor levels 3-5-fold, effectively controlling menstrual hemorrhage through endothelial release of these clotting factors.^[88] Common side effects of hormonal therapies include nausea and gastrointestinal upset, while the risk of venous thromboembolism with COCs is approximately 3-4 per 10,000 users annually, necessitating careful patient screening.^[89] Efficacy should be monitored after 3 months, with adjustments based on response and bleeding patterns.^[90] Recent advances include GnRH antagonists like elagolix, FDA-approved in 2018 for heavy menstrual bleeding associated with uterine fibroids, which suppress ovarian hormone production to achieve 50-75% reduction in bleeding.^[91] A 2022 meta-analysis confirmed elagolix's role in improving bleeding outcomes when combined with add-back therapy to mitigate hypoestrogenic effects.^[92]

Surgical and Procedural Interventions

Surgical and procedural interventions are considered for vaginal bleeding when medical therapies fail or when structural abnormalities, such as fibroids or polyps, are identified as the underlying cause. These options aim to address the source of bleeding directly, with choices depending on the patient's age, desire for future fertility, and overall health. Procedures range from minimally invasive outpatient techniques to more definitive surgeries, balancing efficacy against risks like infection or organ damage.^[93] Endometrial ablation destroys the endometrial lining to reduce or eliminate heavy menstrual bleeding, commonly using thermal balloon or radiofrequency methods. Thermal balloon ablation involves inflating a balloon with heated fluid inside the uterus for about 8-10 minutes, while radiofrequency ablation uses energy to ablate tissue via a mesh device. Patient satisfaction rates range from 80% to 90% at long-term follow-up, though approximately 20% may experience treatment failure requiring reintervention within 5 years.^[94]^[95]^[96] This procedure is not suitable for women desiring future pregnancy, as it impairs fertility and carries high risks of complications like miscarriage or placental issues if conception occurs.^[93] For uterine fibroids causing abnormal bleeding, myomectomy removes the fibroids while preserving the uterus, making it preferable for women wishing to maintain fertility, whereas hysterectomy eliminates the uterus entirely and serves as a definitive treatment. In the United States, approximately 600,000 hysterectomies are performed annually, with fibroids accounting for a significant portion as the primary indication.^[97] Myomectomy and hysterectomy can be conducted via laparoscopic, robotic, or open approaches, with minimally invasive techniques offering shorter recovery times and lower complication rates compared to open surgery.^[98]^[99] Hysteroscopic polypectomy is an outpatient procedure for removing endometrial polyps, which can cause irregular bleeding, using a hysteroscope to visualize and excise the growths with tools like graspers or resection loops. This method effectively resolves symptoms in most cases, with polyp recurrence rates of 10-15% over several years.^[100]^[101] In cases of suspected or confirmed endometrial malignancy presenting as vaginal bleeding, dilation and curettage (D&C) serves both diagnostic and therapeutic roles by sampling and removing uterine tissue for analysis and to control acute bleeding.^[102] For malignant conditions, D&C is often followed by adjunct therapies such as radiation or chemotherapy, alongside staging procedures like hysterectomy.^[103] Contraindications for these interventions include active desire for pregnancy, which precludes endometrial ablation due to fertility destruction and pregnancy risks. Common procedural risks encompass uterine perforation, occurring in 1-2% of cases, particularly with hysteroscopic or ablation techniques, as well as potential bleeding or infection.^[93]^[104]

Prognosis and Prevention

Long-Term Outcomes

The long-term prognosis for vaginal bleeding, particularly abnormal uterine bleeding (AUB), varies significantly by underlying cause, with resolution rates influenced by timely intervention. For hormonal AUB, such as that due to ovulatory dysfunction, medical treatments like levonorgestrel-releasing intrauterine devices achieve blood loss reduction in 71-95% of cases, while oral contraceptives yield improvements in 35-69% of patients.^[16]^[105] In contrast, structural causes like polyps or fibroids often require surgical management; hysteroscopic polypectomy resolves symptoms in 75-100% of cases, and uterine fibroid embolization alleviates heavy bleeding in approximately 85% of patients.^[105]^[106] Post-surgical resolution for structural AUB ranges from 50-90%, though recurrence can occur in up to 20% over five years without adjunctive therapy.^[107] Untreated chronic vaginal bleeding can lead to enduring health impacts, including infertility and cardiovascular complications. In cases linked to polycystic ovary syndrome (PCOS), anovulation contributes to infertility in up to 50% of affected women if left unmanaged, as PCOS accounts for 30% of female infertility diagnoses.^[108]^[109] Persistent anemia from heavy menstrual bleeding elevates cardiovascular event risk, with odds ratios approximately 1.5 for ischemic heart disease and stroke in premenopausal women.^[110] When vaginal bleeding signals endometrial cancer, outcomes depend on stage at diagnosis. Stage I disease carries a five-year relative survival rate of 95-96%, reflecting high curability with surgery.^[111] Diagnostic delays, however, promote progression; advanced-stage disease reduces five-year survival to about 22%, underscoring the need for prompt evaluation.^[111]^[112] AUB affects up to 30% of reproductive-age women, often impacting quality of life through disruptions in work productivity and interpersonal relationships.^[10] Tools such as the Menorrhagia Impact Questionnaire quantify these effects, revealing scores below the 25th percentile in health-related quality of life domains compared to age-matched norms.^[113]

Risk Reduction Strategies

Maintaining a healthy lifestyle is a foundational strategy for reducing the risk of vaginal bleeding associated with common gynecologic conditions. Weight management, particularly achieving and sustaining a body mass index (BMI) below 25 kg/m², substantially lowers the likelihood of developing polycystic ovary syndrome (PCOS), which often manifests with irregular or heavy bleeding due to insulin resistance and hormonal imbalances exacerbated by obesity. Even modest weight loss of 5-10% through diet and exercise can restore ovulatory cycles and alleviate symptoms in a significant proportion of affected women. Complementing this, a balanced diet incorporating iron-rich foods—such as lean meats, leafy greens, and legumes—meets the recommended dietary allowance (RDA) of 18 mg per day for premenopausal women, helping to mitigate anemia risks from potential heavy menstrual losses without supplementation in most cases. Routine screening facilitates early detection and prevention of bleeding-related complications across life stages. Women over 40 are advised to participate in annual gynecological examinations, which include pelvic assessments to identify irregularities before they progress. For those at elevated risk, such as individuals with obesity or diabetes, transvaginal ultrasound (TVUS) serves as a non-invasive tool to evaluate endometrial thickness; these factors confer an odds ratio of 2-3 for developing endometrial hyperplasia, a precursor to more severe bleeding disorders. Strategic contraception selection can further minimize bleeding risks by addressing hormonal influences. Progestin-only methods, such as pills or intrauterine devices, circumvent estrogen excess that might promote endometrial overgrowth and subsequent bleeding in susceptible women, offering a safer profile for those with contraindications to combined hormonal options. Additionally, human papillomavirus (HPV) vaccination, recommended for adolescents and young adults, demonstrates approximately 90% efficacy in preventing infections from high-risk HPV types responsible for cervical precancers and cancers, which can present with abnormal bleeding. Early intervention for endocrine disorders is vital to avert bleeding disruptions. Prompt management of PCOS with agents like metformin improves insulin sensitivity and menstrual regularity, often restoring predictable cycles and decreasing bleeding frequency in insulin-resistant patients. Similarly, timely correction of thyroid dysfunction—whether hypothyroidism or hyperthyroidism—normalizes coagulation factors and hormonal regulation, thereby preventing the irregular or heavy bleeding patterns linked to these conditions. Public health efforts enhance overall risk mitigation by promoting awareness and equity in care. Education programs on normal menstrual cycle characteristics empower individuals to distinguish physiological variations from abnormalities, encouraging timely medical consultation and reducing delays in addressing potential issues. In low-resource settings, expanding access to affordable gynecologic services through community-based initiatives has been shown to decrease untreated cases of abnormal bleeding by facilitating earlier interventions and follow-up.

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