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Overview of causes of genital tract bleeding in women

Official reprint from UpToDate www.uptodate.com 2012 UpToDate

Overview of causes of genital tract bleeding in women Author Annekathryn Goodman, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Apr 2012. | This topic last updated: ene 17, 2012. INTRODUCTION Abnormal bleeding noted in the genital area is often attributed to a uterine source, but may arise from disease at any anatomic site in the lower genital tract (vulva, vagina, cervix) or upper genital tract (uterine corpus, fallopian tubes, ovaries). The source of bleeding may also be a nongynecologic organ, such as the urethra, bladder, or bowel. The differential diagnosis of genital tract bleeding is listed in the table (table 1). It is useful to separate these causes according to age group (table 2) and site (see below). An overview of the differential diagnosis of genital tract bleeding in women will be reviewed here. The evaluation and management of women with this complaint are discussed separately. (See "Initial approach to the premenopausal woman with abnormal uterine bleeding" and "Terminology and evaluation of abnormal uterine bleeding in premenopausal women" and "The evaluation and management of uterine bleeding in postmenopausal women".) UTERINE BLEEDING The likelihood of a particular etiology of uterine bleeding depends upon the age of the patient and the pattern of bleeding (cyclic or noncyclic). Pregnancy Bleeding is a common symptom of a variety of disorders related to pregnancy. All reproductive age women with vaginal bleeding should have a pregnancy test as part of their initial evaluation. (See "Overview of the etiology and evaluation of vaginal bleeding in pregnant women".) Menstruation The uterus is the only organ for which bleeding can be a normal physiologic phenomenon (menstruation). (See "Physiology of the normal menstrual cycle".) Normal menstrual bleeding is characterized by [1]: Duration between two and seven days Flow less than 80 mL Occurring in cycles of 24 to 35 days Moliminal symptoms are often present and include an increase in thin cervical mucus secretions at mid-cycle and premenstrual symptoms such as menstrual cramps, breast tenderness, fluid retention, and appetite or mood changes. (See "Evaluation of the menstrual cycle and timing of ovulation".) Menorrhagia Excessive menstrual blood flow is termed menorrhagia. Menorrhagia may be due to local disturbances in prostaglandins (elevated endomyometrial vasodilatory prostaglandins and decreased vasoconstrictive prostaglandins), or may be related to any of the uterine etiologies described below. (See "Chronic menorrhagia or anovulatory uterine bleeding".) Anovulation In premenopausal nonpregnant women, anovulation is a common cause of abnormal uterine bleeding (AUB). Anovulatory bleeding is characterized by noncyclical bleeding of variable flow and duration. Molimina are typically absent. Many women with chronic anovulation have an adequate amount of biologically active estrogen since androgens can be converted peripherally to estrogens in the absence of normal ovarian function; however, their anovulatory cycles
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Section Editor Robert L Barbieri, MD

Deputy Editor Sandy J Falk, MD

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Overview of causes of genital tract bleeding in women

lack the progesterone secretion normally present in the luteal phase. This puts them at risk of developing endometrial hyperplasia and endometrial cancer. (See "Classification and diagnosis of endometrial hyperplasia" and "Endometrial carcinoma: Epidemiology and risk factors", section on 'Risk factors'.) Causes of anovulation are listed in the table (table 3). Anovulation should be suspected in the following settings: Adolescents Anovulatory cycles are the most common cause of AUB in adolescent girls due to a slowly maturing hypothalamic-pituitary axis during the first two to three postmenarchal years [2]. (See "Definition and evaluation of abnormal uterine bleeding in adolescents", section on 'Abnormal uterine bleeding (AUB) in adolescents' and "Differential diagnosis and approach to the adolescent with abnormal uterine bleeding" and "Management of abnormal uterine bleeding in adolescents".) Menopausal transition Anovulation is also a common cause of AUB in women in the menopausal transition. Ovulatory cycles and the normal cyclic production of estrogen and progesterone become disturbed as women approach menopause. Ovulation occurs intermittently, interspersed with anovulatory (estrogen only) cycles of varying length. As a result, menses become irregular. The duration and volume of blood loss can be short and light, but prolonged heavy bleeding can occur during longer periods of anovulation. (See "Clinical manifestations and diagnosis of menopause".) Polycystic ovary syndrome Chronic anovulation in reproductive-age women is most often attributable to an endogenous disorder, such as the polycystic ovary syndrome (PCOS), which is characterized by oligomenorrhea (irregular infrequent menstrual cycles) and hyperandrogenism (hirsutism, acne, and male pattern balding). Obesity and insulin resistance are common. Women with PCOS have an adequate amount of biologically active estrogen since androgens can be converted peripherally to estrogens even in the absence of normal ovarian function, but low levels of progesterone. Thus, constant mitogenic stimulation of the endometrium leads to endometrial hyperplasia, intermittent estrogen unscheduled (breakthrough) bleeding, and menorrhagia. (See "Diagnosis of polycystic ovary syndrome in adults" and "Treatment of polycystic ovary syndrome in adults".) Endocrine disorders Endocrine disorders may be associated with hormonal changes that affect ovulation. These disorders are uncommon causes of AUB, with the exception of polycystic ovary syndrome, which occurs in 6 percent of reproductive age women [1]. Both hypo- and hyper- thyroid activity are associated with AUB. Women with hypothyroidism, even when subclinical, may have heavy or prolonged uterine bleeding [3]. Hypothyroidism can cause hyperprolactinemia; this usually results in amenorrhea and galactorrhea, but women may develop anovulatory bleeding prior to amenorrhea. Hyperthyroidism may cause anovulation due to alterations in sex hormone binding globulin [4]. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Clinical manifestations of hypothyroidism".) Menstrual irregularities are common in women with Cushing's syndrome [5]. Menstrual abnormalities correlate with increased serum cortisol and decreased serum estradiol concentrations, but not with serum androgen concentrations. The menstrual irregularities may be due to suppression of secretion of gonadotropin-releasing hormone by hypercortisolemia. High doses of corticosteroids have a similar effect. (See "Epidemiology and clinical manifestations of Cushing's syndrome".) Hormone secreting adrenal and ovarian tumors are rare causes of anovulation and menstrual irregularities. (See individual topic reviews). Endocrine changes leading to anovulation may also be caused by strenuous exercise/activity (eg, running, ballet dancing), sudden weight change, or significant stress. Other disorders The level or activity of sex hormones may be affected by disorders unrelated to endocrine glands, such as advanced liver or renal disease, that alter hormone metabolism or binding. Anovulation and AUB may result.
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Overview of causes of genital tract bleeding in women

Neoplasia and other disorders of the hypothalamus and pituitary often cause anovulation, but amenorrhea is more common than AUB because estrogen levels are low. (See "Etiology, diagnosis, and treatment of secondary amenorrhea".) Anatomic abnormalities A significant number of women who complain of abnormal uterine bleeding have uterine abnormalities. This was illustrated in a study of 370 women aged 22 to 82 years with abnormal uterine bleeding unresponsive to treatment with progestin therapy [6]. Hysteroscopy revealed an abnormal uterine cavity in two-thirds of these women: endometrial hyperplasia (23 percent), polyps (22 percent), submucous myomata (11 percent), synechiae (6 percent), endometrial atrophy (2 percent), and adenocarcinoma (1 percent). When anatomic abnormalities are the cause of abnormal bleeding, cyclic menses with molimina typically occur. However, the duration and flow of the menstrual period may be altered or there may be bleeding between menstrual periods. Anatomic abnormalities can often be diagnosed by imaging studies, but excision is sometimes required for confirmation of the diagnosis and treatment. (See "Terminology and evaluation of abnormal uterine bleeding in premenopausal women".) Polyp Uterine polyps are usually benign endometrial growths of unknown etiology that are a common cause of abnormal uterine bleeding in women in the menopausal transition and early postmenopausal women. Irregular bleeding is the most frequent symptom, occurring in about one-half of symptomatic cases. Bleeding after straining or heavy lifting is common. Less frequent symptoms include heavy or prolonged bleeding, postmenopausal bleeding, prolapse through the cervical os, and unscheduled (breakthrough) bleeding during hormonal therapy. Polyps can be stimulated by estrogen replacement or tamoxifen. The uterus is typically normal on bimanual examination. (See "Endometrial polyps".) Fibroids Leiomyomas, also known as fibroids, are the most common pelvic tumors in women, occurring in approximately 25 percent of those who are of reproductive age. There are three uterine locations for fibroids: submucosal, intramural, and subserosal (picture 1). Intramural and submucosal fibroids distort the endometrial cavity, resulting in heavy or prolonged menstrual periods. Intermenstrual bleeding can also occur, but this is less likely and other lesions of cervix or uterus must be considered. The uterus often feels enlarged and asymmetric on bimanual examination. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)".) Adenomyosis Adenomyosis is a disorder in which endometrial glands and stroma are present within the uterine musculature. The ectopic endometrial tissue appears to induce hypertrophy and hyperplasia of the surrounding myometrium, which results in a diffusely enlarged uterus and heavy, prolonged, painful menstrual periods. The diagnosis may be suspected by ultrasound or magnetic resonance imaging, but can only be confirmed by pathologic examination following hysterectomy. (See "Uterine adenomyosis".) Hysterotomy scar Endometrial abnormalities related to previous hysterotomy (particularly cesarean delivery) can lead to postmenstrual or intermenstrual bleeding [7-10]. Other structural abnormalities Case reports have described sarcoidosis of the endometrium detected during the evaluation and treatment of AUB. A rare cause of heavy uterine bleeding is a congenital or acquired uterine arteriovenous malformation [11]. This lesion should be suspected when an invasive procedure (eg, endometrial biopsy, curettage) for unexplained uterine bleeding seems to aggravate the problem. Color Doppler studies can confirm the presence of abnormal blood flow, but pelvic arteriography is the standard for diagnosis. Uterine arteriovenous malformations have traditionally been treated with hysterectomy, but uterine artery embolization is often effective and may preserve fertility [11]. (See "Interventional radiology in management of gynecological disorders".) Malignancy Uterus Adenocarcinoma of the endometrium is the most common gynecologic cancer in women over 45
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Overview of causes of genital tract bleeding in women

years of age; it is rarely seen before age 35. All women who experience postmenopausal uterine bleeding in the absence of estrogen therapy must be evaluated for endometrial cancer since age is a significant risk factor for this disorder. (See "Endometrial carcinoma: Epidemiology and risk factors" and "The evaluation and management of uterine bleeding in postmenopausal women".) Sarcomas of the uterus constitute only 3 to 5 percent of all uterine tumors. These cancers arise from the stroma of the endometrium (endometrial stromal sarcomas) or the myometrium. They may look and feel like benign leiomyomas; diagnosis requires a hysterectomy. Women with leiomyosarcomas usually present with heavy prolonged bleeding or postmenopausal bleeding and a uterine mass. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis".) Other Bleeding from fallopian tube cancer can track through the uterus, but this is a rare cause of uterine bleeding. (See "Fallopian tube cancer".) Abnormal uterine bleeding can also be a symptom of ovarian cancer or gestational trophoblastic disease. (See "Epithelial ovarian cancer: Risk factors, clinical manifestations, and diagnostic evaluation" and "Gestational trophoblastic disease: Epidemiology, clinical manifestations and diagnosis".) Rarely, the endometrium is the site of metastatic disease from nongynecologic malignancy (eg, melanoma). Endometritis and pelvic inflammatory disease Endometritis may be acute or chronic. Premenopausal women with chronic endometritis usually present with abnormal uterine bleeding, which may consist of intermenstrual bleeding, spotting, postcoital bleeding, or heavy prolonged periods. Vague, crampy lower abdominal pain may accompany the bleeding. The most common finding on physical examination is uterine tenderness or cervical motion tenderness. Women with acute endometritis frequently have fever, while it is less common in women with the chronic process. (See "Endometritis unrelated to pregnancy".) Acute endometritis occurs postpartum in women with recent complications of pregnancy: spontaneous or induced abortion, premature rupture of membranes, intrauterine procedures, retained products of conception, or cesarean delivery. Symptoms include fever, uterine tenderness, foul lochia, and leukocytosis. (See "Postpartum endometritis".) Endometritis may also occur after placement of an intrauterine contraception or with pelvic inflammatory disease. Lower abdominal pain is the cardinal presenting symptom of pelvic inflammatory disease. The onset of pain during or shortly after menses is particularly suggestive of this disorder. The abdominal pain is usually bilateral and rarely of more than two weeks' duration. (See "Overview of intrauterine contraception" and "Clinical features and diagnosis of pelvic inflammatory disease".) In contrast, endometritis in postmenopausal women is commonly associated with underlying malignancy. In the setting of cervical stenosis, blood can accumulate in the uterus (hematometra) and become secondarily infected (pyometra). Inflammation of neighboring organs, such as diverticulitis, can occasionally cause corresponding inflammation of the female upper genital tract. A ruptured sigmoid diverticulum may fistulize into the uterus and present as uterine bleeding, discharge, and endometritis. Bleeding diatheses Women with bleeding diatheses usually present with abnormal uterine bleeding, particularly increased flow, but other genital tract bleeding may occur [12]. In one series of women age 18 to 45 years, bleeding disorders were diagnosed in 11 percent of patients with menorrhagia (von Willebrand disease [8/121], factor deficiencies [2/121], platelet abnormality [3/121]), but only in 3 percent of controls without abnormal uterine bleeding [13]. In another series, 19 percent of adolescents with abnormal uterine bleeding had a coagulation disorder, with an even higher risk in those with hemoglobin less than 10 g/dL or requiring hospitalization (25 and 50 percent, respectively) [14]. Abnormal genital bleeding in women and adolescents with bleeding diatheses may be associated with other mucosal bleeding (eg, epistaxis). (See "Approach to the adult with epistaxis" and "Evaluation
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Overview of causes of genital tract bleeding in women

of epistaxis in children".) von Willebrand's disease is a relatively common inherited bleeding disorder that is characterized by a deficiency of a plasma protein that stabilizes factor VIII. It should be suspected in young women who present with menorrhagia from the onset of menarche, particularly if there is a family history of coagulopathy. (See "Clinical presentation and diagnosis of von Willebrand disease".) Thrombocytopenia due to idiopathic thrombocytopenic purpura (ITP), hypersplenism, or systemic diseases, such as chronic renal failure, may cause menorrhagia. Uremia also causes anovulatory menstrual bleeding. Women with acute leukemia or who are undergoing chemotherapy for malignancy may develop a bleeding diathesis and heavy, prolonged uterine bleeding. (See "Heavy or irregular uterine bleeding during chemotherapy".) Advanced liver disease may cause reduced synthesis of vitamin K-dependent clotting factors, fibrinogen, and antithrombins. Anticoagulants enhance the volume of blood loss from menstruation or AUB. Menorrhagia has been reported in women taking SSRIs, presumably related to the effect of these agents on platelets [15]. (See "Unipolar depression in adults and selective serotonin reuptake inhibitors (SSRIs): Pharmacology, administration, and side effects", section on 'Bleeding'.) Drugs Contraception Contraceptive techniques that can cause abnormal vaginal bleeding include combination hormonal contraceptives, intrauterine contraception, and progestin-only contraceptives. Combination hormonal contraceptives Intermenstrual (breakthrough) bleeding is the most common side effect of combination hormonal contraceptives. Its occurrence does not indicate a decrease in efficacy (unless the patient has been noncompliant), but reflects tissue breakdown as the endometrium adjusts to a new thin state in which it is fragile and atrophic. Unscheduled (breakthrough) bleeding is related to a relatively high progesterone-to-estrogen ratio and was less of a problem when high doses of estrogen were used because estrogen stabilizes the endometrium. The frequency of bleeding is independent of the type of progestin [16,17], and is increased in women who smoke cigarettes, probably due to the accelerated metabolism of estrogen caused by smoking [18]. Women should be cautioned that missing pills results in an increase in unscheduled bleeding, as well as a decrease in contraceptive efficacy. (See "Risks and side effects associated with estrogen-progestin contraceptives".) Progestin-only contraceptives Prolonged bleeding and spotting are common complications of progestinonly contraceptives, such as depot medroxyprogesterone acetate (Depo-Provera), the levonorgestrelreleasing intrauterine contraceptive, implantable progestin rods (eg, Implanon), and progestin-only pills. Bleeding tends to be an early complication of these methods; many women develop amenorrhea with continued use. The mechanism of progesterone-breakthrough bleeding is endometrial atrophy and ulceration due to insufficient estrogen. (See "Overview of contraception" and "Overview of intrauterine contraception", section on 'Levonorgestrel-releasing IUD'.) Copper IUC Copper IUCs cause a foreign body reaction in the uterus that creates an inflammatory response. The endometrium may hypertrophy at the site of inflammation with normal cyclic estrogen stimulation, resulting in intermenstrual bleeding. (See "Overview of intrauterine contraception", section on 'TCu380A (copper) IUD'.) Postmenopausal hormone therapy Postmenopausal women who take postmenopausal hormone therapy may develop uterine bleeding; the frequency depends upon the regimen used. (See "Preparations for postmenopausal hormone therapy", section on 'Doses and bleeding patterns with estrogen regimens' and "The
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Overview of causes of genital tract bleeding in women

evaluation and management of uterine bleeding in postmenopausal women".) Other Drugs that can cause hyperprolactinemia may also cause abnormal uterine bleeding (table 4). Although severe hyperprolactinemia results in amenorrhea, mild degrees of hyperprolactinemia may cause oligomenorrhea and menstrual abnormalities. (See "Clinical manifestations and diagnosis of hyperprolactinemia".) Chemotherapy-induced thrombocytopenia can cause menorrhagia, while antipsychotic drugs may lead to anovulation and irregular bleeding. Ruptured ovarian cyst Symptoms include pain and light uterine bleeding (due to a drop in ovarian hormone levels). (See "Evaluation and management of ruptured ovarian cyst".) CERVICAL BLEEDING In contrast to abnormal bleeding from the corpus, which is often heavy and associated with menses, cervical lesions typically cause sporadic spotting, which commonly occurs postcoitally. In addition, cervical lesions can be easily visualized on speculum examination. Cancer Sporadic bleeding, postcoital spotting, and vaginal discharge that is watery, mucoid, or purulent and malodorous are common signs of cervical cancer. Therefore, women with these symptoms should not have cervical cytology postponed. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".) Direct extension from other pelvic tumors, such as uterine cancer, is the most common source of cervical involvement by metastatic tumors. Choriocarcinoma has a relatively high rate of cervical involvement. Rarely leukemias, lymphomas, and other nongynecological cancers involve the cervix. Cervicitis Postcoital bleeding is common in women with cervicitis due to nonspecific inflammatory changes or ulcerative sexually transmitted diseases. A strawberry red cervix with bleeding on contact is pathognomonic for Trichomonas vaginalis infection. (See "Acute cervicitis".) Polyps Cervical polyps commonly cause postcoital spotting and sporadic bleeding. The majority are benign endocervical polyps, which can be seen on visual examination of the cervix and endocervix. (See "Congenital cervical anomalies and benign cervical lesions".) Ectropion Ectropion is the normal physiologic presence of endocervical glandular tissue on the exocervix. This tissue is friable and readily bleeds upon contact, such as during intercourse or cervical cancer screening. (See "Congenital cervical anomalies and benign cervical lesions", section on 'Ectropion'.) Pelvic organ prolapse Defects in pelvic floor support can lead to herniation of the anterior, posterior, or apical portion of the vagina. If part or all of the vagina and cervix is exteriorized, bleeding can occur secondary to ulceration, trauma and infection. This type of bleeding often occurs after straining. (See "An overview of the epidemiology, risk factors, clinical manifestations, and management of pelvic organ prolapse in women".) Endometriosis Ectopic endometriosis can be found in the cervix, especially if the patient has a history of cervical procedures (such as cone biopsy). These endometriotic implants will bleed during menses. Diagnosis is made by biopsy. (See "Pathogenesis, clinical features, and diagnosis of endometriosis".) Vasculitis Isolated necrotizing arteritis is a rare lesion, usually localized to the cervix [19]. Clinical manifestations include menorrhagia or postmenopausal bleeding. Isolated vasculitis involving the cervix, as well as other sites in the female genital tract, is another rare lesion that may be associated with bleeding [20]. VAGINAL BLEEDING As with cervical lesions, vaginal lesions typically cause sporadic or postcoital bleeding and can be easily visualized on speculum examination. Trauma is an exception; vaginal trauma can be associated with major internal and/or external hemorrhage. Vaginitis and vaginal ulcers Vaginal infection or inflammation may lead to significant irritation of the vaginal lining, which then bleeds. (See "Evaluation of women with symptoms of vaginitis".)
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Overview of causes of genital tract bleeding in women

Atrophic vaginitis is an estrogen deficiency state, which occurs in premenarchal girls, postpartum lactating women, and postmenopausal women. Bleeding or spotting may occur. (See "Clinical manifestations and diagnosis of vaginal atrophy".) Ulcerative diseases with vaginal involvement can cause postcoital bleeding. Genital ulcers may be caused by infection, but non-infection related etiologies should also be considered. (See "Approach to the patient with genital ulcers".) Primary and metastatic cancer Primary vaginal cancer constitutes 1 to 2 percent of gynecological malignancies. The majority of patients present with vaginal bleeding, either postmenopausal or postcoital. Other symptoms include a watery, blood-tinged, or malodorous vaginal discharge or a vaginal mass. The upper posterior vaginal wall is the most frequent site of vaginal cancer. It is important to carefully palpate the lateral, anterior, and posterior vaginal walls since the lesion may be obscured by the speculum blades [21]. (See "Vaginal cancer".) Up to 20 percent of children under age 10 with vaginal bleeding have a reproductive tract neoplasm, such as sarcoma botryoides. (See "Rhabdomyosarcoma and undifferentiated sarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis" and "Vulvovaginal complaints in the prepubertal child".) Advanced bladder or colorectal cancer may invade the vagina and cause vaginal bleeding [22], and the vagina may be the site of metastatic disease from distant organs. Radiation therapy Vaginal bleeding can be a late effect of radiation therapy [23]. Obliterative endarteritis and the vascular narrowing of aging and arteriosclerosis lead to devascularization of the radiated tissues. Tissue necrosis causes viscus perforation, tissue sloughing, and bleeding. Hemorrhagic cystitis and proctitis can lead to significant blood loss. Vaginal vault necrosis may cause uncontrolled bleeding and pain. Vaginal trauma Bleeding from the vagina or vulva can occur from genital tract trauma related to intercourse (eg, tearing of an intact hymen during intercourse), foreign bodies that cause ulceration (eg, neglected tampon, pessary, sexual aids), sexual assault, pelvic trauma (eg, from a motor vehicle accident), and straddle-type injuries that result in lacerations or abrasions of the labia (eg, falling on a bicycle rail, fence, or table edge). (See "Evaluation and management of lower genital tract trauma in women".) Female circumcision or infundibulation reduces the vaginal opening. Vaginal bleeding and lacerations can occur when intercourse is attempted. (See "Female circumcision and genital cutting".) Fistulas Vesicovaginal or rectovaginal fistulas related to childbirth, gynecologic surgery, or complications of cancer and cancer therapy can present with vaginal bleeding. (See "Vesicovaginal, urethrovaginal, and ureterovaginal fistulas" and "Rectovaginal, anovaginal, and colovesical fistulas".) Benign growths Gartner's duct cysts, polyps, and aberrant glandular tissue (termed vaginal adenosis) rarely lead to vaginal bleeding in the absence of friction and trauma. (See "Diagnosis and management of congenital anomalies of the vagina".) Toxic epidermal necrolysis and Stevens-Johnson syndrome Toxic epidermal necrolysis and StevensJohnson syndrome may be caused by a variety of drugs, particularly antibiotics. The vulvar and vaginal regions are commonly involved in this sudden and extensive destruction of the skin [24]. Bleeding may occur along with significant ulceration. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Clinical manifestations; pathogenesis; and diagnosis".) VULVAR BLEEDING As with cervical and vaginal lesions, vulvar lesions typically cause sporadic bleeding and can be easily visualized on physical examination. Infection Sexually transmitted diseases can cause characteristic lesions on the vulva, some of which may produce a bloody discharge or bleed easily on contact. Examples include the syphilitic chancre (although this usually produces more serous than bloody drainage), herpes simplex virus, Haemophilus ducreyi (Chancroid), granuloma inguinale (Donovanosis), and lymphogranuloma venereum. (See "Approach to the patient with genital
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Overview of causes of genital tract bleeding in women

ulcers".) Benign lesions Benign lesions, such as sebaceous (epidermal) cysts, condylomata, and angiokeratoma, may bleed due to trauma related to friction from clothing or scratching. (See "Diagnostic evaluation of vulvar lesions" and "Differential diagnosis of vulvar lesions".) Malignant and premalignant lesions Vulvar malignancies account for 3 to 5 percent of gynecologic cancers. Early vulvar cancer is asymptomatic; bleeding occurs when a lesion is extensive enough to ulcerate. Vulvar cancer and vulvar intraepithelial neoplasia are often misdiagnosed. Delay may be related to patient embarrassment, denial, reluctance to be examined, or the tendency of health care practitioners to prescribe topical medications to a patient with vulvar complaints without performing a physical examination. All ulcers associated with skin thickening or mass must be biopsied. (See "Vulvar cancer: Clinical manifestations, diagnosis, and pathology" and "Vulvar intraepithelial neoplasia".) Vulvar trauma The vulva may bleed from trauma due to forceful sexual activity/assault or accidents (sports or exercise related, motor vehicle). (See "Evaluation and management of lower genital tract trauma in women".) NONGENITAL TRACT DISEASE Diseases of the urethra (eg, urethritis, diverticulum, urethral prolapse [caruncle]), bladder (eg, cancer, stone, or infection), and bowel (eg, inflammatory bowel disease, hemorrhoids) may cause bleeding that is misdiagnosed as genital tract bleeding. These disorders should be considered in women with bleeding unrelated to the menstrual cycle, especially when there is no obvious genital tract etiology. Systemic diseases that may present with vulvar involvement include Crohn's disease, Behcet's syndrome, pemphigoid, erosive lichen sclerosus, and lymphoma. Trauma is a common cause genital tract bleeding. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Beyond the Basics topics (see "Patient information: Abnormal uterine bleeding (Beyond the Basics)" and "Patient information: Menorrhagia (excessive menstrual bleeding) (Beyond the Basics)" and "Patient information: Absent or irregular periods (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS The source of abnormal bleeding may be from a problem anywhere in the lower genital tract (vulva, vagina, cervix), upper genital tract (uterine corpus, fallopian tubes, ovaries), or from nearby organs (urethra, bladder, bowel). (See 'Introduction' above.) The likelihood of a particular etiology for uterine bleeding depends upon the patient's reproductive age (premenarchal, adolescent, menopausal status), the pattern of bleeding (heavy, light, prolonged, cyclic or noncyclic), and the occurrence of associated symptoms (eg, pain, fever) and medical conditions. (See 'Uterine bleeding' above.)
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Bleeding is a common symptom of a variety of disorders related to pregnancy; therefore, all reproductive age women with uterine bleeding should have a pregnancy test as part of their initial evaluation. Other common causes of abnormal uterine bleeding include heavy menses, anovulation, anatomic abnormalities (eg, polyps, fibroids, adenomyosis), and side effects of contraceptives. Bleeding is the cardinal symptom of endometrial cancer. Vulvar, vaginal, and cervical bleeding can usually be visualized by physical examination. Causes include trauma, infection, neoplasia, and genital manifestations of systemic disease. (See 'Cervical bleeding' above and 'Vaginal bleeding' above and 'Vulvar bleeding' above.) Diseases of the urethra (eg, urethritis, diverticulum), bladder (eg, cancer, stone, infection), and bowel (eg, inflammatory bowel disease, hemorrhoids) may cause bleeding that is misdiagnosed as genital tract bleeding. (See 'Nongenital tract disease' above.)

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002. 2. Caufriez A. Menstrual disorders in adolescence: pathophysiology and treatment. Horm Res 1991; 36:156. 3. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. Am J Obstet Gynecol 1989; 160:673. 4. Ridgway EC, Maloof F, Longcope C. Androgen and oestrogen dynamics in hyperthyroidism. J Endocrinol 1982; 95:105. 5. Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, et al. Menstrual abnormalities in women with Cushing's disease are correlated with hypercortisolemia rather than raised circulating androgen levels. J Clin Endocrinol Metab 1998; 83:3083. 6. Motashaw ND, Dave S. Diagnostic and therapeutic hysteroscopy in the management of abnormal uterine bleeding. J Reprod Med 1990; 35:616. 7. Thurmond AS, Harvey WJ, Smith SA. Cesarean section scar as a cause of abnormal vaginal bleeding: diagnosis by sonohysterography. J Ultrasound Med 1999; 18:13. 8. Monteagudo A, Carreno C, Timor-Tritsch IE. Saline infusion sonohysterography in nonpregnant women with previous cesarean delivery: the "niche" in the scar. J Ultrasound Med 2001; 20:1105. 9. Fabres C, Arriagada P, Fernndez C, et al. Surgical treatment and follow-up of women with intermenstrual bleeding due to cesarean section scar defect. J Minim Invasive Gynecol 2005; 12:25. 10. Van Horenbeeck A, Temmerman M, Dhont M. Cesarean scar dehiscence and irregular uterine bleeding. Obstet Gynecol 2003; 102:1137. 11. Hoffman MK, Meilstrup JW, Shackelford DP, Kaminski PF. Arteriovenous malformations of the uterus: an uncommon cause of vaginal bleeding. Obstet Gynecol Surv 1997; 52:736. 12. James AH. More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders. Haemophilia 2005; 11:295. 13. Dilley A, Drews C, Miller C, et al. von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia. Obstet Gynecol 2001; 97:630. 14. Shwayder JM. Pathophysiology of abnormal uterine bleeding. Obstet Gynecol Clin North Am 2000; 27:219. 15. Do SSRIs cause gastrointestinal bleeding? Drug Ther Bull 2004; 42:17. 16. Rosenberg MJ, Waugh MS, Higgins JE. The effect of desogestrel, gestodene, and other factors on spotting and bleeding. Contraception 1996; 53:85.
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17. Speroff L, DeCherney A. Evaluation of a new generation of oral contraceptives. The Advisory Board for the New Progestins. Obstet Gynecol 1993; 81:1034. 18. Rosenberg MJ, Waugh MS, Stevens CM. Smoking and cycle control among oral contraceptive users. Am J Obstet Gynecol 1996; 174:628. 19. Francke ML, Mihaescu A, Chaubert P. Isolated necrotizing arteritis of the female genital tract: a clinicopathologic and immunohistochemical study of 11 cases. Int J Gynecol Pathol 1998; 17:193. 20. Abu-Farsakh H, Mody D, Brown RW, Truong LD. Isolated vasculitis involving the female genital tract: clinicopathologic spectrum and phenotyping of inflammatory cells. Mod Pathol 1994; 7:610. 21. Al-Kurdi M, Monaghan JM. Thirty-two years experience in management of primary tumours of the vagina. Br J Obstet Gynaecol 1981; 88:1145. 22. Brand A, Scurry J, Planner R, Leung S. Primary and recurrent colorectal cancer masquerading as gynaecological malignancy. Aust N Z J Obstet Gynaecol 1996; 36:165. 23. Hopewell, JW. The importance of vascular damage in the development of late radiation effects of normal tissues. In: Meyn, RE, Withers, HR (Eds), Radiation Biology in Cancer Research. Raven Press, New York 1980. p.449. 24. Meneux E, Wolkenstein P, Haddad B, et al. Vulvovaginal involvement in toxic epidermal necrolysis: a retrospective study of 40 cases. Obstet Gynecol 1998; 91:283. Topic 5440 Version 7.0

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GRAPHICS
Causes of abnormal genital tract bleeding
Genital tract disorders
Uterus Benign growths:
Polyps Endometrial hyperplasia Adenomyosis Leiomyomas (fibroids)

Trauma
Sexual intercourse Sexual abuse Foreign bodies (including IUD) Pelvic trauma (eg, motor vehicle accident) Straddle injuries

Cancer:
Adenocarcinoma Sarcoma

Drugs
Contraception:
Oral contraceptives C opper intrauterine device Depo-Provera

Infection:
Endometritis

Anovulatory bleeding Cervix Benign growths:

Polyps Ectropion Endometriosis

Hormone replacement therapy Anticoagulants Tamoxifen Corticosteroids Chemotherapy Dilantin Antipsychotic drugs Antibiotics (eg, due to toxic epidermal necrolysis or StevensJohnson syndrome)

Cancer:
Invasive carcinoma Metastatic (uterus, choriocarcinoma)

Infection:
C ervicitis

Systemic disease
Diseases involving the vulva:
C rohn's disease Behcet's syndrome Pemphigoid Pemphigus Erosive lichen planus Lymphoma

Vulva Benign growths

Skin tags Sebaceous cysts C ondylomata Angiokerataoma

Cancer Infection:
Sexually transmited diseases

Coagulation disorders:
von Willebrand's disease Thrombocytopenia or platelet dysfunction Acute leukemia Some factor deficiencies Advanced liver disease

Vagina Benign growths:

Gartner's duct cysts Polyps Adenosis (aberrant

Thyroid disease Polycystic ovary syndrome

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Cancer

glandular tissue)

Chronic liver disease Cushing's syndrome Hormone secreting adrenal and ovarian tumors Renal disease Emotional or physical stress Smoking Excessive exercise

Vaginitis/infection:
Bacterial vaginosis Sexually transmitted diseases Atrophic vaginitis

Upper genital tract disease Fallopian tube cancer Ovarian cancer Pelvic inflammatory disease

Diseases not affecting the genital tract

Urethritis Bladder cancer Urinary tract infection Inflammatory bowel disease Hemorrhoids

Pregnancy complications

Other
Vascular tumors and anomalies in the genital tract

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Usual causes of abnormal genital bleeding by age group

Neonates
Estrogen withdrawal

Reproductive years
Anovulation Pregnancy Cancer Polyps, fibroids, adenomyosis Infection Endocrine dysfunction (PCOS, thyroid, pituitary adenoma) Bleeding diathesis Medication related (eg, contraceptive agents)

Premenarchal
Foreign body Trauma, including sexual abuse Infection Urethral prolapse Sarcoma botryoides Ovarian tumor Precocious puberty

Early postmenarche
Anovulation (hypothalamic immaturity) Bleeding diathesis Stress (psychogenic, exercise induced) Pregnancy Infection

Perimenopausal
Anovulation Polyps, fibroids, adenomyosis Cancer

Menopause
Atrophy Cancer Estrogen replacement therapy

Adapted from APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.

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Causes of anovulation
Primary hypothalamic-pituitary dysfunction
Kallman's syndrome Idiopathic hypogonadotropic hypogonadism Tumors, trauma, or radiation of the hypothalamic or pituitary area Sheehan's syndrome Empty sella syndrome Pituitary adenoma or other pituitary tumors Lymphocytic hypophysitis (autoimmune diseases) Lactational amenorrhea Stress Eating disorders Intense exercise Immaturity at onset of menarche or perimenopausal decline

Other disorders
Polycystic ovary syndrome Hyperthyroidism or hypothyroidism Hormone producing tumors (adrenal, ovarian) Chronic liver or renal disease Cushing's disease Congenital adrenal hyperplasia Premature ovarian failure, which may be autoimmune, genetic, surgical idiopathic, or related to drugs or radiation Turner syndrome Androgen insensitivity syndrome

Medications
Oral contraceptives Progestins Antidepressant and antipsychotic drugs Corticosteroids Chemotherapeutic agents

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Fibroid locations in the uterus

These figures depict the various types and locations of fibroids. A woman may have one or more type of fibroid.

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Partial list of drugs known to cause hyperprolactinemia and/or galactorrhea

Typical antipsychotics
Phenothiazine drugs (eg, chlorpromazine [Thorazine], clomipramine [Anafranil], fluphenazine [Prolixin], prochlorperazine [Compazine], thioridazine [Mellaril]) Haloperidol (Haldol) Pimozide (Orap)

Atypical antipsychotics
Risperidone (Risperdal) Molindone (Moban) Olanzapine (Zyprexa)

Antidepressant agents*
Clomipramine (Anafranil) Desipramine (Norpramin)

Gastrointestinal drugs
Cimetidine (Tagamet) Metoclopramide (Reglan)

Antihypertensive agents
Methyldopa (Aldomet) Reserpine (Hydromox, Serpasil, others) Verapamil (Calan, Isoptin)

Opiates
Codeine Morphine * One study also found an association between hyperprolactinemia in adolescent girls and the use of selective serotoninc reuptake inhibitors, including fluoxetine (Prozac), fluvoxamine (Luvox), and divalproex (Depakote). Jerrell JM, Bacon J, Burgis JT, Menon S. Hyperprolactinemiarelated adverse events associated with antipsychotic treatment in children and adolescents. J Adolesc Health 2009; 45:79.

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