Abnormal uterine bleeding (AUB) is a common cause for concern in adolescents and often results in visits to healthcare providers and emergency departments.¹ Abnormal uterine bleeding is defined as excessively heavy, frequent, and/or prolonged bleeding from the uterine endometrium.^2,3 AUB includes menstrual cycles that occur less than 21 or more than 45 days apart, bleeding that lasts more than 8 days, or blood loss greater than 80 mL.^1,2,4 AUB can present as heavy and prolonged bleeding with associated periods of amenorrhea or frequent and excessive bleeding that occurs every 1 to 2 weeks.⁴ Heavy menstrual bleeding (HMB) refers to excessive blood loss (>80 mL) regardless of the underlying menstrual pattern.⁵

PATHOPHYSIOLOGY

It is important to review normal menstruation in order to understand the pathophysiology that leads to abnormal uterine bleeding. The menstrual cycle consists of the follicular, ovulatory, and luteal phases. It requires a fully functioning hypothalamic-pituitary-ovarian (HPO) axis. During the follicular phase, which lasts between 7 and 21 days, the hypothalamus initiates pulsatile release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the pituitary to release FSH (FSH) and luteinizing hormone (LH). FSH stimulates ovarian follicle development and LH stimulates the ovaries to secrete estrogen and androgens. As estrogen concentrations rise, they stimulate endometrial proliferation. Estrogen exerts positive feedback on LH secretion, leading to the midcycle LH surge, which then leads to ovulation. During the ovulatory phase, a mature ovarian follicle releases an oocyte and then becomes a functioning corpus luteum. The luteal phase begins after ovulation and typically lasts 14 days. During this time the corpus luteum produces progesterone, which helps to stabilize the endometrial lining and promote growth of blood vessels and glandular tissue. If fertilization does not occur, the corpus luteum involutes and the subsequent drop in progesterone leads to sloughing of the endometrial lining.^2,6,7

The median age of menarche is between 12 and 13 years of age and typically occurs within 2 to 3 years of thelarche, at Tanner stage IV for breast development.^8,9 In the first gynecologic year, the mean cycle interval is 32 days, with 90% of cycles occurring 21 to 45 days apart and typically lasting less than 8 days, with average blood loss of 30 to 40 mL.^2,8 This cycle variability reflects the fact that many menstrual cycles in the early menarchal years are anovulatory.

Immaturity of the HPO axis, resulting in anovulatory cycles, is the most common cause of AUB in adolescents within 4 years of menarche. Until this axis is fully mature, ovulation may not occur each month. In fact, up to 85% of all cycles are anovulatory in the first year after menarche and 30% to 50% remain anovulatory 4 years after menarche.^4,5 Without ovulation, there is no corpus luteum or associated progesterone secretion to provide stromal support to an endometrium continuously stimulated by estrogen. As a result, proliferation of the vascular and glandular endometrial elements is unopposed. The endometrium, which continues to grow and thicken under the influence of unopposed estrogen, eventually breaks down in an irregular and often prolonged manner. As the endometrium outgrows its blood supply, there is variable shedding, necrosis, inadequate hemostasis, and HMB.^3,4,7

An adolescent with menstrual irregularities secondary to anovulatory cycles may otherwise have a normal clinical presentation if her hemoglobin has not been dramatically affected. However, blood loss leading to anemia can cause pallor, dizziness, lightheadedness, fatigue, and even hemodynamic instability. Heavy, irregular bleeding can also cause psychological distress in a young adolescent, limiting her activity and perhaps even interfering with school attendance. Vaginal bleeding due to other causes may present with signs and symptoms consistent with the underlying disorder (see subsequent sections).

Although up to 90% of AUB in adolescent females within 4 years of menarche can be attributed to anovulatory cycles,¹⁰ it is important to rule out other organic causes of irregular or heavy vaginal bleeding. The source of bleeding can be the lower reproductive tract (vagina, cervix) or upper reproductive tract organs (uterus, fallopian tubes). The most important diagnosis to consider in any adolescent with abnormal vaginal bleeding is pregnancy. Having a high index of suspicion for bleeding disorders is essential, especially in patients where AUB is severe enough to warrant hospital admission. Available data suggest a prevalence of 3% to 36% for von Willebrand disease (VWD), 13% to 20% for thrombocytopenia, 2% to 44% for platelet dysfunction, and 8% to 9% for clotting factor deficiency among adolescents with HMB.^11,12 Other possibilities include infectious (especially pelvic inflammatory disease [PID])^4,13 or endocrinologic causes (especially polycystic ovary syndrome and thyroid disease),¹⁴ as well as trauma, retained foreign body, systemic or chronic disease,¹⁴ medication effects, structural pathology, and endometriosis (Table 46-1). These disorders can lead to bleeding via inflammation of the vaginal or uterine lining, interference with hemostasis, direct trauma, or disruption of the HPO axis.¹⁴

Evaluation of an adolescent who presents with abnormal or heavy vaginal bleeding should focus on assessing the patient’s hemodynamic stability and degree of anemia and on ruling out underlying causes other than anovulatory cycles from HPO axis immaturity. A menstrual history should include age of menarche, severity of bleeding with first menses, interval between menses, duration and amount of menstrual flow, and presence or absence of cramping. When inquiring about menstrual flow, it is most useful to ask about how often pads or tampons need to be changed and whether or not the patient is soaking through to clothing or sheets.^3,11,15 Uterine cramping, caused by progesterone secreted from the corpus luteum, can serve as a marker of ovulatory cycles. It can be helpful to determine whether cyclic intervals are normal with increased bleeding during each cycle (suggesting bleeding disorder), normal with bleeding between cycles (suggesting trauma or foreign body), or abnormal with no cycle regularity (suggesting anovulatory cycles from HPO axis immaturity, endocrinopathy, or hormonal contraception). Other key elements of the history include abdominal pain or dyspareunia (suggestive of infection or trauma), dysuria or vaginal discharge (suggestive of infection), dizziness or lightheadedness (suggestive of anemia), and history of nosebleeds, easy bruising, or bleeding (suggestive of bleeding diathesis). The review of systems should also include recent weight changes, headaches, visual disturbances, nipple discharge, hirsutism, and symptoms associated with thyroid disorders (for example diarrhea or constipation, palpitations, heat or cold intolerance), or other chronic diseases. When discussing sexual history, it is important to speak to the patient alone in order to foster open communication. Sexual history should include previous history of sexual activity, recent sexual activity, history of trauma or abuse, history of sexually transmitted infections, frequency of condom use, and masturbation with a foreign object. The patient’s medication use (including hormonal contraception), as well as any family history of irregular menses, polycystic ovary syndrome, autoimmune disease, or bleeding disorders, are important.

The physical examination should start with an assessment of the patient’s vital signs. Tachycardia, orthostatic blood pressure changes, or decreased capillary refill, suggesting significant blood loss and anemia, should be addressed immediately. The degree of pallor should be assessed, as well as the presence of any ecchymoses or petechiae. The patient’s sexual maturity rating can help determine whether bleeding is truly menstrual in nature, because menarche usually does not occur prior to Tanner stage III. Special attention should also be given to nutritional status, body habitus, visual fields (abnormalities associated with pituitary lesion), thyroid size, breast examination (evaluating for galactorrhea), evidence of androgen excess (such as hirsutism, significant acne, clitoromegaly), and evidence of chronic illness. All adolescents with abnormal bleeding should have a pelvic examination if they have ever been sexually active. If the history points strongly to anovulatory cycles and the patient has never been sexually active, a pelvic examination may not be indicated; in this situation a bimanual or digital examination may be performed instead of a speculum examination to rule out foreign body or structural abnormality. Alternatively, patients can have pelvic ultrasonography to rule out structural abnormalities.

A pregnancy test must be obtained on every adolescent female presenting with vaginal bleeding, regardless of the sexual history she provides. A complete blood count should also be obtained for evaluation of hemoglobin, white blood cell (WBC) count, and platelet count. The hemoglobin level indicates the degree of blood loss. However, it is important to remember that a patient presenting with acute severe hemorrhage may have a normal hemoglobin level initially. Ongoing or chronic blood loss may present as a normocytic anemia, but more commonly it presents as a microcytic anemia with reduced reticulocyte response due to iron deficiency from blood loss. An elevated WBC count may indicate infection or inflammation. A markedly elevated WBC count or depression of more than one cell line suggests a leukemic process, especially if immature forms (e.g. blasts) are present. The platelet count can identify thrombocytopenia, although it does not reflect platelet function. The presence of thrombocytosis may be a marker for inflammation.

If a speculum examination is performed, a wet mount can be obtained to look for Trichomonas, and cervical specimens can be obtained for chlamydia and gonorrhea. Alternatively, urine or vaginal swabs can be collected for nuclear DNA testing (e.g. polymerase chain reaction, ligase chain reaction) for chlamydia and gonorrhea.

If a bleeding disorder is suspected based on history or severity of current symptoms, additional laboratory studies should include prothrombin time, activated partial thromboplastin time, VWD studies (VWF antigen, ristocetin cofactor activity, Factor VIII activity), and fibrinogen. It is important to collect these tests prior to initiation of hormonal therapy because estrogen can elevate VWD studies and provide falsely reassuring results.¹⁵ If these tests are normal and there is a high index of suspicion for an underlying bleeding disorder, studies of platelet function should also be considered. These tests should be ordered in consultation with a hematologist and may include light transmission platelet aggregometry or flow cytometry. The PFA-100 is no longer recommended due to poor sensitivity and specificity.^11,15,16