Since the average teenage girl in the United States will reach menarche by her 13th birthday, pediatricians are caring for adolescents who will present to them with complaints of vaginal bleeding. Therefore it is incumbent upon the physician to be skilled in the evaluation and management of this common adolescent problem. The goal of this clinical evaluation is to differentiate between those processes that are potentially dangerous and those that are physiological and require only reassurance and observation. This review will focus primarily on vaginal bleeding that is excessive in amount or duration, that occurs more frequently than every 20 days, or that is associated with anemia. The vast majority of abnormal vaginal bleeding in adolescents is due to dysfunctional uterine bleeding secondary to an immature hypothalamic-pituitary-gonadal axis. However, this diagnosis should be made only after careful consideration of the possible etiologies and performance of a stepwise evaluation of the patient based on an understanding of the normal anatomic and physiologic changes that occur during adolescence. The purpose of this paper is to discuss briefly, using an anatomic framework, those entities that must be considered before a diagnosis of dysfunctional uterine bleeding is made.
ANATOMIC AND STRUCTURAL CONSIDERATIONS
Foreign bodies are more common in préadolescents, and they can cause a foul-smelling bloody discharge. Tampons, diaphragms, or contraceptive sponges are foreign bodies that might be found in the vaginal vault of the adolescent. Vaginal lacerations are often misdiagnosed unless a history of sexual abuse, rape, masturbation with intravaginal objects, or pain during intercourse is obtained.1·2 Diethylstilbesterol (DES), an estrogen commonly used in the past to suppress spontaneous abortion, causes several abnormalities in the fetus that years later can lead to bleeding. It has been estimated that up to 80% of DES daughters have some gross or microscopic abnormality of the vagina, cervix, or uterus. Adenosis occurs in 35% of exposed daughters, while clear cell adenocarcinoma is much rarer, with an incidence of O. 14 to 1.4 out of 10,000 of those exposed.3 The diagnosis of DBS-related disorders in adolescents is less common now that the last cohort of women exposed are presently reaching adulthood. Botryoid sarcoma is a rare malignant rhabdomyosarcoma that can involve the vagina, cervix, uterus, or bladder. This tumor, also called embryonal rhabdomyosarcoma, tends to involve structures higher up in the genitourinary tract with advancing age and is rarely found in the vagina beyond childhood.4
Cervical friability (in the area of squamous metaplasia), hemangiomas, cervical polyps, or condylomata are possible causes of bleeding, although they usually only produce spotting.
Roughly one million teenagers a year become pregnant, 13% of which end in spontaneous abortion.5 A quantitative test for pregnancy6 should be performed when evaluating vaginal bleeding in all teenagers who have reached Tanner III stage of sexual maturation, regardless of a denial of sexual activity. The patient should be informed that the pregnancy test is being performed. The possible complications of pregnancy include spontaneous abortion, incomplete abortion, threatened abortion, ectopie pregnancy, molar pregnancy, and the complications of the legal or illegal termination of a pregnancy. Bleeding occurs in approximately 20% of pregnancies, of which approximately 50% go on to abort spontaneously.8'9 Ectopie pregnancies have increased threefold from 1970-1980, with 15- to 24-year-olds accounting for 36% of all ectopie pregnancies,10 Ectopie pregnancies are potentially fatal and should be considered whenever there is abnormal vaginal bleeding, even in the absence of abdominal pain. Uterine tenderness, in the absence of adnexal tenderness, raises the suspicion of retained products after a spontaneous abortion or the termination of a pregnancy.
Submucosal myomas, although unusual in adolescents, can result in irregular bleeding.
Functional ovarian cysts may be either follicular or of the corpus luteum. The majority of these cysts are follicular and represent a failure of ovulation. Corpus luteum cysts may mimic an ectopie pregnancy by presenting with amenorrhea and an adnexal mass, which is followed by vaginal bleeding and abdominal pain upon rupture of the cyst. Ovarian tumors, both malignant and benign, may be associated with vaginal bleeding. Surgical investigation is usually required when ovarian masses are greater than 5 cm and enlarge, persist over one or two menstrual cycles, or do not diminish in size after a cycle of oral contraceptives. Polycystic ovary disease (PCO) is the most common endocrine disorder in women during the reproductive years. u In an article reviewing multiple case series of women with PCO, Goldzieher and Green12 described the following findings on presentation. Seventy-four percent presented with infertility, 69% presented with hirsutism, 51% with amenorrhea, 29% with functional uterine bleeding, and 21% with virulization. The polycystic ovary is believed to secrete abnormal levels of androgens. Screening lab tests should include the ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH), since PCO classically presents with an elevated LH and an LH/FSH ratio greater than 2.5/1.
Prolactinomas are by far the most common pituitary tumor associated with menstrual irregularities. Increased prolactin production suppresses follicular maturation and leads to inadequate corpus luteum function and decreased progesterone production. This results initially in irregular bleeding, followed by oligomenorrhea and finally by amenorrhea.13'14 If oral contraceptive pills (OCP) are used for contraception in a woman with irregular menses, especially if her cycles are longer than 40 days, then prolactin measurements should be obtained periodically. The OCP could potentially mask the amenorrhea that would have occurred if she were not continued on OCR
The two major adrenal causes of vaginal bleeding are Addison's disease and congenital adrenal hyperplasia (CAH). Although Addison's disease is not a common disorder, 25% of patients with this disorder will have vaginal bleeding.15 The bleeding in CAH can present in a patient with late onset disease or in a previously diagnosed patient who is noncompliant with her steroid medication.
Either hyperthyroidism or hypothyroidism can be the cause of abnormal vaginal bleeding. Thyroid function should be assessed in all patients with abnormal bleeding in whom there is no obvious cause found on the initial evaluation. If a patient is already on thyroid medication compliance should be investigated since noncompHance can result in bleeding. 16
SEXUALLY TRANSMITTED DISEASES
A vaginitis from Trichomonas vaginalis can cause a bloody discharge.
Cerviciris from Chhimydia trachomatis or Neisseria gonorrhoeas can cause friability and vaginal bleeding or spotting.
Uterus and Salpinx
Pelvic inflammatory disease (PID) is believed to cause bleeding due to endocervicitis or endometritis. One million cases of PID are reported each year, with 16% to 20% being adolescents. 17'20 The risk of PID is one of eight 15-year-olds versus one out of eighty 24year-olds.19'21 There may be significant overlap in the symptoms of PID and those of ectopie pregnancy.
Endometriosis is probably underdiagnosed in adolescence. In one study of endometriosis in 66 adolescents, 18 presented with irregular bleeding. The other presenting symptoms were 42 with cyclic pain, 24 with acyclic pain, 17 with dyspareunia, 14 with GI distress, 8 with vaginal discharge, and 3 with bladder dysfunction.22
Complications of Contraceptives
An adolescent with vaginal bleeding should always be questioned about sexual activity and contraceptive use. A teenager might be brought in by a parent who has no knowledge of their teenager's sexual activity or contraceptive use. Care must be taken to elicit a complete history from the patient without compromising confidentiality.
Mid-cycle bleeding is a relatively common occurrence for women on oral contraceptives. One study reports that breakthrough bleeding on the day following a missed pill (with two pills taken the next day) is 13 to 16 times more likely than when no pill is missed.2,3
Intrauterine devices are often associated with bleeding, and although we feel that there is little justification for their use in teenagers, they are still being used and should not be overlooked as a possible cause of bleeding.
Anticoagulants, gonadal and adrenal steroids, reserpine phenothiazines, monoamine oxidase inhibitors, morphine, and anticholinergics have been associated with vaginal bleeding.24·25
Any chronic illness can have an effect on the menstrual cycle. Severe illnesses often cause amenorrhea but they may be associated with increased amounts or frequency of bleeding. Hemodialysis especially may be associated with excessive blood loss due to vaginal bleeding.
Emotional stress, eating disorders, crash diets, obesity, and exercise all have been cited as causes of abnormal vaginal bleeding although, as with chronic illnesses, they are more often associated with amenorrhea than excessive bleeding. The mechanism is unciear, but it is believed to be secondary to hypothalamic-pituitary dysfunction. 15-26"28
Excessive vaginal bleeding can occur in patients with hereditary or acquired thrombocytopenia, hereditary or acquired defects of platelet function, von Willebrand's disease, and factor VlII or IX deficiencies. Bleeding can occur in patients with a known bleeding disorder or it can be the initial manifestation of a previously undiagnosed disorder.
A study of 59 patients hospitalized at a large referral center with the diagnosis of menorrhagia found bleeding disorders in 20%. Dysfunctional uterine bleeding was the cause in 74%. In these 59 patients, a bleeding disorder was discovered in one quarter of patients presenting with a hemoglobin less than 10, one third of patients requiring a transfusion, and one half of the patients who presented at menatene. The bleeding disorders were idiopathic throinbocy topen ic purpura, von Willebrand's hemophilia, platelet dysfunction, thalassemia major, and Fanconi's anemia.29
DYSFUNCTIONAL UTERINE BLEEDING
Dysfunctional uterine bleeding (DUB) is abnormal vaginal bleeding that occurs in the absence of pregnancy, infection, neoplasms, or any other demonstrable pathologic condition or disease. The definitions for abnormal vaginal bleeding in this context vary widely.15,26,27,30,31 For our purposes, the definition is vaginal bleeding that occurs in cycles less than 20 days or greater than 40 days, that lasts longer than 8 days, results in blood loss greater than 80 ml, or that is associated with anemia.
During puberty there is a maturation of the hypothalamic-pituitary-gonadal axis. There is a decrease in the negative feedback of estrogen on luteinizing hormone releasing hormone (LH-RH) and the development of a positive feedback mechanism that allows estrogen to trigger the mid-cycle LH surge. In DUB it is believed that the positive feedback mechanism is not fully mature, resulting in a failure of the LH surge, chronic anovulation, and a tonic production of estrogen. This causes an increase in the thickness of the endometrial lining which, with the lack of progesterone withdrawal, results in irregular and incomplete sloughing. A frequent pattern of bleeding in DUB is 2 to 4 months of amenorrhea followed by several days of vaginal bleeding.27·32·33 Menstrual cycles are frequently anovulatory in the girl of perimenarchal age. Apter found that 55% of cycles were anovulatory in the first two postmenarchal years.34 Talbert et al demonstrated ovulatory cycles in 32% of women 18 months after menarche, 46% at 19 to 31 months, and 61% at 31 months after menarche.35 Lemarchand et al noted that 37% of women were not ovulatory during the cycle they studied in the women's fifth postmenarchal year.36
The evaluation of a patient with vaginal bleeding should be performed in a thoughtful and systematic manner, initially excluding those causes with the highest immediate morbidity. Checklists 1 and 2 are examples of information to be obtained on the initial history and physical examination.
The goal of this initial evaluation is to assess the acuity and amount of blood loss, the need for surgical intervention (in cases such as ectopie pregnancy, spontaneous abortion with hemorrhage, or vaginal lacerations), and the need for hospitalization. All patients should have a blood count with platelets and a quantitative pregnancy test. Patients with vaginal bleeding and an acute abdomen or a positive pregnancy test should have immediate consultation with a gynecologist. If the pregnancy test is negative and the pelvic exam is abnormal, then the evaluation is dependent on the suspected abnormality, the amount of blood loss, and the remainder of the history and physical exam. If the pregnancy test is negative and the pelvic exam is normal, then the evaluation should be focused on quantification of the amount of bleeding, review of the medical history, and a complete physical examination looking for possible disorders that might be associated with vaginal bleeding. Any patient with blood loss significant enough to cause anemia or who presents with excessive bleeding at menatene should be evaluated for a bleeding disorder with a prothrombin time, partial thromboplastin time, platelet count, and a bleeding time. An evaluation of thyroid function, using T3, T4, and thyroid-stimulating hormone (TSH), should be made in any patient for whom a specific etiology is not apparent on initial evaluation and in whom the diagnosis of DUB is being entertained.
The need to obtain endocrine studies such as prolactin, LH, and FSH should be determined on a caseby-case basis, taking into consideration the history and physical exam. Although both prolactinomas and PCO classically present with amenorrhea, they initially can be indistinguishable from DUB. A prolactin level should be obtained if the patient has cycles longer than every 40 days OT in any patient with irregular menses who will be regulated with OCP and will be maintained on them for the purpose of contraception. A prolactin level should be obtained about every 6 months, in spite of a normal initial value, until the patient's bleeding pattern can be observed off OCP. If the prolactin level is elevated, the LH/FSH ratio should be obtained, since one third of patients with PCO have increased prolactin.10 An LH/FSH should be obtained if the menstrual cycles are longer than 40 days or if any of the stigmata of PCO are present.
A description of the management of all the various causes of vaginal bleeding is beyond the scope of this article. The initial management of a patient with vaginal bleeding is dependent on the amount of blood lost and the patient's symptoms. All patients with a significant orthostatic change in their blood pressure or heart rate, severe lower abdominal pain, or a history of the passage of large amounts of bright red blood over a brief time should have a large-bore intravenous catheter placed and blood sent for type and cross match. Regardless of etiology, shock should be treated aggressively with volume expansion and blood products as needed. If blood products are to be used, blood samples should be saved for clotting studies, since blood transfusion might make the determination of an underlying bleeding disorder difficult. The subsequent management of the patient depends on the disorder under consideration.
The remainder of this section will discuss the management of dysfunctional uterine bleeding. The management of DUB is dependent on the amount, frequency, and effect on the patient's lifestyle of the bleeding. If the episodes of bleeding are infrequent, are not associated with anemia, and there is not currently a desire for contraception, then reassurance, recording of menses on a menstrual calendar, and visits every 2 to 3 months is adequate. If contraception is desired, then a low-dose 1,35 OCP may be started.
If the bleeding is frequent or is associated with mild anemia, then cyclic treatment with 1,35 OCPs should be initiated and continued for 6 months. If bleeding is moderately severe, the hemoglobin is less than 10, or bleeding is especially brisk on presentation, there are a number of medical regimens that might be used for acute management of the bleeding and then for menstrual cycling (See Treatment Guide). Our method of choice is the standard 1 , 50 OCP given from two to four times a day until the bleeding stops. The dose is then decreased to one to two pills a day (the lowest amount that controls the bleeding) for one cycle, at the end of which a brief withdrawal bleed is allowed (3 to 5 days) and a new cycle is begun using one pill per day (again with the lowest dose that controls the bleeding). The pills are continued for 6 months, at which time the patient is given a trial off them. Iron replacement should be considered in any patient with excessive vaginal bleeding, especially in the face of a secondary anemia. Iron replacement should be continued for 3 months after the hemoglobin has returned to normal.
If the bleeding is associated with shock, significant signs of volume loss, or is not controlled by OCPs, then the patient should be treated with intravenous estrogene in consultation with a gynecologist.
The evaluation and management of abnormal vaginal bleeding should be tailored to the individual case. Pediatricians caring for adolescents need to be skilled in the evaluation and management of this common adolescent problem. Physicians who do not feel comfortable with their skills in the performance of a pelvic exam should obtain consultation from an adolescent specialist or a gynecologist who has experience with adolescents.
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