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Adolescent Gyn Series

Contemporary Management of Abnormal Uterine Bleeding in Adolescents

Jeffrey W. Wall, MD; Julie L. Strickland, MD, MPH

The adolescent years represent a time of increasing maturity both physically and emotionally. As puberty takes the adolescent through the fragile transition from childhood to young adulthood, the onset of menses signals a profound change. While many adolescents experience some degree of menstrual irregularity in the early years after menarche, the presence of irregular and heavy cycles can be both frightening and distressing to both the adolescent and her parents. A careful examination of the adolescent that is mindful of her changing physiology as well as her emerging independence will, in most cases, lead to a successful diagnosis and resolution of the problem.

THE MENSTRUAL CYCLE

The course of the mature menstrual cycle represents the complex interrelationships between the hypothalamus, the pituitary, and the ovary—the culmination of which will result in either menstrual flow or pregnancy. The menstrual cycle is separated into two distinct parts, the follicular phase and the luteal phase. The follicular phase begins with the onset of menses and is characterized by the growth and development of ovarian follicles. Estrogen secreted by these follicles stimulates growth of the endometrium. At midcycle, ovulation occurs and the follicle transforms into the corpus luteum, which begins producing progesterone. Estrogen and progesterone have specific effects on the endometrium. Estrogen promotes the proliferation of endometrial glands, stroma, and spiral arterioles, while progesterone stabilizes the endometrium and promotes its maturation in anticipation of pregnancy.¹ In the absence of pregnancy, the corpus luteum involutes, withdrawing progesterone support, and the menses commence. When the hypothalamic-pituitary-ovarian (HPO) axis is functioning normally, the stages of the menstrual cycle proceed in an orderly and sequential fashion.

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DIFFERENTIAL DIAGNOSIS

The differential diagnosis of abnormal bleeding in adolescents can be varied and may incorporate several different systems. Eliciting an adequate history from an adolescent can be difficult at times. The teenager should understand that the visit is confidential, and it is important to offer her the opportunity to be interviewed both with a parent and by herself.2

Despite falling rates of adolescent pregnancy, the incidence still remains high, with almost 1 million unplanned teenage pregnancies each year.3 Many teenagers are hesitant to openly admit the possibility of pregnancy, so it is of paramount importance to discuss sexual activity and rule out pregnancy first in any adolescent presenting with abnormal bleeding.

Anovulatory bleeding is responsible for most episodes of irregular menses in teenagers, accounting for up to 74% of all inpatient admissions for bleeding.⁴ Menarche is not the conclusion of the changes of puberty, but rather a milestone of the pubertal process that can last for several years after the initial menstrual episode. The HPO axis will continue to mature for approximately 5 years after menarche. Initial hormonal levels will remain low and irregular, resulting in anovulatory cycles 55% to 82% of the time. Subsequent maturation of the HPO axis leads to progressively higher follicle-stimulating hormone and luteinizing hormone levels, and by the end of the first 5 years only 20% of cycles are anovulatory.^4,5 Episodes of anovulation can lead to an excessive estrogen effect on the endometrium, resulting in endometrial fragility with abnormal, irregular, and frequently heavy bleeding. It is important to distinguish this developmental process from other disorders that can also lead to anovulatory cycles, including polycystic ovary syndrome (PCOS) and other endocrinopathies such as congenital adrenal hyperplasia, hypothyroidism, and virilizing tumors.

Episodes of severe anemia with heavy bleeding can lead to a diagnosis of a coagulation defect in up to 28% of girls experiencing heavy menses.⁶ Bleeding disorders should be suspected in all girls who present with heavy, prolonged bleeding—especially in those for whom this bleeding pattern has been established since menarche. In fact, abnormal menstrual bleeding is frequently the initial presenting symptom of an underlying coagulation disorder. Von Willebrand disease, factor XI disease, aplastic anemia, and leukemia—as well as acquired platelet disorders such as immune thrombocytopenic purpura—are all possibilities; therefore, the index of suspicion should remain high for such disorders. It is estimated that 13% of adolescents admitted for menorrhagia will be found to have thrombocytopenia.⁷ Other medical conditions such as end-stage liver and renal disease have also been implicated, as these patients frequently have low levels of fibrinogen and erythropoeitin.

One of the negative consequences of teenagers' initiation into sexual activity can be the acquisition of sexually transmitted diseases (STDs). Infection is a frequent cause of heavy bleeding in adolescents, especially when coupled with abdominal or pelvic pain. Young women frequently engage in high-risk sexual behavior, and it is between 15 and 19 years of age that they are most likely to contract an STD.⁸ Gonorrhea and chlamydia are common diagnoses, and can lead to cervicitis and endometritis with subsequent endometrial fragility and bleeding.

The vulva, perineum, and vagina are highly vascular organs susceptible to trauma and genital injury. "Straddle" injuries are common, especially in younger adolescents, and can frequently lead to hemorrhage if not recognized and repaired in a timely fashion. Teenaged sexual activity (as well tampon use) can result in vaginal laceration. Rape and sexual abuse are serious potential causes of genital injury, and any such suspicions must be investigated promptly.

Other, less common gynecologic disorders in adolescents that may infrequently present with heavy bleeding include leiomyomata, cervical and endometrial polyps, and occasionally endometriosis. A history of prolonged and painful cyclic bleeding should alert the physician to the possibility of a congenital anomaly.

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CLINICAL EXAMINATION

As in any patient with a serious medical condition, the examination should always begin with a complete history. Initial questions concentrating on the current bleeding episode should focus on the duration and severity of menses. The presence and size of clots should be documented, as well as the color of flow. When documenting pad or tampons counts, it is important to realize that this is highly variable among individuals and can be a subjective and inaccurate measure of the actual amount of bleeding.⁹ It is therefore important to note not only how often the patient changes the pad, but also what type of pad or tampon she has been using and the degree to which the pad is soaked. Symptoms of acute or chronic volume loss such as fatigue, dizziness, and lightheadedness should be elicited, as they can provide information about the gravity of the current episode.

The patient should be questioned about the general nature of her prior menses and her age at menarche. The frequency, quality, and amount of bleeding since menarche are important, as are any menstrual symptoms such as pain and cramping. Symptoms suggesting premenstrual syndrome can help to validate ovulatory cycles. Many teenagers will track their menses in a diary, so this should be elicited if it is available, and any recent changes in menses or premenstrual symptoms recorded. A general medical history should be obtained, including weight loss or gain, exercise patterns, cold intolerance, and any prior bleeding irregularities such as bleeding from the gums. The family history should include any relatives with irregular menses, a history of bleeding disorders, or major hemorrhage after surgery or childbirth.

A gentle, caring environment is essential for an adequate physical examination in all adolescents. It is essential that the procedure not be hurried in any way. As recent pubertal changes may have made the adolescent more self-conscious and apprehensive, it may be helpful to discuss the examination and what it may entail before beginning. Often, pictures and models can aid in reducing anxiety.

Vital signs should be obtained, including weight, body mass index, temperature, pulse, respiration, and orthostatic blood pressure. An elevated pulse rate may indicate hemodynamic compromise and the need for more aggressive treatment. The patient should be allowed to disrobe and change into an examination gown of appropriate size and modesty in privacy.

A complete examination of all major body systems is necessary. A visual assessment of the Tanner stage of pubertal development should be made as well. General weight distribution, patterns of hair growth (especially male patterns), acne, and other findings of androgen excess are important to note. Discrete areas of bruising or petechial hemorrhage may indicate an undiagnosed bleeding disorder. The heart and lungs should be examined in the usual fashion, and the abdomen should be palpated for tenderness or masses in the lower quadrants.

An evaluation of the external genitalia is essential, but the decision to proceed with speculum and bimanual examinations should be individualized depending on the severity of the bleeding, the patient's age, and the level of comfort for her and her family. A speculum examination may not be necessary in the young girl with infrequent periods who is not sexually active. In adolescents with frequent or heavy bleeding who cannot tolerate a speculum examination, it may be permissible to begin hormone therapy without one as long as follow-up is possible within 24 to 48 hours.

Should a speculum examination be deemed necessary, this can be accomplished by using a Huffman speculum, which features an adequate length to allow complete visualization of the vagina and cervix. Particular attention should be paid to the introitus and vaginal vault for evidence of bruising, laceration, or blunt penetrating trauma. Cervical and vaginal culture for STDs should be obtained if the patient is sexually active. Endometrial sampling may be performed by Pipelle biopsy at this time if indicated, but the incidence of endometrial hyperplasia and cancer remains low among adolescents, and this step is unnecessary in most instances.¹⁰ A gentle bimanual examination can usually be performed using only the index finger. Rarely, it may be necessary to administer sedation or anesthesia for an adequate pelvic examination, but in general, a gentle, professional, caring approach can help the patient to relax sufficiently. A rectoabdominal examination may be an acceptable alternative in some patients.

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LABORATORY TESTING

Initial laboratory evaluation should include a pregnancy test and a complete blood count with a platelet study. These should be obtained early in the examination, and may aid in deciding whether there is a need for resuscitative measures. Additional testing can be performed as indicated depending on the patient's presentation and history, and may include fibrinogen, partial thromboplastin time, prothrombin time, international normalized ratio, and platelet function tests. If the patient has had heavy or prolonged menses since menarche or the current episode is severe, then the index of suspicion for a bleeding disorder should remain high. In these situations, evaluation of von Willebrand factor antigen, factor VIII, factor XI, ristocetin C cofactor, and platelet aggregation should also be considered. In all cases, the advisability of referral to a hematologist should be weighed carefully. If the patient has any signs of systemic disease such as hypothyroidism or hyperandrogenism, then thyroid-stimulating hormone, free and serum testosterone, dehydroandrostenedione sulfate, and 17-hydroxyprogesterone levels should be checked. While not essential, fasting insulin and glucose determinations may aid in the diagnosis of PCOS. Ideally, all blood studies should be performed prior to initiation of treatment.

Procedures such as ultrasonography and magnetic resonance imaging may be helpful in elucidating the cause of abnormal bleeding in adolescents. Uterine anomalies, endometrial thickness, ovarian cysts, and (more rarely) leiomyomata and gynecologic malignancies may be visualized on radiologic studies.

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TREATMENT

Primary treatment of patients with severe bleeding should focus on initiating resuscitative measures (if necessary), and stopping the current flow. Secondary treatment should focus on preventing recurrence and ensuring that the adolescent develops more regular and predictable menses. In most cases of severe or prolonged bleeding, hormonal therapy with intravenous estrogen is the most effective treatment. Initially, estrogen causes direct hemostasis by acting on clotting factors such as fibrinogen, factors V and IX, and platelet aggregation.¹¹ In the long-term, it enhances endometrial proliferation in chronically denuded areas and helps to rebuild the endometrium. Patients whose initial hemoglobin level is less than 7 g/dL, or who exhibit signs of hemodynamic compromise, should receive aggressive fluid resuscitation with volume expanders and blood products as needed. Intravenous conjugated equine estrogens (CEE), 25 mg, should be the first line of treatment. More than 93% of patients respond to this treatment.⁶ This dosage is continued every 4 hours until the bleeding resolves (usually within 24 hours); in 72% of patients, severe bleeding stops after two doses.¹¹


These patients should then start using combination oral contraceptives (OCs) as first-line therapy, with treatment continuing for 3 to 6 months. An alternative is a continuous estrogen regimen—eg, oral equine estrogens, 2.5 mg/d for 20 to 25 days, with 10 mg/d of medroxy-progesterone acetate (MPA) added for the last 10 days. Patients with bleeding disorders may require additional treatment with anti-
fibrinolytics or desmopressin as indicated.¹²


Girls who have moderate bleeding not associated hemodynamic symptoms, but in whom prolonged bleeding or mild anemia is interfering with daily life, are candidates for hormonal cycle control. Combination OCs given in an accelerated fashion is an acceptable treatment for prolonged and heavy menses. The pills are given twice daily for 1 week, and then once daily for another 3 weeks.¹³ This can be followed by another 3 to 6 months of low-dose OCs taken in the normal fashion, or cyclic treatment with progestins. An alternate regimen is 25 mg/d of oral CEE, with 10 mg/d of MPA added for the last 10 days of each month for 3 to 6 months. Long-term treatment with combination OCs has the added benefits of contraception and acne control, in addition to providing a more regular and lighter menstrual cycle with fewer premenstrual symptoms. Moreover, compliance is improved when the adolescent only has to take one pill per day. The transdermal contraceptive patch has a mode of action and side-effect profile similar to OCs, and may provide better compliance in girls who have difficulty in remembering to take OCs.


If the bleeding episode has been heavy but of relatively short duration, the patient may respond to treatment with MPA, 10 mg/d, taken alone for 10 days. However, response to this treatment may take some time if the bleeding has been severe or of long duration, as there must first be some rebuilding of the endometrium by estrogen. Long-term treatment with depot medroxy- progesterone acetate (DMPA), 150 mg given intramuscularly every 1 to 3 months, will over time induce amenorrhea in most girls. However, side effects including weight gain, acne, hair loss, depression, menstrual irregularity, and spotting frequently limit its use among adolescents. Recent reports of decreased bone mineral density in women using DMPA are of concern, and the implications of long-term use in this population are unclear.¹⁴ The levonorgestrel-containing intrauterine device may be preferable to DMPA in some patients due to its more favorable side-effect profile and similar ability to induce amenorrhea, but its safety and efficacy in adolescents has not yet been demonstrated.^15-17


While hormonal manipulation remains the most effective treatment for controlling abnormal bleeding in adolescents, the addition of non-steroidal anti-inflammatory drugs may also be beneficial. Naproxen sodium and mefenamic acid have been shown to decrease menstrual flow by almost 50% when taken at the onset of bleeding and continued through the menses.¹⁶ Any girl who has experienced anemia as the result of heavy or prolonged bleeding should also use iron supplementation until her hemoglobin levels return to a normal level.


Girls in whom the menses are only mildly heavy or prolonged, and who are not anemic, can be reassured and encouraged to keep a menstrual diary. Adolescents who have previously experienced heavy or prolonged cycles and who have achieved therapeutic control should also keep menstrual diaries. When plotted on a calendar, this gives the adolescent a visual representation of her menstrual cycle, allowing her to anticipate and prepare.

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CONCLUSION

Irregular, prolonged, heavy menstrual bleeding is a common event among adolescents. Immaturity of the HPO axis or other medical conditions frequently predispose young women to this serious cyclic pattern. A carefully elicited history and an examination that respects the adolescent's sensitivity and emerging autonomy should lead to a diagnosis. Reassurance, education, and a plan of treatment individualized to each patient are paramount, and should guide the physician to a successful resolution in most cases.

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Jeffrey W. Wall, MD, is assistant professor, and Julie L. Strickland, MD, MPH, is associate professor; both are at the Department of Obstetrics and Gynecology, University of Missouri, Kansas City.

References

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17. Hubacher D, Grimes D. Noncontraceptive health benefits of intrauterine devices: a systematic review. Obstet Gynecol Surv. 2002;57(2):120-128.

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