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Home , Anovulation, Vaginal bleeding

ADOLESCENT GYNECOLOGY Abnormal Uterine in the Adolescent Patient

Nirupama K. DeSilva, MD

Common Clinical Scenario: A 14-year-old fe- due to an immature hypotha- FOCUSPOINT male presents to your office with the complaint lamic-pituitary-ovarian (HPO) of menses “every 2 weeks” for the past few axis, causing anovulatory cy- months. She states that her periods started at cles and irregular bleeding.4 age 13, and after her first period she did not Before the diagnosis of imma- have another menses for 3 months. After her sec- ture HPO axis can be assumed, Many patients ond , her periods started “hap- more serious disorders must complain of pening all the time.” She notes that menses be ruled out (Table).5,6 While menstrual problems sometimes come once a month, sometimes “skip there are numerous etiologies a month,” and lately have been coming twice a for abnormal uterine bleeding that actually fall month. Her menses last for 5 days, during which in the adolescent, this article within normal she changes 3 pads per day. She is in good will concentrate on the evalua- variations. health, with no medical problems or history of tion and management of DUB surgeries. Urine test is negative. in the adolescent female.

enstrual disorders are among the EVALUATION most common complaints of adoles- When an adolescent presents cents. This is in part because adoles- with the complaint of DUB, she should be asked cents and their families often have detailed questions about her menstrual history, Mdifficulty understanding what normal cycles or including the age at and the timing, patterns of bleeding are and in part because duration, and quantity of her uterine bleeding. there is considerable menstrual cycle variabil- The presence of cramping and/or clots can be ity in the adolescent years.1 Regular ovulatory useful information as well. menstrual cycles occur every 21 to 35 days and Review of systems should address psychosocial last up to 7 days, with an average loss of stressors, weight changes, eating and exercise 25 to 69 mL.2 Many patients complain of men- habits, medications, and symptoms of hyperan- strual problems that actually fall within nor- drogenism. Family history of bleeding disorders mal variations. In the first year after menarche, and menstrual history is imperative, as is a sex- 50% of cycles are anovulatory, but 80% still fall ual history.7 in the normal range for duration. By the third Physical examination should include vital year of menarche, 95% of menstrual cycles fall signs and evaluate for signs of hyperandrogen- into this range.3 Charting the menstrual flow ism and bleeding. The Sexual Maturity Rating on a calendar can be helpful to clarify normal scale should be determined to be at the appro- versus abnormal cycles. Cycles that fall outside priate stage for the patient’s age. The nipples of the norm should be evaluated for underlying should be assessed for discharge. In most pa- pathology. tients, especially those who are not sexually ac- While there are multiple causes for abnormal tive, an internal pelvic exam is not necessary to uterine bleeding in adolescents, the most likely evaluate the pelvic anatomy. In such patients, cause is dysfunctional uterine bleeding (DUB) an ultrasound may be sufficient to evaluate for pelvic pathology. If a pelvic exam is absolutely Nirupama K. DeSilva, MD, is Assistant Professor, Department needed in cases of massive bleeding, trauma, of Obstetrics and Gynecology, University of Oklahoma School or suspected congenital anomolies, one can be of Community Medicine, Tulsa. performed under anesthesia. Sexually active

Follow The Female Patient on and The Female Patient | VOL 35 JULY 2010 25 ADOLESCENTGYNECOLOGY Abnormal Uterine Bleeding in the Adolescent Patient

TABLE. Causes of Abnormal Uterine Bleeding in the Adolescent5,6

Anovulation • Progestins (eg, Depo-Provera) Bleeding associated with pregnancy • • Abortion (threatened or incomplete) Ovarian failure • Ectopic Pathology involving the reproductive tract • Retained products of conception • /carcinoma Coagulation defects • Congenital malformation of the Systemic diseases • Adrenal insufficiency • Chronic renal disease Exercise-induced • Cushing syndrome Hyperprolactinemia • Diabetes mellitus Infections • Late-onset congenital adrenal hyperplasia • Condyloma of the / • Liver disease • Pelvic inflammatory disease • Polycystic syndrome • / (trichomonas/gonorrhea) • Systemic lupus erythematosis Medications • abnormalities • Anticoagulants Trauma • Chemotherapy drugs • Danazol Tumor • Exogenous steroids • or tumor • Oral contraception (eg, midcycle bleeding • Sarcoma botryoides or continuous use)

females should receive testing for sexually trans- antigen, and plasma VWF activity (ristocetin mitted infections. cofactor activity). Laboratory work-up of adolescents with ab- As well, in any patient with abnormal uterine normal uterine bleeding should include a preg- bleeding, thyroid function tests should be con- nancy test, regardless of whether the history sidered, as this can be a common cause of ab- reveals sexual activity. Once pregnancy has normal uterine bleeding. In patients with head- been ruled out, the practitioner should con- aches or nipple discharge, testing is sider additional lab work to rule on other diag- warranted. In those with signs of polycystic noses in the differential based on the present- ovary syndrome or resistance, the practi- ing signs and symptoms. A complete blood tioner should consider appropriate lab testing, count may be helpful to evaluate for . including , insulin, and glucose ACOG recommends that all patients younger levels. Evaluating the adrenal glands to look for than 18 who present with abnormal uterine abnormalities in suspected cases may be war- bleeding be screened for coagulation disor- ranted as well. ders, particularly , as this disorder has a prevalence of 1% and is the MANAGEMENT most common disorder that causes menorrha- After other diagnoses have been ruled out, the gia at menarche.1,6 Screening for such disorders management of DUB can occur as an outpatient should include a partial thromboplastin time, in the majority of cases. Occasionally, however, prothrombin time, and assessment of platelet hospitalization is required due to hemodynamic function, plasma von Willebrand factor (VWF) instability.

26 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com. DeSilva

Mild Uterine Bleeding (Hgb >12 mg/dL) Severe Uterine Bleeding/Menorrhagia Management of mild abnormal bleeding consists (Hgb <10 mg/dL) of observation and reassurance. If hemoglobin Excessive menstrual bleeding is diagnosed as (Hgb) concentration is normal (>12 mg/dL), girls menses more often than every 21 days or bleed- with mild DUB should be asked to keep a men- ing resulting in a loss of more than 80 mL of strual calendar and can be given the option to blood.2 Menstrual flow requir- avoid treatment with hormonal therapy. They ing changes of menstrual FOCUSPOINT should follow up in 3 to 6 months, unless bleed- products every 1 to 2 hours is ing becomes more severe, in which case they considered excessive, espe- should be seen acutely. cially if the flow lasts longer Menstrual flow than 7 days.1 While it may be requiring changes Moderate Uterine Bleeding (Hgb 10-12 mg/dL) due to , this type of of menstrual Moderate DUB is characterized by moderately bleeding may be associated prolonged or frequent menses every 1 to 3 with a bleeding disorder, and products every weeks.8 Menstrual flow is moderate to heavy. work-up for this should ensue. 1 to 2 hours is con- Mild anemia (Hgb 10-12 mg/dL) is often present Hospitalization is necessary sidered excessive, but without signs of or hemody- for patients who are hemody- namic instability. Moderate DUB can usually be namically unstable, who have especially if the managed in the outpatient setting. The treatment low Hgb concentration (<7 mg/ flow lasts longer typically involves hormonal therapy to stabilize dL), or who have symptomatic than 7 days. endometrial proliferation and shedding. The anemia.8 Heavy active bleeding choice of agent(s) depends, to some extent, upon and Hgb lower than 10 mg/dL how heavily the patient is bleeding.9 Girls with are also considered by some to moderate DUB should be provided with be an indication for hospitaliza- supplementation. tion. If the Hgb is between 8 and 10 mg/dL, and There is a paucity of data from randomized the patient is hemodynamically stable, and the trials regarding the treatment of DUB in adoles- patient and family are reliable and can maintain cents. Nonetheless, there are a variety of regi- close telephone contact, home management may mens that appear to be equally effective. Pa- be possible with daily monitoring. tients who have complaints of heavier bleeding The need for should be in- may have a better response to oral contracep- dividualized, and it should be administered as tives (OCs) that have a combination of deemed necessary by the clinician based on and progestin rather than to progestin-only the patient’s initial blood count, amount of preparations, as estrogen provides hemostasis. bleeding, and any other comorbidities. Thus, one option is to use monophasic contra- Girls who require hospitalization for DUB ceptive pills in the traditional fashion of 1 per should undergo evaluation for a bleeding disor- day. Another regimen states that OC pills be der. Coagulation disorders are the second most taken 3 times per day until the bleeding ceases common cause of menorrhagia in adolescents (usually within 48 hours), then tapered to twice and have been noted in 20% of adolescents hos- daily for 5 days, and then decreased to once pitalized with menorrhagia.10 Blood for evalua- daily to complete 21 days of therapy.9 tion of bleeding disorders should be obtained Once the 21-day course is finished, patients before administration of blood products or es- start another pack and take 1 pill per day in the trogen (exogenous estrogen may elevate VWF typical fashion. If bleeding recurs when the into the normal range).8 Assessment should in- dose is decreased to once per day, twice-per- clude a complete blood count with platelets, day dosing may be necessary for an extended platelet function analyzer, examination of the period of time. Close follow-up is essential dur- peripheral blood smear, prothrombin time, acti- ing twice-per-day dosing. High-dose estrogen vated partial thromboplastin time, plasma VWF therapy can cause nausea, which may result in antigen, plasma VWF activity (ristocetin cofac- noncompliance. Antiemetic therapy (ie, pro- tor activity), factor VIII activity, blood group typ- methazine or ondansetron) is often required ing (blood group O is associated with lower lev- before each dose of the pill.8 Progestin-only els of VWF), and thyroid stimulating hormone. therapy is an alternative for girls with moderate Any underlying disorder noted should be DUB who cannot tolerate, dislike, or have a promptly treated. Consultation with a hematol- contraindication to estrogen therapy. ogist is recommended.

Follow The Female Patient on and The Female Patient | VOL 35 JULY 2010 27 ADOLESCENTGYNECOLOGY Abnormal Uterine Bleeding in the Adolescent Patient

For patients who can tolerate oral intake, ther- FOLLOW-UP AND LONG-TERM CARE apy typically includes a monophasic combina- After treatment is initiated, patients should be tion OC pill with 50 μg and 0.5 mg seen at regular intervals to ensure that their norgestrel (eg, Ovral, Ogestrel) bleeding profile has improved to their satisfac- or 50 μg estradiol and 1 mg nor- tion and that they are tolerating any medicines FOCUSPOINT ethindrone (eg, Ovcon 50), ad- that may have been started. Long-term man- ministered according to vari- agement depends on the anemia and the de- ous schedules. A common sire for contraception. Most experts recom- schedule is to take it 4 times mend continuing hormonal therapy for at least Long-term a day until bleeding is con- 6 months. After therapy is discontinued, the management trolled, then wean to 3 times patient should still be followed to ensure regu- depends on the daily for 3 days, and then to lation of . twice daily to complete a 21- anemia and the day course of pills.8 Then the The author reports no actual or potential conflict desire for patient starts a new pack of of interest in relation to this article. contraception. pills (without using the place- bo pills). REFERENCES For patients who can take 1. ACOG Committee on Adolescent Health Care. ACOG Com- oral medications but in whom mittee Opinion No 349, November 2006. Menstruation in girls and adolescents: using the menstrual cycle as a vital estrogen is contraindicated (eg, sign. Obstet Gynecol. 2006;108(5):1323-1328. those with thromboembolic 2. Adams Hillard PJ, Deitch HR. Menstrual disorders in the col- disease, estrogen-dependent lege age female. Pediatr Clin North Am. 2005;52(1):179-197. 3. Golden NH, Carlson JL. The pathophysiology of amenorrhea tumors, or hepatic disease), a progestin such as in the adolescent. Ann N Y Acad Sci. 2008;1135:163-178. norethindrone acetate (5 to 10 mg daily) or mi- 4. Benjamins LJ. Practice guideline: evaluation and manage- cronized progesterone (200 mg before bedtime) ment of abnormal in adolescents. J Pediatr Health Care. 2009;23(3):189-193. can be used. 5. Matytsina LA, Zoloto EV, Sinenko LV, Greydanus DE. Dys- In patients who need intravenous treatment, functional uterine bleeding in adolescents: concepts of conjugated equine estrogen (Premarin) may be pathophysiology and management. Prim Care Clin. 2006; 33(2): 503-515. used. In cases of severe menorrhagia unrespon- 6. ACOG Committee on Practice Bulletins—Gynecology. sive to 24 hours of hormonal therapy or in those ACOG practice bulletin: management of anovulatory bleed- with platelet dysfunction, nonhormonal hemo- ing. Int J Gynaecol Obstet. 2001;72(3):263-271. 7. Strickland J, Gibson EJ, Levine SB. Dysfunctional uterine static drugs may be used. These include the an- bleeding in adolescents. J Pediatr Adolesc Gynecol. 2006; tifibrinolytic compounds, aminocaproic acid or 19(1):49-51. 8. Emans SJ. Dysfunctional uterine bleeding. In: Emans SJ, tranexamic acid, or desmopressin, which is clas- Laufer MR, Goldstein DP, eds. Pediatric and Adolescent sically used for the treatment of von Willebrand Gynecology. 5th ed. Philadelphia, PA: Lippincott Williams & disease.11 Treatment is continued for approxi- Wilkins; 2005:270. 9. Rimsza ME. Dysfunctional uterine bleeding. Pediatr Rev. mately 8 hours or until the bleeding has been 2002;23(7):227-233. controlled. Once the bleeding has been con- 10. Kulp JL, Mwangi CN, Loveless M. Screening for coagulation trolled and the patient can tolerate oral intake, disorders in adolescents with abnormal uterine bleeding. J Pediatr Adolesc Gynecol. 2008;21(1):27-30. she should be transitioned to oral hormonal 11. Mannucci PM. Treatment of von Willebrand’s disease. N therapy for maintenance. Engl J Med. 2004;351(7):683-694.

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28 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com.