Pediatric And Adolescent Gynecology

Educational Objectives

The goal of this program is to improve the recognition and management of abnormal uterine bleeding in adolescents. After hearing and assimilating this program, the clinician will be better able to:

1. Define normal menstrual parameters in adolescents.

2. Recognize common causes of abnormal uterine bleeding in adolescents.

3. Identify the characteristics of an anovulatory menstrual cycle.

4. Perform an appropriate workup for abnormal uterine bleeding.

5. Choose an appropriate treatment option for an adolescent with abnormal uterine bleeding.

Summary

Abnormal Uterine Bleeding in Adolescents

Normal menstrual bleeding: during first year of menstruation, majority of cycles 3 to 6 wk (first day of one period to first day of next); adult pattern established by 2 yr after menarche, with ≈75% of women menstruating every 3 to 5 wk; cycles >90 days abnormal, even between first and second menses (>95th percentile), requiring evaluation but not necessarily treatment; normal duration and flow difficult to define because research studies use impractical methods of measuring blood volume; cutoffs of 80 mL, or 3 to 6 pads or tampons per day, not helpful (ie, size of products not specified); patient perception of “normal” and thorough history important

Abnormal uterine bleeding (AUB): term “dysfunctional uterine bleeding” (DUB) no longer used; AUB used to describe any bleeding outside normal parameters; acute AUB requires urgent intervention; older terms (menorrhagia [regular, heavy bleeding] and metrorrhagia [irregular, heavy bleeding]) replaced by AUB; International Federation of Gynecology and Obstetrics (FIGO) standardized terminology by cause of bleeding; polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified (PALM-COEIN); PALM issues structural and infrequent in adolescents; cause of AUB in majority adolescents ovulatory dysfunction; other causes include coagulopathy (acquired or inherited) and iatrogenic

Ovulatory dysfunction: most girls have anovulatory cycles at menarche; estrogen predominance causes proliferation of endometrium, but surge of luteinizing hormone (LH) that causes ovulation absent; ovulation increases progesterone, which stabilizes endometrium; progesterone withdrawal triggers menses; medroxyprogesterone acetate (MPA; Provera) triggers menses by simulating ovulation; when ovulation absent, endometrium not stabilized and withdrawal bleeding not triggered; in addition, because fewer prostaglandins produced, uterine contractions that limit bleeding less likely to occur; anovulatory cycles result in irregular “overflow” or no bleeding; regular ovulation usually established few years after menarche (patient may present with concern about newly painful menses)

Causes: immaturity of hypothalamic-pituitary-ovarian (HPO) axis — accounts for majority of anovulatory bleeding; watchful waiting appropriate if patient hemodynamically stable and menses not overly disruptive; dysfunction of HPO axis — hypothalamic etiology common in adolescents (eg, eating disorders cause decreased estrogen production; inadequate stimulation of endometrium leads to amenorrhea or irregular shedding); in polycystic ovary syndrome (PCOS), irregular menses result from unopposed estrogen (ovulation and progesterone surge absent); androgens independent risk factor for impaired ovulation; role of insulin resistance not understood; obesity (independent of PCOS) risk factor for ovulatory dysfunction; adipose tissue produces estrogen, contributing to predominance of estrogen; other mechanisms probable; other causes — although thyroid dysfunction and abnormal prolactin rare, testing warranted because conditions easily treatable; weight gain and obesity associated with thyroid dysfunction more likely to affect menses than is thyroid itself

Coagulopathy: menses affected from onset; bleeding disorder present in ≥20% of women with AUB that necessitates admission (majority have von Willebrand disease [VWD]); less common — factor deficiencies; hemophilia; quantitative or qualitative platelet disorders; acquired coagulopathy (eg, cancer, chemotherapy [thrombocytopenia], liver failure [clotting dysfunction and factor deficiency])

Iatrogenic: breakthrough bleeding common with extended-cycle oral contraceptives (OCs); bleeding seen with depot MPA (DMPA; Depo Provera), particularly at initiation of use or if dose delayed; etonorgestrel implant (Implanon, Nexplanon) associated with high rate of irregular bleeding; copper intrauterine device (IUD; ParaGard) causes heavy bleeding; levonorgestrel IUDs (Mirena) may cause irregular bleeding; anticoagulation (eg, warfarin, enoxaparin [Lovenox]); high-dose long-term nonsteroidal anti-inflammatory drugs (NSAIDs); herbal medications (eg, ginkgo, ginseng, motherwort)

History: determine age at menarche, length and duration of cycle (define patient’s use of “irregular”), and heaviness of bleeding; “on the heaviest day, how often do you need to change your pad or tampon?”; if answer prompt and specific (eg, soaking through every 90 min), heavy bleeding likely; if answer more vague (eg, 4 times daily), ask whether bleeding through onto clothes or bedsheets; ask about related symptoms (eg, cramping requiring medication, mood changes, nausea, diarrhea [more likely in ovulatory cycles]); determine whether change in bleeding pattern related to change in medical problem, weight (>5 lb), eating, exercise, stress, mood, sleep, skin, hair, acne, growth of dark hair (eg, chin, neck, breasts, belly, back) requiring depilation, bowel movements, temperature tolerance, headaches, vision, or galactorrhea (eg, pituitary issue); ask about symptoms of anemia, other personal or family history of bleeding, family history of hysterectomy for bleeding, or blood transfusion for delivery or surgery

Screening for coagulopathy: tool used in adults includes heavy bleeding since menarche (“heavy” undefined) and history of postpartum hemorrhage or bleeding with surgery or dental work; adaptation for adolescents — menses lasting ≥7 days with “gushing” or “flooding” sensation; bleeding through clothes (including overnight); interference with school attendance and activities; personal history of anemia requiring treatment; bleeding with surgery or procedures; personal history of blood transfusion; family history

Physical examination: examine growth chart (for, eg, changes in weight); obtain orthostatic vital signs if concerned about anemia; look for signs of anemia, thrombocytopenia, or androgen excess; if concerned about pelvic foreign body, trauma, or malpositioned IUD, perform pelvic examination (speculum or one-finger bimanual) or ultrasonography (US)

Laboratory evaluation: pregnancy test (all patients); complete blood count (CBC); if bleeding heavy, check ferritin level (if abnormal or bleeding sufficiently heavy to warrant screening for coagulopathy, check iron and coagulation studies and consider thyrotropin [TSH] level); testing for VWD — perform if screening tests positive; some components acute-phase reactants (falsely elevated if acutely bleeding and anemic); abnormal results (low) represent true positive; if normal, retest when bleeding controlled; testing may be delayed unless blood transfusion indicated (compromises later test); effect of estrogen in OCs on testing unclear (possible with high-dose [eg, 50 µg] pills [not usually used]); irregular menses — check follicle-stimulating hormone (FSH), LH, estradiol, TSH, and prolactin; if signs of clinical hyperandrogenism present (eg, severe refractory acne, hirsutism), check total testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate (DHEA-S) to rule out PCOS and androgen-producing tumors; sexually active — test for sexually transmitted infections (STIs) using blind swab or urine testing (however, Trichomonas not currently included in urine tests)

Imaging: contributes little to evaluation of AUB; Pecchioli et al — retrospective review of adolescents with AUB; heavy bleeding present in 75%; two-thirds underwent US, majority with normal results; PCOS morphology seen in 6% (US not used to diagnose PCOS in adolescents as morphology common); US did not change management of any patient; obtain US only if checking for specific finding (eg, IUD placement, polyp [rare in adolescents]), or if AUB persistent despite adequate treatment (to measure thickness of endometrium)

Hemodynamic stability: if patient unstable, send to emergency department (ED); have intravenous (IV) line in place; check CBC, type and screen, and order transfusion if indicated

Control of acute bleeding: most management based on expert opinion or consensus; need for surgery (eg, dilation and curettage [D&C]) extremely rare in adolescents

IV estrogen: only treatment approved by Food and Drug Administration; data supporting use derived from single adult randomized controlled trial (DeVore et al, 1982); bleeding stopped in ≤8 hr in 75% of women on IV estrogen and one-third on placebo (ie, estrogen more effective, but many women stop bleeding regardless); probably safe in women with contraindications to estrogen; short-term treatment; must be transitioned to outpatient regimen that includes progesterone

Combined OCs: single study in adults (Munro et al, 2006) used OC taper (3 times daily for 1 wk, then once daily for 3 wk); bleeding stopped in ≈3 days in majority; recommendations for dose vary widely; with taper or continuous use, use monophasic pill (same hormone dose every day crucial; changing progesterone dose triggers bleeding); use higher-dose pill (eg, 30-35 µg) with potent progestin; Centers for Disease Control and Prevention (CDC) website lists contraindications to estrogen and drug interactions

Progestins: have short half-lives, with rapid saturation and stabilization of endometrium (similar to ovulation); few contraindications or side effects; MPA — best studied; review of 24 adolescents with AUB (Aksu et al) who used 60 to 120 mg on first day, then 20 mg for 10 days showed bleeding stopped in ≤24 hr in 25% (lower response than in placebo group in DeVore et al); all patients stopped bleeding by day 4; Munro et al (2008) used MPA 3 times daily for 1 wk, then daily for 3 wk; rate of bleeding cessation lower than in OC group but satisfaction higher; other progestins — no data available; megestrol acetate (Megace) potent progestin used to stimulate appetite; norethindrone acetate (Aygestin) 5 mg used 3 times daily for 1 wk, then “tapered” (undefined); high rate of initial bleeding seen with DMPA (not ideal for heavy bleeding requiring hospitalization); in adult study of DMPA plus oral MPA 3 times daily for 3 days (“bridging” MPA; Ammerman et al), all women stopped bleeding in ≤5 days (mean, 2.5 days), with minimal side effects and good satisfaction scores; bridging MPA with levonorgestrel IUD another option

Antifibrinolytic therapy: tranexamic acid (Lysteda) not approved for children or adolescents but used off-label; used in Europe and Canada for outpatient management of heavy menses; increasingly used for intraoperative bleeding; not currently used for acute AUB

Nonacute AUB: treatment reasonable for patients complaining of heavy, prolonged, or irregular menses; AUB responsible for one-third of adult visits to gynecologists (possibly higher in adolescents); if menses disrupting life, treatment warranted (even if criteria for bleeding abnormality not met); Wang et al — heavy menstrual bleeding in adolescents significantly impairs participation in school and activities; outpatient treatment — acceptable if patient hemodynamically stable (not well defined; speaker considers hemoglobin (Hb) >10 g/dL stable, or >8 g/dL if not actively bleeding); even with lower values (eg, 6.9 g/dL), close follow-up and bleeding precautions acceptable

Combination OCs and other combined methods (eg, transdermal patch, ring [NuvaRing]): estrogen increases clotting factors and perhaps VW factor; modest reduction in bleeding seen in adults; extended-cycle OCs can cause irregular bleeding in first 3 mo (counsel patient or use monthly OCs for 2-3 mo, then use continuously for 2-3 packs); OCs with short placebo phase available

Contraceptive progesterone-only pills (POPs; minipill): all brands contain 35 µg norethindrone; taking at same time every day crucial; irregular bleeding seen in ≈40%; may be considered if estrogen contraindicated

Noncontraceptive oral progesterone: not adequate for contraception (inform patients); oral MPA — used cyclically (10-14 days every month or every 3 mo; latter regimen useful in patients with secondary amenorrhea and obesity); used to stabilize endometrium and provoke shedding in patients with prolonged bleeding; norethindrone acetate — metabolized to estrogen-like product plus norethindrone (contraceptive effect possible but not proven); similar to selective estrogen receptor modulators in that estrogen-like effects differ in different tissues; unlike other progesterones, beneficial for bone health; has fewer estrogen effects in liver and endometrium; progestin effects cause acute stabilization of endometrium and atrophy over time; used in United States for endometriosis, with amenorrhea in almost 100%

DMPA: overall, reduces bleeding days and flow; rate of amenorrhea 55% at 1 yr; counsel patient to try ≥2 doses, and use shorter window (eg, 11 wk) if bleeding at end of treatment period; side effects — initial irregular bleeding; mood changes (may worsen depression but improves premenstrual syndrome); weight gain (from increased appetite); decreased bone density (reversible)

Etonorgestrel implant: provides excellent contraception but poor control of bleeding; rate of amenorrhea ≈20%; irregular bleeding common, with no improvement after 3 mo of use; side effects similar to those with DMPA

Levonorgestrel IUD: only IUD approved for heavy menses; decreases endometrial thickening; has antifibrinolytic and anti-inflammatory effects; more effective for heavy bleeding than OCs, NSAIDs, and POPs; blood loss reduced significantly by 3 mo; rate of amenorrhea ≈50% at 1 yr (almost all patients have much lighter menses); initial irregular bleeding and cramping improve over time

Use of IUDs in adolescents: concerns debunked; may use in nulliparas (levonorgestrel IUD used off-label in young adolescents); expulsion rate 5% to 7% and perforation rate 1 to 2 in 1000 (no higher than in adult women); risk for pelvic inflammatory disease [PID] increased only for 3 wk after insertion if active untreated STI present at insertion (screen at time of insertion; if positive, treat without removing IUD)

Antifibrinolytics: tranexamic acid modestly reduces heavy bleeding in adults; Srivaths et al — small crossover study in adolescents using OCs and tranexamic acid showed equal efficacy and fewer side effects with tranexamic acid; aminocaproic acid (Amicar) — another option; theoretical risk for venous thromboembolic events (VTE) — older study showed no increased risk in women at high risk for VTE; recent study of use in immediately postpartum women (risk for VTE 4-6 times higher than with OC use) showed no increased risk

Questions and answers: check ferritin even if Hb normal; replace iron until ferritin >20 ng/mL, then prescribe multivitamin with iron (recommended for all menstruating women)

Readings

Aksu F et al: High-dose medroxyprogesterone acetate for the treatment of dysfunctional uterine bleeding in 24 adolescents. Aust NZ J Obstet Gynaecol 1997 May;37(2):228-31; American College of Obstetricians and Gynecologists: ACOG Committee Opinion No. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol 2013 Apr;121(4):891-6; American College of Obstetricians and Gynecologists: ACOG Committee Opinion No. 651: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Obstet Gynecol 2015 Dec;126(6):e143-6. doi: 10.1097/AOG.0000000000001215; American College of Obstetricians and Gynecologists: ACOG Practice Bulletin No. 110: Noncontraceptive uses of hormonal contraceptives. Obstet Gynecol 2010 Jan;115(1):206-18; Ammerman SR et al: A new progestogen-only medical therapy for outpatient management of acute, abnormal uterine bleeding: a pilot study. Am J Obstet Gynecol 2013 Jun;208(6):499.e1-5. doi: 10.1016/j.ajog.2013.02.013; Bennett AR et al: What to do when she’s bleeding through: the recognition, evaluation, and management of abnormal uterine bleeding in adolescents. Curr Opin Pediatr 2014 Aug;26(4):413-9; Committee on Adolescent Health Care Long-Acting Reversible Contraception Working Group; The American College of Obstetricians and Gynecologists: ACOG Committee Opinion No. 539: Adolescents and long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol 2012 Oct;120(4):983-8; DeVore GR et al: Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding — a double-blind randomized control study. Obstet Gynecol 1982 Mar;59(3):285-91; Huguelet PS et al: Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties? J Pediatr Adolesc Gynecol 2016 Jun;29(3):286-91; Kaunitz AM et al: Levonorgestrel-releasing intrauterine system for heavy menstrual bleeding improves hemoglobin and ferritin levels. Contraception 2012 Nov;86(5):452-7; Lethaby A et al: Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev 2000;(4):CD000249; Matteson KA et al; Society of Gynecologic Surgeons Systematic Review Group: Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol 2013 Mar;121(3):632-43; Mullins TL et al: Evaluation and management of adolescents with abnormal uterine bleeding. Pediatr Ann 2015 Sep;44(9):e218-22. doi: 10.3928/00904481-20150910-09; Munro MG et al: Oral medroxyprogesterone acetate and combined oral contraceptives for acute uterine bleeding: a randomized controlled trial. Obstet Gynecol 2006 Oct;108(4):924-9; Munro MG et al; FIGO Working Group on Menstrual Disorders: FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011 Apr;113(1):3-13; Pecchioli Y et al: The utility of routine ultrasound in the diagnosis and management of adolescents with abnormal uterine bleeding. J Pediatr Adolesc Gynecol 2017 Apr;30(2):239-42; Srivaths LV et al: Oral tranexamic acid versus combined oral contraceptives for adolescent heavy menstrual bleeding: a pilot study. J Pediatr Adolesc Gynecol 2015 Aug;28(4):254-7; Wang W et al: Iron deficiency and fatigue in adolescent females with heavy menstrual bleeding. Haemophilia 2013 Mar;19(2):225-30.

Disclosures

For this program, the following has been disclosed: Dr. Schwartz has received grant/research support from Bayer HealthCare Pharmaceuticals. The planning committee reported nothing to disclose. In her lecture, Dr. Schwartz presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Schwartz was recorded at Pediatric Kaleidoscope: Clinical Challenges for the Practitioner, presented by the Nemours/Alfred I. DuPont Hospital for Children and its Office of Continuing Medical Education, and held May 24, 2017, in Wilmington, DE. For information about upcoming CME conferences from the Nemours/Alfred I. DuPont Hospital for Children and its Office of Continuing Medical Education, please visit www.pedsuniversity.org. The Audio Digest Foundation thanks Dr. Schwartz and the Nemours/Alfred I. DuPont Hospital for Children for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD633101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.