{"paper_id":"2c18bc08-0c95-48bb-8fb0-0c3ad83a9ea3","body_text":"Curr Treat Options Peds (2016) 2:184 –195\nDOI 10.1007/s40746-016-0054-8\nPediatric Gynecology (L Breech and K Stambough, Section Editors)\nTreatment Options\nfor the Adolescent Patient\nExperiencing Abnormal\nUterine Bleeding\nRachael L. Polis, DO *\nS. Paige Hertweck, MD\nAddress\n*Kosair Children ’s Hospital, 3991 Dutchmans Lane, Suite 303, Louisville, KY,\n40207, USA\nEmail: RLeighPolis@gmail.com\nPublished online: 8 July 2016\n* Springer International Publishing AG 2016\nThis article is part of the Topical Collection on Pediatric Gynecology\nKeywords Adolescent I AUB I PALM-COEIN I Menstruation I Treatment\nOpinion statement\nAbnormal uterine bleeding (AUB) is one of the most common reasons adolescent\npatients present for gynecologic care. A new classification system has been\nc r e a t e dt op r o v i d eau n i v e r s a l l ya c c e p ted system of nomenclature to describe\nuterine bleeding causes in reproductive -aged women. The acronym PALM-COEIN\n(polyp, adenomyosis, leiomyoma, malig nancy and hyperplasia, coagulopathy,\novulatory dysfunction, endometrial, iatrogenic and not yet classified) was intro-\nduced in 2011. This classification will help to target not only treatment but also\nfuture research into treatment options in the AUB population. In order for\ntreatments to be effective, an accurate diagnosis is paramount. Adolescents\ntend to have anovulatory, infectious, or pregnancy-related causes of AUB.\nTraditional treatment modalities have been hormonal in nature, the most com-\nmon being the use of oral contraceptive pills. The latest development has been\nthe recognition of the effective use of the levonorgestrel intrauterine systems\n(LNG-IUS) in successful treatment of AUB in the adolescent population.\nIntroduction\nAbnormal uterine bleeding (AUB) is one of the\nmost common reasons that adolescent females\npresent for gynecologic care. The underlying diag-\nnosis is important in determining a treatment plan.\n\nIn 2011, the Internati onal Federation of\nGynecology and Obstetricians (FIGO) published a\nclassification system for abnormal uterine bleeding\nknown as PALM-COEIN [ 1]. The system was also\nadopted by the American College of Obstetricians\nand Gynecologists [ 2]. The system is comprised of\nfour categories defined by structural entities, which\ncan be measured with imaging techniques or via\nhistopathology (PALM: polyp, adenomyosis,\nleiomyoma, and malignancy and hyperplasia).\nStructural abnormalities such as polyps,\nadenomyosis, and leiomyomas are uncommon in\nthe adolescent patient however are possible and\nshould remain in the differential diagnosis.\nCervical polyps in the adolescent, while rare, have\nbeen reported in the literature [3 ].\nThe remaining acronym is defined as nonstruc-\ntural and is unrelated to histopathology or imaging\n(COEIN: coagulopathy, ovulatory dysfunction, en-\ndometrial, iatrogenic, and not yet classified) [ 1].\nThe etiology of adolescents ’ causes of abnormal\nuterine bleeding will primarily present as a result\nof these nonstructural causes (COEIN). See Table 1.\nThe most common cause of AUB in the adoles-\ncent is anovulation [ 4]. Anovulation can result\nfrom abnormalities at any levels of the\nhypothalamic-pituitar y-ovarian (HPO) axis\nresulting in the interruption of ovulation [ 4]. The\nmost common causes of anovulation in the adoles-\ncent include immaturity of the HPO axis,\nhypothalamic hypogonadism, and polycystic ovari-\nan syndrome.\nThe second most common cause of AUB in\nadolescents is coagulopathy [ 5–7]. Patients with\nheavy menstrual bleeding should be evaluated for\nboth inherited and acquired disorders of coagula-\ntion [ 8]. Platelet dysfunction has been noted to be\nthe most common hemostatic defect found in ad-\nolescents with AUB [ 9–12, 13].\nVon Willebrand disease is the most common\ninherited bleeding disor der among American wom-\nen [ 8] and may present in the adolescent as AUB.\nThe possibility of an underlying hematologic disor-\nder in adolescents should be considered when they\npresent with heavy menses and a hemoglobin level\nbelow 10 g/dL. This presentation should warrant a\ndetailed hematologic investigation [ 14, 15]. Despite\nguidelines to screen for v on Willebrand and other\nbleeding disorders in adolescents with heavy men-\nses, a recent study determined that less than 25 %\nof adolescents were screened [ 15].\nAdditional causes of AUB that would be more\nlikely in an adolescent include pregnancy, sexually\ntransmitted infections [ 16 ], and sexual trauma.\nTherefore, patients should also be questioned about\nsexual history and a part of their evaluation should\ninclude pregnancy testing, an appropriate physical\nexamination, screening for chlamydia and gonorrhea\nas well as a hematologic evaluation. Similarly, a re-\nview of current medications should be completed as a\nTable 1. Differential diagnosis for nonstructural causes of abnormal uterine bleeding in the adolescent (COEIN)\nCoagulopathy Ovulatory\ndysfunction\nEndometrial Iatrogenic Not yet\nclassified\nPlatelet function\ndisorder\nAnovulatory bleeding Endometritis Breakthrough bleeding\n(hormonal contraception—\nLNG-IUS, hormonal\nimplant, depo\nmedroxyprogesterone)\nTrauma\nVon Willebrand\ndisease\nPolycystic ovarian\nsyndrome (PCOS)\nInfection (chlamydia,\ngonorrhea, pelvic\ninflammatory disease)\nForeign body\nClotting factor\ndeficiency\nThyroid disease\nThrombocytopenia Other\nAnticoagulants\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 185\n\ncommon side effect of contraceptive medications (use\nof continuous oral contraceptive pills, subdermal\nimplant, levonorgestrel in trauterine device) can be\nbreakthrough bleeding perceived as AUB.\nTreatment\nThe initial management of AUB in the adolescent is based on whether the AUB\nis acute or chronic. In cases of acute AUB, the patient ’s hemodynamic stability\nand identification of the underlying cause of bleeding will determine manage-\nment [17]. The proceeding medical management will also be based on the\netiology and the severity of the patient’s anemia. Surgical interventions are rare\nin the adolescent, as most patients improve with medical treatment. Treatment\ngoals include cessation of current bleeding, prevention of worsening anemia,\nimprovement of an adolescent’s quality of life, and the establishment of a\nregular menstrual cycle [17]. As hormonal methods of treatment are com-\nmonly used to treat AUB, prior to their use, it is important to rule out any\ncontraindication by obtaining a complete personal and family history and\nconsulting the Centers for Disease and Control and Prevention ’s Medical\nEligibility Criteria for Contraceptive Use [18], the World Health Organization for\npublished criteria on contraceptive use [19], and the U.S. Food and Drug\nAdministration labeling information website [20]. This is particularly impor-\ntant in that many of these adolescents may require both the contraceptive\nefficacy of the treatment in addition to the hormonal treatment of AUB.\nChronic AUB occurs when uterine bleeding is abnormal in volume, regularity,\nand/or timing and has occurred for most of the past 6 months. Unlike acute\nAUB, which requires immediate intervention, chronic AUB does not [ 1].\nPharmacologic treatment\nHormonal\nCombination estrogen and progestin-containing contraceptives\nThe goal of medical therapy in acute AUB is to stabilize the endometrium with\nestrogen to provide initial hemostasis with the addition of progestins for\nendometrial stability. Combination oral contraceptive pills (COCP) taken\ncontinuously for several months stop menstruation and allow patients to regain\ntheir hemodynamic stability [17]. COCP is cost effective as most pills are also\nfound in generic formulations. Mention of brand names does not imply en-\ndorsement of particular products.\nLo Ovral® (Akrimax Pharmaceuticals LLC, Cranford, NJ) is a monophasic\ncombination contraceptive containing 0.3 mg norgestrel and 30 mcg ethinyl\nestradiol. For severe bleeding with a moderate hemoglobin level (Hgb 8–10 g/\ndL), COCP taper can be initiated [ 21]. A commonly used taper dose would be\none tablet by mouth every 6 h for 2 days, followed by one tablet every 8 h for\n2 days, then one tablet every 12 h for 2 days, and continue to take one tablet\ndaily skipping placebo pills and starting a new pack with active pills. If bleeding\nresumes as the tapering dose is decreased, one can increase pills to a dose of\ntwice daily until completing the 21-day cycle [ 21]. Patients may often\n186 Pediatric Gynecology (L Breech and K Stambough, Section Editors)\n\nexperience nausea with increased dosages of estrogen, and therefore, an anti-\nemetic can be administered before the patient receives the dose of oral contra-\nceptive.\nPatients with severe anemia (Hgb ≤7 g/dL) or moderate anemia (Hgb 8-\n10 g/dL) with active bleeding may often need to be hospitalized if hemody-\nnamically unstable. They can be treated with a similar COCP taper but may\nrequire one tablet every 4 to 6 h until bleeding decreases. This can take up to\n24–36 h. Upon significant decrease of bleeding, the pill taper can be decreased\nto one pill three times a day for 3 days and then one pill twice a day until\nhematocrit is above 30 % [ 21].\nIntravenous or intramuscular estrogen is rarely indicated in patients\nexperiencing acute AUB and is used primarily when patients are unable to\ntolerate oral medications or continuous bleeding results despite maximum oral\ntherapy. Conjugated estrogens, Premarin® 25 mg (Wyeth Pharmaceuticals Inc,\nPhiladelphia, PA), can be administered intravenously every 4–6 h for two or\nthree doses as it has a proven indication for treatment for acute AUB. The use of\nestrogens has been associated with increased risk of a blood clot [ 21]. While\nestrogen will cause cessation of acute bleeding, it is important to add progestin\ntherapy as re-bleeding from estrogen withdrawal can occur when IV estrogen is\ndiscontinued [21]. Many practitioners will address this issue by placing a\npatient on a COCP following cessation of bleeding with IV Premarin®.\nUse of continuous oral contraceptive pills (using the active pills continu-\nously from a pack of 28-day oral contraceptives and discarding the inactive\nplacebo pills) or an extended cycle of 84-day oral contraceptives such as\nSeasonale® (Teva Pharmaceuticals USA, Inc, Sellersville, PA), a monophasic\ncombination contraceptive containing levonorgestrel 0.15 mg and ethinyl es-\ntradiol 0.03 mg, can help anemic patients skip monthly menses.\nOther options for extended or continuous regimens of hormonal therapy\nhave been described in the adult population [ 22]. These include the use of the\nvaginal ring (NuvaRing®, Merck & Co., Inc., Whitehouse Station, NJ) containing\n11.7 mg etonogestrel/2.7 mg ethinyl estradiol or the 6-mg norelgetromin/0.75-\nmg ethinyl estradiol transdermal contraceptive patch (Ortho Evra®, Janssen\nPharmaceuticals, Inc., Titusville, NJ). The ring may be used continuously by\nplacing one ring monthly [23]. The ring can be removed for 4 days when\nbreakthrough bleeding occurs and then re-inserted [23]. The extended patch\ncycle can consist of weekly patch use for 12 consecutive weeks followed by a\npatch-free week [24].\nThe traditional choice of treatment of heavy menstrual bleeding due to von\nWillebrand disease is COCP [25–27]. COCP have been found to reduce men-\nstrual blood loss and increase hemoglobin concentrations in anemic women\n[25]. They can be administered continuously or in an extended regimen to\nreduce the frequency and severity of bleeding and control the timing of bleed-\ning [28]. There are reports of successful treatment of AUB with COCP in\nconjunction with tranexamic acid [28]. However, clinicians should be aware\nthat this combination is listed as a contraindication in the tranexamic pre-\nscribing information as of 2013 due to the potential risk of thromboembolic\nevents [29].\nPatients with contraindications for receiving estrogen due to a history of\nblood clots, uncontrolled chronic hypertension, migraines with aura, or specific\nchronic illnesses can be treated with alternative medications. COCP should also\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 187\n\nbe used with careful consideration in adolescents who are immobile as they\nmight be at increased risk for a blood clot.\nThe most common reason for chronic AUB in the adolescent is typically the\nresult of anovulation associated with polycystic ovarian syndrome (PCOS).\nCOCP suppress ovarian and adrenal androgen production and increase sex\nhormone-binding globulin resulting in improved symptoms of acne and hir-\nsutism associated with PCOS. Treatment with 20–35 mcg of ethinyl estradiol\nremains common among anovulatory adolescents [4]. In addition to regulating\nmenstrual cycles, COCPs can improve unwanted hair growth in 50 to 70 % of\nwomen [30].\nProgesterone-only methods\nIn those patients experiencing acute AUB who have contraindications to COCP,\ntreatment with progesterone-only methods is an alternative. Norethindrone\nacetate (Aygestin®, Teva Women’s Health Inc, Sellersville, PA) can be adminis-\ntered as a taper taking 5 or 10 mg orally four times a day for 4 days, three times a\nday for 3 days, and twice a day for 2 weeks [ 21]. Medroxyprogesterone acetate\n(Provera®, Pfizer, New York, NY) 20 mg orally three times a day for a week can\nalso be given to patients with acute vaginal bleeding [31]. Santos et al. noted the\nfirst use of a norethindrone 0.35 mg taper to treat heavy bleeding episodes in\nthe adolescent population (Ortho Micronor®, Janssen Pharmaceuticals Inc.,\nTitusville, NJ) [32]. Two regimens of use were described: either taking one\ntablet of norethindrone 0.35 mg twice daily for a week, followed by one tablet\ndaily for 21 days, or one tablet taken three times daily for 3 days, followed by\none tablet twice daily for a week and then taken daily [ 32]. The most com-\nmonly noted side effects included irregular bleeding, nausea/vomiting, mood\nswings, and hot flashes. Discontinuation rates were high secondary to side\neffects of breakthrough bleeding [32].\nProgestins are also an option for adolescents who are experiencing anovula-\ntory bleeding, without hirsutism or acne, and for whom contraception is not a\nconcern. Progestins can be prescribed cyclically to induce a withdraw bleed [30]\nby prescribing Provera® 10 mg orally for 10 days either monthly or every\n3 months. For those patients who wouldprefer complete menstrual suppression\nor significantly decreased flow, a continuous progestin-only pill Ortho\nMicronor® or higher doses of Aygestin® 10 to 15 mg daily may be prescribed [30].\nMedroxyprogesterone acetate 150 mg injectable (Depot Provera®, Pharmacia\n&Upjohn Co, Division of Pfizer Inc, New York, NY) is administered intramus-\ncularly every 12 weeks and has been used for treatment in AUB. While amenor-\nrhea is associated with prolonged use [33], it occasionally results in irregular\nmenstrual bleeding that many adolescents find bothersome and unacceptable.\nDepot Provera® users have been noted to have a decrease in bone mineral density\nwhen compared to normal menstruating controls [34, 35]. However, no high-\nquality data is available to inform us whether the decrease in bone mineral\ndensity associated with use will affect eventual fracture risk in adolescents [35].\nDepo Provera® may be a good option for temporary use in some patients. It\nshould be used with caution in adolescents with immobility as they might\nalready have a low baseline bone density for their age. Additionally, Depo\nProvera® use has been associated with increased weight gain which can be\nproblematic for this population [36].\n188 Pediatric Gynecology (L Breech and K Stambough, Section Editors)\n\nNonhormonal\nAnti-inflammatory medications\nIndividuals who experience mild bleeding (longer than normal periods\nor shortened menstrual cycles for more than 2 months) and have\nnormal hemoglobin [ 21] may benefit from a nonsteroidal anti-\ninflammatory (NSAID). A Cochran e review demonstrated NSAIDs are\nmore effective than placebo at reducing menstrual blood loss in\nwomen with regular menstrual cycles. However, they were less effective\nthan tranexamic acid, danazol, and the levonorgestrel-releasing intra-\nuterine device (LNG-IUS) [ 37]. Studied dosages of naproxen\n(Naprosyn®, Roche Laboratories Inc, Nutley, NJ) varied between 250\nand 500 mg twice a day or up to four times daily and ibuprofen\nregimens from 600 to 1200 mg daily [ 37]. Patients with von\nWillebrand disease or other coagulation disorders should avoid NSAID\nproducts that prevent platelet adhesion as they may increase blood loss\n[8, 21].\nAntifibrinolytic agents\nAntifibrinolytic agents such as tranexamic acid (Lysteda®, Ferring\nPharmaceutics Inc, Parsippany, NJ, USA) are nonhormonal and\nnoncontraceptive methods for women who experience heavy menstrual\nbleeding. This plasminogen activator in hibitor decreases fibrinolysis and\npromotes clot formation resulting in reduced menstrual blood loss.\nAntifibrinolytics cause a greater reduction of heavy menstrual bleeding\nwhen compared to placebo [ 38]. Lysteda is prescribed as 1300 mg orally\nthree times daily for a total of 5 days during monthly menses [ 29]. The\nmost common side effects include headaches, backaches, nasal sinus\nproblems, abdominal pain, nausea, and vomiting [ 29].\nContraindications include but are not limited to thrombotic or throm-\nboembolic disease [ 31].\nLysteda® is not approved by the FDA for use in premenarcheal girls\nand is only indicated for women of reproductive age as its use was not\noriginally studied in young women under the age of 18. However,\nantifibrinolytics have been demonstrated to decrease menstrual blood\nloss in adolescents [28]. Srivaths et al. conducted a small pilot study\ncomparing oral tranexamic acid to combination oral contraceptives for\nadolescents with heavy menstrual bleeding [ 39]. The results demon-\nstrated tranexamic acid appeared to be as effective in the management of\nadolescent heavy menstrual bleeding in reducing menstrual blood loss\nand improving the participant ’s quality of life [ 39].\nVasopressin analog\nDesmopressin acetate (DDAVP®, Ferring Pharmaceuticals Inc, Parsippany,\nNJ) is a synthetic analog of vasopressin that improves bleeding in\npatients with von Willebrand disease and decreases heavy menstrual\nbleeding. Kouides et al. conducted a prospective crossover study between\nintranasal desmopressin and oral tra nexamic acid, which demonstrated\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 189\n\nthat while both improved quality of life and reduced menstrual blood\nl o s s ,t r a n e x a m i ca c i dp r o v e dt ob em o r ee f f e c t i v e[40]. A Cochrane\nreview by Ray et al. compared nonsurgical interventions for treating\nheavy menstrual bleeding in women with bleeding disorders [ 41]. There\nis a paucity of data showing improvement of heavy menstrual bleeding\nwith the use of desmopressin when compared to placebo [ 41].\nAdditional randomized controlled trials are needed. Patients who do opt\nto try desmopressin acetate require r estrictions on their fluid intake\nsecondary to the risk of hyponatremia. In the majority of cases, use of\nDDAVP® is reserved for those pati ents with a bleeding disorder who\nhave been found to be DDAVP® responders and is typically prescribed\nand managed by a hematologist.\nVitamins\nPatients with AUB and anemia should receive iron replacement therapy.\nNo specific iron preparation is more effective than another. The target\ndosage is 150 to 200 mg/day of elemental iron in one to three divided\ndoses per day [ 42]. Iron should be taken on an empty stomach with\norange juice to assist absorption. If the patient experiences severe ane-\nmia (Hgb ≤ 7 g/dL), they might benefit from folate or multivitamin\nsupplementation [ 17]. In patients who are intolerant of oral iron\npreparations and have heavy menstrual bleeding, IV iron therapy may be\nindicated [ 43]. Regardless of the iron preparation product used, IV iron\ntherapy has been found to be effectiv e and safe to increase hemoglobin\nlevels to near normal with no serious adverse affects [ 43].\nInterventional procedures\nExam under anesthesia and dilatation and curettage (D&C)\nIn most cases of AUB, medical therapy is sufficient. In those patients for\nwhom medical management does not decrease bleeding and in whom\nvital signs are unstable, surgical evaluation may be warranted with an\nexam under anesthesia. A D&C can be both diagnostic and therapeutic\nbut is rarely needed in the adolescent patient [ 21]. The risks of a D&C\nprocedure include anesthesia, uterine perforation, infection, and\nAshermans syndrome (intr auterine adhesions).\nFoley catheter for mechanical tamponade\nAdolescents who fail medical treatment and have continued profuse\nbleeding might benefit from a mechanical measure to tamponade\nbleeding within the uterine cavity until medical treatments can be ef-\nfective. After evacuation of clots from the uterine cavity, a 16- or 18-\nFrench Foley catheter with a 30-cc ba lloon can be placed into the uterus\n[44]. Cervical dilation may be required to pass the catheter through the\ncervix. Once inside the uterine cavity, the balloon is inflated with saline\nuntil it is filled and bleeding stops. The positioning of the catheter can\nbe confirmed by ultrasound and is kept in place for up to 24 h. Foley\ncatheters have been used to control postpartum hemorrhage [ 45], and\n190 Pediatric Gynecology (L Breech and K Stambough, Section Editors)\n\ninformation about their use has been extrapolated to the adolescent\npatient [ 44].\nAssistive devices\nHormonal\nLevonorgestrel intrauterine system\nLNG-IUS is an excellent management option for a patient experienc-\ning chronic abnormal uterine ble eding. A recent Cochrane review\npublished in 2015 by Lethaby et al. concluded the LNG-IUS is more\neffective than oral medication (oral contraceptive pill, mefenamic\nacid, medroxyprogesterone acetate, norethindrone acetate) as a treat-\nment for heavy menstrual bleeding and is associated with greater\nreduction in heavy menstrual bleeding and improvement in quality of\nlife, and appears to be more acceptable long term. However, the LNG-\nIUS is associated with more minor ad verse effects than oral therapy\n[46].\nMirena® (Bayer Healthcare Pharmaceuticals Inc., Whippany, NJ,\nUSA), a 5-year intrauterine devi ce (IUD), and Liletta® (Medicine360,\nSan Francisco, CA, USA, and Actavis ,P a r s i p p a n y ,N J ,U S A ,t r a d e m a r k\nof Odyssea Pharma SPRL [Belgium], an Actavis affiliate), a 3-year\nIUD, both contain 52 mg of levonorgestrel. Not only is LNG-IUS a\nlong-term management option for AUB in adolescents but it is also a\nhighly effective contraception opt i o ni na na t - r i s kp o p u l a t i o n .T h e\nLNG-IUS has been found to be more effective at reducing menstrual\nblood loss with greater increases in hemoglobin and ferritin compared\nwith other oral medical management [ 47–49]. It is a well-tolerated\nmethod for patients with heavy menses and in women with inherited\nbleeding disorders [ 50]. In adolescents with AUB secondary to\nanovulation, the LNG-IUS has been demonstrated to be effective and\nshould be considered in all age groups [ 4].\nLNG-IUS use has been noted to be more effective than medical\ntreatment in reducing the effects heavy menstrual bleeding has on\nquality of life [ 51]. The 2-year continuation rates in women using the\nLNG-IUS are higher than in women rec eiving typical medical treatment\nfor AUB [ 51]. A cohort study among adolescents in New Zealand using\nthe LNG-IUS had a 1-year continuation rate of 85 % [ 52]. A study in\nthe UK also identified LNG-IUS as th e most cost-effective treatment\nwhen using their quality-of-life measu res to estimate the quality-adjusted\nlife years (QALY) as a primary indicator of treatment success [ 53].\nSanghera et al. concluded using UK guidelines the LNG-IUS would be\nthe recommended treatment for heavy menstrual bleeding [ 53].\nSide effects of the LNG-IUS include pa in with insertion, risk of expulsion,\nirregular bleeding or spotting, headaches, pelvic pain, breast tenderness, and\novarian cysts [ 46]. Adolescents should also be advised that uterine size can\npreclude insertion. The Mirena® requires a uterine sound depth of 6 cm and\nthe Liletta® 5.5 cm. The presence of a uterine anomaly may also preclude\ninsertion of an IUS.\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 191\n\nThere is a smaller 3-year intrauterine system, Skyla®, containing 13.5 mg of\nlevonorgestrel (Bayer Healthcare Pharmaceuticals Inc., Wayne, NJ), but there is\nno medical literature at this time regarding its use in treatment of AUB.\nSubdermal implant\nThe 68-mg etonorgestrel subdermal implant is a rod placed subdermally in the\narm for 3 years (Nexplanon®, Merck & Co Inc., Whitehouse Station, NJ). The\nsubdermal implant is associated with an overall decrease in bleeding with\ncontinued use [54]. However, its use has not been described as a primary\ntreatment for AUB. It is an effective long-term form of contraception for the\nadolescent patient. Users should be counseled about the side effect of unpre-\ndictable breakthrough bleeding. Patients also may report acne, headaches,\nmood swings, weight gain, and nausea.\nDiet and lifestyle\nExercise\nAnovulation and therefore AUB can be associated with an increased body mass\nindex. Exercise with associated weight loss may improve ovulatory function [4,\n55, 56] and therefore improve AUB. While diet and exercise education is an\nimportant adjunct to the medical management of these patients, most patients\nwho present with AUB are in need of immediate treatment to manage their\nbleeding symptoms.\nPediatric considerations\nClinicians in the care of young female patients need to be anticipatory in their\nmanagement of menarche in patients with known bleeding disorders. A study\nby Dowlut-McElroy et al. identified prepubertal girls with known bleeding\ndisorders who do not have a plan of care in the event they had heavy menstrual\nbleeding after menarche [6]. They conclude a consultation with a pediatric\ngynecologist or hematologist prior to menarche would be helpful to review\nabnormal bleeding patterns and discuss possible treatment options should they\nexperience heavy menses. Adolescents with bleeding disorders should also be\nencouraged to wear medical alert bracelets [8]. Today, there are many fashion-\nable medical jewelry options available including Lauren’s Hope® Medical ID\nJewelry [57] and American Medical ID® [ 58].\nConclusion\nOver the past 5 years, AUB has a new classification system (PALM-COEIN) that\nshould be used in the evaluation of AUB in all reproductive-aged women\nincluding the adolescent. This classification will help to define the cause of the\nbleeding and thereby target treatment. Adolescents more commonly have\nanovulatory bleeding, a bleeding disorder, infectious causes of bleeding, and\npotentially pregnancy-related bleeding. Awareness of this information should\nhelp the clinician to focus the history and physical examination. Traditionally,\nCOCPs have been used to treat AUB in the adolescent but recent literature\n192 Pediatric Gynecology (L Breech and K Stambough, Section Editors)\n\nshows the advancement and success of the use of LNG-IUS, which may surpass\nthe use of COCPs for treatment of AUB in this patient population in the future.\nA recent study by Haguelet et al. demonstrated variations in strategies of\ntreatment among pediatric subspecialties in treating adolescents with acute\nAUB and identified a lack of standardized care for adolescents [ 59]. Future\nevaluations of standardized management of AUB in adolescents would be\nhelpful to identify the optimal treatment plan [ 59].\nCompliance with Ethical Standards\nConflict of Interest\nRachael L. Polis declares that she has no conflict of interest. S. Paige Hertweck declares that she has no conflict of\ninterest.\nHuman and Animal Rights and Informed Consent\nThis article does not contain any studies with human or animal subjects performed by any of the authors.\nReferences and Recommended Reading\nPapers of particular interest, published recently, have been\nhighlighted as:\n Of importance\n1. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO\nclassification system (PALM-COEIN) for causes of ab-\nnormal uterine bleeding in nongravid women of re-\nproductive age. Int J Gynecol Obstet. 2011;113:3–13.\n2. Diagnosis of abnormal uterine bleeding in\nreproductive-aged women. Practice Bulletin No. 128.\nAmerican College of Obstetricians and Gynecologists.\nObstet Gynecol 2012; 120:197-206\n3. Soyer T, Demirdag G, Gucer S, Orhan D, Karnak I.\nGiant cervical polyp with mesonephric duct remnants:\nunusual cause of vaginal bleeding in an adolescent girl.\nFetal Pediatr Pathol. 2014;33:176–81.\n4. Management of abnormal uterine bleeding associated\nwith ovulatory dysfunction. Practice Bulletin No. 136.\nAmerican College of Obstetricians and Gynecologists.\nObstet Gynecol. 2013;122:176-185\n5. Basaran HO, Akgul S, Oksuz-Kanbur N, Gumruk F,\nCetin M, Derman O. Dysfunctional uterine bleeding in\nadolescent girls and evaluation of their response to\ntreatment. Turk J Pediatr. 2013;55:186–9.\n6. Dowlut-McElroy T, Williams KB, Carpenter SL,\nStrickland JL. Menstrual patterns and treatment of\nheavy menstrual bleeding in adolescents with bleeding\ndisorders. J Pediatr Adolesc Gynecol. 2015;28:499–\n501.\n7 . K a n b u rN O ,D e r m a nO ,K u t l u kT ,G u r g e yA .C o -\nagulation disorders as the cause of menorrhagia\nin adolescents. Int J Adolesc Med Health.\n2004;16:183– 5.\n8. Von Willebrand disease in women. Committee Opin-\nion No. 580. American College of Obstetricians and\nGynecologists. Obstet Gynecol. 2013; 122:1368-1373\n9. Amesse LS, Pfaff-Amesse T, Gunning WT, Duffy N,\nFrench JA. Clinical and laboratory characteristics\nof adolescents with platelet function disorders\nand heavy menstrual bleeding. Exp Hematol\nOncol. 2013;2:3. doi: 10.1186/2162-3619-2-3.\n10. Vo KT, Grooms L, Klima J, Holland-Hall C,\nO’Brien SH. Menstrual bleeding patterns and\nprevalence of bleeding disorders in a multidisci-\nplinary adolescent haematology clinic.\nHaemophilia. 2013;19:71 –5.\n11. Philipp CS, Dilley A, Miller CH, Evatt B, Baranwal A,\nSchwartz R, et al. Platelet defects in women with un-\nexplained menorrhagia. J Thrombo Haemost.\n2003;1:477–84.\n12. Philipp CS, Faiz A, Dowling N, Dilley A, Michael LA,\nAyers C, et al. Age and the prevalence of bleeding\ndisorders in women with menorrhagia. Obstet\nGynecol. 2005;105:61–6.\n13. Seravalli V, Linari S, Peruzzi E, Dei M, Paladino E, Bruni\nV. Prevalence of hemostatic disorders in adolescents\nwith abnormal uterine bleeding. J Pediatr Adolesc\nGynecol. 2013;26:285–9.\nThe study identified AUB in adolescents most frequently asso-\nciated with an underlying bleeding disorder and the most\ncommon disorder of hemostasis was a platelet function\ndisorder.\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 193\n\n14. Oral E, Cagas A, Gezer A, Kaleli S, Aygin Y, Ocer F.\nHematological abnormalities in adolescent menorrha-\ngia. Arch Gynecol Obstet. 2002;266:72–4.\n15. Khamees D, Klima J, O ’Brien SH. Population screening\nfor Von Willebrand disease in adolescents with heavy\nmenstrual bleeding. J Pediatr. 2015;166:195–7.\n16. Toth M, Patton DL, Esquenzi B, Shevchuk M, Thaler H,\nDivon M. Association between Chlamydia trachomatis\nand abnormal uterine bleeding. Am J Reprod\nImmunol. 2007;57:361–6.\n17. Bennett AR, Gray SH. What to do when she ’s bleeding\nthrough: the recognition, evaluation, and management\nof abnormal uterine bleeding in adolescents. Curr\nOpin Pediatr. 2014;26:413–9.\nA thoughtful review in the evaluation and management of AUB\nin adolescents.\n18. Centers for Disease Control and Prevention (CDC). US\nmedical eligibility criteria for contraceptive use, 2010.\nMMWR. 2010;59(RR-04):1–85.\n19. Medical eligibility criteria for contraceptive use. 5th\nedition. Geneva: World Health Organization; 2015.\n20. Food and Drug Administration. FDA online label re-\npository. Available at: http://labels.fda.gov.R e t r i e v e d\nDecember 25, 2015.\n21. Gray SH, Emans SJ. Abnormal vaginal bleeding in the\nadolescent. In: Emans SJ, Laufer MR, editors. Emans,\nLaufer, Goldstein’s pediatric adolescent gynecology.\n6th ed. Philadelphia, PA: Lippincott; 2012. p. 159–67.\n22. Jacobson JC, Likis FE, Murphy PA. Extended and con-\ntinuous combined contraceptive regimens for men-\nstrual suppression. J Midwifery Womens Health.\n2012;57:585–92.\n23. Sulak PJ, Smith V, Coffee A, Witt A, Kuehl AL, Kuehl TJ.\nFrequency and management of break through bleeding\nwith continuous use of the transvaginal contraceptive\nring. Obstet Gynecol. 2008;112:563–71.\n24. Stewart FH, Kaunitz AM, LaGuardia KD, Karvois DL,\nFisher AC, Friedman AJ. Extended use of a transdermal\nnorelgestromin/ethinyl estradiol: a randomized trial.\nObstet Gynecol. 2005;105:1389–96.\n25. James AH. Von Willebrand disease. Obset Gynecol\nSurv. 2006;61:136–45.\n26. James AH, Manco-Johnson MJ, Yawn BP, Dietrich JE,\nNichols WL. Von Willebrand disease: key points from\nthe 2008 National Heart, Lung, and Blood Institute\nguidelines. Obstet Gynecol. 2009;114:674–8.\n27. Nichols WL, Hultin MB, James AH, Manco-Johnson\nMJ, Montgomery RR, Ortel TL, et al. von Willebrand\ndisease (VWD): evidence-based diagnosis and man-\nagement guidelines, the National Heart, Lung, and\nBlood Institute (NHLBI) expert panel report.\nHaemophilia. 2008;14:171–232.\n28. Chi C, Pollard D, Tuddenham E, Kadir RA. Menorrha-\ngia in adolescents with inherited bleeding disorders. J\nPediatr Adolesc Gynecol. 2010;23:215–22.\n29. Highlights of Prescribing Information. Lysteda.com\nwebsite.http://www.lysteda.com/assets/pi_ferring2013-\n1f2d77bcb42b5738c55afab5280d7e9c.pdf.U p d a t e d\nOctober 2013. Accessed January 24, 2016.\n30. DiVasta AD, Emans SJ. Androgen abnormalities in the\nadolescent girl. In: Emans SJ, Laufer MR, editors.\nEmans, Laufer, Goldstein’s pediatric adolescent gyne-\ncology. 6th ed. Philadelphia, PA: Lippincott; 2012. p.\n168–87.\n31. Management of acute abnormal uterine bleeding in\nnonpregnant reproductive-aged women. Committee\nOpinion No. 557. American College of Obstetricians\nand Gynecologists. Obstet Gynecol 2013;121:891-896\n32. S\nantos M, Hendry D, Sangi-Haghpeykar H, Dietrich JE.\nRetrospective review of norethindrone use in adoles-\ncents. J Pediatr Adolesc Gynecol. 2014;27:41–4.\nFirst published study to address the use of a norethindrone\ntaper for heavy bleeding episodes in the adolescent\npopulation.\n33. Hubacher D, Lopez L, Steiner MJ, Dorflinger L. Men-\nstrual pattern changes from levonorgestrel subdermal\nimplants and DMPA: systemic review of evidence\nbased comparisons. Contraception. 2009;80:113–8.\n34. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP.\nBone mineral density in adolescent females using depo\nmedroxyprogesterone acetate. J Pediatr Adolesc\nGynecol. 2004;17:17–21.\n35. Depo medroxyprogesterone acetate and bone effects.\nCommittee Opinion No. 602. American College of\nObstetricians and Gynecologists. Obstet Gynecol 2014;\n123:1398-1402\n36. Menstrual manipulation for adolescents with disabil-\nities. ACOG Committee Opinion No. 448. American\nCollege of Obstetricians and Gynecologists. Obstet\nGynecol 2009; 114:1428-1431\n37. Lethaby A, Duckitt K, Farquhar C. Non-steroidal anti-\ninflammatory drugs for heavy menstrual bleeding.\nCochrane Database Sys Rev. 2013;1, CD000400.\n38. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for\nheavy menstrual bleeding. Cochrane Database Syst Rev\n2000; CD000249.\n39. Srivaths LV, Dietrich JE, Yee DL, Sangi-Haghpeykar H,\nMahoney D. Oral tranexamic acid versus combination\noral contraceptives for adolescent heavy menstrual\nbleeding: a pilot study. J Pediatr Adolesc Gynecol.\n2015;28:254–7.\n40. Kouides PA, Byams VR, Philipp CS, Stein SF, Heit JA,\nLukes AS, et al. Multisite management study of menor-\nrhagia with abnormal laboratory hemostasis: a pro-\nspective crossover study of intranasal desmopressin and\noral tranexamic acid. Br J Haematol. 2009;145:212–20.\n41. Ray S, Ray A. Non-surgical interventions for treating\nheavy menstrual bleeding (menorrhagia) in women\nwith bleeding disorders. Cochrane Database Sys Rev.\n2014;11, CD010338.\n42. Rydz N, Jamieson MA. Managing heavy menstrual\nbleeding in adolescents. Contemporary OB/GYN.\n2013;58:49–52.\n43. Mantadakis E. Advances in pediatric intravenous iron\ntherapy. Pediatr Blood Cancer. 2016;63:11–6.\n44. Wilkinson JP, Kadir R. Management of abnormal uter-\nine bleeding in adolescents. J Pediatr Adolesc Gynecol.\n2010;23:S22–30.\n194 Pediatric Gynecology (L Breech and K Stambough, Section Editors)\n\n45. Post partum hemorrhage. ACOG Practice Bulletin No.\n76. American College of Obstetricians and Gynecolo-\ngists. Obstet Gynecol. 2006; 108:1039-1047\n46. Lethaby A, Hussain M, Rishworth JR, Rees MC. Pro-\ngesterone or progesterone-releasing intrauterine system\nfor heavy menstrual bleeding. Cochrane Database Sys\nRev. 2015;4:CD002126.\nThe Cochrane review identified the LNG IUS as more effective\nthen oral medication in the treatment of heavy menstrual\nbleeding and is associated with greater reduction in heavy\nmenstrual bleeding and improvement in quality of life.\n47. Shabaan MM, Zakherah M, El-Nashar SA, Sayed GH.\nLevonorgestrel-releasing intrauterine system compared\nto low dose combined oral contraceptive pills for idi-\nopathic menorrhagia: a randomized clinical trial.\nContraception. 2011;83:48–54.\n48. Kauntiz AM, Bissonnette F, Monteiro I, Lukkari-Lax E,\nMuysers C, Jensen JT. Levonorgestrel-releasing intra-\nuterine system or medroxyprogesterone for heavy\nmenstrual bleeding. Obstet Gynecol. 2010;116:625–\n32.\n49. Kaunitz AM, Bissonnette F, Monteiro I, Lukkari-Lax E,\nDeSanctis Y, Jensen J. Levonorgestrel-releasing intra-\nuterine system for heavy menstrual bleeding improves\nhemoglobin and ferritin levels. Contraception.\n2012;452–457.\n50. Kingman CE, Kadir RA, Lee CA, Economides DL. The\nuse of levonorgestrel-releasing intrauterine system for\ntreatment of menorrhagia in women with inherited\nbleeding disorders. BJOG. 2004;111:1425–8.\n51. Gupta J, Kai J, Middleton M, Pattison H, Gray R, Dan-\niels J. Levonorgestrel intrauterine system versus medical\ntherapy for menorrhagia. N Engl J Med. 2013;368:128–\n37.\n52. Paterson H, Ashton J, Harrison-Woolrych M. A na-\ntionwide cohort study of the new use of the\nlevonogestrel intrauterine device in New Zealand ado-\nlescents. Contraception. 2009;79:433–8.\n53. Sanghera S, Roberts TE, Barton P, Frew E, Daniels J,\nMiddleton L, Gennard L, Kai J, Gupta JK.\nLevonorgestrel-releasing intrauterine system vs. usual\nmedical treatment for menorrhagia: an economic\nevaluation alongside a randomised controlled trial.\nPLos ONE 2014; 9(3):e91891. doi:10.1371/journal.\npone.0091891.\n54. Bachmann G, Korner P. Bleeding patterns associated\nwith non-oral hormonal contraceptives: a review of the\nliterature. Contraception. 2009;79:247–58.\n55. Frishman GN. Evaluation and treatment of menorrha-\ngia in an adolescent population. J Minim Invasive\nGynecol. 2008;15:682–8.\n56. Guzick DS, Berga SL, Wing R, Winters SJ, Smith D.\nEndocrine consequences of weight loss in obese,\nhyperadrogenic, anovulatory women. Fertil Steril.\n1994;61:598–604.\n57. Lauren ’s Hope medical ID jewelry. Available at:https://\nwww.laurenshope.com. Retrieved December 24, 2015.\n58. American Medical ID. Available at: http://www.\namericanmedical-id.com. Retrieved December 24,\n2015.\n59. Huguelet P, Buyers E, Lange-Liss J, Scott S. Treatment of\nacute abnormal uterine bleeding in adolescents: what\nare providers doing in various subspecialties? J Pediatr\nAdolesc Gynecol. 2015. doi:10.1016/j.jpag.2015.\nTreatment Options for the Adolescent Patient Experiencing AUB Polis and Hertweck 195","source_license":"CC0","license_restricted":false}