Oral Contraceptives/Abnormal Uterine Bleeding in Teenagers

Management of Abnormal UterineBleeding in AdolescentsPamela S. Greene, M.D.Medical Director, Scott & White Hospital Forensic ProgramAssistant Professor, Texas A&M Health Science CenterDepartment of Obstetrics and Gynecology andJoint Appointment, Department of PediatricsScott and White HealthcareTemple, Texas

Learning Objectives1. Review terminology and causes ofabnormal uterine bleeding2. Outline the clinical evaluation of thepatient with abnormal uterine bleeding3. Discuss treatment options with emphasison extended oral contraceptives

Abnormal Uterine Bleeding (AUB)• It is one of the most common medicalproblems in adolescents (12-37%)• It includes several different types ofbleeding patterns.• The terminologies are not agreed upon.Wilkinson, Kadir: Management of Abnormal Uterine Bleeding inAdolescents. J Pediatr Adolesc Gynecol (2010) 23:S22-S30

Menorrhagia• Prolonged (more than 7 days) or excessive(greater than 80 ml) uterine bleedingoccurring at regular intervalsHeavy Menstrual Bleeding (HMB)• Heavy menstrual blood loss, regardless ofthe pattern of the cycles• Synonymous with hypermenorrheaWilkinson, Kadir: Management of Abnormal Uterine Bleeding inAdolescents. J Pediatr Adolesc Gynecol (2010) 23:S22-S30

Polymenorrhea: Frequent irregularbleeding at less than 18-day intervals.Oligomenorrhea: Infrequent irregularbleeding at intervals of more than 45days.Metrorrhagia: Intermenstrual bleedingbetween regular periods.

Dysfunctional Uterine BleedingExcessive, prolonged orunpatterned bleeding from theuterine endometrium that isunrelated to anatomic lesionsof the uterus.

Dysfunctional Uterine Bleeding• The most common cause of DUB isanovulation secondary to a disturbance ofthe normal hypothalamic-pituitary-ovarianaxis.• ACOG considers DUB synonymous withanovulatory uterine bleeding.

Anovulation• The adolescent female often hasanovulatory cycles for the first 2-4 years.• Anovulation is the most common cause ofAUB in adolescents.Wilkinson, Kadir: Management of Abnormal Uterine Bleeding inAdolescents. J Pediatr Adolesc Gynecol (2010) 23:S22-S30

Anovulation• No cyclic production of progesterone• A state of unopposed estrogen occurs• The endometrial lining becomesabnormally thickened• Spontaneous superficial breakage of liningresults in asynchronous bleeding

Differential Diagnosis of AbnormalUterine Bleeding (AUB)• Bleeding (coagulation) disorders• Medications• Uterine polyps or myomas• Trauma / sexual assault• Foreign body

Differential Diagnosis of AUB• Pregnancy: abortion, ectopic, GTD• Genital tract infection• Neoplasms of the genital tract• Endocrine disorders

Endocrine Disorders• Anovulation• Polycystic ovariansyndrome• Hyperprolactinemia• Thyroid disorder

Bleeding (Coagulation) Disorders• Prevalence rates range from 7to 48% of adolescents withheavy menstrual bleeding• Low threshold for screeningWilkinson, Kadir: Management of Abnormal Uterine Bleeding inAdolescents. J Pediatr Adolesc Gynecol (2010) 23:S22-S30

Bleeding (Coagulation) Disorders:• Von Willebrand disease• Immune thrombocytopenicpurpura or platelet functiondefects

History• Age of menarche; Last menstrual period• Menstrual interval; Duration of flow• How heavy? (How often does patientchange pad or tampon during a schoolday? Is she passing clots?)• Heavy: changing a pad every 1-2 hours;>6 pads/day; passing clots; anemiaWilkinson, Kadir: Management of Abnormal Uterine Bleeding inAdolescents. J Pediatr Adolesc Gynecol (2010) 23:S22-S30

History• Medications– Contraceptive agents; seizure or psychotropicmedications• Sexual history• Bleeding after surgery, wounds or toothextraction

Review of Systems• Hirsutism• Acne• Galactorrhea• Weight changes• Abnormal bruising or bleeding• Stress

Physical Examination• Tanner staging• Weight / BMI• Acne• Hirsutism• Source of bleeding• Foreign body• Pregnancy• Neoplasm

Laboratory Evaluation• CBC, TSH• Pregnancy test, if indicated• PCR (if sexually active)• If patient has hirsutism:– Total testosterone– DHEAS– 17OH Progesterone

Laboratory Evaluation• PT, PTT• Von Willibrand screen if history ofexcessively heavy bleeding or anemia* Do Von Willibrand testing before startinghormone therapy

Management• Tranexamic acid• Combined contraceptive hormones• Progestins: pills, injections, implants orLNG-IUS

Combined Contraceptive Hormones• Combined oral contraceptives (COC)• Transdermal patches• Vaginal rings

Benefits of Combined ContraceptiveHormones• Regular, predictable menses• Shorter, lighter menses• Less menstrual pain and premenstrualsymptoms• Can extend pills/ring and space out menses

Concerns of COC• Must remember to take a pill daily• Possible side effects:breakthrough bleeding, weight gain,nausea, headaches, venousthromboembolism

Reasons To Modify The Standard21/7 COC Regimen• Decreases estrogen withdrawalsymptoms during the hormone freeinterval: headaches, bloating, pelvicpain, & breast tenderness• Helps prevent: endometriosis anemia,ovarian cysts, seizures, etc• ConvenienceSulak et al., Obstet Gynecol 2000, 95:261-6.

Changing the Standard COCRegimen: Current/Future Ideas1. Shorten the hormone free interval from 7 daysto 3 to 5 days to provide greater ovariansuppression and decrease theincidence/severity of hormone withdrawalsymptoms2. Extend the # of days of active OCs to greaterthan 21 days3. Add estrogen during the hormone free interval

Types of COC Use• Cyclic: 21/7 24/4• Extended: 6 weeks on/4 days off or 84/7• Continuous*Vaginal ring can also be used in acontinuous fashion

Extended COC Regimen:Helpful Hints• When initiating COCs, begin with thestandard regimen for 3- 4 monthsbecause of high incidence of BTB.• Have patient return during the third orfourth cycle to assess compliance &side effects

Extended COC Regimen:Helpful Hints• If patient having withdrawal symptomsduring the hormone free interval or wantsto delay menses, discuss extending theactive pills.• Instruct to extend active pills to 6-9 weeksor until BTB occurs; take a 3- 4 dayhormone free interval and restart (relabelpack to correct day of week).

Extended COC Regimen:Helpful Hints• Or do continuous pill regimen (seeinstructions- “Rule of 3’s”)• Make sure your patient understandsand is comfortable with this extendedor continuous regimen; if not, usestandard regimen or 84/7 COC

Extended COC Regimen:Negatives• Increases counseling time in theoffice; your patient mustunderstand how to extend• Side effects?? - no extensivedata; studies underway

Extended COC Regimen:Negatives• Possibly increased cost because moreactive weeks per year (prescribe 3months at a time/4 packs)• Some insurances/pharmacy will onlygive patient one pack at a time• Confusing for some patients

Extended COC Regimen:Negatives• Increased lifetime steroid use, but notheoretical reason to anticipate increasedcomplications (i.e. DVT, MI, stroke, etc.);no extensive data• No reported increase in complications;extended regimens used for decades inpatients with endometriosis

Which pill do I pick?If heavy, prolonged or painful bleeding:COC with a strong progestin-Levonorgestrel or NorgestrelIf acne, hirsuitism, weight concerns, PMDD:COC with a less androgenic progestin-Desogestrel or Drosperinone

COC-strong progestinsOriginal BrandNameBranded GenericNamesEthinylEstradiolProgestin (mg)RegimenNordetteLevora30Levonorgestrel 0.1521/7LevlenPortiaAlesseLevlite20Levonorgestrel 0.121/7AvianeLessinaLuteraSronyxSeasonaleQuasense3084/7JolessaLevonorgestrel 0.15SeasoniqueIntera3084/7 EELo/OvralLow-Ogestrel3021/7CryselleNorgestrel 0.3

COC-medium strength progestinsOrtho-NovumNecon 1/353521/7Nortel 1/35Norinyl 1+35Norethindrone 1ModiconBrevicon3521/7Necon 0.5/35Norethindrone 0.5Nortel 0.5/35Ortho Novum 777Ovcon-35Femcon FE (chewable)Balziva3535Norethindrone 0.421/721/7 (with iron)Loestrin Fe 1/20Junel Fe 1/202021/7 (with iron)Microgestin Fe 1/20Norethindrone acetate 1Loestrin 24 Fe2024/4 (with iron)Loestrin Fe 1.5/30Junel Fe 1.5/3030Norethindrone acetate 1.521/7 (with iron)Microgestin Fe 1.5/30Demulen 1/35Kelnor 1/35Zovia 1/3535Ethynodiol diacetate 121/7Ortho-CyclenSprintecMononessa35Norgestimate 0.2521/7

COC-less androgenic progestinsOriginal Brand NameBrandedGeneric NamesEthinylEstradiolProgestin (mg)RegimenDesogenApri3021/7Ortho-CeptReclipsenDesogestrel 0.15SoliaMircetteKariva2021/2/5 EE10 mcgAzuretteYasminOcella3021/7Drosperinone 0.3YazGianvi2024/4

Other Progestins that alter menstrualbleeding• LNG-IUS• Depot medroxyprogesterone acetate(DMPA)• Levonorgestrel implants• Progesterone only oral contraceptives

Levonorgestrel Intrauterine System(LNG IUS)Steroidreservoir32 mmlevonorgestrel20 mcg/day

LNG IUS: Percentage Reduction ofMenstrual Blood Loss0-25LNG IUSPlacebo-50-75ProstaglandinSynthetase InhibitorCombination OCs-100Milsom et al. Am J Obstet Gynecol 1991;164:879

LNG IUS Counseling: Changes inBleeding• Bleeding characteristics:• 1 – 4 mo frequent spotting• 1 – 6 mo reduced duration and amount ofbleeding• Reduction in menstrual blood loss• After 12 mo, about 20 % have no bleedingPakarinen et al. Fertil Steril 1997;68:59

LNG IUS Counseling: Absence ofBleeding• Local effect– No proliferation of endometrium• This is expected. It is not a sign of:– Pregnancy– Ovarian or pituitary dysfunction– Menopause• Rapid return to menstruation after removal

LNG IUS: Endometrial EffectMonthsOvulationDays of cycleChanges in the endometrium during normal menstrual cycle

LNG IUS: Endometrial EffectMonthsOvulationDays of cycleEndometrium in “resting state” with LNG IUS

DMPA Intramuscular Injections• Menstrual changes occur in almost allusers• Most experience unpredictable bleedingpatterns in first few months of use• With continued use, frequency and lengthof bleeding episodes decreases with mostbecoming amenorrheic over time

Bleeding Patterns In DMPA Users100%80%60%40%20%11-308-101-700%3 9 15 21 27 33 39 45 54 60 66MonthFertil Steril 1973; 24:331

Levonorgestrel Implants• Menstrual changes occur in almost allwomen• During the first year, the majority (2/3’s)experience irregular bleeding with theremainder having regular menses (1/4) oramenorrhea (about 10%)• Over 5 years of use, the majority eventuallyresume a regular bleeding pattern

Bleeding Patterns in Norplant Users706050403020Regular CyclesIrregualr CyclesAmenorrhea100Year 1 Year 2 Year 3 Year 4 Year 5Obstet Gynecol 1991; 77: 256

Progestin Only Oral ContraceptiveOriginal BrandNameBranded GenericNamesProgestinRegimencontinuousNorethindroneCamila0.35Errin0.35Micronor0.35Nor-Q-D0.35JolivetteNorgestrelOvrette0.075

Conclusion1. AUB in adolescents is a common problem.2. The initial evaluation of the patient can bestarted by the pediatrician.3. Treatment can be initiated with acombined oral contraceptive in a cyclicmanner.4. Extended or continuous COC is the mostcommon treatment, but LNG-IUS is alsobeing used in certain situations.

STOP HERE

Trends in HRTTraditional HRTregimensMore recent HRTregimens! Days 1-25 ! Continuousestrogenestrogen withcyclic progestin! Days 16-25 ! Continuousprogestincombined! Days 26-31no meds

Trends in Oral ContraceptivesTraditional OCMore recent OCregimensregimens! Days 1-21 EE+P ! Less hormone free days! Days 22-28 Placebo ! Extended regimen! Shift to lower doses ! New progestinsof estrogen! Shift to lessandrogenic progestins

Contraceptive Effects on Menstruation:SUMMARY• Most women prefer lighter, less frequentmenses• Current and future contraceptive methodswill favorably affect menstruation• Counseling regarding alterations inmenstruation will be critical to initiation andcontinuation of these contraceptivemethods

Contraceptive Effects onMenstruation: Elimination ofMonthly MensesPatricia J. Sulak, M.D.ProfessorTexas A&M College of MedicineDirector, Division of Ambulatory CareDepartment of Ob/GynDirector, Scott and White Sex Education ProgramScott and White Clinic/Hospital, Temple, Texas

Which BCP?Necon 1/35 (generic) Estrogen 35 mcg; medium strengthNorethindrone 1 mgDesogen Estrogen 30 mcg; low progestindesogestrel 0.15 mgMircette Estrogen 20 mcg; low estrogendesogestrel 0.15 mg(and 5 days of estrogen only 10 mcg)Nordette (generic) Estrogen 30 mcg; strong progestinlevonorgestrel 0.15 mcgYasmin Estrogen 30 mcg; low progestindrosperinone 3 mg

Is Monthly Menstruation Natural???• Late menarche• Early childbearing• High parity• Prolongedbreastfeeding• Early menopauseVS• Early menarche• Late childbearing• Low parity• Shortenedbreastfeeding• Late menopause

Why Alter Menstruation: Frequency,Duration, Amount• Menstrual Disorders Affect Millions ofReproductive Age Women:– menorrhagia– dysmenorrhea– premenstrual symptomatology– “menstrual” migraines

Problems of IncessantOvulation/Bleeding• Anemia• Endometriosis• Ovarian cysts• Ovarian cancer

Is Monthly Menstruation Natural???• Late menarche• Early childbearing• High parity• Prolongedbreastfeeding• Early menopauseVS• Early menarche• Late childbearing• Low parity• Shortenedbreastfeeding• Late menopause

$$ Costs $$ of Monthly Menstruation• Sanitary protection• Medical expenses:– pain meds– office visits– procedures• Lost wages/productivity

Is Monthly Menstruation Natural???• Late menarche• Early childbearing• High parity• Prolongedbreastfeeding• Early menopauseVS• Early menarche• Late childbearing• Low parity• Shortenedbreastfeeding• Late menopause

Oral Contraceptive Effectson Menstruation• Bleeding duration/quantity decreased• Dysmenorrhea decreased• Regulation of cycle length: predictability

Combination Oral Contraceptives• Standard Regimen:– 21 days of estrogen + progestin– 7 hormone free days• Rationale: mimic an average cycle length of28 days• Drawback: monthly hormone withdrawalsymptoms

Hormone Withdrawal Symptoms InOral Contraceptive UsersObjective• Measure the frequency and severityof symptoms during the pill freeinterval compared to the active pillintervalSulak et al., Obstet Gynecol 2000, 95:261-6.

Hormone Withdrawal Symptoms InOral Contraceptive UsersStudy Design• Prospective study of OC users• 69 New Starts: No OC use in last 3 months• 193 Current Users: OC use " 12 monthsSulak et al., Obstet Gynecol 2000, 95:261-6.

Hormone Withdrawal Symptoms InOral Contraceptive UsersData Collection• Demographics• Daily calendars to subjectively recordheadaches, pelvic pain, bleeding, analgesicuse, and other symptomatologySulak et al., Obstet Gynecol 2000, 95:261-6.

Hormone Withdrawal Symptoms inOral Contraceptive Users21 active7 hormonefreep valuePelvic pain21%70%

Hormone Withdrawal Symptoms InOral Contraceptive UsersHeadaches• Headaches were more frequentand more severe during thehormone free interval95:261-6.Sulak et al., Obstet Gynecol 2000,

Frequency of Headaches100[A]80CURRENT USERSPERCENT60402010080[B]NEW STARTS0Active PillActive PillPERCENT6040200Active PillActive PillActive Pill(Sulak et al.; Obstet Gynecol 2000; 95:261-6)6)

Hormone Withdrawal Symptoms InOral Contraceptive UsersPelvic Pain/Cramps• Pelvic pain/cramps were morefrequent and more severe duringthe hormone free intervalSulak et al., Obstet Gynecol 2000, 95:261-6.

Frequency of Pelvic Pain and Cramps10080[A]CURRENT USERSPERCENT60402010080[B]NEW STARTS0Active PillActive PillPERCENT6040200Active PillActive PillActive Pill(Sulak et al.; Obstet Gynecol 2000; 95:261-6)6)

Hormone Withdrawal Symptoms InOral Contraceptive UsersBloating/Swelling• Bloating and swelling were morecommon during the hormone freeinterval• Symptoms began in the preceding weekprior to the hormone free intervalSulak et al., Obstet Gynecol 2000, 95:261-6.

Frequency of Bloating and Swelling10080[A]CURRENT USERSPERCENT60402010080[B]NEW STARTS0Active PillActive PillPERCENT6040200Active PillActive PillActive Pill(Sulak et al.; Obstet Gynecol 2000; 95:261-6)6)

Hormone Withdrawal Symptoms InOral Contraceptive UsersBreast Tenderness• Breast tenderness was more commonduring the hormone free interval• Symptoms began in the preceding weekprior to the hormone free intervalSulak et al., Obstet Gynecol 2000, 95:261-6.

Frequency of Breast Tenderness10080[A]CURRENT USERSPERCENT60402010080[B]NEW STARTS0Active PillActive PillPERCENT6040200Active PillActive PillActive Pill(Sulak et al.; Obstet Gynecol 2000; 95:261-6)6)

Extending the Duration of Active Oral Contraceptive Pills toManage Hormone Withdrawal SymptomsObjective• Test the hypothesis that extending thenumber of consecutive active OCs willdecrease the frequency of menstrualrelated problemsSulak et al., Obstet. Gynecol. 1997; 89: 179-83

Extending the Duration of Active OralContraceptive Pills to Manage HormoneWithdrawal SymptomsMethodProspective analysis of 50 patients on OCs whoexperienced hormone withdrawal symptomsduring the pill free interval and were allowed toextend the number of consecutive active OCsSulak et al., Obstet. Gynecol. 1997; 89: 179-83

Symptoms During the Pill FreeInterval*SymptomsMigrainesDysmenorrheaMenorrhagiaPMSOther**TotalRanking of Symptoms*#1 #2 #3 #4 Total48% 14% 6% 8% 76%22% 40% 16% 78%18% 12% 6% 36%12% 10% 10% 32%6%100% 82% 38% 8%*Most patients reported more than one symptom+ most severe symptoms** Acne, endometriosis, recurrent vuvular cystsSulak et al., Obstet. Gynecol. 1997; 89: 179-83

Method of Extending Numberof Active Weeks• Instructed to take 6 consecutive weeks ofactive OCs followed by a hormone free week• The interval of active pills was increased by3 weeks each consecutive cycle (6 wks, 9wks, 12 wks), followed by a hormone freeweek• If a patient experienced intolerable sideeffects, she remained on the regimen thatworked best for herSulak et al., Obstet. Gynecol. 1997; 89: 179-83

Study Results of the 50 Patients*• 37 patients (74%) stabilized on an extendedregimen– 6 week 8– 9 week 13– 12 week 16• 13 patients (26%) not stabilized on anextended regimen– Most common reasons– Breakthrough bleeding– Breakthrough spotting– Headaches*All patients were on a low dose monophasic pillSulak et al., Obstet. Gynecol. 1997; 89: 179-83

Menstrual Reduction With Extended Use ofCombination OCPs: Randomized Controlled Trial• 90 patients randomized to 21/7 day versus42/7 day regimen of a 30 mcg monophasicOC• 59% completed the 48 week study• The 42/7 day regimen resulted in fewerbleeding days and no increase in meanspotting days or bleeding episodesMiller L, Notter K: Obstet Gynecol 2001; 98: 771 - 778

Acceptance of Altering the Standard 21day/7 day Oral Contraceptive Regimen toDelay Menses and Reduce HormoneWithdrawal SymptomsPatricia J. Sulak, M.D., Thomas J. Kuehl, Ph.D.,Miriam Ortiz, R.N., and Bobby L. Shull, M.D.Am J Obstet Gynecol 2002; 186: 1142-9

Study Design• Retrospective review of patients on 30-35 mcg OCs withhormone withdrawal symptoms during the hormone freeinterval, offered alterations to their 21/7 day regimen• Electronic medical record search of the phrase“extending the number of active pills” by Patricia J.Sulak, M.D.• Initial counseling was between December 93 andOctober 2000• Counseled on increasing the number of active pills +/-decreasing the number of hormone free days

Results• 318 counseled on “extending the number ofactive pills”• 292 had follow up• 26 lost to follow up• hormone withdrawal symptoms: headache,dysmenorrhea, menorrhagia, premenstrualsymptomatology

Reasons For Extending Active PillsHeadacheDysmenorrheaHypermenorrheaPremenstrual SxsOther ***(292 Patients)Primary Reason*35%21%19%13%12%% with Sx**46%41%30%22%100%* most severe symptom, ** most had more than one Sx*** convenience, endometriosis, acne

Characteristics of the 292 Patients• Average age 35.4 with 101 age 40 or greater• Patients citing dysmenorrhea were younger• Patients citing menorrhagia had a greaterBMI

Results of 292 Patients# %I: Did not extend 25 9II: Extended then D/Ced OCs 57 19III: Extended then returned to 21/7 38 13IV: Continuing to extend 172 59292 100

Group I: Chose Note To Extend[25 patients (9%)]Reasons: Preference for monthly mensesSymptoms not severe enoughFears/concernsBTB on current 21/7 regimenIncreased cost of pills

Group II: Extended,then discontinued OCs[57 patients (19%)]Reasons: Desire for pregnancySterilizationBecame menopausalPelvic surgery including hysterectomyNo longer sexually activeWorsening of numerous symptomsCost of pills

Group III: Extended,then returned to 21/7[38 patients (13%)]Reasons: Bleeding issues: BTB, BTSSide EffectsFear/concernsIncreased costs

Group IV: Continuing to extend[172 patients (59%)]• typical pattern was 12 # 12 (mean # SD) weeksof active pills with a median of 9 weeks and arange up to 104 weeks• typical pill-free interval was 6 # 2 days with amedian of 5 days and a range of 0 to 7; 46%reported