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Abnormal Uterine Bleeding in Midlife Women
Ivy M. Alexander, PhD, APRN, ANP-BC, FAANProfessor, Yale University School of Nursing
Midlife Women’s Health Consultant, Yale HEALTH
NPACE, Women’s Health Conference, June 2012
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ObjectivesFollowing this presentation, participants will
be able to:
1.Identify the most common causes of abnormal uterine bleeding among midlife women
2.Evaluate a midlife woman with abnormal uterine bleeding
3.Develop a management plan for presented causes of AUB in a midlife woman
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Disclosures
• Consultant, Speaker’s Bureau and/or Presentation (within past 12 months) for:– PDR Network– Medscape– NPACE, CT APRN Society, NPWH– Engage– Amgen– Datamonitor– Pfizer
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PHYSIOLOGY
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Characteristics of Normal Menses
Menarche 12-13 yrs 8-16 yrs
Interval 28-30 days 24-35 days
Duration 4-5 days 2-8 days
Amount of flow
30-40 mL 20-80 mL
Menopause 50-52 yrs 40-60 yrs
Average Range
Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234; Oehler MK, Rees MC. ActaObstet Gynecol Scand. 2003;82:405-422; Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.; Stenchever MA, et al. Mishell D. Comprehensive Gynecology. 2001.
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Actions of Estrogen• Stimulates development of ovaries, fallopian
tubes, uterus, vagina, and of secondary sexual characteristics; eg, growth of the breasts during puberty
• Interacts with hypothalamic and pituitary hormones to regulate normal menstrual cycle
• Promotes cyclic proliferation of endometrium
Goldfien. Basic and Clinical Pharmacology. 1998; Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234; Oehler MK, Rees MC. Acta Obstet Gynecol Scand. 2003;82:405-422; Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.; Stenchever MA, et al. Mishell D. Comprehensive Gynecology. 2001.
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Actions of Progesterone• Interacts with hypothalamic and pituitary
hormones to regulate normal menstrual cycle
• Induces secretory changes in the endometrium to prepare for possible pregnancy
• Increases viscosity of cervical mucus• Prepares breasts for lactation
Goldfien. Basic and Clinical Pharmacology. 1998; Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234; Oehler MK, Rees MC. Acta Obstet Gynecol Scand. 2003;82:405-422; Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.; Stenchever MA, et al. Mishell D. Comprehensive Gynecology. 2001.; Williams, Stancel. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 1996.
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Hypothalamic-pituitary-ovarian axis
Pituitary HypothalamusGnRH (+)
Estradiol Progesterone
LH FSH Inhibins
Ovary
Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234; Oehler MK, Rees MC. ActaObstet Gynecol Scand. 2003;82:405-422; Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.; Stenchever MA, et al. Mishell D. Comprehensive Gynecology. 2001.
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Endocrinologic Factors of Normal MensesEnvironmental Factors
CNS
Hypothalamus
Pituitary
Ovary
Endometrium
Menses
GnRH
FSH and LH
Estrogen/Progesterone
Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234; Oehler MK, Rees MC. ActaObstet Gynecol Scand. 2003;82:405-422; Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.; Stenchever MA, et al. Mishell D. Comprehensive Gynecology. 2001.
Inhibin
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AUB: DEFINITION
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Def: Abnormal Uterine Bleeding
• Uterine bleeding outside of the normal menstrual parameters– duration: <2 or >7 days– heavier than normal flow, or flow > 80 ml
(Chronic loss of > 80 mL /cycle anemia)– cycle length <24 or >35 days– intermenstrual bleeding or postcoital spotting
Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.
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Abnormal Uterine Bleeding Includes...
• Dysfunctional uterine bleeding (DUB)
• Oligomenorrhea• Menorrhagia• Intermenstrual
bleeding
• Amenorrhea• Polymenorrhea• Metrorrhagia• Menometrorrhagia• Premenstrual
spotting• Hypermenorrhea /
Hypomenorrhea
Speroff L., Fritz MA. Clinical Gynecologic Endocrinology and Infertility, 8th Ed. 2008.
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The Fe′de′ration Internationale de Gyne′cologie et d’Obste′′trique
(FIGO) – 2011
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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Definitions per FICO• Provides clarity and consistency in
identification of root causes of genital bleeding
• Recommend retiring the terms menorrhagia, metrorrhagia and dysfunctional uterine bleeding (DUB)
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208; Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead top international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007;87:466-76
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Nine (9) Categories per FIGO:PALM-COEIN
• P – Polyp • A – Adenomyosis• L – Leiomyomas (Submucosal, Other)• M – Malignancy & Hyperplasia• C – Coagulopathy• O – Ovulatory disorders• E – Endometrium• I – Iatrogenic• N – Not classified
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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PALM-COEIN Categorization• Structural Problems• Measured by
– direct Visualization– Imaging– use of Histopathology
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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PALM-COEIN Categorization• Nonstructural• Not defined via histopathology or
imaging
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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PALM COEIN Categorization• Not yet classified
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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PALM-COEIN Categorization• Recognizes that a woman may have
one or more entities that could cause bleeding
• May have entities that are asymptomatic and not contributing to presenting problem – leiomyomas, adenomyosis, polyps
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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AUB: PREVALENCE
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AUB: Prevalence
• Abnormal bleeding is the most common reason for non-annual gyn visit– 10-35% of all women have heavy bleeding
– 11% of postmenopausal women have spontaneous bleeding
– Annovulation and irregular cycles very common among adolescent and perimenopausal women
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AUB: PATHOPHYSIOLOGY
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AUB: DDx (Pathophysiology)• Pathophysiology of AUB = DDx• DDx affected by:
– Age– Menstrual status– Pregnancy
• Most common DDx are:– Anovulation – Devices – Infxn/STI– Pregnancy – Cancer – Trauma – Structural Prob – Systemic Dz – Medications
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Pathophysiology of Anovulatory Cycles
• Abnormal Estradiol stimulation of endometrium
• E2 levels either too high or too low to start cascade leading to ovulation
• Altered E2 effects cause: – long periods of amenorrhea– polymenorrhea– hemorrhage– spotting
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Pathophysiology of Anovulatory Cycles con’t
• Minor deficiency in the E2 signal can result in:– subnormal central response– impaired or inappropriate degree of
follicular growth and function– disturbed feedback mechanisms
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Pathophysiology of Anovulatory Cycles con’t
• Abnormal feedback upsets the synchrony of the cycle– E2 levels must fall enough to allow
sufficient FSH response for the initial growth stimulus
– E2 levels may be inadequate to produce the positive stimulatory effects for an LH surge
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AUB: PRESENTATION & ASSESSMENT
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Presentation
• Altered bleeding pattern:– Longer, shorter, or irregular cycle– Heavier or lighter flow– Longer or shorter length of flow– Change in flow characteristics (mid-cycle
bleeding, spotting, etc)
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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Presentation (con’t)
• Acute– Episode of heavy bleeding; requires intervention
to stabilize woman and prevent further blood loss • Chronic
– Altered bleeding pattern (amount, timing, regularity) for most of a 6 month period
• Intermenstrual– Bleeding in between predictable menses and
defined cycles; can be random or predictable (replaces “metrorrhagia”)
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208; Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead top international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007;87:466-76
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Evaluating a Woman with Abnormal Bleeding
HistoryPhysical Exam
Diagnostic Evaluation
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History: Key Questions
• Usual menses? Signs of ovulation?• Nature of the abnormal bleeding?
– Frequency– Duration– Volume– Relationship to activities (eg, coitus, exercise)– When occurs– Associated symptoms
Goodman, A. Initial Approach to the premenopausal woman with abnormal uterine bleeding. UpToDate, 2010.
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History: Key Questions, con’t
• What is her age?• Where does blood originate?• Is she sexually active? Pregnant?• Systemic illness(es)? • Medications?• Personal or Family Hx of bleeding d/o?• Weight change – eating d/o, excessive
stress, excessive exercise or illness?Goodman, A. Initial Approach to the premenopausal woman with abnormal uterine bleeding. UpToDate, 2010.
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History: Quantifying Patient Measures of Abnormal Bleeding
• An increase of ≥ 2 pads or tampons/day• Menstrual bleeding lasting 3 days longer
than usual • Blood clots that have increased in size
and/or number• Sanitary product needs that interfere with
her usual activities, need to change pad at night
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History: Screening for Bleeding Disorders
1. + if Heavy bleeding since menarche2. + if Postpartum hemorrhage; Surgical
related bleeding; and /or Bleeding associated with dental work
3. + if >2: Bruising 1-2x/ms; Epistaxis 1-2x/ms; frequent Gum Bleeding; Family hx of bleeding sxs
• Positive screen → consider further evaluation
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208
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History: Documenting AUB• Regularity
– Regular, irregular, absent• Duration of Flow
– Normal, prolonged, shortened• Frequency
– Normal, frequent, infrequent• Volume
– Normal, heavy, light
Munro, MG., Critchley, HOD., Fraser IS., & FIGO Menstrual Disorder Working Group. 2011. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertility & Sterility. 95(7): 2204-2208; Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead top international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007;87:466-76
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PE: Identify Pathology, Identify Bleeding Source
• General appearance, BMI, sexual maturity• Systemic eval for Sx of systemic cause:
– Body habitus, skin and hair (distribution, hirsute), mucosal color, petechaie
• Head / Neck, Thyroid exam• Breast exam• Genital / Pelvic (cerv cytol, cxs)• Rectal exam (hemoccult stool)• Blood on toilet tissue or sanitary
pad may not be uterine
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AUB: DIAGNOSTICS
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AUB: Diagnostic StudiesAge Laboratory Tests13-18 years
Coag studies (INR, PT/PTT, fibrinogen, von Willebrand Factor, ristocetin cofactor)
CBC with platelet count to id coag defects, leukemia, anemia
19-50 years
HCG, cervical cytology, cultures
TSH – hypo- / hyperthyroidism, esp if untested in 5 years
FSH (controversial) , maybe with E2 Pg and LH
CBC with platelet count and serum Fe, blood drawn early in cycle (day 3) – coag defects, anemia
UA – UTI, renal calculi, bladder cancer
Guiac – colon polyps, diverticula, GI cancer, ulcer, hemorrhoids, fissures
Ultra Sound – leiomyomata , structural abn; ?endometrial Bx
?Fasting serum prolactin – pituitary adenoma (if bleeding is infrequent or minimal), ?CNS imaging
?Coag studies, ?LFTs, ?Renal Function Studies
ACOG. Int J Gynaecol Obstet. 2001;73:263-271; Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 8th ed. 2008; James AH, et al. Hematology Am Soc Hematol Educ Program. 2006:474-485. Munro et al 2011 Fert Ster.
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AUB: DDX
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Secondary Work-up and When No Signs of Ovulation
• Determine ovulatory status– cycle charting– basal temperature monitoring– progesterone testing– OTC test kits– EMBx
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DDx of AUB:Pregnancy-Related Conditions
• Pregnancy is a common cause of bleeding– >33% of women experience bleeding
during the first 20 weeks• Pregnancy-related conditions:
– Ectopic pregnancy– Trophoblastic disease – Miscarriage – incomplete, threatened,
or missed abortion Shwayder JM. Obstet Gynecol Clin North Am. 2000;27:219-234.
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• Endocrine disorders – Thyroid dz, Hyperprolactinemia, Polycystic ovary syndrome
• Hematologic disorders – up to 20% have coagulopathy, most often von Willebrand1
• Adrenal hyperplasia/Cushing disease• Renal / Liver disease• Mucosal diseases (Chron’s, Bechet’s)• Stress• Extreme exercise• Medications• Eating Disorders (obesity, anorexia)• Weight loss
DDx of AUB: Systemic Causes
1James AH, et al. Hematology Am Soc Hematol Educ Program. 2006;474-485.
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• Infections– STIs, cervicitis, vaginitis, endometritis
• Benign structural abnormalities– Polyps, ectropian, cysts, etc– Leiomyomata (eg, submucosal)
• Premalignant/malignant lesions• Trauma/irritation
– Intercourse, Sexual assault– Presence of a foreign body
DDx of AUB: PALM (Structural Abnormalities)
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• Oral contraceptives (esp intermenstrual, oligo- / amenorrhea)
• Intrauterine devices• Hormone replacement• Selective serotonin reuptake inhibitors• Antipsychotics• Anticoagulants• Corticosteroids• Herbal supplements
DDx of AUB: Iatrogenic (Other Causes, Medications, Devices)
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Diagnostic Reasoning
• Primary or secondary?
• Is she pregnant?• Is it drug related?• Is there a problem
with the HPO?
• Is there a problem with the uterus?
• Is there a structural problem?
• Is there a chronic endocrine problem?
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AUB – Not Specified
• Diagnosis of exclusion – no organic or structural cause for bleeding identified
• Defined as: periodic uterine blood loss >80 mL /cycle that occurs in the absence of structural uterine abnormalities
• Negatively impacts her quality of life• Associated with increased healthcare costs
Bongers MY, et al. Maturitas. 2004;47:159-174; Cote I, et al. Am J ObstetGynecol. 2003;188:343-348; Cote I, et al. Obstet Gynecol. 2002;100:683-687; Munro MG et al, F+S 2011; Fraser IS et al, F+S 2011.
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AUB – Not Specified in a Premenopausal Adult Woman• What is your most important rule out?
– pregnancy• What will you include for PE?
– General survery, thyroid, pelvic exam• Will you order any diagnostics?
– HCG– Cervical cytology, cultures– TSH, LFTs– ?coag studies, prolactin
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DDx by Age• Reproductive Years
- anovulation - endocrine dz- pregnancy - bleeding disorder- benign growths - liver dz- medication induced - infection
• Perimenopausal- anovulation - benign growths- cancer
• Postmenopause- cancer - atrophy- medication induced - benign growths
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Consider Common Lesions
• Benign pelvic lesions– leiomyomata / fibroids
• Heavy menstrual bleeding– polyps
• intermittent spotting • post coital bleeding
– Adenomyosis• ectopic endometrial glands within the
myometrium
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CHRONIC AUB: MANAGEMENT
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Chronic AUB Management
• Adjust medications (esp, OCs)• Treat infection• Manage systemic disease• Refer as needed for systemic disease
or coagulopathy management
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Chronic AUB Management
Step 1Pelvic Exam, Cervical cytol, CxHCTHCGPossible PT, PTT, vWF, ristoPossible TSH US, ?EMBx
Step 2UltrasoundEMB
Step 3 - Therapy
E-P hormonal contraceptionProgestin onlyNSAIDsRarely IV estrogenAntibiotics, Iron as appropriate
Step 4Long-term hormonal therapy
-IUS-DMPA
GnRH
Step 5Consultation
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Amenorrhea and Oligomenorrhea
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Essentials of Diagnosis: Amenorrhea and Oligomenorrhea
• Exclude pregnancy• Rule-out endometrial neoplasia,
hormonal abnormality• Exclude hypothalamic causes
– Anorexia– Exercise– Stress
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Amenorrhea ManagementStep 1
Check: TSH PRL HCG FSH
Normal
Progestin Challenge Test
No BleedingBleeding
+ Test
Treat Problem
Step 2Estrogen-Progestin Challenge Test
No Bleeding
Bleeding
FSH normal: possible uterine problem
FSH abnormal: possible hypothalamic amenorrheaConsider Hormonal therapyReferral
AnovulationUterus intact
Hormonal Management
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Progestin Therapy
• Oligomenorrhea– Progestin Challenge Test
• absence of withdrawal bleed requires work-up– monthly administration of 5-10 mg MPA or
200-400mg Prometrium for minimum of 10 days
– some women prefer P Rx less often: Why?– OCPs better choice if contraception needed
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E2 Add Back: Depo, Norplant, POPs
• Endometrium shrinks from pharmacologically induced pseudoatrophy– endometrium consists of pseudodecidual stroma
and blood vessels with minimal glands– more like the fragile tissue typical of pure estrogen
stimulation bleeding • Rx: Add CEE 1.25 mg or Estradiol 2 mg for 7
days to OCs or depo
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Anovulatory Cycles
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Essentials of Dx: Anovulation• Rule-out Central Causes
– GnRH levels (production, stress, anxiety, anorexia, excessive exercise, etc)
– Hyperprolactinemia– PCOS – Systemic Disease affecting E clearance (thyroid,liver
disease)• Rule-out ovarian causes
– Infection, endometriosis, abnormal receptors• Usually multi-factorial, id of precise etiology
unnecessary in most instances• Can be normal at midlife approaching menopause
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Physical Characteristics Accompanying Anovulation
• Hirsutism• Acne• Galactorrhea• Thyroid enlargement• Evidence of an eating disorder• Bruises• Abnormalities on pelvic exam such as?
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Anovulatory Bleeding: Evaluation
• History, PE• Cervical cytology• Pregnancy• CBC• TSH
• ?LFT, renal panel• ?Prolactin level• ?EMB• ?TVS
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Anovulatory Bleeding: Management
• PCOS• Systemic disease• OC• Cyclic progestin• Progestin IUD• GnRH agonist
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Progestin Therapy: When? Who?
• Teens and premenopausal women– may not ovulate or sustain corpus luteum
function or duration• Usual presentation?
– Oligomenorrhea followed by heavy bleeding
• Progestin acts like an antiestrogen– diminishes effect of E on target cells
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AUB: Ovulatory
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Essentials of DDx – AUB: Ovulatory (Hvy Menstrual Bldg)• Adolescents
– (usually anovulatory)– coagulopathy– systemic illness
• Adult Women– benign growths– coagulopathy– systemic disorder– chronic endometritis– neoplasia
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AUB – Ovulatory: Evaluation
• History, PE• Cervical cytology• Beta-HCG• CBC• Coagulation studies
• TSH• LFTs• Renal function tests• Endometrial biopsy• Transvaginal Ultrasound
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Pre-Menopausal AUB: When to Biopsy?
Age Group
Endometrial CA Incidence (per
100,000 women)
ACOGRecommendations
for Biopsy13-18 years
0.1 Only consider if anovulatory>2 years and obese
19-34 years2.3
Consider if chronic anovulation or unresponsive to medication35-39 years
6.1
40-49 years
36.0
Biopsy unless pregnant or another clear reason to avoid sampling the endometrium
ACOG. Int J Gynaecol Obstet. 2001;73:263-271.
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Endometrial Biopsy
• To identify endometrial cancer or premalignant lesions
• Women >35 • Women 18-35 if risk factors for
endometrial cancer• Performed at or after cycle day 18
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Transvaginal Ultrasound
• To measure endometrial thickness & identify structural lesions
• ?before or after EMB• Performed on cycle day 4, 5, or 6
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Endometrial Cancer• Absence of growth limiting influence of
progesterone• no regular shearing of the lining• endometrium achieves abnormal height
without structural support• fragile tissue suffers spontaneous
superficial breakage and bleeding• one site heals/ another breaks down
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Hyperplasia vs Neoplasia
Two distinct and biologically unrelated diseases
• Hyperplasia without atypia = endometrial hyperplasia (not usually a precursor to CA)
Treatment Hormones
• Hyperplasia with cytologic atypia = Endometrial intraepithelial neoplasia (EIN)
Treatment Surgery
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Management of Acute Bleeding
• Moderate to severe not hemodynamicallystable– hospitalize– IV CEE and antiemetics
• Moderate to severe hemodynamically stable– outpatient treatment– high dose OCs
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Should You Rx: Estrogen Alone?
• Use E alone after prolonged bleed – scant lining of basalis layer, atrophic
endometrium– biopsy reveals little tissue
• When patient has been on a progestin– POPs, depoprovera
• When follow up is uncertain because E will stop all categories of bleeding
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Unopposed E Therapy
• High doses can precipitate…– thrombotic event
• Little data to quantify risk, dose• Risk benefit ratio individualized• Avoid in woman with past history of
idiopathic venous thromboembolism
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Medical Therapies for AUB –Ovulatory (Hvy Menstrual Bldg)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)– If bleeding does not improve with NSAIDs, consider the
possibility of a coagulation disorder, or liver or kidney dz• Combination oral contraceptives• Progestins
– Cyclic or continuous administration– Levonorgestrel intrauterine system
• Danazol• Gonadotropin-releasing hormone agonists• Antifibrinolytics• Desmopressin
Working Party for Guidelines for the Management of Heavy Menstrual Bleeding.NZ Med J. 1999;112:174-177; Lethaby A, et al. Cochrane Database Syst Rev. 2002;(1):CD000400.
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Medical Therapy for Heavy Menstrual Bleeding: Nonsteroidal Anti-
inflammatory Drugs (NSAIDs)• Systematic review of studies evaluating NSAIDs versus
placebo– Mefenamic acid, meclofenamic acid, diclofenac, ibuprofen, and
naproxen were compared– Treatment was given only during menses
• All NSAIDs, except ibuprofen, reduced menstrual flow when compared to placebo– Reduction in flow averaged 35 mL (95% CI: 27-43)– Pain relief was an additional benefit
• Adverse effects– Gastrointestinal symptoms (i.e., nausea, vomiting, indigestion)
Working Party for Guidelines for the Management of Heavy Menstrual Bleeding.NZ Med J. 1999;112:174-177; Lethaby A, et al. Cochrane Database Syst Rev. 2002;(1):CD000400.
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Medical Therapy for Heavy Menstrual Bleeding: Oral Contraceptives
• Oral contraceptives reduce endometrial thickness as visualized by uterine ultrasonography
• Paucity of data on use of oral contraceptives for heavy menstrual bleeding
• One small, randomized clinical trial (Fraser & McCarron, 1991) reported a 43% reduction in menstrual blood loss with a low-dose monophasic combined oral contraceptive
Iyer V, et al. Cochrane Database Syst Rev. 2000;(2): CD000154; Fraser IS, McCarron G. Aust N Z J Obstet Gynaecol. 1991;31:66-70.
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Medical Therapy for Heavy Menstrual Bleeding: Oral Progestins
• Administration during the luteal phase of the menstrual cycle is less effective than other methods of administration
• Progestin therapy for 21 days of the menstrual cycle is more effective but causes more side effects
• In practice → progestins for 10-14 days q mo– Induces stabilizing predecidual stromal changes– Followed by a withdrawal bleed (“medical D&C”)– If no correction then reevaluate/ refer
Lethaby AE, et al. Cochrane Database Syst Rev. 2005;(4):CD002126.
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Oral Progestin Dosages
Medroxyprogesteroneacetate
5 to 10 mg daily for 5-10 days. Give monthly
Norethindrone acetate 2.5 to 10 mg daily for 5 –10 day. Give monthly
Micronized progesterone 200 mg daily for 12 days. Give monthly
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0%
20%
40%
60%
80%
100%
3 9 15 21 27 33 39 45 54 60 66
Month
Pe
rce
nta
ge
of
pa
tie
nts
11-30 8-10 1-70
Medical Therapy for Heavy Menstrual Bleeding: Injectable Depot Medroxyprogesterone Acetate
Bleeding / spotting days per 30-day month
Schwallie PC, Assenze JR. Fertil Steril 1973;24:331-339; Greydanus DE, et al. Pediatrics. 2001;107:562-573; Kaunitz AM. J Reprod Med. 2002;47:785-789; Jain J, et al. Contraception. 2004;70:269-275; ScholesD, et al. Arch Pediatr Adolesc Med. 2005;159:139-144.
Off-label Use
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Medical Therapy for Heavy Menstrual Bleeding: Levonorgestrel IUS
• Releases 20 μg of levonorgestrel every 24 hrs
• amount of menstrual blood loss
• Consider a bleeding disorder if she does not respond to treatment
• FDA approved for contraception and to treat heavy menstrual bleeding in IUD users; also used off-label for endometrial protection in PM women taking estrogenAndersson JK, Rybo G. Br J Obstet Gynaecol. 1990;97:690-694.
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Medical Therapy With the LevonorgestrelIntrauterine System Reduces Heavy
Menstrual BleedingM
en
stru
al
blo
od
lo
ss (
mL)
Andersson JK, et al. Br J Obstet Gynaecol. 1990;97:690-694. Fedele L, et al. FertilSteril. 1997;68:426-429; Soysal S, Soysal ME. Gynecol Obstet Invest. 2005;59:29-35.
0
100
200
300
400
Before treatment
3 6 12Months of use
Range of normal
blood loss
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Levonorgestrel Intrauterine SystemDecreases Menstrual Blood Loss
Milsom I, et al. Am J Obstet Gynecol. 1991;164:879-883.
Perc
enta
ge R
educ
tion
of
Men
stru
al B
lood
Los
s
LNG-IUS = levonorgestrel-releasing intrauterine system
-100
-75
-50
-25
0
LNG-IUS
Antifibrinolytic agent
Nonsteroidal anti-inflammatory drug
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Surgical Therapies for Heavy Menstrual Bleeding
• Dilation and curettage (acute bleeding)• Endometrial ablation techniques
– First-generation techniques• Rollerball ablation• Transcervical resection
– Second-generation techniques• Bipolar impedance• Cryoablation• Balloon ablation• Hydrothermal ablation
• Hysterectomy• Myomectomy
Bongers MY, et al. Maturitas. 2004;47:159-174. Sowter MC, et al. Cochrane Database Syst Rev. 2002;(3):CD001124.
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Levonorgestrel Intrauterine System Versus Endometrial Ablation
Med
ian
Pic
tori
al
Blo
od
Lo
ssA
ssess
men
t C
hart
Sco
re
Follow-up Period (Months)
Busfield RA, et al. Br J Obstet Gynaecol. 2006;113:257-263.
LNG-IUS=levonorgestrel intrauterine system
0
20
40
60
80
3 6 12 24
LNG-IUS Thermal Balloon Ablation
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Levonorgestrel Intrauterine System as an Alternative to Hysterectomy for Heavy Menstrual Bleeding
Lahteenmaki P, et al. BMJ. 1998;316:1122-1126; Hurskainen R, et al. Lancet. 2001;357:273-277.
Perc
en
tag
e o
f W
om
en
Can
celi
ng
H
yst
ere
cto
my
64.3%
14.3%
0
10
20
30
40
50
60
70
LNG-IUS Medical Therapy
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AUB – Ovulatory (Hvy Menstrual Bldg): Management con’t
• Consider risk of repeat hemorrhage• May need periodic P if not on OC• May require treatment change or re-eval• If persistent DUB, consider:
– submucus fibroids– polyps– missed diagnosis of serious pathology– wrong diagnosis on endometrial biopsy
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Intermenstrual Bleeding
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Essentials of Dx: Intermenstrual Bleeding
• OC misuse / problem• STIs• Pregnancy • Ovulatory bleeding• Endometrial cancer /
premalignant lesion
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Progesterone Related Intermenstrual Bleeding
• Progesterone withdrawal bleeding– When stop exogenous source of P
• Eg, COCs, P challenge– Occurs as normal menstrual bleed
• Progestin breakthrough bleeding– Unfavorable high ratio of P to E– Not enough E or too much P
• Eg, depoprovera, COCs
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Intermenstrual Bleeding: Evaluation
• History, PE• Cervical cytology• Beta-HCG• Wet prep• Cultures
• ?CBC• ?LFT, renal studies• TSH• ?EMB• ?TVS
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Intermenstrual Bleeding: Management
• Educate / adjust OC• Treat infection• Pregnancy management
or termination• Surgery
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Not Classified AUB: Management
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Essentials of Diagnosis
• Exclude pregnancy
• Quantify amount of bleeding with HCT
• Evaluate for neoplasia, structural abnormalities and hormone abnormalities
• Rule out coagulopathy– Usually identified in younger women
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Estrogen Effects
• Estrogen withdrawal bleeding– low levels = intermittent spotting
• may be prolonged• light
– high levels = sustained availability leading to• prolonged periods of amenorrhea• followed by acute episodes of profuse bleeding
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Management
• Same as for ovulatory menorrhagia• Hormone management as first line • Reserve surgical treatment for refractive
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• Despite a doubling in the use of OCs since the 1970s, the incidence of unintended pregnancy in women aged ≥40 years is >50%
• Because pregnancy is still possible, contraception remains a concern– consider OCs, barrier methods, IUDs
• ACOG: The lowest effective estrogen dose should be used
ACOG, American College of Obstetricians and Gynecologists.ACOG Educational Bulletin 247. Int J Gynecol Obstet. 1998; Henshaw. Fam Plann Perspect. 1998; North American Menopause Society. www.menopause.org/edumaterials/guidebook/mgtoc.html.
Perimenopause: Contraception
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Physiology of the Menopausal Transition
• Variable cycle length1
• Endocrinologic milieu shifts– Inhibin2-4
– FSH2-4
– Variable changes in E15
– Testosterone: no change3,6
1. Treolar et al. Int J Infertil. 1967;12:77.2. Burger. Hum Reprod. 1993;8(suppl 2):129.3. Burger et al. J Clin Endocrinol Metab. 1995;80:3537.
4. Lenton et al. J Clin Endocrinol Metab. 1991;73:1180.5. Santoro et al. J Clin Endocrinol Metab. 1996;81:1495.6. Bancroft et al. Clin Endocrinol. 1996;45:577.
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AUB Evaluation in Post-Menopausal Women • History
– How long since any bleeding has occurred?
• PE– Maturation index
• Labs– EMBx
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DDx in Post-Menopausal Women
• Cancer – until proven otherwise
• Medication induced (HT, other systemic medications)
• Systemic disease (liver, renal, coagulopathies)
• Atrophy
• Benign growths
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Remember:
Postmenopausal bleeding is endometrial cancer until proven otherwise
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AUB Management in Post-Menopausal Women
• If new onset HT, may be related –consider US prior to EMBx
• If no HT – EMBx
• Management based on results of Hx, PE and Diagnostic evaluation (infection treatment, atrophy management, systemic disease management, medication adjustment, etc)
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Post-Menopausal Atrophy Management
• Start with local estrogen – is Progestin needed?
• If significant systemic symptoms consider systemic HT
• Later management – lubricants, moisturizers, titrate local estrogen dose
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Summary• The diagnosis of AUB bleeding involves
elimination of other causes such as pregnancy, pregnancy-related conditions, systemic diseases, medication side effects, iatrogenic causes, genital tract pathology and malignancy.
• Hormonal therapy should be the first-line option for most pre-menopausal women
• Surgical techniques should be reserved for women in which medical therapy fails and childbearing is no longer desired
ACOG practice bulletin. Int J Gynaecol Obstet. 2001;72:263-271.
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CASES
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Case – Cheryl Cheryl comes to your office complaining of increasingly heavy menses. She is a 45 year old Black woman. Cheryl describes increasing cramping with her periods and significantly increased flow, but her periods remain regular (q 30 days, 7 days flow). She wants to know if she is beginning “the change.”
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Case – MarthaMartha is 57. She had her last menses 2.5 years ago. She is managing her hot flashes with lifestyle changes –avoidance of caffeine, alcohol, and sugar; wearing layered breathable fabrics, etc. Today she presents because she got her period last evening.
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Resources
• NIH - National Heart, Lung, and Blood Institute– http://www.nhlbi.nih.gov/
• The Hormone Foundation– http://www.hormone.org/
• Nat’l Center for Complimentary and Alt Medicine– http://nccam.nih.gov/
• Herbal Product Information– http://consumerlabs.com
• North American Menopause Society– http://www.menopause.com
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Acknowledgements
• Slides courtesy of:– NAMS (purchased slide set)– NOF – NPWH– Council on Hormone Education– Colleagues
• Used with permission, copyright held by original authors