Post on 15-Jan-2016
Disorders of MenstruationPathophysiology, Evaluation and Management
Jennifer Mersereau, MD
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics & Gynecology
University of North Carolina
March, 2009
Objectives
What defines abnormal menstruation? Burden of disease Differential diagnosis of abnormal
menstruation patterns Classification of abnormal menstruation Evaluation Treatment
Physiology of Menstruation
•Exact hormone levels not crucial
•Exact cycle day not crucial
•General sequence crucial
Ovulatory Cycles
Orderly proliferation Synchronous, stable
endometrial development Lysosomal digestion,
vasoconstriction & ischemia desquamation, coagulation, hemostasis
MensesMenses
22 44 66 88 1010 28281212 1414 1616 1818 24242020 2222 2626
Estrogen
Progesterone
NORMAL MENSTRUAL BLEEDING IS SELF-LIMITED
Menstrual CycleWhat is normal?
Menses
Normal
Abnormal
Duration Volume Interval
4-6 days Approx
30 ml
24-35 days
< 2
> 7
days
> 80 ml < 24
> 35
days
PolymenorrheaOligomenorrhea
Menorrhagia
Metrorrhagia
Menometrorrhagia
Menstrual Cycle CharacteristicsAge Variations
Highest variation in early adolescent and perimenopausal years
Adolescent: long intervals for 5-7 years after menarche
Reproductive years: • Majority of cycles 25-28 days• Cycle length can change around age 40-42
until menopause
Health, 1986; Belsey, 1997; Volman, 1977; Treolar, 1967; O’Connor, 2001; Taffe, 2002.
Abnormal Menstruation: Burden of Disease
Most common reason for GYN visits 600,000 hysterectomies each year
• ¼ US women will have a hysterectomy by age 60• 2nd most frequent surgery among reproductive-aged
women• Annual cost of $5 billion
Most common conditions for hysterectomy:• Fibroids, endometriosis, prolapse• If < 30 years old, menstrual disturbances and
dysplasia
Surveillance for Reproductive Health, Hysterectomy Surveillance—United States, 1994-1999.
Evaluation of Abnormal Menstruation
Consider differential diagnosis Target history to narrow differential Exam Labs Imaging
Evaluation of Abnormal MenstruationDifferential Diagnosis
Pregnancy complication!• Threatened or incomplete abortion• Ectopic pregnancy• Gestational trophoblastic disease• Retained products of conception
Benign anatomical lesion• Cervical or endometrial polyp• Leiomyoma• Adenomyosis
Malignancy• Cervical or uterine cancer (esp HIV + women)
Evaluation of Abnormal Menstruation
Differential Diagnosis Trauma/foreign body
• Children
Inflammatory conditions• Endometritis
Systemic illness• Thyroid dysfunction• Hyperprolactinemia• Renal failure• Hepatic dysfunction
Bleeding disorder• Thrombocytopenia• Platelet function
abnormalities• von Willebrand’s disease
Medications• Steroidal • Psychiatric
Or…..
Dysfunctional Uterine Bleeding
DUB is a diagnosis of exclusion! DUB is:
• Abnormal bleeding pattern, AND• NO ATTRIBUTABLE UNDERLYING ILLNESS OR
PATHOLOGY Causes:
• Anovulation (90%)Polycystic ovarian syndromeTeenagers or peri-menopausal women
• Rarely short follicular or luteal phase
Evaluation of Abnormal MenstruationStep 1: History
Detailed menstrual history• Inter-menstrual intervals
Consistent, normal (q 24-35 days)Variable
• Character, volume• Duration
Normal (3-7 days)Prolonged
• Initial onset of symptoms
Evaluation of Abnormal MenstruationStep 1: History
Other associated symptoms• Dysmenorrhea• Post-coital bleeding• Galactorrhea• Hirsutism• Fatigue, weight gain, constipation (thyroid)
Temporal associations w/ other events• Weight changes• Medication changes
Medical history & medications
GOAL OF HISTORY:• Does she ovulate? If not, DUB LIKELY!• What labs do you need to confirm you initial diagnosis?
Ovulation - does she or doesn’t she?• Menstrual history• Basal body temperature (BBT) monitoring (biphasic)• Ovulation predictor kits• Timed serum progesterone (> 3 ng/ml)• Ultrasound
Implications: if ovulatory…• Search for an anatomical/pathological cause
Evaluation of Abnormal Menstruation
Weight Thyroid exam Signs of other illnesses Signs of hyperandrogenism
• Hirsutism• Acne
Pelvic exam• Cervical and vaginal lesions• Size, shape of uterus
Evaluation of Abnormal MenstruationStep 2: Exam
EndocervicalPolyps
Squamous CellCarcinoma of Cervix
All patients: screen for• Pregnancy (history or urine hcg)• Thyroid disorder (TSH)• Anemia, thrombocytopenia (CBC)
Select patients:• Hyperprolactinemia (PRL)• Bleeding disorders (coagulation panel, vWF)• Chemistry (AST, ALT, Creatinine)• Endometrial biopsy????
Evaluation of Abnormal MenstruationStep 3: Laboratory Tests
Risk of endometrial carcinoma:• Age 30-34: 2.3/10,000• Age 35-39: 6.1/10,000• Age 40-49: 36.2/10,000
Duration of time exposed to unopposed estrogen is more important than age
Possible results: proliferative, secretory, hyperplasia, atypia, carcinoma, acute or chronic endometritis
Evaluation of Abnormal MenstruationEndometrial Biopsy
Ash, J Reprod Med, 1996.; ACOG Practice Bulletin 14, 2000.
Endometrial Biopsy
Chronic endometritis
Endometrial Hyperplasia
Adenocarcinoma
Who needs imaging?
Evaluation of Abnormal MenstruationStep 4: Imaging
Regular cyclesvolumeduration
Regular cyclesintermenstrual
bleeding
Abnormal bleeding,
evidence of ovulation
Failedmedical
management
RULE OUT ANATOMIC LESION
Ultrasound can help diagnosis:• Fibroids• Polyps• Adenomyosis• Endometrial stripe
< 5 mm, denuded, atrophic 5-12 mm, normal > 12 mm, thick, biopsy!
Hydrosonogram: increases sensitivity to detect endometrial lesions, 70% 90%
Hysteroscopy
Evaluation of Abnormal MenstruationStep 4: Imaging
Becker, 2002.
Normal endometrium
Late proliferative or luteal phase
Thin endometrium
Early proliferative phase or atrophy
Uterine ImagingUltrasound
Submucous myomaEndometrial
polyp
Uterine Imaging
Routine Ultrasound
Saline Sonogram
Polyps
Myoma
Atrophy
Adenocarcinoma
Hyperplasia
Uterine ImagingHysteroscopy
Treatment of Abnormal Menstruation
DUB Restore growth,
development and shedding of a stable endometrium
Prevent development of hyperplasia or neoplasia
Bleeding from Specific Cause
What is the diagnosis?
Cycle Physiology
22 44 66 88 1010 28281212 1414 1616 1818 24242020 2222 2626
Menses
Estrogen
Progesterone
Ovulatory CycleDUB/Anovulation
Estrogen
Endogenous estrogen
Rx Progestin Rx Progestin
1 5 9 13 17 21 25 1 5 9 13 17 21 25
Calendar DayCalendar Day
Treatment: DUBTreatment: DUB
Progestins: 1. Medroxyprogesterone (MPA) 10mg qd
2. Norethindrone acetate 5 mg qd
Option 1: Cyclic Progestins
Treatment: DUBTreatment: DUB
Option 2: Oral Contraceptives
Endogenous estrogen
1 5 9 13 17 21 25 1 5 9 13 17 21 25
Pill Cycle DayPill Cycle Day
Rx Cyclic OCP
Progestin
Estrogen
Progestin
Estrogen
Rx Cyclic OCP
Treatment of Anovulation with Acute, Heavy Bleeding
Hemodynamically stable??• IVF, CBC, transfusion• D&C
Strongly consider biopsy Ultrasound Treatment – High dose OCP taper
• Goal: Restore regular menstrual bleeding patterns• Prevent endometrial cancer!!
• Failed management = further workup
Treatment of AnovulationMaintenance Therapy
Kurman et al, Cancer, 1985
Histology Cytologic Atypia
Architectural Pattern
Risk of neoplasia
Simple hyperplasia
-- Regular 1%
Complex hyperplasia
-- Irregular, crowded
3%
Simple + atypia
+ Regular 8%
Complex + atypia
+ Irregular, crowded
29%
Treatment: Anovulatory BleedingPreventing Endometrial Hyperplasia & Neoplasia
ATYPIA
Present Absent
Cyclic progestins or OCPS
Rebiopsy if abnormal bleeding occurs
Fertility desired?
Yes No
Megace 40-80mg x 3-6 months
Re-biopsy
Hysterectomy
Treatment: AnovulationPreventing Endometrial Neoplasia
Treatment of Abnormal Menstruation
DUB Bleeding from Specific Cause
Treat underlying cause Decrease volume and
duration of menses
What is the diagnosis?
Ectopic pregnancy• Salpingostomy• Salpingectomy• Methotrexate
Threatened abortion• Observation
Incomplete/inevitable abortion• Curettage
TreatmentComplications of Pregnancy
TreatmentComplications of Pregnancy
Ectopic
Empty Sac
Indirect cause of bleeding Twice as common in HIV+ patients Doxycycline 100mg bid x 10 days
Kerr-Layton et al, Infect Dis Obstet Gynecol, 1998
TreatmentChronic endometritis
TreatmentChronic endometritis
Medical treatment• OCPs: decrease volume/duration of
menses• NSAIDS• GnRH agonists
Surgical treatment• Myomectomy• Hysterectomy
TreatmentLeiomyomas
TreatmentLeiomyomas
TreatmentSmall Submucous Myomas,
Polyps
TreatmentSmall Submucous Myomas,
Polyps
11 22 33
Hysteroscopic Resection
TreatmentProlapsing, Large Myomas
TreatmentProlapsing, Large Myomas
VaginalMyomectomy
Abdominal or LaparscopicMyomectomy
Abdominal Hysterectomy
TreatmentMultiple Myomas
Completed Childbearing
TreatmentMultiple Myomas
Completed Childbearing
Treatment: Ovulatory Patient with Unexplained Menorrhagia Medical Options
• NSAIDS: 20-40% decrease• OCPs: 40% decrease• Levonorgestrel IUD: 75-95% decrease
Excellent option with chronic illnessesWomen highly satisfied
• GnRH agonists Surgical Options
• Endometrial ablation• Hysterectomy
Hall, Br J Obstet Gynecol, 1987; Fraser, Aust NZ J Obstet Gynecol, 1995; Cochrane Database Syst Rev, 2002.
Absence of Menstruation
Outflow obstruction, Mullerian abnormalities
Androgen insensitivity syndrome – 46 XY
Ovarian failure• Turners syndrome, 45
XO• Autoimmune• Cancer treatments
Other causes
Asherman’s syndrome Premature ovarian
failure Pituitary lesion
• Most common = prolactinoma
• Sheehan’s syndrome
Hypothalamic hypogonadism
Other causes
Primary Amenorrhea Secondary Amenorrhea
Abnormal Puberty
<8 years old GnRH-dependent
• Idiopathic – most common
• CNS abnormality GnRH-independent
• Ovarian cyst/tumor• McCune Albright
syndrome Treatment:
• Surgery when appropriate
• GnRH agonist
See primary amenorrhea
Precocious Puberty Delayed Puberty
Conclusions
Abnormal menstruation is extremely common Most common cause of a sudden change in bleeding
patterns is a complication of pregnancy! Careful menstrual history Use labs and imaging to support your clinical
suspicions Anovulatory bleeding: goal is to restore normal
menstrual patterns Bleeding from other causes: correct underlying
pathology and decrease volume/duration of menses
Questions?
14 28Follicular Phase Luteal Phase
Endogenous Progesterone
Provera C
Provera B
Provera A
Ovulation
Examples of Effects of Exogenous Progestin in Ovulatory Cycles
Simple Hyperplasia Complex Hyperplasia
Treatment: Anovulatory Bleeding
Preventing Endometrial Hyperplasia & Neoplasia
Complex Atypical Hyperplasia
Menstrual Cycle Definitions of Abnormalities
Irregular intervals• Oligomenorrhea, > 35 days• Polymenorrhea, < 24 days
Excess amount and/or duration• Menorrhagia
Irregular interval• Metrorrhagia
Irregular interval and amount/duration• Menometrorrhagia
Submucous myoma
Adenomyosis
Intramural myoma
Uterine ImagingUltrasound
ADD: (4/7)• Info about PCOS vs. hypo-hypo.• Look up DUB (is it almost always PCOS??)• More about HIV?
MensesMenses
Endogenous Estrogen
Estrogen
Rx OCP (monophasic) bid X 7d, qd X 7-14d
Progestin
Treatment: Acute bleedingHigh dose OCP ‘Taper’
MensesMenses
Endogenous Estrogen
Rx Estrogen (CEE 1.25-2.5 mg/d or micronized estradiol 2.0 mg/d, q4h prn;
CEE 25 mg i.v. q4h prn)
RxProgestin
Treatment: Atrophic EndometriumSequential Estrogen and Progestin