Transcript Slide 1
Abnormal Uterine Bleeding (AUB) /
Dysfunctional Uterine Bleeding (DUB)
Herbert L. Muncie, Jr., M.D.
The main issues!
How to control current bleeding?
How to prevent future abnormal bleeding?
Jeanie
16 year old comes in complaining of irregular heavy periods for 2 years No medical problems and using condoms for contraception since she became sexually active 3 months ago • • What can reduce current heavy bleeding?
• Not currently bleeding What can reduce her risk of future irregular heavy bleeding?
Jeanie - More History
Question Answer When did her last period start?
10 days ago
When was her PMP? How irregular are her periods?
How heavy is the bleeding with most periods?
Will sometimes have to change her tampon every hour, has soaked her clothes at times
Is this heavy bleeding unusual?
6 weeks ago, usually every 6 - 8 weeks Has had heavier periods for almost 2 years, lasting 4 - 5 days
Jeanie - More Data
• • • • • Interval between cycles – 21 - 28 days Proliferative (follicular) phase – 7 - 21 days
Ht - 64 in; Wt - 126
Secretory (luteal) phase – 14 ± 2 days Bleeding duration – 2 - 6 days
physical No bruising or petechia
Coagulation panel TSH - reflex Pending
Pelvic exam - normal
GC/Chlamydia probe Pending
Normal Menstrual Cycle
• • • Maturation of endometrium relatively ~ uncomplicated Dependent on
estrogen
and
progesterone
~ First half of cycle is
estrogen
- dominant Halts menstrual flow & promotes proliferation (proliferative or follicular phase) ~ Second half is
progesterone
dominant Stops endometrial growth, then promotes differentiation (secretory or luteal phase)
Normal Menstrual Cycle
• • • • • Interval between cycles – 21 - 28 days Proliferative (follicular) phase – 7 - 21 days Secretory (luteal) phase – 14 ± 2 days Bleeding duration – 2 - 6 days Average blood volume lost - 45 ml
Abnormal bleeding
• • • » Heavy – > 80 ml blood loss with period • Doubtful clinical utility or significance » » Changing pad > q 1 h at some point Soaking through to her clothes Irregular intervals – > 35 days or < 21 days between periods Prolonged duration Flow > 7 days
Jeanie - Follow-up Visit 3 days later
Tests ordered
CBC Coagulation panel TSH
Results
Hgb – 10.6 g/dL Hct – 31% MCV – 76 fl Platelet count 215,000 PT – 12 sec INR – 1.1
aPTT – 22 sec 1.76 mU/L GC/Chlamydia probe Negative
Definitions
Dysfunctional uterine bleeding (DUB) abnormal bleeding with no organic cause (neoplasm, inflammation, infection or pregnancy) but which can co-exist with organic pathology Abnormal uterine bleeding (AUB) - includes DUB and bleeding from structural or organic causes
Assess for organic pathology
• • • • • History Physical exam including pelvic ~ ~ ~ ~ Diagnostic tests Pregnancy test PAP smear if indicated CBC, TSH, coagulation panel Chlamydia, gonorrhea probe Pelvic/transvaginal ultrasound ~ Endometrial biopsy in women over age 35 Only 2% of endometrial cancers occur in women < 40 years old
DUB & Bleeding Disorders
• Screening for von Willebrand (vWD) disease with heavy menstrual bleeding?
~ ACOG recommends screening adolescents with severe menorrhagia, women whom abnormal bleeding etiology cannot be established & women ~ undergoing hysterectomy » However, not sufficient evidence that it helps 1% prevalence in general population
DUB & Bleeding Disorders
• Case finding with heavy menstrual bleeding ~ Up to 16% have vWD [James 2009] ~ Consider if any of the following: » » » » » Menorrhagia since menarche Minor wound bleeding > 5 minutes Bleeding oral cavity/GI tract without anatomic lesion Prolonged bleeding after dental extraction Unexpected postsurgical bleeding
DUB & Bleeding Disorders
• Case finding evaluation ~ Order CBC, PTT, PT & vWF level (ideally during menses) ~ ~ » » No single test will establish the diagnosis Positive family history usually necessary ~ Ask about any bleeding with dental procedures, T&A, peripartum bleeding OCPs can mask type 1 vWD but don’t stop them Patients with type O blood have 25 – 30% lower levels of » vWF In these patients with a lower level, a family history would be needed to confirm or exclude the diagnosis
Menorrhagia – vWD treatment
• If caused by vWD & not trying to get ~ ~ ~ pregnant Oral contraceptive would be treatment of choice Progestin IUD alternative Desmopressin (DDAVP ® ) or antifibrinolytics if pregnancy desired ~ Avoid NSAID with symptomatic vWD
Jeanie
Probable diagnosis – DUB
vWF ordered to be drawn during next menses vWF results – 35 IU/dL (low but not diagnostic) No family history or bleeding • • • What can reduce her risk of future irregular heavy bleeding?
Because combination oral contraceptives (OCP) are not contraindicated She was started on a monophasic OCP to decrease her flow and regulate her cycles
• •
Fran
A 23 year old woman complaining of heavy menstrual bleeding. Her period started 2 days ago & today is very heavy. She has to change her tampon at least every hour.
She has no medical problems Periods are usually regular What can reduce her current heavy bleeding?
What can she do to reduce her risk of future heavy bleeding?
Terminology/Descriptions
Does Fran Have
Hypomenorrhea Oligomenorrhea Menorrhagia
Definition
Abnormally reduced menstrual flow Infrequent periods with normal flow Regular periods with heavy flow Metrorrhagia Irregular periods with normal flow Menometrorrhagia Irregular heavy periods
Terminology/Descriptions
• • • There has been a lack of uniformity in definitions and descriptions of menstrual bleeding abnormalities February 2005, 35 international MDs met in Washington DC to define terms Settled on 4 key menstrual dimensions for description
Terminology/Descriptions
Dimension
Regularity Frequency Duration Volume
Categories
Irregular Regular Absent Frequent Normal frequency Infrequent Prolonged Normal Shortened Heavy Normal Light
Terminology/Descriptions
Old terminology
Hypomenorrhea
Regularity
Regular
Frequency
Normal
Duration
Normal
Volume
Light Oligomenorrhea Irregular Infrequent Normal Normal Menorrhagia Metrorrhagia Regular Normal Irregular Frequent Menometrorrhagia Irregular Frequent Prolonged Heavy Normal Normal Prolonged Heavy
Is It Ovulatory or Anovulatory?
• • With any abnormal bleeding it is helpful to • • determine if it is ovulatory or anovulatory Most DUB is anovulatory In adolescents ovulatory cycles may take up to 3 years to be established How can you determine if it is ovulatory or not?
Normal Ovulatory Cyclic Function
• • • Depends on regular pulsatile release of GnRH from hypothalamus ~ Which stimulates FSH & LH pulses from anterior pituitary Pulsatile FSH & LH leads to: ~ ~ ~ Folliculogenesis (proliferative or follicular phase) Ovulation Corpus luteum formation which sustains luteal phase (luteal phase) Atrophy of corpus luteum results in menses
Is It Ovulatory or Anovulatory?
Estrogen FSH
Menstruation
Follicular phase LH Day 14 Progesterone Luteal phase
Is It Ovulatory or Anovulatory?
• ~ ~ ~ ~ ~ Ovulatory Cycles regular intervals mittelschmerz serum P4 > 3 ng/ml ~ 2 nd half cycle biphasic BBT Serum LH > 25 mIU/ml • ~ ~ ~ Anovulatory cycles irregular intervals no ovulatory pain serum P4 < 3 ng/ml ~ 2 nd half cycle ~ ~ monophasic BBT Serum LH < 25 mIU/ml
Fran – more information
Answer Vital signs
Ht – 67”; Wt – 146 lbs; BMI 22.9
BP 124/76; P 88; T 98.8 (O)
Any other symptoms?
Contraception Physical exam
A little dizzy when standing Used OCP until 6 months ago Using condoms past 4 weeks Normal general exam Pelvic – active bleeding from os Uterus small nontender No adenexal mass
Additional information
Tests ordered
Stat CBC Pregnancy test TSH GC/Chlamydia probe
Results
Hgb – 11.6 g/dL Hct – 34% MCV – 76 fl Negative Results pending Results pending
Indicative of Heavy bleeding
• • • • Soaking through pad or tampon < 1 hour Soaking through bed clothes Below normal ferritin ~ Anemia [James 2009]
Regular heavy prolonged bleeding
(Menorrhagia)
• • ~ Age Any age ~ Etiologies » Anovulatory in younger & older women Immature hypothalamic-pituitary-ovarian axis in adolescents » Fluctuating estrogen levels each end of reproductive age ~ Typically due to anatomic lesion (e.g. fibroid) in women 30 – 50 years old
•
Regular heavy prolonged bleeding
~ Etiologies » Ovulatory – either: Corpus luteum insufficiency » Inadequate progesterone from primary ovarian failure or central/metabolic defect » Corpus luteum prolonged activity » Over stimulation of LH - irregular shedding » Do not have 14 day luteal phase
Regular heavy bleeding
• Etiologies ~ Up to 20% adolescents have bleeding disorder as etiology [Claessens 1981] ~ ~ Consider Von Willebrand disease especially with family history of bleeding If isolated prolonged PTT or normal PTT, PT, platelet count & fibrinogen with bleeding then specific test for VWD indicated
Acute Bleeding - Treatment
• Outpatient treatment ~ Start monophasic OCP ~ ~ ~ ~ 1 pill QID for 4 days 1 pill TID for 3 days 1 pill BID for 2 days then ~ 1 pill a day for 3 weeks If OCP contraindicated cycle with Provera ® ~ ~ Give 10 mg daily for 14 days, then stop for 14 days Continue this cycle for 3 months
Acute Bleeding –Treatment
• ~ Outpatient treatment Oral conjugated estrogens (Premarin ® ) 2.5 mg » QID until bleeding is controlled Consider giving antiemetic with medication ~ D&C if no response after 2 - 4 doses or sooner if needed
Fran – 23 year old
• • • What can reduce her current heavy bleeding?
Started on combination OCP 1 pill qid for 4 days Bleeding subsided significantly in 12 hours
Acute Bleeding – Treatment
• ~ Inpatient treatment Conjugated Estrogens (Premarin
®
) H until bleeding is controlled 25 mg IV Q 4 ~ Give antiemetic prophylactically ~ D&C if no response after 2 - 4 doses or sooner if needed
Acute Bleeding - Treatment
• Inpatient treatment ~ ~ ~ Simultaneous with IV Conjugated Estrogens (Premarin
®
) start monophasic OCP 1 pill QID for 4 days 1 pill TID for 3 days ~ ~ 1 pill BID for 2 days then ~ 1 pill a day for 3 weeks If OCP contraindicated cycle with Provera ® ~ ~ Give 10 mg daily for 14 days, then stop for 14 days Continue this cycle for 3 months
•
Fran
After the acute bleeding is controlled.
What can she do to reduce her risk of future heavy bleeding?
Regular heavy bleeding
• ~ Evaluation ACOG does not recommend routine CBC, TSH or prolactin ~ Endometrial sampling rarely necessary since regular bleeding is less concerning for endometrial cancer
Menorrhagia - Treatment
• • • NSAIDs ~ Inhibit prostaglandin which increases platelet aggregation ~ Increase uterine vasoconstriction Mefenamic acid (Ponstel ® ) 500 mg tid had 30-50% decrease in flow Naproxen 375 mg bid effective
Menorrhagia - Treatment
• Tranexamic acid (Lysteda ® ) ~ ~ Two 650 mg tablets tid Stabilizes a protein that helps blood clot ~ ~ ~ Concern about increased risk of clots has not been confirmed in ongoing studies Caution if combined with oral contraceptive Contraindicated with history or increased risk of thrombosis or VTE
Menorrhagia - Treatment
• ~ Treatment » Danazol 200 mg qd acceptable short-term Synthetic androgen, suppresses LH & FSH » » which suppresses ovulation Can start low 100 mg/d & titrate up Rare side effects if < 600 mg/d
Menorrhagia
• ~ Treatment Levonorgestrel-releasing IUD (Mirena ® ) » Improved health quality of life » [Hurskainen 2004] Reduces blood loss more than NSAID, Danazol, OCPs, oral progesterone [Kaunitz 2010]
Menorrhagia – treatment
• • ~ Unlikely to be beneficial Oral progesterone (longer cycle) ~ Likely to be ineffective or harmful Oral progesterone (luteal phase)
Fran
• • • • What can she do to reduce her risk of future heavy bleeding?
Because she did not want to become pregnant & had no contraindications to OCP She was started on a monophasic combination OCP & will return in 3 months She was given a prescription for mefenamic acid to be used if her next period was heavy
Joan
• • • 47 year old female with hypertension & ~ type 2 diabetes Complains of irregular heavier periods for the past 7 ~ ~ months Married, non-smoker, BTL at age 32 Ht 63”; Wt 187 lbs; BMI 30.5; BP 146/92; P 74 What other information do you need? What tests do you want to order?
More information
LMP PMP Duration of flow PMH: Hypertension Type 2 diabetes Physical exam Tests ordered
Results
12 days ago 37 days before LMP 8 days Medications: Lisinopril/HCTZ Metformin, ASA General exam normal Pelvic – uterus 6 week size CBC TSH Pelvic ultrasound Pap smear
Joan
• • • • Probable diagnosis is anovulatory DUB Probably perimenopausal etiology What can be done about the irregular menses? What can be done to decrease the duration and excessive flow?
Irregular Heavy Menstrual Bleeding
(Menometorrhagia)
• ~ Etiology Get decrease in estrogen & cannot initiate LH ~ ~ surge, therefore anovulatory FSH level > 40 IU/L suggest impending ovarian failure LH-FSH ratio > 2 compatible with chronic anovulation
Irregular menstrual bleeding
• ~ ~ Treatment None medically required if that is only issue OCPs will regulate menses if patient wants birth ~ control & no contraindications If OCP contraindicated cycle with Provera ® ~ ~ Give 10 mg daily for 14 days, then stop for 14 days ~ Continue this cycle for 3 months Postmenstrual bleeding – “endometritis” ~ Doxycycline 100 mg bid for 10 days
Irregular Heavy Menstrual Bleeding
• ~ Treatment – for non-acute active bleeding » » » Therapy indicated for these patients: Bleeding > 7 days Anemia from blood loss Interferes with normal life activities
Irregular Heavy Menstrual Bleeding
• Treatment ~ » Combination oral contraceptives » To reduce bleeding slowly over several days Give standard OCP dosing » » » To reduce bleeding quickly in 24 hours 1 pill qid for 5-7 days then 1 pill bid for three weeks ~ May need to pre-medicate with antiemetic
Treatment Menorrhagia – EBM
• • For women considering hysterectomy, placement of levonorgestrel-releasing IUD resulted in similar outcomes & was more cost effective ~ InfoRetriever Randomized controlled trial after 5 years found no ~ difference in outcomes (SOR 1b) http://www.infopoems.com/irsearch/search_details.cfm?ID=60625&ResultKey=E&title=Prog esterone%20IUD%20effective%20for%20menorrhagia
Summary of MedicalTherapies – Irregular Heavy Prolonged Bleeding
Drug Levonorgestrel IUD Oral PG (day 5-25) Danazol NSAIDs OCP Oral PG (day 12-26) Mean reduction blood loss (%) 94 87 Women benefiting (%) 100 86 50 29 43 -4 76 51 50 18
Joan Follow-up visit
Tests ordered
CBC TSH Pelvic ultrasound
Results
Hgb – 11.1 g/dL Hct – 33.4% MCV – 88 fl 2.6 mU/L (nl – 0.45 – 4.5) Diffuse uterine enlargement Endometrial stripe < 4 mm Ovaries normal appearance
Menometrorrhagia - EBM
• • Various types of surgery or IUD hormone device are effective in reducing heavy bleeding & suit most women better than oral medications ~ ~ Cochrane Review Controlled randomized trials Surgery reduced bleeding better at 1 yr. than medical therapy & IUD equally effective to surgery ~ ~ Oral therapy suits minority of women http://www.cochrane.org/reviews/en/ab003855.html
Joan Treatment Options
Treatment option
Oral contraceptive Will control bleeding & make her regular Not contraindicated NSAIDS Progestine IUD Would reduce flow but not effect regularity Would control flow & frequency Would obviate the need for more invasive procedure Surgical options Ablative therapies would be a reasonable option
Key Points - DUB
• • • • History determines the pattern & probable etiology Four aspects: Regularity, frequency, duration & volume • Always assess for organic etiology Pregnancy test, STDs, infection, etc • Assess desire for contraception Oral contraceptive can frequently control the problem
Key Points - DUB
• Provide medical therapy that is effective and lowest • risk for patient NSAIDs usually safe, OCPs, progesterone IUD, then surgery • Discuss progesterone IUD for significant bleeding in older women who want to avoid surgery • • Surgery is final therapeutic option Multiple new modalities are effective