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Cyclic Heavy Menstrual Bleeding. David Hilmers , M.D. MLK Clinic Lecture. Objectives. Explain the role that hemostatic mechanism play in cyclic heavy menstrual bleeding (HMB)

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Cyclic heavy menstrual bleeding l.jpg

Cyclic Heavy Menstrual Bleeding

David Hilmers, M.D.

MLK Clinic Lecture

Objectives l.jpg

  • Explain the role that hemostatic mechanism play in cyclic heavy menstrual bleeding (HMB)

  • Describe the risks and benefits of options for managing cyclic HMB, with a focus on nonsurgical, noncontraceptive therapy

  • Incorporate evidence-based treatment into clinical practice

  • Provide individualized counseling to help patients choose customized optimal treatment plans

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Consequences of HMB

  • Associated with increased health care utilization

  • Lost work estimated at $1692 annually (in 1999)

  • May cause discomfort, anxiety, and impaired quality of life

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Characteristics of Normal Menstrual Cycles

  • Cycle length: 21-35 days

  • Bleeding duration: < or = 7 days

  • Average blood loss: 35 ml (range 20-60 ml)

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Cyclic HMB defined

  • Excessive or prolonged (> 7 days) uterine bleeding occurring at regular intervals, every 21-35 days

  • Clinically defined as menstrual blood loss (MBL) > or = 80 ml per cycle

  • Also referred to as hypermenorrhea or menorrhagia

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Causes of HMB

Organic (organ

Dysfunction, bleeding



Anatomic (fibroids)

Iatrogenic (IUD,

Chemo, anticoags)

Thyroid disorders

Pituitary tumors

Clinical Causes of HMB

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Causes of Cyclic HMB: Hemostatic disorders

  • Systemic hemostatic disorders

    -Inherited coagulation disorders

    -Acquired disorders


  • Local hemostatic disorder

    -Endometrial hemostatic dysfunction

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Causes of Cyclic HMB: Systemic Hemostatic Disorders

  • Inherited coagulation disorders

    -von Willebrand disease


  • Acquired disorders


    -Liver disease


  • Iatrogenic



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Von Willebrand’s Disease

  • Most common inherited bleeding disorder—AD with variable penetrance

  • Seen in 1/3 of adolescents with HMB

  • Symptoms: easy bruising, excessive bleeding after procedures, nose bleeds, HMB

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Age, parity

Cyclic vs. noncyclic bleeding

Singular vs. chronic episodes

Duration and amount of bleeding


Contraceptive method

Marital status/sexual history

History of bleeding disorders

Medical illnesses


Family history

Evaluation of Abnormal Bleeding History

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Women’s Perception of Menstrual Bleeding

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Diagnosis of Cyclic HMB

  • Subjective

    -Patient perception

    -Patient history

  • Objective—NOT required for diagnosis

    -Examination during heaviest flow

    -Completed menstrual calendar


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Evaluation of Cyclic HMB: Lab

  • CBC, platelet count

  • Pap smear (only if indicated, i.e., if patient is due)

  • Coagulation studies should be considered if:

    -HMB since menarche

    -Hx of bleeding (postpartum, surgery, dental, bruising, epistaxis, gum bleeding)

    -Family history of bleeding symptoms

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Evaluation of Cyclic HMB: Procedures and Imaging

-Endometrial biopsy—if at risk for endometrial hyperplasia

-Transvaginal U/S – if pelvic exam is inadequate or findings are abnormal

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Medical Management of Cyclic HMB

  • Off-label therapies



    -Depot Provera

  • FDA-approved therapies

    -Hormonal: Progestins

    -Nonhormonal: Tranexamic acid

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NSAIDs: Off-label Use

  • Several studies show reduction in blood loss compared to placebo

  • Initiated immediately before or on first day of menses for up to 5 days

  • Less effective than other medical modalities

  • Approximately 20% decrease in blood loss

  • No evidence of differences among NSAIDs

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Combination OCPs Off–label use

  • Often used off label for HMB, despite limited data

    -Continuous OCP use may be superior to standard regimen

    -For break-through bleeding with continuous OCPs, stop 3 days and then restart (>90% resolution in bleeding)

  • Recent study compared phasic OCP (E2 valerate/dienogest) to placebo

    -Approximately 70% reduction in mean blood loss in OCP group

    -19% reduction in placebo group

    -Regimen approved for treatment of HMB in Europe

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DMPA: Off-label use

  • Dose: 150-250 mg IM q 2-3 months

    -FDA-approved for contraception only (150 mg q 3 mos)


    -High incidence of irregular bleeding

    -Bone loss with long-term use

    -Weight gain

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FDA-Approved Therapies

  • Hormonal: Progestins

  • Nonhormonal: Tranexamic acid

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Oral progestins

  • In a randomized trial of women with HMB, low dose medroxyprogesterone (MPA) 10 mg x 10 days (beginning on cycle day 16) reduced blood loss by only 21.5% at 6 months (Kaunitz AM, et al. Obstet Gynecol. 2010.116:625-632._

  • In another study, norethindrone 6 mg tid on cycle days 5-26 reduced bleeding by 87% after 3 cycles

    -Only 22% wished to continue treatment

    (Irvine GA, et al. Br J Obstet Gynecol 1998. 105:592-98)

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Levonorgestrel IUD

  • Recommended for women who have had a child

  • Indicated to treat HMB in women who choose to use IUD as their method of contraception

  • Use off label in women who do not require contraception

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Changes before and after IUD insertion

Xiao. Treatment of menorrhagia with LNG-IUS. Fertil Steril 2003.

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Levonorgestrel IUD vs. Hysterectomy for HMB

  • 5 year study

  • 236 Women were randomized

    -Levonorgestrel (LNG) IUD (n=119) and hysterectomy (n=117)

    -58% of the LNG IUD group did not require subsequent hysterectomy

  • Quality of life benefits were equal in both groups

    -Costs were lower in the LNG IUD group

    -Satisfaction with treatment similar between groups

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Medical Mgt of HMB – Tranexamic Acid

  • Approved by the FDA 2009 to treat cyclic HMB

    -Long history of use for HMB in other countries

  • Mechanism of action: synthetic lysine amino acid derivative; diminishes the dissolution of hemostatic fibrin by plasmin, stabilizing fibrin matrix (antifibrinolysis)

  • Concern about thromboembolic events not substantiated in recent studies

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Tranexamic Acid

  • Only FDA-approved nonhormonal therapy of cyclic HMB

  • Dose: Two 650-mg tabs 3 times/day for a maximum of 5 days during menstruation

  • Contradindicated if history of or increased risk for venous thromboemboloism

  • Use with OCPs may increase risks of arterial/venous thrombosis

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MBL with tranexamic acid vs placebo

Lukes A, et al. Obstet Gyn. 2010.116(4):865-875

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Medical Management of Cyclic HMB: Factors to Consider

  • Need for contraception

  • Patient preference: may desire to avoid hormones, devices, or surgery

  • Contraindications to hormonal therapies

  • Size of uterus; presence, size, and location of fibroids

  • Cost

  • Compliance

  • Social/cultural considerations

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Case 1: Susan. Avoiding Surgery, Hormones

  • 33 yo G3P3 with monthly HMB, anemia

  • Was offered surgery (ablation/hysterectomy, but is wary; seeking a second opinion)

  • Strong family history of breast cancer (mother and sister); wants to avoid hormone use

  • Husband has had a vasectomy

  • No history of surgery, illness, normal pelvic exam

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  • What would be the most appropriate option for her to consider?

    • She should proceed with surgical management

    • Medroxyprogesterone acetate

    • Tranexamic acid

    • Levonorgestrel IUD

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Case 2: Celeste. A smoker with no need for contraception

  • 35 yo G2P2 with monthly HMB

  • Does not want to be pregnant at this time

  • History of acne treated with isotretinoin

  • Smokes half a pack per day

  • Hx/PEX otherwise unremarkable

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  • What is best option

    • She should proceed with surgical management

    • Medroxyprogesterone acetate

    • Tranexamic acid

    • Levonorgestrel IUD

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Case 3: Celia

  • 20 yo G0P0 complains of HMB

  • Not sexually active currently or in the bpast, but is dating the same man for the past 6 months

  • No other menstrual problems or complaints

  • PMHx: Unremarkable

  • PEX: Normal

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Would you advise Celia to consider…

  • OCPs. She can use contraception even if she isn’t currently sexually active.

  • Levonorgestrel IUS; effective treatment for pregnancy prevention and HMB.

  • Tranexamic acid. It is highly effective for the treatment of HMB, but does not provide contraception.

  • NSAIDs. Efficacy is not optimal, but they are readily available OTC and may provide some benefit.

  • All of the above.

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Hemostatic disorders

  • Systemic hemostatic disorders can be either inherited, acquired or iatrogenic.  Which of the following inherited disorders is the most common in adolescents with HMB?

    • ITP / TTP

    • Von Willebrand's Disease

    • Hemophilia

    • Endometrial hemostatic dysfunction

Conclusions l.jpg

  • Cyclic HMB is common and disruptive to life of many women

  • --Most cyclic HMB can be medically managed

  • --Several progestin dominant formulations are available for management

  • --An FDA-approved nonhormonal option is now available