heavy%20menstrual%20bleeding
HEAVY MENSTRUAL BLEEDING
Heavy menstrual bleeding is prolonged (>7 days) or excessive (>10 mL) uterine bleeding occurring at regular intervals over several menstrual cycles.
It is menstrual blood loss that is excessive and interferes with patient's physical, emotional, social and quality of life.
It is also referred to as menorrhagia or hypermenorrhea.
It is a common problem in women of reproductive age that usually causes anemia.
Uterine fibroids and polyps are the most common pathology identified.

Principles of Therapy

  • Recommended for patients with no structural or histological abnormalities, or with fibroids <3 cm in diameter that did not cause deformation of the uterine cavity
  • Should include iron supplements if iron-deficiency anemia (IDA) is present secondary to heavy menstrual bleeding (HMB)

 

Pharmacotherapy

Non-Hormonal Therapies

  • Treatment of choice for patients who desire to maintain fertility and be pregnant in the near future
  • Alternative treatment for patients who do not desire hormonal therapy or those awaiting workup and definitive treatment 
  • Discontinue if no improvement in symptoms is seen after use for 3 cycles

Hemostatic Therapy

  • Antifibrinolytic agents
    • Eg Tranexamic acid
    • Competitively inhibits plasminogen activation and other factors associated with blood clotting
    • Decreases breakdown of fibrin in a preformed clot
    • Used to treat heavy menstrual bleeding (HMB) that is cyclic or has predictable timing
    • Studies showed that it reduced menstrual bleeding by 29-58% through reduction of liquefaction of clotted blood from spiral endometrial arterioles
    • High-dose Tranexamic acid may aid in reducing or stopping acute HMB
    • Does not reduce dysmenorrhea nor regulate cycles and not a contraceptive
  • Desmopressin (DDAVP)
    • Stimulates release of von Willebrand factor (VWF) from endothelial cells
    • Given to patients with type 1 and some cases of type 2 von Willebrand’s disease (VWD) with HMB
    • Not recommended in patients with type 2B VWD due to possible worsening of thrombocytopenia and thrombosis
    • Not more effective than oral contraceptives in controlling HMB
  • Coagulation factor replacement
    • Used in patients with VWD-related HMB where antifibrinolytics and DDAVP are not effective
    • VWF/factor VIII replacement therapy can be considered definitive therapy, particularly in massive hemorrhage (eg severe VWD)

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

  • Reduce prostaglandin synthesis, which is implicated in uterine bleeding and cramps
    • Cause 20-49% decrease in menstrual blood loss
    • Preferred treatment for patients with HMB and dysmenorrhea
  • Used to treat HMB that is cyclic or has predictable timing
    • Should be taken from the start of menstruation until heavy blood loss has stopped
  • Not as effective as Tranexamic acid or Danazol, but has less side effects than Danazol
  • Not recommended for patients with HMB secondary to bleeding disorders

Hormonal Therapies

  • Considered 1st-line therapy (combined with conservative medical management) if future fertility is desired but pregnancy is not wanted in the near future

Levonorgestrel-Releasing Intrauterine System (LNG-IUS)

  • 1st line of treatment for patients suitable for pharmacological therapy, provided long-term use is expected
    • Reduces bleeding by 71-96%, but full benefit may not be seen after at least 6 cycles  
    • Bleeding patterns may vary for the 1st 6 months of use
  • A small plastic device placed in the uterus that slowly releases 20 mcg/day of Levonorgestrel
  • Used for contraception, management of idiopathic HMB and as a progestogen content of hormone replacement therapy regimen   
  • Prevents proliferation of the endometrium and thickening of cervical mucus, and suppresses ovulation in some women
  • Approved for 5 years of use  
  • Preferred treatment option for long-term use or when patient opted for long-term reversible contraception
  • May be considered as a treatment option for obese women  
  • Comparable with endometrial ablation in reducing menstrual blood loss up to 24 months
    • May be considered an option before surgery
  • Most cost-effective approach in treating patients with HMB after 1 year of COC use or when COC therapy has failed

Combined Oral Contraceptives (COCs)

  • Contain estrogen and progestogen that inhibit ovulation and fertility through action on the hypothalamo-pituitary axis
    • Prevent proliferation of the endometrium
  • Used in 21-day treatment cycle followed by 7 days’ rest where breakdown and loss of endometrium occur
    • Regulate and reduce bleeding, also decrease breast pain and dysmenorrhea
  • A study showed that COCs (Ethinyl estradiol and Levonorgestrel) reduced menstrual bleeding by 43%
  • Most cost-effective approach in the 1st year of treatment for women with HMB with no pathological cause
  • Not suitable for smoking women >35 years old and women with risk factors for cardiovascular (CV) disease
  • High-dose estrogen may be used initially to treat HMB then transitioned within a few days to standard estrogen-progestin contraceptive pills  
  • Estrogen-progestin preparations may be given continuously for prevention of recurrent HMB 

Oral Progestogens

  • Eg Norethisterone, Medroxyprogesterone
  • Prevents proliferation of the endometrium  
  • Use for 7-10 days during the luteal phase of the menstrual cycle showed no effect on menstrual bleeding
    • May reduce menstrual bleeding for up to 83% after long-term use 
  • A progestin, eg Megestrol acetate, can be given to prevent recurrent HMB 
  • A case series showed premenopausal women with symptomatic uterine fibroids had an improvement in abnormal uterine bleeding with 6 months of depot Medroxyprogesterone acetate therapy

Gonadotropin-Releasing Hormone Analogue (GnRH-a)

  • Induces reversible hypogonadism secondary to deficient production of follicle stimulating hormone or luteinizing hormone (FSH or LH) that causes poor follicular development and estrogen production, anovulation, lack of progesterone production and amenorrhea
    • Reduces menstrual blood loss in the form of amenorrhea
    • When treatment is discontinued, effects are not maintained
  • May be given to patients with uterine fibroids prior to undergoing surgery, or when surgery or uterine artery embolization (UAE) is contraindicated
    • Causes reduction in fibroids’ size making surgery easier
    • May be given to patients with enlarged or distorted uterus secondary to uterine fibroids 3-4 months prior to hysterectomy or myomectomy
  • Associated with significant adverse effects (eg perimenopausal symptoms, headache, nausea), which prevent long-term use
    • Hormone replacement add-back therapy may be given to prevent undesirable effects or if GnRH use is >6 months

Ulipristal acetate

  • Ulipristal acetate is used for preoperative management of women with moderate to severe symptoms of uterine fibroids
    • Has established efficacy in the management of HMB due to fibroids with reduction of fibroid size prior to surgery
  • Patients with HMB may be offered up to 4 courses (20 months) of Ulipristal acetate if with fibroids of >3 cm in diameter and hemoglobin level of <102 g/L
  • Benign and reversible changes occur in the endometrial tissue with use of Ulipristal acetate  
  • Data showed Ulipristal acetate is non-inferior to GnRH agonist with less menopausal side effects 

Danazol

  • Synthetic androgenic steroid with anti-estrogen and antiprogestogen activity
  • Has antiproliferative effect on the endometrium and inhibitory effect on the production of gonadotropins by the pituitary gland causing anovulation 
  • Reduces menstrual bleeding by 50%
  • Associated with significant androgenic adverse effects
    • Not routinely given for the treatment of HMB

Summary of Therapeutic Effects of Drugs Used in Heavy Menstrual Bleeding (HMB)
Drugs Effects
Reduction in Blood Loss Contraception Dysmenorrhea Fertility
LNG-IUS 95% after 6 months Yes No No
Tranexamic acid 58% No No No
NSAIDs 25% No Yes No
COCs 43% Yes Yes No
Oral Progestogens 83% in long-term Yes No No
GnRH-a amenorrhea No No No
Ulipristal acetate  amenorrhea  Yes1  No  No
1Emergency contraceptive
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