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Cruz, Rivera, Tai, Veloso. ABNORMAL UTERINE BLEEDING. Menorrhagia - menses lasting longer than 7 days or exceeding 80 mL of blood loss Metrorrhagia - intermenstrual bleeding. menometrorrhagia . hypomenorrhea - diminished flow or shortening of menses

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Menorrhagia - menses lasting longer than 7 days or exceeding 80 mL of blood loss

  • Metrorrhagia - intermenstrual bleeding.
  • menometrorrhagia.
  • hypomenorrhea - diminished flow or shortening of menses
  • Oligomenorrhea - intervallonger than 35 days (normal 28 days ± 7 days)

withdrawal bleeding refers to the predictable bleeding that often results from abrupt progestin cessation.

  • Assessment: lack of correlation between patient perception of blood loss and objective measurement
  • passing clots more than 1.1 inches in diameter and changing pads more frequently than every 3 hours

FIGO Classification system for causes of abnormal uterine bleeding in nongravidwomen of reproductive age

p polyps
P- Polyps
  • Endometrial and endocervical
  • epithelial proliferations comprise a variable vascular, glandular, and fibromuscular and connective tissue
  • often asymptomatic, but generally accepted that at least some contribute to the genesis of AUB
a adenomyosis
A- Adenomyosis
  • presence of endometrial tissue within the uterine wall (myometrium)
  • Relationship unclear
l leiomyoma
L- Leiomyoma
  • Benign fibromuscular tumors of the myometrium
  • submucosal lesions are the most likely to contribute to the genesis of AUB
m malignancy
M- Malignancy
  • Endometrial carcinoma is the most common invasive cancer of the female genital tract
  • Risks: obesity, diabetes, hypertension, infertility, unopposed estrogen stimulation
c coagulopathy
C- Coagulopathy
  • Coagulation disorders
    • von Willebrand's disease
    • prothrombin deficiency
  • Platelet deficiency
    • leukemia, severe sepsis, idiopathic thrombocytopenic purpura, and hypersplenism, can also cause excessive bleeding.
o ovulatory dysfunction
O – Ovulatory dysfunction
  • Unpredictable timing of bleeding and variable amount of flow
o ovulatory
O - Ovulatory
  • absence of predictable cyclic progesterone production from the corpus luteum every 22–35 days
  • later reproductive years: “luteal out-of-phase” events
o ovulatory1
O - Ovulatory
  • Endocrinopathies
    • polycystic ovary syndrome, hypothyroidism, hyperprolactinemia, mental stress, obesity, anorexia, weight loss, or extreme exercise such as that associated with elite, athletic training).
e endometrial
E - Endometrial
  • predictable and cyclic menstrual bleeding, and particularly when no other definable causes are identified
e endometrial1
E - Endometrial
  • deficiencies in local production of vasoconstrictors such as endothelin-1 and prostaglandin F2α; and/or,
  • accelerated lysis of endometrial clot because of excessive production of plasminogen activator
  • increased local production of prostaglandin E2 and prostacyclin (vasodilators)
e endometrial2
E - Endometrial
  • deficiencies in the molecular mechanisms of endometrial repair secondary to:
    • endometrial inflammation or infection;
    • abnormalities in the local inflammatory response; or aberrations in endometrial vasculogenesis.
i iatrogenic
I - Iatrogenic
  • Gonadal steroid therapy
    • breakthrough bleeding (BTB)
  • Systemically administered single-agent or combination gonadal steroids
    • impact the control of ovarian steroidogenesis via effects on the hypothalamus, pituitary, and/or ovary itself, and also exert a direct effect on the endometrium.
i iatrogenic1
I - Iatrogenic
  • Poor compliance
  • Use of anticonvulsants and antibiotics
  • Cigarette smoking
i iatrogenic2
I - Iatrogenic
  • Tricyclic antidepressants and phenothiazines
  • Use of anticoagulant drugs (e.g. warfarin, heparin and LMW heparin)
n not yet classified
N – Not yet classified
  • Chronic endometritis
  • Arteriovenous malformations
  • Myometrial Hypertrophy
medical treatment
Medical Treatment
  • Estrogen
  • Progestogen
  • NSAIDs
  • Anti-fibrinolytics agents
  • Danazol
  • Gonadotropin-releasing hormone (GnRH) agonists
  • Used for acute management of AUB
  • Causes rapid endometrial growth
    • Preferred if endometrial lining is <5mm
  • Oral Conjugated Equine Estrogen (CEE)
    • 10 mg/day, administered in 4 divided doses
    • May also promote platelet adhesiveness (
  • IV Estrogen
    • Several hours needed to induce mitotic activity (DeVore,
    • No great advantage to oral estrogen
estrogen and progestin
Estrogen and Progestin
  • Estrogen + progestin (high dose) after bleeding has stopped
    • Most acute heavy bleeding episodes is due to anovulation
    • Progestin addition: Medroxyprogesterone acetate (MPS) 10mg OD
    • Estrogen and Progestin are given for 7-10 days then stopped
estrogen and progestin1
Estrogen and Progestin
  • OCPs that contain estrogen and progestin
    • Four tablets of an oral contraceptive containing 50 μg of estrogen q 24 h in divided doses
    • Not as effective as high doses of CEE
  • Slows down endometrial growth by organizing and supporting endometrial tissue
    • Organized slough to basalis layer stops bleeding quickly
  • Stimulates arachidonic acid formation in endometrium
  • Opposes effects of anovulation
  • Menometrorrhagia – MPA 10mg/day for 10 days monthly
progesterone releasing iud
Progesterone-releasing IUD
  • needs to be reinserted annually
    • rapid diffusion of progesterone through polysiloxone
  • Levonorgestrol-releasing intrauterine system (LNG-IUS)
    • duration of action: more than 5 years
    • Increases hemoglobin
    • Decreases dysmenorrhea
    • Reduces blood loss secondary to fibroids and adenomyosis
    • Good alternative to hysterectomy
  • Ideal for decreased endometrial bleeding
    • Stop prostaglandin pathway
    • Allow thromboxane formation (for platelet aggregation)
  • NSAIDs blocks
    • Thromboxane formation
    • Prostaglandin pathway
  • More effective in ovulating women
  • If bleeding does not cease within 24 hours  consider curretage
  • Invasive and fast
  • For volume-depleted and anemic patients
  • Thick endometrium ( >10-12 mm)
  • Anatomic problem
antifibrinolytic agents
Antifibrinolytic Agents
  • Examples: ε-Aminocaproic acid (EACA), tranexamic acid (AMCA), and para-aminomethylbenzoicacid (PAMBA)
  • Study by Nilsson and Rybo
    • significant reduction in blood loss after treatment with EACA, AMCA, and oral contraceptives, and use of each of these agents resulted in about a 50% reduction in MBL
    • greatest reduction in blood loss with antifibrinolytic therapy occurred in women who exhibited the greatest MBL
antifibrinolytic agents1
Antifibrinolytic Agents
  • Preston et al
    • AMCA reduced MBL by 45%, but there was a 20% increase with norethindrone
    • side effects (in decreasing order of frequency): nausea, dizziness, diarrhea, headaches, abdominal pain, and allergic manifestations

*much more common with EACA than with AMCA

antifibrinolytic agents2
Antifibrinolytic Agents
  • Produce a reduction in blood loss
  • Can be used by ovulating women with menorrhagia
  • Best combined with other agents like oral contraceptives for greater effect
  • Use limited by side effects
    • Mostly GI
    • Minimized by reducing dose and use to first 3 days of bleeding
  • Contraindications: Renal failure and pregnancy
antifibrinolytic agents3
Antifibrinolytic Agents
  • Ergot – Not recommended
    • Rarely effective
    • High incidence of side effects: nausea, vertigo, abdominal cramps
    • Nilsson and Rybo no reduction in blood loss among 82 women with menorrhagia who were treated with methylergobaseimmaleate
androgenic steroids danazol
Androgenic Steroids (Danazol)
  • MBL markedly reduced in studies from more than 200 mL to less than 25 mL with increased interval between bleeding episodes
  • Most common side effects: weight gain and acne (Reduction of dosage from 400 to 200 mg daily decreased the side effects but did not alter the reduction in blood loss)
androgenic steroids danazol1
Androgenic Steroids (Danazol)
  • Dockeray et al  Danazol was more effective in reducing MBL, 60% compared with 20% for mefenamicacid but side effects were more severe with Danazoland occurred in 75% of patients
  • Appears to be more effective than placebo, progestogens, oral contraceptives and NSAIDs. However, side effects were 7x greater as compared to NSAIDS and 4x more when compared with progestogens
  • Expensive with moderate side effects
gnrh agonists
GnRH Agonists
  • Possible to inhibit ovarian steroid production with GnRHagonists (not based on any large scale studies)
  • Due to expense and side effects, use for menorrhagia caused by ovulatory DUB  limited to women with severe MBL who fail to respond to other methods of medical management and wish to retain their childbearing capacity
  • Will help prevent bone loss if used with an estrogen and/or progestin (add-back therapy)
dilatation and curettage
Dilatation and Curettage
  • Can be diagnostic and is therapeutic for immediate management of severe bleeding
  • Markedly excessive uterine bleeding with possible hypovolemia quickest way to stop acute bleeding (Treatment of choice for hypovolemia from DUB)
  • Preferred to stop acute bleeding in women older than 35 (higher incidence of pathologic findings)
  • Rarely curative for DUB
  • Temporary cure for chronic anovulation  removes hyperplastic endometrium but has no effect on underlying pathology
  • Not useful for ovulating women with menorrhagia

* Nilsson and Rybo  No difference or an in increase in MBL 1 month S/P D&C

  • Indications:
    • Acute bleeding that results in hypovolemia
    • Older women (Higher risk for endometrial neoplasia)

Otherwise: Medical therapy after ruling out organic disease via endometrial biopsy, sonohysteroscopy or diagnostic hysteroscopy

endometrial ablation
Endometrial Ablation
  • Laser photovaporization of the endometrium for menorrhagia
    • Minimum endometrial regeneration
    • Causes varying degrees of uterine contraction, scarring and adhesion formation but complications are minor and uncommon
    • Erian  56% amenorrhea, 38% reduced menses, 7% no reduction requiring 2nd treatment with good response
    • Cochrane database  preoperative GnRH agonists or danazol is beneficial
endometrial ablation1
Endometrial Ablation
  • Laser photovaporization
    • Nd-YAG laser (expensive)
    • Electrocautery by urologic resectoscope through a hysteroscope (Transcervical resection)
    • Magos et al  30% amenorrhea, 90% improvement in 1 treatment group
endometrial ablation2
Endometrial Ablation
  • Thermal destruction via electrocautery through a ball-end electrode attached to a urologic resectoscope
    • Larger contact area, better fit into cornual area and easier contact with tissue as compared to loop electrode
    • Outpatient procedure with general anesthesia
    • Preop endometrial suppresion with at least 1 month danazol, GnRH analogues or progestin
    • Paskowitz 60% decreased bleeding
    • Easier to learn and equipment less expensive
endometrial ablation3
Endometrial Ablation
  • Thermal balloon
    • Does not require pretreatment regimens or hysteroscopy training
    • Local anesthesia

Meyer et al  Thermal balloon and rollerball – 80% return to normal bleeding

endometrial ablation4
Endometrial ablation
  • VestaBlate new balloon device with a silicone inflatable electrode carrier
  • Hydrotherablator  heated free fluid system
    • Does not allow passage of fluid into fallopian tubes
    • May be used with endometrial distortions including fibroids
    • 35% amenorrhea, 87% decreased blood flow
  • Novasure  3D bipolar device and generator with suction
endometrial ablation5
Endometrial ablation
  • Microwave, Cryoablation, Photodynamic therapy
  • Becoming more popular for women with menorrhagia without uterine lesions who are unresponsive to medical therapy
  • Alternative to hysterectomy (Less cost, mortality, days in hospital)
  • For women contraindicated for hysterectomy or those with ovulatory DUB who don’t want to take medication
  • Not for those who want to maintain their reproductive capacity
endometrial ablation6
Endometrial ablation
  • Complications: fluid overload, uterine hemorrhage, uterine perforation, thermal damage to adjacent organs, and hematometria
    • When ablation extends too deep, opening up uterine vessels and exposing adjacent tissues to thermal injury
endometrial ablation7
Endometrial ablation
  • Should be restricted to women with heavy MBL in the absence of organic distress
  • Should destroy all of the endometrium but only the superficial myometrium to reduce posttreatment problems
  • Suggested that the surgeon should perform 15 supervised procedures before being credentialed
  • Decision should be made on an individual basis
  • For women with other indications for hysterectomy like leiomyomas or uterine prolapse
  • Only for persistent ovulatory DUB after all medical therapy has failed and with excessive amount of MBL by direct measurement or that causes abnormally low serum ferritin
  • Levonorgestrel releasing IUD (LNG-IUS) may be beneficial when hysterectomy/ablation are being considered
  • Uterine artery embolization  not effective unless fibroids cause excessive bleeding
approach to treatment
Approach to Treatment
  • Depends on acute and chronic needs or short-term and long-term therapy
acute bleeding
Acute bleeding
  • Requires immediate cessation
  • Pharmacologic doses of estrogen or curettage (the latter to be used more liberally in older women with risk factors or in those who are hemodynamicallycompromised)

* not dependent on whether the patient is anovulatoryor ovulatory

  • Estrogenwill be temporarily helpful, even if there are abnormal anatomic findings, such as fibroids
  • If pathology is suspected  Curettage preferable
acute bleeding1
Acute bleeding
  • After the acute episode, it is imperative to know if the patient is bleeding from an anovulatory or ovulatory “dysfunctional” state
  • Majority of women: Anovulatory
less significant bleeding
Less significant bleeding

*Warrants treatment, but not necessitating the immediate cessation of blood loss

  • High doses of progestogen alone may be used (Popular practice but no good supporting data)
for adolescents
For Adolescents
  • 10 mg of MPA for 10 days each month for at least 3 months should be prescribed with careful observation
  • Additional diagnostic studies to detect possible defects in the coagulation process, particularly if bleeding is severe
for women of reproductive age
For women of reproductive age
  • Long-term therapy depends on whether she requires contraception, induction of ovulation, or treatment of DUB alone
  • DUB alone  oral contraceptive or MPA can be administered, monthly for at least 6 months, whereas oral contraceptives and clomiphene citrate are used for the other indications
for the perimenopausal
For the perimenopausal

*Have lower amounts of circulating estrogen

  • Use of cyclic progestogen alone is frequently not curative
  • Abnormal bleeding is best treated by low-dose oral contraceptives
  • The cyclic use of CE (0.625–1.25 mg) given for 25 days, with 10 mg of MPA or another progestogen+ CE from days 15 to 25 can also be used after ruling out abnormal endometrial histologic findings
ovulatory women with menorrhagia
Ovulatory women with menorrhagia
  • A challenge to treat chronically
  • No anatomic abnormalities  need long term therapy to reduce MBL
    • NSAIDs, progestins, oral contraceptives, danazol, and GnRH analogues are all useful
    • Combination of two or more of these agents is often required to obviate the need for endometrial ablation or hysterectomy