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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 - interval longer
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 NONGRAVID WOMEN OF REPRODUCTIVE AGE
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
presence of endometrial tissue within the uterine wall (myometrium)
Relationship unclear
L- Leiomyoma
Benign fibromuscular tumors of the myometrium
submucosal lesions are the most likely to contribute to the genesis of AUB
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
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
absence of predictable cyclic progesterone production from the corpus luteum every 22–35 days
later reproductive years: “luteal out-of-phase” events
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
predictable and cyclic menstrual bleeding, and particularly when no other definable causes are identified
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 - 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
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 - Iatrogenic
Tricyclic antidepressants and phenothiazines
Use of anticoagulant drugs (e.g. warfarin, heparin and LMW heparin)
Medical Treatment
Estrogen Progestogen NSAIDs Anti-fibrinolytics agents Danazol Gonadotropin-releasing hormone
(GnRH) agonists
Estrogen
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
(Livio et.al)
Estrogen
IV Estrogen Several hours needed to induce mitotic
activity (DeVore, et.al) No great advantage to oral estrogen
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 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
Progestogen
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
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
NSAIDs
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
Curretage
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
Examples: ε-Aminocaproic acid (EACA), tranexamic acid (AMCA), and para-aminomethylbenzoic acid (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 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 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 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 methylergobase immaleate
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 (Danazol) Dockeray et al Danazol was more
effective in reducing MBL, 60% compared with 20% for mefenamic acid but side effects were more severe with Danazol and 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
Possible to inhibit ovarian steroid production with GnRH agonists (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
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)
D&C
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
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
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 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 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 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 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 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 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 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
Hysterectomy
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
Hysterectomy
Levonorgestrel releasing IUD (LNG-IUS) may be beneficial when hysterectomy/ablation are being considered
Uterine artery embolization not effective unless fibroids cause excessive 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 hemodynamically compromised)
* not dependent on whether the patient is anovulatory or ovulatory• Estrogen will be temporarily helpful, even if
there are abnormal anatomic findings, such as fibroids
• If pathology is suspected Curettage preferable
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
*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
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 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
*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
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