Comprehensive Gynecology 12th Ed: Abnormal Uterine Bleeding

Abnormal Uterine Bleeding Take many forms

1. Infrequent episodes2. Excessive flow3. Prolonged duration of menses4. Intermenstrual bleeding.

Alterations in the pattern or volume of blood flow of menses are among the most common health concerns of women.

Infrequent uterine bleeding OLIGOMENORRHEA

Intervals between bleeding episodes vary from 35 days to 6 months

AMENORRHEA No menses for at least 6 months

Normal menstrual flow Mean interval between menses: 28 days (7 days)

Abnormal if bleeding occurs at intervals of 21 days or less Mean duration of menstrual flow is 4 days

Bleeding for longer than 7 days is abnormally prolonged (MENORRHAGIA)

It is useful to document the duration and frequency of menstrual flow with the use of Menstrual Diary Cards It is difficult to determine the amount of menstrual blood loss (MBL) by

subjective means. Several studies have shown that there is poor correlation between

subjective judgment and objective measurement of MBL. Subjective methods are used in predicting blood loss

1. Pictorial Bleeding Assessment Chart2. Alkaline Hematic Method

More accurate method Measures Hematin

Average menstrual blood loss is 35 mL Total volume is twice this amount

Being made up of endometrial tissue exudate Amount of MBL increases with parity but not age in the absence of

disease MENORRHAGIA

MBL of 80 mL or greater Occurs in 9% to 14% of women

CAUSES Causes of abnormal bleeding can be divided into

1. Organic Causes2. Dysfunctional (or hormonally related)

Dysfunctional Uterine Bleeding (DUB) Further divided into

a) Anovulatory Bleedingb) Ovulatory Bleeding

ORGANIC CAUSES Subdivided into

a) Systemic Diseaseb) Reproductive Tract Disease.

Systemic Disease Particularly disorders of blood coagulation such as von Willebrand disease

and Prothrombin Deficiency Initially present as abnormal uterine bleeding Other disorders that produce platelet deficiency, such as Leukemia, Severe

Sepsis, Idiopathic Thrombocytopenic Purpura, and Hypersplenism can also cause excessive bleeding.

Routine screening for coagulation defects is mainly indicated for the adolescent who has prolonged heavy menses beginning at menarche, unless otherwise indicated by clinical signs such as petechiae or ecchymosis.

Claessens and Cowell: Coagulation disorders are found in Approximately 20% of adolescent girls who require hospitalization for

abnormal uterine bleeding. Present in approximately 25% of those whose hemoglobin levels fall

below 10 g/100 mL One third of those who require transfusion 50% of those whose severe menorrhagia occurred at the time of the

first menstrual period Falcone and associates: Indicated that a coagulation disorder was found in

only 5% of adolescents hospitalized for heavy bleeding. Both studies indicated that the likelihood of a blood disorder in adolescents

with heavy menses is sufficiently high that all adolescents should be evaluated to determine whether a coagulopathy is present.

In the adult, abnormal bleeding may be encountered frequently in women receiving anticoagulation for a variety of medical disorders Pattern of bleeding is usually menorrhagia but abnormal intracycle

bleeding also occurs. Any other chronic systemic diseases can result an abnormal bleeding

Include hepatitis, renal disease, and cardiac disease, as well as coronary vascular disorders

Mechanism is usually anovulation related to hypothalamic causes and/or problems with estrogen metabolism.

Endocrine disorders may lead to abnormal bleeding Include disorders of hormones such as thyroid, prolactin (PRL), and

cortisol

REPRODUCTIVE TRACT DISEASE Most common causes of abnormal uterine bleeding in women of reproductive

age are accidents of pregnancy Such as Threatened, Incomplete, or Missed Abortion and Ectopic

Pregnancy. Trophoblastic Disease must be considered in the differential diagnosis of

abnormal bleeding in any woman who has had a recent pregnancy Sensitive b-Human Chorionic Gonadotropin (β-hCG) assay should be

performed as part of the diagnostic evaluation. Any malignancy of the genital tract, particularly Endometrial and Cervical

Cancer, may present as abnormal bleeding. Less commonly, Vaginal, Vulvar, and Fallopian Tube Cancer may produce

abnormal bleeding Estrogen-producing Ovarian Tumors may become manifest by abnormal

uterine bleeding. Granulosa Theca Cell Tumors may present with excessive uterine

bleeding. Infection of the upper genital tract, particularly Endometritis

May present as prolonged menses Episodic intermenstrual spotting is a more common symptom.

Endometriosis May also result in abnormal bleeding Frequently presents as premenstrual spotting Relate to the location of the endometriosis implants.

Anatomic uterine abnormalities such as Submucous Myomas, Endometrial Polyps, and Adenomyosis frequently produce symptoms of prolonged and excessive regular uterine bleeding Secondary to abnormal vasculature and blood flow, as well as

increased inflammatory changes. Cervical lesions such as Erosions, Polyps, and Cervicitis

May cause irregular bleeding, particularly postcoital spotting Usually be diagnosed by visualization of the cervix

Traumatic vaginal lesions, severe vaginal infections, and foreign bodies have been associated with abnormal bleeding.

Foreign bodies in the uterus, such as an Intrauterine Device (IUD), frequently produce abnormal uterine bleeding.

Iatrogenic causes include Oral and injectable steroids such as those used for contraception

and hormonal replacement or for the management of dysmenorrhea, hirsutism, acne, or endometriosis.

Tranquilizers and other psychotropic drugs May interfere with the neurotransmitters responsible for

releasing and inhibiting hypothalamic hormones, thus causing anovulation and abnormal bleeding.

DYSFUNCTIONAL CAUSES After organic, systemic, and iatrogenic causes for the abnormal bleeding have

been ruled out, the diagnosis of DUB can be made Two types of DUB

a) Anovulatoryb) Ovulatory

Predominant cause of DUB in the postmenarchal and premenopausal years is anovulation secondary to alterations in neuroendocrinologic function

Anovulatory DUB There is continuous estradiol production without corpus luteum formation and

progesterone production Steady state of estrogen stimulation leads to a continuously proliferating

endometrium, which may outgrow its blood supply or lose nutrients with varying degrees of necrosis

Uniform slough to the basalis layer does not occur which produces excessive uterine blood flow

Occurs most commonly during the extremes of reproductive life in the first few years after menarche and during perimenopause.

Adolescent: Cause of the anovulation is an immaturity of the hypothalamic-pituitary ovarian (HPO) axis and failure of positive feedback of estradiol to cause a luteinizing hormone (LH) surge

Perimenopausal: a lack of synchronization between the components of the HPO axis occurs as the woman approaches ovarian failure.

Pattern of anovulatory bleeding may be oligomenorrhea, menometrorrhagia, metrorrhagia, or menorrhagia

Different patterns of bleeding occur within a distinct entity of anovulatory DUB is related to variations in the integrity of the endometrium and its support structure.

Up to 20% of women reporting normal menses may also be anovulating Pattern of Ovulatory DUB is mainly that of menorrhagia. Causes of Anovulatory DUB

Extremes of reproductive life

By: Rem Alfelor Page 1 of 6

Women in their reproductive years: Frequently because of polycystic ovary syndrome (PCOS),

Suggested by other symptoms and signs, such as acne, hirsutism, and increased body weight

Hypothalamic dysfunction which could have no known cause or be related to weight loss, severe exercise, stress, or drug use.

Abnormalities of other (nonreproductive) hormones can lead to anovulatory DUB Not considered to be DUB but are closely related Lead to anovulatory bleeding Most common hormones involved are thyroid hormone, prolactin,

and cortisol. Hypothyroidism

Elevated thyroid stimulating hormone (TSH) level can lead to anovulatory bleeding.

Unexplained causes of ovulatory DUB (see later) may also be explained by subtle hypothyroidism.

Hyperprolactinemia PRL level >20 ng/mL can also lead to anovulatory bleeding, as

can hypercortisolism Cushing’s syndrome is rare

May be considered only if other signs are present e.g., obesity, moon facies, buffalo hump, striae, weakness

TSH and PRL assays should be part of the normal workup.

Ovulatory Dysfunctional Uterine Bleeding Women who present with menorrhagia without causes such as uterine

lesions, polyps, fibroids It is important to understand how menstrual bleeding ceases each month to

appreciate what can go wrong in ovulatory DUB. Primary line of defense is a platelet plug

Followed by uterine contractility Largely mediated by Prostaglandin F2α (PGF2α) prolonged and heavy bleeding can occur with abnormalities of

the platelet plug and/or inadequate uterine levels of PGF2a women have excessive uterine production of prostacyclin, a vasodilatory prostaglandin that opposes platelet adhesion and may also interfere with uterine contractility

Deficiency of uterine PGF2α or excessive production of PGE (another vasodilatory prostaglandin) may also explain ovulatory DUB Ratio of PGF2a/PGE correlates inversely with menstrual blood

loss Other uterine factors affecting blood flow, such as the Endothelins and

Vascular Endothelial Growth Factor, which controls blood vessel formation, may be abnormal in some women with ovulatory DUB.

DIAGNOSTIC APPROACH It is essential to take a thorough history of frequency, duration, and amount

of bleeding Inquire whether and when the menstrual pattern has changed

Extremely important for determining whether the menstrual abnormality is Polymenorrhea, Menorrhagia (Hypermenorrhea), Metorrhagia, Menometorrhagia, or Intermenstrual Bleeding.

History and physical examination provide clues about the diagnosis of PCOS and other disorders.

Providing the woman with a calendar to record her bleeding episodes is helpful way to characterize definitively the bleeding episodes

Objective criteria should be used to determine if menorrhagia (blood loss>80 mL) is present. Direct measurement of MBL is not generally possible Indirect assessment by measurement of hemoglobin concentration,

serum iron levels, and serum ferritin levels is useful Serum Ferritin Level provides a valid indirect assessment of

iron stores in the bone marrow Additional useful laboratory tests include

Sensitive β-hCG level determination Sensitive TSH assay PRL If PCOS is suspected, Androgen Level measurements may be

considered, but are not necessary. For adolescent girls, as well as older women with systemic disease, a

Coagulation Profile should be obtained to rule out a coagulation defect.

If the woman has regular cycles, it is important to determine whether she is ovulating Ovulatory DUB displays a pattern of repetition with heavy bleeding. If bleeding is very irregular, it may be difficult to determine the phase

of the cycle to document ovulatory function by means of serum progesterone level determination or other methods Endometrial biopsy may be indicated If obtained at the onset of bleeding, will show secretory

changes Transvaginal ultrasound can be helpful in ruling out pathology and helping to

guide the need for endometrial biopsy. Endometrial biopsy

Women who are older (>35 years) and/or have a long history of excessive bleeding

Endometrial lining > 8 mm has a greater sensitivity for picking up endometrial pathology.

If bleeding has been prolonged and an ultrasound endometrial thickening is < 4 mm, there is little benefit for a biopsy in this setting

Biopsy at the time of bleeding can also help determine whether the bleeding is caused by ovulatory function if it reveals a secretory endometrium.

It is often valuable to assay the SHG level in women with menorrhagia. To rule out an intracavity lesion before ascribing the diagnosis to

ovulatory DUB Saline or sterile water (1015 mL) is usually introduced through the

cervix with an insemination catheter, or with a special Hysterosalpingography (HSG) catheter that has a balloon for inflation in the cervical canal, allowing continuous infusion. If this is not available, HSG may be ordered.

Hysteroscopy Excellent diagnostic technique Has the potential advantage of being able to treat the abnormality at

the same time such as removal of a polyp It is not cost-effective as a diagnostic test if it cannot be carried out in

an office setting. Can be performed in the office, with or without local anesthesia More accurate diagnostic procedure than a dilation and curettage

(D&C) D&C

Blind technique Does not always detect focal lesions

Apart from an SHG or similar technique to rule out lesions before a diagnosis of ovulatory DUB is made in some women presenting with menorrhagia A subtle hypothyroidism can also be found. If this is found, it is strictly

not ovulatory DUB. A third-generation ultrasensitive TSH assay should be

performed and elevations should be assessed further Coagulation defects can also present in this setting

Studies have found a fairly high prevalence of coagulation disorders in women presenting with menorrhagia.

Most abnormalities are platelet-related Single most common abnormality is a form of von Willebrand

disease Prevalence of von Willebrand disease is 13% in women with

menorrhagia. von Willebrand factor is responsible for proper platelet

adhesion and protects against coagulant factor degradation. History is key before a comprehensive

Hematologic workup is undertaken History of menorrhagia Family history of bleeding Epistaxis Bruising Gum bleeding Postpartum hemorrhage Surgical bleeding

In the absence of these clues, a comprehensive workup is probably unnecessary at outset but should be considered in cases refractory to treatment

Hematologist should be consulted. Treatment involves a variety of options, including:

a) Oral contraceptives for milder cases Levonorgestrel Releasing Intrauterine System

(Mirena IUS) Tranexamic Acid, 1 g every 6 hours during

menses Desmopressin (DDAVP) intranasally, one puff

per nostril for the first 3 days of mensesTREATMENT In the absence of an organic cause for excessive uterine bleeding, it is

preferable to use medical instead of surgical treatment, especially if the woman desires to retain her uterus for future childbearing or will be undergoing natural menopause within a short time.

Includes: a) Estrogensb) Progestogen (Systemic Or Local)c) Nonsteroidal Anti-Inflammatory Drugs (Nsaids)d) Anti-Fibrinolytic Agentse) Danazolf) Gonadotropin-Releasing Hormone (Gnrh) Agonists

Type of treatment depends on whether it is used to stop an acute heavy bleeding episode or is given to reduce the amount of MBL in subsequent menstrual cycles.

Before instituting long-term treatment, definitive diagnosis is required and should be made on the basis of hysteroscopy, sonohysterography, or directed endometrial biopsies, if indicated, with definitive treatment determined by the diagnosis.

By: Rem Alfelor Page 2 of 6

Anovulatory Dysfunctional Uterine Bleeding In adolescents, after ruling out coagulation disorders, the main direction of

therapy is to temporize because with time and maturity of the HPO axis, the problem will be corrected Cyclic progestogen: Medroxyprogesterone Acetate

10 mg for 10 days each month for a few months All that is needed to produce reliable and controlled menstrual

cycles. May be continued for up to 6 months with the situation

reevaluated thereafter Oral Contraceptive (OC)

May not be necessary and does not allow the HPO to mature on its own.

If the problem persists beyond 6 months, OCs may be an option in that the condition may be more chronic.

In the perimenopausal woman who has dysregulation of the HPO axis, there is much variability and unpredictability of cycles because the HPO axis is in flux, moving toward ovarian failure Most of the bleeding in this setting is caused by anovulation,

occasional ovulation can occur, with or without a normal luteal phase, which is highly variable and erratic

More efficient to use a Low-Dose (20-mg) OC pill (OCP) in a nonsmoking woman. Progestogens used cyclically

Preventing endometrial tissue from building up because of anovulation will help the endometrium but will not reliably control bleeding because of the unpredictability of the hormonal situation.

During reproductive life, chronic anovulatory DUB, after a careful workup Primarily caused by hypothalamic dysfunction leading to anovulation

or PCOS. OCPs work well in this setting Alternative is Cyclic Progestogens Women may also wish to conceive, in which case ovulation induction

is indicated.

Ovulatory Dysfunctional Uterine Bleeding For women with menorrhagia for whom there is no known cause and

anatomic lesions have been ruled out, the aim of therapy is to reduce the amount of excessive bleeding

Some women with ovulatory DUB have abnormal prostaglandin production and some have alterations of endometrial blood flow.

Options for treatment to reduce blood loss includea) More prolonged regimen of Progestogens (3 weeks each month)

Shorter cyclic therapy does not work here Doses in excess of 10 mg daily of Medroxyprogesterone

Acetate (MPA) have been used Large doses can cause side effects and weight gain

when used for several months and may not be necessary.

OCPs will reduce the blood loss by 50% in women with ovulatory DUB.

b) Use of the Levonorgestrel IUS Menorrhagia can be substantially reduced

It should be noted that in ovulatory DUB, although all obvious lesions have been ruled out, some anatomic abnormalities cannot be easily diagnosed. These include endometriosis and Adenomyosis, although this might be

improved with imaging. Thus, other options also have to be considered for reducing blood

loss. Local progestogen exposure

Progesterone-Releasing IUD Effective for the treatment of women with ovulatory DUB This device needs to be reinserted annually because of the

rapid diffusion of progesterone through polysiloxane No longer available

Levonorgestrel-Releasing Intrauterine System (LNG-IUS) Effective duration of action of more than 5 years At the end of 3 months, it caused an average 80% reduction in

MBL, which increased to 100% at the end of 1 year Reduction in MBL is significantly greater than that achieved

with an antifibrinolytic agent or a prostaglandin synthetase inhibitor

Effective in increasing hemoglobin levels, decreasing dysmenorrhea, and reducing blood loss caused by fibroids and Adenomyosis.

Nonsteroidal Anti-inflammatory Drugs Prostaglandin synthetase inhibitors that inhibit the biosynthesis of the cyclic

endoperoxides, which convert arachidonic acid to prostaglandins These agents block the action of prostaglandins by interfering directly at their

receptor sites. To decrease bleeding of the endometrium, it would be ideal to block

selectively the synthesis of prostacyclin alone, without decreasing thromboxane formation, because the latter increases platelet aggregation

All NSAIDs are cyclooxygenase inhibitors and thus block the formation of both thromboxane and the prostacyclin pathway

Have been shown to reduce MBL, primarily in women who ovulate Administered during menses to groups of women with menorrhagia and

ovulatory DUB and have been found to reduce the mean MBL by approximately 20% to 50% Mefenamic Acid (500 mg, three times daily) Ibuprofen (400 mg, three times daily) Meclofenamate Sodium (100 mg, three times daily) Naproxen Sodium (275 mg, every 6 hours after a loading dose of 550

mg) Usually given for the first 3 days of menses or throughout the bleeding

episode. Have similar levels of effectiveness. Not all women treated with these agents have reduction in blood flow, but

those without a decrease usually had only a mildly increased amount of MBL Greatest amount of MBL reduction occurs in women with the greatest

pretreatment blood loss Fraser and coworkers: treatment of menorrhagia with Mefenamic Acid in for

longer than 1 year results in a significantly sustained reduction in amounts of MBL and a significant increase in serum ferritin levels Can be used for long-term treatment because side effects, mainly

gastrointestinal (GI), are mild with this intermittent therapy. Can also be given in combination with OCs or Progestins approach,

Reduction in MBL can be achieved more effectively than with the use of any of these agents alone.

Anti-fibrinolytic Agentsa) Ɛ-Aminocaproic Acid (EACA)b) Tranexamic Acid (AMCA)c) Para-Aminomethyl Benzoic Acid (PAMBA) Potent inhibitors of fibrinolysis and have therefore been used in the of

various hemorrhagic conditions Nilsson and Rybo: Compared the effect on blood loss of EACA, AMCA, and

oral contraceptives in women with EACA 18 g/day for 3 days and then 12, 9, 6, and 3 g daily on

successive days total dose was always at least 48 g

AMCA 6 g/day for 3 days followed by 4, 3, 2, and 1 g/day on successive days total dose of at least 22 g

Significant reduction in blood loss after treatment with EACA, AMCA, and OCs

Use of each of these agents resulted in approximately a 50% \ reduction in MBL

The greatest reduction in blood loss with anti-fibrinolytic therapy occurred in women who exhibited the greatest MBL.

Preston and colleagues: Compared the effects of 4 g of AMCA daily for 4 days each cycle with 10 mg of norethindrone for 7 days each cycle in a group of women with ovulatory menorrhagia with a mean MBL of 175 mL. AMCA reduced MBL by 45% 20% increase with Norethindrone Side effects of this class of drugs, in decreasing order of frequency,

are nausea, dizziness, diarrhea, headaches, abdominal pain, and allergic manifestations. Much more common with EACA than with AMCA. Other

investigators have compared the use of AMCA with placebo in double-blind studies

Found no significant differences in the occurrence of side effects. Renal failure and pregnancy are contraindications to the use of Anti-

fibrinolytic agents. Clearly produce a reduction in blood loss May be used as therapy for women with menorrhagia who ovulate. Use is

somewhat limited by side effects Mainly GI side effects and can be minimized by reducing the dose and limiting

therapy to the first 3 days of bleeding As with NSAIDS, they are best combined with another agent, such as oral

contraceptives, for a greater effect on MBL reduction.

Androgenic Steroids (Danazol)DANAZOL Has been used by several investigators for the treatment of menorrhagia. Doses of 200 and 400 mg daily given over 12 weeks after careful

pretreatment observation and evaluation. MBL was markedly reduced in these studies from more than 200 to less than

25 mL There was an increased interval between bleeding episodes Most common side effects are 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

Some women may ovulate when receiving this dose of Danazol Further reduction to 100 mg daily did not effectively reduce MBL in most

women. Although Danazol is effective, it is also expensive and has moderate side

effects. Dockeray and associates: Women with DUB

By: Rem Alfelor Page 3 of 6

Danazol was more effective in reducing MBL, 60% compared with 20% for Mefenamic Acid

Adverse side effects were more severe with Danazol and occurred in 75% of patients, compared with side effects in only 30% of patients treated with Mefenamic Acid

Cochrane review: Danazol appears to be more effective than placebo, oral

progestogens, oral contraceptives, and NSAIDs. However, compared with NSAIDs, the side effects of weight gain and skin problems were sevenfold and fourfold greater when compared with Progestogens.

Gonadotropin-Releasing Hormone Agonists Inhibit ovarian steroid production Daily administration of a GnRH agonist for 3 months markedly reduced MBL

from 100 to 200 mL per cycle to 0 to 30 mL per cycle. Unfortunately, after therapy was discontinued, blood loss returned to

pretreatment levels Because of the expense and side effects of these agents, their use for

menorrhagia caused by ovulatory DUB is limited to women with severe MBL who fail to respond to other methods of medical management and wish to retain their childbearing capacity.

Use of an Estrogen and/or Progestin (add-back therapy) together with the agonist will help prevent bone loss.

MANAGEMENT OF ACUTE BLEEDING In women who are bleeding very heavily and are hemodynamically unstable,

the quickest way to stop acute bleeding is with a Curettage Should also be the preferred approach for older women and those with

medical risk factors for whom high-dose hormonal therapy might pose a great risk.

PHARMACOLOGIC AGENTS To stop acute bleeding that does not require curettage; the most effective

regimen involves High-Dose Estrogen. This treatment, aimed at stopping acute bleeding, is diagnosis-independent

and is merely a temporary measure.Estrogens Rationale for treatment of DUB is based on the fact that estrogen in

pharmacologic doses causes rapid growth of the endometrium. This is for the acute management of abnormal bleeding Bleeding those results from most causes of DUB will respond to this therapy

because a rapid growth of endometrial tissue occurs over the denuded and raw epithelial surfaces Effect is independent of the cause of abnormal bleeding.

To control an acute bleeding episode: Use of oral conjugated Equine Estrogen (CEE) 10 mg/day, in four divided doses, is a therapeutic regimen that has been found to be clinically useful In addition to the rapid growth mechanism of action, these large doses

of CEE may alter platelet activity, thus promoting platelet adhesiveness.

Livio and coworkers: Reported that 6 hours after infusion of an average dose of 30 mg of CEE to individuals with a prolonged bleeding time caused by renal failure, the bleeding time was significantly shortened Measurements of various clotting factors were unchanged after CEE

infusion. Acute bleeding from most causes is usually controlled, but if bleeding does

not decrease within the first 24 hours, consideration must be given to an organic cause, e.g., accident of pregnancy should be considered, and curettage be considered.

IV administration of Estrogen is also effective in the acute treatment of menorrhagia.

DeVore and associates: Significantly greater percentage of women had cessation of bleeding 2

hours after the second of two 25-mg doses of CEE was administered IV, 3 hours apart.

No significant difference in cessation of bleeding between women administered Estrogen and those given a placebo 3 hours after the first infusion

At least several hours are required to induce mitotic activity and growth of the endometrium, whether the Estrogen is administered orally or parenterally

IV Estrogen therapy accompanied by its rapid metabolic clearance does not appear to offer a significant advantage compared with the same dose of Estrogen given orally

If IV therapy is chosen, it usually requires that women remain in the office or clinical setting for 4 to 6 hours to receive at least a second dose.

Estrogen therapy reduces the amount of uterine bleeding within the first 24 hours after treatment is initiated.

Because most women with an acute heavy bleeding episode bleed because of anovulation, Progestin treatment is also required

After bleeding has ceased, oral Estrogen therapy is continued at the same dosage and a Progestin, usually MPA, 10 mg once daily, is added.

Both hormones are administered for another 7-10 days, after which treatment is stopped to allow withdrawal bleeding, which may have an increased amount of flow but is rarely prolonged.

After the withdrawal bleeding episode, one of several other treatment modalities should be used. Before instituting long-term treatment, a definitive diagnosis should be

made after reviewing the endometrial histology. Definitive treatment should be based on these findings.

OC’s are usually the best long-term treatment. More convenient method to stop acute bleeding than the sequential

high-dose Estrogen-Progestin regimen is the use of a combination oral contraceptive containing both estrogen and progestin.

Four tablets of an Oral Contraceptive containing 50 mg of Estrogen taken every 24 hours in divided doses will usually provide sufficient Estrogen to stop acute bleeding and simultaneously provide Progestin.

Treatment is continued for at least 1 week after the bleeding stops. This is successful and convenient, and is thus the preferred method of

some clinicians. Found not to be as effective as of high doses of CEE.

Combined use of estrogen and progestin does not cause as rapid endometrial growth as estrogen alone, because the progestin decreases the synthesis of estrogen receptors and increases estradiol dehydrogenase in the endometrial cell, thus inhibiting the growth-promoting action of estrogen.

High-dose estrogen, even for a short course, may be contraindicated for some women Those with prior thrombosis Certain rheumatologic diseases Estrogen responsive cancer Options are therapy with Progestogen Alone given continuously or

intermittently Invasive Curettage

Remains the fastest way to stop acute bleeding Should be used in women who are volume-depleted and severely

anemic (hemodynamically unstable). When ultrasound is available

It is more logical to use Estrogen therapy if there is prolonged heavy bleeding in the setting of a thin endometrium (<5-mm stripe)

If the endometrium is thick (>10 to 12 mm), or if an anatomic finding is suspected, Curettage should be considered

Unless bleeding is extremely heavy (where Estrogen Therapy is preferred), Progestogens may be used initially and will help by organizing the endometrium

In the setting of a thickened irregular endometrium, if curettage is not performed, an endometrial biopsy should be obtained.

ProgestogensProgestogens Not only stop endometrial growth but also support and organize the

endometrium so that an organized slough occurs after their withdrawal. In the absence of progesterone, erratic unorganized breakdown of the

endometrium occurs. With progestogen treatment, an organized slough to the basalis layer allows a

rapid cessation of bleeding Stimulate Arachidonic Acid formation in the endometrium, increasing the

PGF2a/PGE ratio. There is no evidence that progestogen will stop acute bleeding. After stabilization of the endometrium occurs (2 to 3 days), bleeding slows

down and eventually stops As initial therapy, a regimen of progestogen only may be appropriate,

but only for those with less significant acute bleeding who do not require immediate cessation of bleeding

Administered actively, do not stop bleeding but may slow it down as organization of the tissue occurs.

Higher doses of Norethindrone, however, which have been suggested to stop bleeding more acutely, may be efficacious on the basis of some conversion to Ethinyl Estradiol Mimicking the use of a low-dose OCP

Mainstay of progestogen therapy is opposing the effects of estrogen in anovulatory women.

For women with a history of bothersome Menometorrhagia, it is advisable to use intermittent Progestogens for several months or an OC.

MPA, 10 mg/day for 10 days each month, is a successful therapeutic regimen that produces regular withdrawal bleeding in women with adequate amounts of endogenous Estrogen to cause endometrial growth. 19-Norprogestogens, such as Norethindrone or Norethindrone

Acetate (2.5 to 5 mg) may be used in the same regimen

By: Rem Alfelor Page 4 of 6

More androgenic progestogens are less favorable for metabolic parameters High-Density Lipoprotein [HDL] Cholesterol Carbohydrate Tolerance

Short term cyclic therapy is considered to be safe.

SURGICAL THERAPYDilation and Curettage Performance can be diagnostic and is therapeutic for the immediate

management of severe bleeding. For women with markedly excessive uterine bleeding who may be

hypovolemic, D&C is the quickest way to stop acute bleeding. Treatment of choice in women who suffer from hypovolemia. May be preferred as an approach to stop an acute bleeding episode in

women older than 35 when the incidence of pathologic findings increases. Use of D&C for the treatment of DUB has been reported to be curative only

rarely. Temporary cure of the problem may occur in some women with chronic

anovulation, because the curettage removes much of the hyperplastic endometrium The underlying pathophysiologic cause is unchanged

Not proved useful for the treatment of women who ovulate and have menorrhagia.

Nilsson and Rybo: Shown that more than 1 month after the D&C, there was no difference or an increase in MBL in women with menorrhagia who ovulate. D&C is only indicated for women with acute bleeding resulting in

hypovolemia and for older women who are at higher risk of having endometrial neoplasia.

All other women, after having an endometrial biopsy, sonohysteroscopy, or diagnostic hysteroscopy to rule out organic disease, are best treated with medical therapy without D&C.

Endometrial Ablation Abnormal bleeding may be treated by endometrial ablation (EA) if medical

therapy is not effective. Exceptions are women who have very large uteri caused by fibroids or

abnormal pathology, such as endometrial hyperplasia or cancer. Alternative to hysterectomy or to the use of the Levonorgestrel IUS, which is

also highly effective Laser-based approaches were largely replaced with Resectoscopic

Techniques to resect, vaporize, or electrodessicate the endometrium Most commonly nonresectoscopic devices have been approved by the U.S.

Food and Drug Administration (FDA) for this type of treatment. Resectoscopic EA

Usually carried out with a loop electrode, roller ball, or grooved or spiked electrode to vaporize the endometrium.

Hysteroscopic Surgical Techniques Have the advantage of dealing definitively with associated pathology

(e.g., polyps, submucous fibroids) Require greater surgical skill Have longer procedure times compared with nonresectoscopic

methods. Various nonresectoscopic methods are given in Table 37-2 which lists the

success rates and limitations based on anatomy.

Most systems, except the Hydro Therm Ablator are carried out without hysteroscopic monitoring.

Cryotherapy may be performed in approximately 10 minutes using a 4.5-mm disposable cryoprobe (HER option) which is moved from one uterine cornual recess to the other.

Hydro Therm Ablator Uses heated normal saline delivered through a 7.8-mm sheath Uterus is distended and causes a closed circuit process, heating the

saline to 90°C and maintaining this temperature for 10 minutes, followed by a 1min cooling process

Closed system is automated to shut down if there is 10 mL or more leakage of fluid via the cervix or fallopian tubes.

Microwave Endometrial Ablation Carried out with an 8- mm reusable or disposable probe. Once the port is inserted into the fundus, transmission of endometrial

tissue temperature is available, and the microwave system is activated when the tissue temperature is 30° C.

Movement within the uterus of the microwave probe allows endometrial destruct to occur within 2-4 mins.

Novasure Radiofrequency Electricity System

Uses a 7.2-mm probe with a bipolar gold mesh electrode that opens to conform to the shape of the uterus

Fixed volume of CO2 is injected and monitored to confirm the integrity of the endometrial cavity.

Suction is carried out during the application of radiofrequency energy to remove debris stream.

Vaporization and desiccation is carried out over 80 to 90 secs. Thermachoice System

Uses a balloon-tipped catheter (5.5 mm) through which heated 5% dextrose in water is injected up to a pressure of 160-HD 160-1BO mm Hg

Controller unit heats the fluid and monitors the pressure and treatment time.

Destruction of the endometrium is carried out in approximately 8 mins. Prior to any EA techniques, Endometrial Sampling is required as part of the

workup evaluation of the woman with abnormal bleeding Uterine cavity should be evaluated for size and presence of pathology

that may limit come of the techniques. With the possible exception of the use of the NovaSure system, a review by

Sowter has confirmed the benefit of pretreatment with Danazol or a GnRH Agonist before an ablation

More successful when a thin endometrial lining is present. Most systems typically treat to a depth of 4-6 mm.

In the evaluation, it is important to note that there is no thinning of the myometrium from some other cause, such as prior surgery, particularly with the microwave method Myometrium should be no less than 10 mm anywhere in the uterus.

Most methods of EA, with the exception of the Her option, may be beneficial in treating submucous fibroids up to 3 cm in size, with the strongest data coming from the use of the Microwave and Thermachoice Systems

Complications are infrequent with EA if adherence occurs to the manufacturer’s guidelines. Cervical lacerations and perforations occur more commonly with

endometrial resection. Lower genital tract burns may occur, as well as endometritis (1%) Syndrome of tubal pain post-EA caused by trapping of endometria at

the cornual recesses. Less likely in women with a tubal ligation.

If pregnancy occurs unexpectedly, there is a high incidence of poor outcomes, including prematurity and placenta accreta.

Most procedures can now be safely performed in an office setting with paracervical block and conscious sedation.

Although amenorrhea may not always occur (only up to 55% of the time), bleeding is significantly improved for most women.

Hysterectomy is thus avoided in 86% of women Success is slightly worse in women with a retroverted uterus.

Hysterectomy The decision to remove the uterus should be made on an individual basis and

should usually be reserved for the woman with other indications for hysterectomy, such as leiomyoma or uterine prolapse.

Should only be used to treat persistent ovulatory DUB after all medical therapy has failed and the amount of MBL has been documented to be excessive by direct measurement or abnormally low serum ferritin levels.

With increasing use of EA to treat this problem, the use of hysterectomy as therapy for ovulatory DUB should decrease.

As many as 50% of women older than 40 years with menorrhagia without uterine lesions have been treated by hysterectomy 20% of all hysterectomies in women of reproductive age are

performed for excessive uterine bleeding. Benefits of the LNG-IUS when hysterectomy or ablation is being considered. Uterine artery embolization is not particularly effective unless fibroids are the

cause of excessive bleeding. If hysterectomy is chosen, many different options are available, including

Vaginal Hysterectomy Laparoscopic-Assisted Vaginal Hysterectomy (LAVH) Laparoscopic or Supracervical Hysterectomy Laparoscopic Total Hysterectomy Abdominal Supracervical Hysterectomy

SUMMARY OF APPROACHES TO TREATMENT An important perspective is to approach the woman according to her acute

and chronic needs or short-term and long-term therapy. Acute bleeding

Necessitates immediate cessation of bleeding Requires the use of pharmacologic doses of Estrogen or Curettage;

the latter is used more liberally in older women with risk factors or in those who are hemodynamically compromised. This approach is not dependent on whether the woman is

anovulatory or ovulatory. Although estrogen will be temporarily helpful, even if there are

abnormal anatomic findings, such as fibroids, it is preferable to perform Curettage if pathology is suspected.

For less significant bleeding that warrants treatment, but not necessitating the immediate cessation of blood loss High doses of Progestogen alone may be used.

By: Rem Alfelor Page 5 of 6

It is imperative to know whether the woman is bleeding from an anovulatory or ovulatory dysfunctional state. Most women fall into the anovulatory category. In the adolescent, 10 mg of MPA, 10 days each month for at least 3

months, should be prescribed and observed carefully thereafter. Additional diagnostic studies should be performed to detect possible defects

in the coagulation process, particularly if bleeding is severe. For the woman of reproductive age, long-term therapy depends on whether

she requires contraception, induction of ovulation, or treatment of DUB alone. In the latter case, oral OCs or MPA can be administered monthly for

at least 6 months OCs and Clomiphene Citrate are used for the other indications.

For the perimenopausal woman who characteristically has fluctuating amounts of circulating estrogen Use of Cyclic Progestogen alone is frequently not curative Best treated by low-dose OCs.

Most difficult type of DUB to treat is chronic treatment of ovulatory women with menorrhagia. If anatomic abnormalities are absent, long-term treatment is necessary

to reduce MBL NSAIDs, Progestins, Oral Contraceptives, Danazol, and

GnRH analogues are all useful therapeutic modalities Combination of two or more of these agents is often required to

obviate the need for endometrial ablation or hysterectomy. LNG-IUS has become one of the most successful options.

KEY POINTS Mean amount of menstrual blood loss in one cycle in normal women was

previously reported to be approximately 35 ml but may be as much as 60 ml Average loss of 13 mg of iron

Menorrhagia occurs in 9% -14% of healthy women, and most have a normal duration of menses.

DUB can be caused by anovulation but also occurs in women who ovulate. Diagnostic tests in women with menorrhagia include

Measurement of hemoglobin Serum Iron Serum Ferritin β-hCG TSH PRL levels Endometrial Biopsy Hysteroscopy Sonohysterography Hysterosalpingography

High doses of oral or IV Estrogen will usually stop acute bleeding episodes in most cases of abnormal bleeding.

Anovulatory DUB can be treated by cyclic use of Progestins or Oral Contraceptives.

Patients with ovulatory DUB are best treated with oral contraceptives, NSAIDs (Antiprostaglandins), Danazol, or Progestins during the luteal phase or Progesterone or Progestins released locally from an IUD.

NSAIDs administered during menses reduce MBL by 20-50% in women with ovulatory DUB.

D&C should be used to stop the acute bleeding episode in patients with hypovolemia or those older than 35 years

D&C only treats the acute episode of excess uterine bleeding, not subsequent episodes.

Various endometrial ablation techniques achieve a 22-55% amenorrhea success rate at 1 year but an 86-99% satisfaction rate.

Within 4 years after endometrial ablation, approximately 25% of women so treated will have a hysterectomy.

By: Rem Alfelor Page 6 of 6