DR. ARSLA MEMON

GOALS

INTRODUCTION FIGO CLASSIFICATION COMMON TERMINOLOGY APPROACH TO PATIENT INVESTIGATION MANAGEMENT OPTIONS RECOMMENDATIONS

INTRODUCTION

The normal menstrual cycle lasts 28 ± 7 days, the flow lasts 4 ± 2 days, and the average blood loss is 40 ± 20 ml, upper limit is 80 ml

Abnormal uterine bleeding (AUB) is defined as changes in frequency of menses, duration of flow or amount of blood loss.

PREVALENCE

30 percent of reproductive age women suffer from menorrhagia

Menorrhagia and uterine fibroids account for up to 75 percent of all hysterectomies.

25% surgeries are due to AUB. One national study found that

menstrual disorders were the reason for 19.1 percent of 20.1 million visits to physician offices for gynaecologic conditions over a two-year period.

TYPES OF AUB

ACUTE, CHRONIC, AND INTERMENSTRUAL AUB

Chronic AUB is defined as bleeding from the uterine corpus that is abnormal in volume, regularity, and/or timing that has been present for the majority of the last 6 months.

Acute AUB is an episode of heavy bleeding that is sufficient severity to require immediate intervention to prevent further blood loss.

Acute AUB may present in the context of

existing chronic AUB or might occur without such a background history

Intermenstrual aub

IMB occurs between clearly defined cyclic periods.

PREDICTABLE (endometrial, hormonal)

Midcycle Premenstrual UNPREDICTABLE “occur any time in

cycle and can arise from any where in lower genital tract

AUB

MIDCYCLE Usually last for 12-

72 hrs Destabilization of

endometrium due to sudden fluctuation of estradiol level

Physiological 1-2% Spotting around

ovulation

PREMENSTRUAL BLEEDING

Occur upto 10 days prior to menses

Endometrium shed early due to lack of progesterone

Often termed as luteal phase deficiency

FIGO CLASSIFICATION OF AUB FIGO) oncology staging systems are practical,

universally accepted, and aid clinicians and investigators in the guidance of research,treatment, and prognosis of gynecologic cancers .

describes the new PALM-COEIN Classification for Causes of Abnormal Bleeding

The system was developed with contributions from an international group of both clinical and nonclinical investigators from 17 countries on six continents.

Recommended standardized nomenclatures.

The classification system is stratified into nine basic categories that are arranged according to the acronym PALM-COEIN . Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia,Coagulopathy, Ovulatory Disorders, Endometrium, Iatrogenic, andNot Classified

In general, the components of the PALM group are discrete (structural) entities that are measurable visually, by use of imaging techniques, and/or by use of histopathology

While the COEIN group is related to entities that are not defined by

imaging or histopathology (nonstructural).

The categories were designed to facilitate the current or subsequent development of sub classification systems.

Polyps (AUB-P)

Polyps are categorized as being either present or absent as defined by one or a combination of ultrasound (including saline infusion sonography) and hysteroscopic imaging with or without histopathology.

Although there is no current distinction regarding the size or number of polyps, it is probably important to exclude polypoid-appearing endometrium from this category, for such an appearance may well be a variant of normal.

Adenomyosis (AUB-A)

The relationship of adenomyosis to the genesis of AUB is unclear.

criteria for diagnosing adenomyosis have traditionally been based on histopathologic evaluation of the depth of ‘‘endometrial’ tissue beneath the endometrial–myometrial interface from hysterectomy specimens, the histopathologic criteria vary substantially and the requirement to diagnose adenomyosis limited value in a clinical classification system

In this system adenomyosis is diagnosed by uterine imaging the limited access of women to MRI in the world community, it is proposed that sonographic criteria for adenomyosis comprise the minimum requirements for daignosis.

Leiomyomas (AUB-L)

Most leiomyomas (fibroids) are asymptomatic, and frequently their presence is not the cause of the complaint of AUB.

Malignancy and Premalignant Conditions (AUB-M

Although relatively uncommon in reproductive-aged women, atypical hyperplasia and malignancy are important potential cause of AUB.

This diagnosis must be considered in any woman in the reproductive years and especially where there may be predisposing factors such as obesity or a history of chronic anovulation.

Consequently, when an investigation of a women in her Reproductive years with AUB identifies a premalignant hyperplastic or malignant process, it would be classified as AUB-M .

(AUB-C)

The term coagulopathy is used to encompass the spectrum of systemic disorders of hemostasis that may cause AUB.

13% of women with heavy menstrual bleeding (HMB) have biochemically detectable systemic disorders of hemostasis, most often von Willebrand disease ..

(AUB-O)

Ovulatory dysfunction can contribute to the genesis of AUB, generally manifesting in some combination of unpredictable timing of bleeding and a variable amount of flow, which in some cases results in HMB.

Some of these manifestations relate to the absence of predictable, cyclic production of progesterone, but in the later reproductive years may be a consequence of luteal out of phase events

PCO ,hypothyroidism, hyperprolactinemia, mental stress,obesity, anorexia, weight loss, or extreme exercise such as that associated with elite athletic training).

In some instances, the disorder may be iatrogenic, caused by gonadal steroids or drugs that impact dopamine metabolism such as phenothiazines and tricyclic antidepressants

Endometrial Causes (AUB-E)

There may be primary endometrial se, but may disorders that do not manifest HMB, IMB, such as endometrial inflammation or infection, abnormalities in the local inflammatory response, or aberrations in endometrial vasculogenesis. At the present time, there are no available specific tests for these disorders, so the diagnosis of AUB-E should be determined by exclusion of other identifiable abnormalities in women of reproductive years who appear to have normal ovulatory function

Iatrogenic (AUB-I)

Unscheduled endometrial bleeding that occurs during the use of exogenous gonadal steroid therapy is termed ‘‘breakthrough bleeding’’ (BTB),the major component of the AUB-I .

Included in this category are the women using the levonorgestrel-releasing intrauterine system (LNG-IUS), who frequently experience BTB in the first 6 months of therapy .

When AUB is thought to be secondary to anticoagulants such as warfarin or heparin, or systemic agents that contribute to disorders of ovulation such as those that interfere with dopamine metabolism, it is categorized as AUB-C or AUB-O, respectively .

Not Classified (AUB-N)

There exist a number of entities that may or may not contribute to or cause AUB in a given woman for they have been either poorly defined, inadequately examined, and/or are extremely rare. Examples arteriovenous malformations and myometrial hypertrophy.

TERMINOLOGY

Oligomenorrhea Bleeding occurs at intervals of > 35 days and usually is caused by a prolonged follicular phase.

Polymenorrhea Bleeding occurs at intervals of < 21 days and may be caused by a luteal-phase defect.

Menorrhagia Bleeding occurs at normal intervals (21 to 35 days) but with heavy flow ( ≥ 80 mL) or duration ( ≥ 7 days).

Menometrorrhagia Bleeding occurs at irregular, noncyclic intervals and with heavy flow ( ≥ 80 mL) or duration ( ≥ 7 days).

Amenorrhea Bleeding is absent for 6 months or more in a non menopausal woman.

intermenstrual cervical disease, intrauterine device, endometritis, polyps, submucous myomas, endometrial hyperplasia, and cancer.

Midcycle spotting Spotting occurs just before ovulation, usually because of a decline in the estrogen level.

Postmenopausal bleeding Bleeding recurs in a menopausal woman at least 1 year after cessation of cycles.

Dysfunctional uterine This ovulatory or anovulatory bleeding is diagnosed after the exclusion of bleeding pregnancy or pregnancy-related disorders, medications, iatrogenic causes, obvious genital tract pathology, and systemic conditions

CLINICAL CONSEQUENCES

Impact on quality of life Anemia Infertility Endometrial cancer Financial

DIFFERENTIAL DAIGNOSIS

Systemic conditions Adrenal hyperplasia and Cushing’s disease Blood dyscrasias, including leukemia and thrombocytopenia Coagulopathies Hepatic disease Hypothalamic suppression (from stress, weight loss, excessive exercise) Pituitary adenoma or hyperprolactinemia Polycystic ovary syndrome Renal disease Thyroid disease

Genital tract pathology Infections: cervicitis, endometritis, myometritis, salpingitis Neoplastic entities Benign anatomic abnormalities: adenomyosis, leiomyomata, polyps of the cervix or endometrium Premalignant lesions: cervical dysplasia, endometrial hyperplasia Malignant lesions: cervical squamous cell carcinoma, endometrial adenocarcinoma, estrogen-producing ovarian tumors, testosterone-producing ovarian tumors, leiomyosarcoma Trauma: foreign body, abrasions, lacerations, sexual abuse or assault

DIFFERENTIAL DAIGNOSIS

Pregnancy and pregnancyrelated

conditions Abruptio placentae Ectopic pregnancy Miscarriage Placenta previa Trophoblastic disease

Medications and iatrogenic causes

Anticoagulants Antipsychotics Corticosteroids Herbal and other

supplements: ginseng, ginkgo, soy Hormone replacement Intrauterine devices Oral contraceptive pills, including progestin-only pills Selective serotonin reuptake inhibitors7 Tamoxifen (Nolvadex)7 Thyroid hormone replacement

DAIGNOSTIC APPROACH TO AUB

Pelvic pain Miscarriage, ectopic pregnancy, PID, trauma,

sexual abuse or assault Nausea, weight gain, urinary

frequency, fatigue Pregnancy Weight gain, cold intolerance,

constipation, fatigue Weight loss, sweating,

palpitations Easy bruising, tendency to bleed Jaundice, Hirsutism, acne, acanthosis

nigricans, obesity Postcoital bleeding Cervical

dysplasia, endocervical polyps Galactorrhea, headache, visual-

field disturbance Weight loss, excessive exercise,

stress

Hyperthyroidism Coagulopathy Jaundice, history of hepatitis

Liver disease obesity Polycystic ovary syndrome

Pituitary adenoma Hypothalamic suppression

PHYSICAL EXAMINTION

Pallor , exopthalmos BMI ,Thyromegaly, weight gain, edema

Thyroid tenderness, tachycardia, weight loss, velvety skin,stigmata of endocrine disorder,secondary sexual charscterstics

Bruising, jaundice, hepatomegaly Enlarged uterus leiomyoma, ascites, Firm, fixed uterus Adnexal mass, Uterine tenderness, cervical motion

tenderness

INVESTIGATION

Beta-subunit human chorionic gonadotropin Pregnancy

Complete blood count with platelet count ,ferritin

coagulation studies Liver function tests,

prothrombin time Thyroid-stimulating hormone Prolactin Blood glucose DHEA-S, free testosterone,

17 -hydroxyprogesterone (Ovarian or adrenal tumor if hyperandrogenic)

Papanicolaou smear Cervical testing for infection

Imaging and tissue Endometrial biopsy or

dilatation and curettage Transvaginal

ultrasonography Saline-infusion

sonohysterography Hysteroscopy MRI

TRAETMENT OF AUB

Age desire to preserve fertility coexisting medical conditions, patient preference the patient should be aware of the risks

and contraindications to allow informed choice.

patient satisfaction may be influenced by efficacy, expectations, cost, inconvenience, and side effects.

PREGNANCY

MALGNANCY TO BE RULED OUT

AUB

ORGANIC CAUSE PELVIC PATHOLOGY INFECTION

(contact tracing) ECTROPION MEDICAL DISEASE

NO CAUSE DUB

MILD MODERATE SEVERE

MEDICAL TREATMENT NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Endometrial prostaglandins are elevated in women with heavy menstrual bleeding.

(NSAIDs) inhibit cyclo-oxygenase and reduce endometrial prostaglandin levels,taken with menses decrease menstrual blood loss by 20 to 50 percent.

Improve dysmenorrhea in up to 70 percent of patients.

Therapy should start at the first day of menses and be continued for five days or until cessation of menstruation.

ANTIFIBRINOLYTIC AGENTS Tranexamic acid a synthetic derivative of the

amino acid lysine, exerts an antifibrinolytic effect through reversible blockade on plasminogen.

The drug has no effect on blood coagulation parameters or dysmenorrhea.

One third of women experience side effects, including nausea and Leg cramps.

Tranexamic acid one g every six hours for the

first four days of the cycle reduces menstrual blood loss by up to 40%.

DANAZOL

a synthetic steroid with mild androgenic properties, inhibits steroidogenesis in the ovary and has a profound effect on endometrial tissue, reduce menstrual blood loss by up to 80 percent.

Following danazol therapy (100-200 mg daily), 20 percent of patients reported amenorrhea and 70 percent reported oligomenorrhea.

Approximately 50 percent of the patients reporte no side effects

most common complaint was weigh gain of two to six pounds in 60 percent of patients.

The recommended treatment is 100 to 200 mg daily for three months.

PROGESTINS

Randomized controlled trials have shown cyclic progestins to be ineffective in controlling regular heavy menstrual bleeding compared to NSAIDs and tranexamic acid.

Progestins may be useful for women with irregular cycles and with anovulatory cycles when given for 12 to 14 days of each month.

Medroxyprogesterone acetate given for contraception induces amenorrhea within the first year in 80 percent of women, although as many as 50 percent experience irregular bleeding.

COMBINED ORAL CONTRACEPTIVE PILL The reduction of menstrual blood loss is

probably the result of induced endometrial atrophy.

A randomized controlled trial of women taking an Ocp containing 30 μg ethinyl estradiol showed 43 percent reduction in menstrual blood loss compared to baseline.

Two longitudinal case control studies have found that users were less likely to experience heavy menstrual bleeding or anemia.

Additional advantages of OCPs include contraception and reduction of dysmenorrhea,Best cycle control WITH

PROGESTIN INTRAUTERINE SYSTEM Progesterone impregnated

intrauterine devices (IUDs) reduce menstrual bleeding. levonorgestrel intrauterine system (LNG-IUS) is a T-shaped IUD which releases a steady amount of levonorgestrel (20 μg/ 24 hrs) from a steroid reservoir around the vertical stems of the device.

GNRH AGONISTS

GnRH agonists induce a reversible hypoestrogenic state, reducing total uterine volume by 40 to 60 percent.

Myomas and uterine volume expand to pretreatment levels within months of cessation of therapy.

GnRH agonists are effective in reducing menstrual blood loss in perimenopausal women, but are limited by their side effects, including hot flashes and reduction of bone density.

Surgical management

DILATATION AND CURETTAGE temporary reduction in menstrual

blood loss immediately after the procedure;

however, losses returned to previous levels or higher by the second menstrual period .

may have a diagnostic role when endometrial biopsy is inconclusive and the symptoms persist or when underlying pathology is suspected.

ENDOMETRIAL DESTRUCTION

HYSTRECTOMY

The risks of major surgery must be weighed against alternatives.

Hysterectomy is a permanent solution for the treatment of menorrhagia and abnormal uterine bleeding, and is associated with high levels of patient satisfaction in properly selected patients.

For the woman who has completed her childbearing, reviewed the alternatives, and has tried conservative therapy without acceptable results, hysterectomy is often the best choice.

RECOMMENDATIONS

1. Women with irregular menstrual bleeding should be investigated for endometrial polyps and/or submucous fibroids.

2. Women presenting with menorrhagia should have a current cervical cytology and a complete blood count. Further investigations are individualized.

It is useful to delineate if thebleeding results from ovulatory or anovulatory causes.

Clinicians should perform endometrial sampling based on the methods available to them. An office endometrial biopsy should be obtained if possible in all women presenting with abnormal uterine bleeding over 40 years of age or weighing more than or equal to 90 kg.

4. Hysteroscopically-directed biopsy is indicated for women wit persistent menstrual bleeding, failed medical therapy or transvaginal saline sonography suggestive of focal intrauterine pathology such as polyps or myomas. Women with persistent symptoms but negative tests should be reevaluated.

Progestogens given in the luteal phase of the ovulatory menstruaL cycles are not effective in reducing regular heavy menstrual bleeding .

While dilatation and curettage (D&C) may have a diagnostic role, it is not effective therapy for women with heavy menstrual bleeding.

The endometrium can be destroyed by several different techniques but reoperation rate at five years may be up to 40 percent This should be reserved for the woman who has finished her childbearing and is aware of the risk of recurrent bleeding.