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Abnormal Genital Tract Bleeding

Annekathryn
Assistant Professor Associate

Goodman,

MD

of Obstetrics, Gynecology, and Reproductive Harvard Medical School Director, Division of Gynecologic Oncology Massachusetts General Hospital Boston, Massachusetts

Biology

The etiology of abnormal genital tract bleeding encompasses a wide range of disorders that can be secondary to anatomic changes of the female genital tract, infection, endocrinologic disorders, malignancies, and systemic illness. Appropriate workup is guided by age-related differential diagnoses for abnormal bleeding. Modern diagnostic tools can quickly focus the evaluation and allow timely intervention. Most abnormal genital tract bleeding is uterine bleeding, which is one of the most common gynecologic problems that health care providers will face. It accounts for approximately 15% of office visits and 25% of gynecologic operations. Abnormal uterine bleeding in reproductive-age women is defined as bleeding at abnormal or unexpected times or by excessive flow at the time of an expected menses. The average menstrual cycle length and duration of flow is 28 days and 4 days, respectively, with an average blood loss of 35cc (1). Any bleeding should be considered abnormal in premenarchal girls and in postmenopausal women except for those with predictable withdrawal bleeding taking hormone replacement therapy. This article will review the categories of abnormal genital tract bleeding and the diagnostic tools needed to establish the correct diagnosis. Common clinical cases will be presented to illustrate the presenting symptoms, differential diagnoses, workup, treatment, and long-term follow-up.

CLASSIFICATION GENITALTRACT

OF ABNORMAL BLEEDING

Table I lists the various causes of abnormal genital tract bleeding. Although the majority of abnormal bleeding comes from the uterus, a careful physical examination will rule out~vulvar, vaginal, and cervical pathology.

(DUB). DUB is defined as that caused by anovulation or oligo-ovulation (2). It is erratic in nature and results in bleeding that is irregular in both timing and quantity. DUB is a diagnosis of exclusion after more serious pathology has been ruled out.

EVALUATION ABNORMAL BLEEDING

OF PATIENTS GENITALTRACT

WITH

Terminology for uterine bleeding is listed in &bk II. The pathogenesis of abnormal uterine bleeding may be divided into 2 general categories: organic causes and dysfunctional uterine bleeding

Initial evaluation must include a detailed history. Important information includes timing and nature of the bleeding, the precipitating factors, the patients sexual history, and associated symptoms, such as pain, fever, or changes in bowel or bladder function. A menstrual calendar diary can be helpful in determining if the bleeding is ovulatory or anovulatory. The patients medical history and the medications she is taking may influence her bleeding pattern. It is equally important to determine

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General Category Anatomic

Infection

Endocrine

Malignancies

Systemic

Trauma

Pregnancy

Specific Conditions Atrophic endometrium Leiomyomas Polyps (cervical, uterine) Adenomyosis Endometriosis Intrauterine devices Cervicitis Vaginitis Endometritis Oophoritis Anovulatory bleeding Polycystic ovaries Thyroid disease Exogenous hormones -Oral contraceptives -Progestin-only contraceptives -Hormone replacement therapy -Tamoxifen Cervical cancer Endometrial hyperplasia Endometrial cancer Vaginal cancer Vulvar cancer Endometrial stimulation by estrogen-producing ovarian neoplasm Metastatic disease (leukemia, gastrointestinal cancers) Coagulopathies Liver disease Sepsis Sexual assault Pelvic fracture Hymenal tear after first tampon use or first vaginal intercourse Spontaneous miscarriage Incomplete, threatened, or missed abortion Ectopic pregnancy Complication of therapeutic abortion Gestational trophoblastic disease

what nonprescription drugs and herbal mixtures the patient may be taking. For instance, the combined use of aspirin and Ginkgo biloba can cause easy bruisability and may play a role in menorrhagia (3). Causes of abnormal genital tract bleeding can be stratified by age. Prepubertal girls can develop abnormal bleeding. In newborn girls, this

can be secondary to placental estrogen stimulation of the endometrium. In girls <9 years of age, the most common causes are trauma, intravaginal foreign bodies, vulvovaginitis, and urethral prolapse (4). The possibility of sexual abuse must also be considered. Precocious puberty should be considered if the development of secondary sexual char-

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Term Menorrhagia Menometrorrhagia Intermenstrual Polymenorrhea Postmenopausal bleeding bleeding

Definition Excessive bleeding at regular intervals Excessive bleeding during and between menses Bleeding between menses Bleeding at <21-day intervals Bleeding occurring >l year after menopause

acteristics has occurred; benign and malignant ovarian and adrenal tumors must be ruled out. Primary lower genital tract neoplasms, such as sarcoma botryoides, are rare. Abnormal bleeding in adolescence is most commonly due to DUB, which is secondary to the lack of maturation of the pituitary-hypothalamic axis (2). Pregnancy must always be ruled out even in the absence of a reported history of sexual activity. Infection and hematologic abnormalities make up the remainder of cases in this age-group. Malignancies are rare. Reproductive-age women have a wide range of reasons for abnormal bleeding. Pregnancy and malignancy are the most common serious conditions. Anatomic alterations, such as fibroids, endometriosis, and adenomyosis, can cause significant bleeding in this age-group. DUB is common, and other endocrinopathies, such as thyroid disorders and hyperprolactinemia, should be considered. Other categories include infection and hematologic abnormalities (5). Perimenopause is defined as the 5- to loyear period prior to complete amenorrhea. Ovarian function wanes and anovulatory bleeding is common (6). Anatomic alterations and an increasing incidence of endometrial pathology, such as polyps, endometrial hyperplasia, and cancers, become important causes of abnormal bleeding. Menopause is defined as the time period after 1 full year of amenorrhea. Any bleeding should be considered abnormal. A careful history should determine if the bleeding occurs at the appropriate time on a cyclic hormone replacement regimen. While overall 10% of women with post-

menopausal bleeding have cancer, this incidence increases with age (7,X). The most common cause of bleeding in this age-group is vaginal or endometrial atrophy (9).

DIAGNOSTIC TOOLS Table III lists the various tools that can establish
the appropriate diagnosis for a woman with abnormal genital tract bleeding.

Examination
A careful physical examination of the external and internal female genital tract is mandatory. A diagnosis and treatment plan cannot be developed without a pelvic examination. Small children can be examined while they are sitting in their parents lap. However, it may be necessary to perform an examination under anesthesia with the use of a hysteroscope. Examination under anesthesia may also be necessary for an adult woman who has vaginismus and cannot be evaluated adequately in the office. Vaginismus, the involuntary spasm and closure of the vaginal wall, can occur secondary to deep psychologic distress resulting from a history of abuse

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Physical examination

Office examination Examination Hysteroscopy under anesthesia

Biopsy

Papanicolaous

test punch)

Vulvar biopsy (dermatologic Cervical biopsy Endometrial Dilation Laboratory testing biopsy

and curettage gonadotropin

Human chorionic

Complete blood count Coagulation profile hormone

Follicle-stimulating Luteinizing Thyroid Prolactin Testosterone hormone

function tests

Dehydroepiandrosterone Vaginal culture, wet prep Chlamydia, Radiology Ultrasound Sonohysterogram

sulfate

herpes, HIV testing

Magnetic resonance imaging

or secondary to a pathologic condition, such as infection, traumatic lacerations, or neoplasms. With the woman in lithotomy position, the external skin, vulvar appendages, urethra, hymen, and perianal region are carefully inspected. The focus of the examination is to determine the bleeding site. A speculum is then placed in the vagina and the walls of the vagina and the cervix are inspected. Vaginal lesions can be easily missed in a multiparous woman with redundant vaginal tissue. A large Graves speculum can help retract redundant vaginal tissue. A condom with the tip cut off can be slipped over a speculum to retract the vaginal walls and allow better visualization of the cervix. Conversely, lesions may not be obvious in a woman with an atrophic vagina and narrowing

of the vaginal apex. A short course of estrogen vaginal cream (1 g applied intravaginally every other day for 2 weeks) can reduce the discomfort

from atrophy and allow better visualization in the postmenopausal woman. Digital palpation of all sides of the vagina is crucial to fully evaluate the vagina and the cervix.

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Name Pipelle Vabra aspirator Novak curette Tis-u-trap Z-sampler Randall curette Explora

Manufacturer Unimar Berkeley Milex Milex Zinnanti Cooper Milex

Biopsy
Ah lesions should be biopsied. A vulvar lesion is amenable to a dermatologic punch biopsy after the injection of intradermal lidocaine. Papanicolaous (Pap) tests can be taken of the vagina and cervix. However, the false-negative rate for Pap tests can range from 10% to 25% and is increased in the presence of severe inflammation or bleeding (10). Therefore, all visible vaginal and cervical lesions should be biopsied even in the setting of a negative Pap test. An endometrial biopsy can be performed in the office or more completely in the operating room during a dilation and curettage (D&C) (11). All women >40 years of age and younger women with a history of polycystic ovary syndrome (PCOS), infertility, anovulation, or a family history of endometrial cancer should be considered for endometrial biopsy. Many different office endometrial biopsy instruments are available (Table IV). All instruments use a suction mechanism to sample the endometrial lining. Except for the Tis-u-trap, which has an inner diameter ranging from 1.8 mm to 4.0 mm, the office instruments have inner diameters of 2.6 mm to 3.2 mm. Antibiotic prophylaxis is indicated for patients with prosthetic heart valves, but is not required in patients with valvular prolapse with benign murmurs. Complications are rare. The most common is uterine perforation with an incidence of 0.1% to 0.2%. Patients can also develop a transient vasovagal reaction after manipulation of the cervix. The indications to proceed to a D&C under general anesthesia include patient discomfort, severe cervical stenosis, inadequate tissue sampling in the office, and a high suspicion of malignancy but a negative office biopsy. D&Cs are usually coupled with hysteroscopy.

The endometrial cavity can be visualized by either office or intraoperative hysteroscopy. Hysteroscopy is superior to all other diagnostic tools in the evaluation of intrauterine pathology (12) and can directly visualize a lesion and allow for a directed biopsy. This tool can be used to evaluate submucosal fibroids, polyps, and rule in or out a hyperplastic or malignant endometrial lesion. Complications are rare but include uterine perforation and infection. Hyponatremia can occur if hypotonic distension media is used and a fluid deficit occurs. The decision to refer to a gynecologist for this procedure will be based on the patients history, symptoms, and other diagnostic testing (see Case 3).

Laboratory Testing
All women of reproductive age should have a pregnancy test. A complete blood count can be useful in assessing the volume and duration of the bleeding. If the woman has other associated bleeding manifestations, such as easy bruising and nose and gum bleeding, a coagulation profile should be checked. Many authorities recommend a coagulation panel in teenage girls with bleeding that is heavy enough to require hospitalization. The

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gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) can be helpful in the diagnosis of PCOS-women with this condition have higher mean concentrations of LH but low or low-normal levels of FSH or an LH:FSH ratio >2.5 compared with normal women (13). FSH and LH are rarely useful to evaluate the perimenopausal state as these hormones are secreted in a pulsatile manner and the levels change throughout the day (6). Women with PCOS may also have associated hirsutism and mildly increased androgen levels, such as testosterone and dehydroepiandrosterone sulfate (DHEAS) (13). Serum testosterone and DHEAS should be ordered in women with oligomenorrhea and hirsutism. Extreme elevations of androgen levels should trigger a search for a testosterone-secreting ovarian or adrenal tumor. Thyroid disorders are very common in young women and can contribute to an anovulatory state. Less commonly, prolactinsecreting pituitary adenomas will cause anovulation and galactorrhea. Visual field defects can develop with large tumors. Serum prolactin and thyroidstimulating hormone levels should be ordered only in patients with recurrent episodes of DUB. A wet prep should be performed if there is a vaginal discharge. Chlamydia trachomatis and herpes simplex virus cultures should be considered if a woman has cervicitis. Candidal infections can sometimes cause vaginal bleeding from severe irritation Human immunodeficiency testing should always be considered in women with intractable and recurrent yeast infections (14).

abnormalities, such as polyps, fibroids, or endometrial neoplastic changes, is low-ranging from 88% to 96%. TVUS has a high false-positive rate in women receiving tamoxifen. The majority of patients taking tamoxifen who develop endometrial pathology will have abnormal bleeding. Screening in the asymptomatic tamoxifen user is controversial, but these women should be screened either by TVUS or sonohysterogram if they have cervical stenosis, present with a difficult office examination, or have additional risk factors for endometrial cancer such as a family history. TVUS cannot distinguish between a thickened endometrial stripe and subendometrial edema, which is a common benign finding in tamoxifen users. Fibroids and large polyps can distort the uterine cavity making endometrial stripe measurements inaccurate. TVUS and transabdominal ultrasound are useful for imaging fibroids. TVUS is usually unable to identify fibroids smaller than 2 cm. TVUS can be a useful adjunct in the evaluation of abnormal bleeding when an office biopsy shows scant tissue. An abnormal ultrasound finding would necessitate a follow-up D&C with hysteroscopy. In the premenopausal woman, TVUS gives additional information about fibroids and adnexal abnormalities but is less relevant for information about the endometrial stripe.

Radiology
A transvaginal ultrasound (TVUS) can evaluate the endometrial stripe. A thickness of less than 4 mm is normal in a postmenopausal woman (7). The stripe evaluation is less useful in premenopausal women because it will fluctuate with the menstrual cycle. Thenormal endometrial thickness varies during the menstrual cycle: 1 to 4 mm during menses, 4 to 8 mm during the proliferative phase, and 7 to 14 mm during the secretory phase. Postmenopausally, the upper limit of normal increases by approximately 2 mm if the patient is taking unopposed estrogen replacement therapy with tamoxifen. The diagnostic sensitivity of TVUS for differentiating intracavitary

Saline infusion sonography or sonohysterography can increase information about the endometrial cavity (15). This technique involves the infusion of saline into the endometrial cavity followed by a TVUS. Sonohysterography can rule out lesions in the presence of tamoxifen-induced subendometrial edema, distinguish polyps from endometrial hyperplasias, and detect small intracavitary lesions. It cannot distinguish between polyps and submucosal fibroids.

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Magnetic resonance imaging (MRI) can be used to distinguish leiomyomas from ovarian pathology (16). It can also be helpful in preoperative planning of myomectomies by distinguishing between subserosal, intramural, and submucosal locations. MRI is also the only nonoperative diagnostic tool for detecting adenomyosis, a benign glandular infiltration of the myometrium that can cause significant bleeding and pelvic pain. CASE STUDIES

the intervention is to rebuild the lining with highdose estrogen as described. The brand of OCP and the dosage are not important. The number of pills can be titrated by symptoms. For patients who need >2 pills a day, an antiemetic may be necessary. With normal and mature secondary sexual characteristics and normal anatomy, no other intervention is needed. She will start ovulating in the next few years. There are no long-term fertility and endocrinologic concerns.

Case 2 Case 1
A 17-year-old presented with a 2-month history of daily heavy vaginal bleeding with clots. Her onset of menarche was age 13. She had 2 to 3 periods a year since then, all very heavy and lasting 2 weeks. She denied sexual activity. She had no other medical problems and did not take any medicines. She had no history of gastrointestinal symptoms, urinary problems, easy bruising, or dysmenorrhea. Workup: She was a pale-appearing teenager in no acute distress. She had normal and mature (Tanner stage V) breast and external genitalia development. There were no lesions, evidence of trauma, or abnormal anatomy. Laboratory data: urine human chorionic gonadotropin (hCG) negative, hemoglobin 6, normal white blood count and differential, normal coagulation profile. Treatment: She was given iron supplements and oral contraceptive pills (OCP). She was instructed to take 2 OCPs daily until completing the first pack. She then immediately started on the second OCP pack, one pill daily, without an intervening period. She had a normal withdrawal bleed. She has been maintained on OCPs since then with no further bleeding. Comment: This is a classic case of DUB secondary to anovulatory bleeding from an immature pituitary-hypothalamic axis. The history of menorrhagia, oligomenorrhea, and lack of dysmenorrhea leads to the diagnosis without the need for other testing. The patient had an exhausted endometrium secondary to excessive bleeding. The first step in The patient was a 42-year-old G2P2 woman who developed increasing menorrhagia over the past 12 months. She had a history of normal menstrual cycles every 28 days that were 4 to 6 days in length. In the year prior to presentation, she developed flooding during the first 3 days of her periods with clots and the need to use 2 to 3 pads at a time. She then continued to bleed for another week. She had severe dysmenorrhea with aching down her legs and in the base of her spine. She denied intermenstrual or postcoital bleeding. Her husband had a vasectomy. She had no medical problems, no bleeding diathesis, and took no medicines. Workup: Her general examination was normal. There were no vulvar, vaginal, or cervical lesions. On bimanual examination she had a 20-week size midline mass that was inseparable from her uterus. On rectal exam, the mass was impacted in the pelvis and externally compressing her rectum. Her Pap test and endometrial biopsy were normal. Laboratory data: hCG negative, hemoglobin 7. A pelvic ultrasound showed the mass to be her uterus with multiple fibroids. Both ovaries were normal. There was no evidence of hydronephrosis. Treatment: The patient was given iron replacement and stool softeners. The various options for the management of symptomatic fibroids were presented: close observation, myomectomy, or hysterectomy. Other options included use of a gonadotropinreleasing hormone (G&H) agonist to temporarily shrink the fibroids by putting her into pseudomenopause. A newer technique of arterial emboli-

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zation of the fibroids was also discussed. The patient chose to take a GnRH agonist for 3 months while she considered her options. She decided to undergo an abdominal hysterectomy with preservation of her ovaries. Now at 1 year out from surgery, she has no gynecologic complaints, normal sexual function, and normal ovarian function. Comment: Menorrhagia secondary to the distortion of the uterine cavity causes heavy and prolonged menses. An endometrial biopsy should be performed to rule out other causes. This occurs because the uterus is unable to contract down on the open venous sinuses in the zona basalis of the endometrium. Adenomyosis may also be a consideration. This is a structural problem and hormonal intervention will not help. GnRH agonists help by shutting down the pituitary-hypothalamic axis and preventing menses. This is only a temporary solution because long-term use of GnRH agonists can cause osteoporosis. Asymptomatic fibroids can be managed by observation alone. Indications for intervention include anemia from menorrhagia, hydronephrosis secondary to ureteral compression, pain secondary to mass effect. The gold standard is operative intervention. Myomectomy is an option for women who have not completed their childbearing or who wish to preserve their uterus. Arterial embolization is a newer procedure that causes infarction and shrinkage of the fibroid. Immediate side effects include pain and fever. Preliminary studies are promising but long-term follow-up is needed (17). Case 3 The patient was a 57-year-old GOP0 woman who presented with one episode of painless vaginal spotting. Her last normal period was at age 48. She never took estrogen replacement therapy. She denied weight loss, and bowel or bladder symptoms. She was obese with diet-controlled diabetes, hypertension, and hypothyroidism. She was taking a beta-blocker, a diuretic, and thyroid replacement. Workup: Her general examination was nonfocal. On pelvic examination, there were no vulvar, vaginal, or cervical lesions. There was some old blood

in the vagina. On bimanual examination, the uterus and adnexa were not palpated secondary to her obesity. A Pap test was normal. An office endometrial biopsy showed scant tissue and some fragments of crowded endometrial glands with complex atypical hyperplasia. Laboratory tests showed hemoglobin at 8.5. A pelvic ultrasound showed a 4-mm endometrial stripe with slight heterogeneity at the fundus. She was taken to the operating room and underwent a D&C and hysteroscopy. Her endometrial lining was atrophic except near the right tubal ostia where there was a shaggy 3-mm lesion. Pathology showed a grade 1 endometrioid adenocarcinoma in a background of complex hyperplasia. She was treated with a total abdominal hysterectomy and bilateral salpingooophorectomy. The tumor was confined to the endometrium. She is alive without evidence of recurrence at 5 years. Comment: This woman presented with postmenopausal bleeding. Although her office biopsy only showed a premalignant lesion, a malignant lesion was not ruled out by the office biopsy. A 4mm endometrial stripe is normal in an asymptomatic postmenopausal woman, but cancers can still be seen with this finding. The clue here was the heterogeneous change seen in the stripe. If she had had a sonohysterogram, it would have revealed a small polypoid lesion that correlated with the cancer. In the presence of abnormal bleeding, however, a normal endometrial stripe is not completely reassuring. An endometrial biopsy should always be performed.

REFERENCES 1. Haynes FJ, Hodgson H, Anderson ABM. Measurement of menstrual blood loss in patients complaining of menorrhagia Br J ObstetGynaecol. 1977;84:
763-768.

2. Fraser IS, Michie EA, Wide L, et al. Pituitary gonadotropins and ovarian function in adolescent dysfunctional uterine bleeding. J Clin Endocrinol Metab. 1973;37:407-414. 3. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drugherb interactions. Arch Intern Med. 1998;158: 2200-2211.
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4. Fishman A, Paldi E. Vaginal bleeding in premenarchal girls: a review. Obstet Gynecol Surv. 1991;46:

457-460. 5. Long CA. Evaluation of patients with abnormal

uterine bleeding. Am J Obstet Gynecol. 1996;175:

784-786. 6. Sherman BM, West JH, Korenman SG. The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women. J Clin Endocrinol Metab. 1976;42:629-636. 7. Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding: a Nordic multicenter study. Obstet Gynecol. 1995;172:
1488-1494.

8. Indman PD. Abnormal uterine bleeding: accuracy of vaginal probe ultrasound in predicting abnormal hysteroscopic findings. J Reprod Med. 1995;40:

545-548. 9. Iatrakis G, Diakakis I, Kourounis G, et al. Postmenopausal uterine bleeding. Clin Exp Obstet Gynecol. 1997;24:157-165. 10. Lee KR, Ashfaq R, Birdsong GG, et al. Comparison of conventional Papanicolaou smears and a fluid based, thin-layer system for cervical cancer screen-

ing. Obstet Gynecol. 1997;90:278-284. 11. Grimes DA. Diagnostic dilation and curettage: a reappraisal. Am J Obstet Gynecol. 1982;142:1-6. 12. Gimpelson RJ, Rappold HO. A comparison study between panoramic hysteroscopy with a directed biopsy and dilation and curettage: a review of 276 cases. Am J Obstet Gynecol. 1988;158:489-492. 13. Naether OGJ, Fischer R, Weise HC, et al. Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril. 1993;60:88-94. 14. Shah PN, Kell PD, Barton SE. Gynaecological disorders and human immunodeficiency virus infection. Znt JSTDAZDS. 1994;5:383-386. 15. Widrich T, Bradley LD, Mitchinson A, et al. Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium. Am JObstet Gynecol. 1996;174:1327-1334. 16. Weinreb JC, Barkoff ND, Megibow A, et al. The value of MR imaging in distinguishing leiomyomas from other solid pelvic masseswhen sonography is indeterminate. Am J Roentgenol. 1990; 154: 295-299. 17. Walker W, Green A, Sutton C. Bilateral uterine artery embolization for myomata: results, complications and failures. Minimally Invasive Ther Allied Technol. 1999;8:449%454.

ADVISORY

BOARD

In managing bleeding in the female patient with DUB, what determines whether you prescribe a progestin agent alone versus an estrogen/progestin regimen as you did in your case study?
GOODMAN Generally, there are 2 scenarios that occur in DUB. There is the patient who has been bleeding for a month or so before she comes in to see you. This patient doesnt have much endometrial lining remaining and is likely to require some estrogen to help slow the hemorrhaging occurring on the raw endometrial surface. On the other hand, there is the patient who has been anovulatory and hasnt had a period and then suddenly begins to bleed. If this patient presents within a week or so of the onset of bleeding and before shes had time to drop her

hematocrit or has exhausted the endometrial lining, you usually can adequately treat her with a progestin agent alone. ADVISORY BOARD

In the former situation, where you would favor using the birth control pill to treat DUB, is there a pill formulation that you prefer?
GOODMAN The formulation doesnt matter. Simply titrate up the number of pills as required to stop the bleeding. As far as im concerned, youre likely to get the same desired effect prescribing a pill containing 30 to 35 ng of estrogen 4 times a day as you would prescribing a 50-pg formulation twice a day. Once control is achieved, taper the dose down and cycle her on the pill you prescribed. Although some

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experts may have a favorite pill for doing this and advocate a specific regimen, I dont think it really matters. Just make sure the patient doesnt inadvertently take the inert pills present in a 2%day pack. ADVISORY BOARD With regard to the role of the endometrial hiopsy in the workup of abnormal uterine bleeding, many textbooks recommend that a biopsy be routinely performed in all patients >40 years of age. Do you agree with this cutoff? GOODMAN Generally speaking, yes. I would agree that bleeding in patients <40 years of age is not likely to be caused by an endometrial malignancy. Having said that, there are certain subsets of women ~40 years of age who are considered to be at increased risk for endometrial cancer and should undergo an endometrial biopsy. One subset includes women who are anovulatoty and are chronically exposed to unopposed estrogen. Women with PCOS also fall into this category of patients at risk for preinvasive and invasive endometrial lesions. Another subset are women with a strong family history of endometrial cancer. The classic case is a woman with hereditary nonpolyposis colon cancer (HNPCC) syndrome, in which an autosomal dominant gene is responsible for a >.50% risk of endometrial cancer plus colon and breast cancer. These are the types of women for whom you should immediately jump to thinking about doing an endometrial biopsy in your evaluation of abnormal bleeding. For everyone else in their 3Os, my first thought would be that Im likely dealing with DUB or possibly fibroids. Conversely, I would seriously consider adding an endometrial biopsy to my evaluation of abnormal bleeding in all women who are in their 40s.

ADVISORY BOARD Would you perform an endometrial biopsy in a 42 year-old woman with 5 children if there was nothing suspicious in her medical or family history? GOODMAN I probably wouldnt initially do it, but I would if she didnt respond as expected to my interventions or if she had atypical bleeding. Regardless, in such a patient, it is important that you follow her course over time and make sure the bleeding resolves to your satisfaction. ADVISORY BOARD In a postmenopausal woman who develops abnormal bleeding, does a normal endometrial stripe on the TVUS preclude the need for an endometrial biopsy? GOODMAN No, I view the TVUS as playing primarily an adjunctive role in such a patient. Thus, I would perform an endometrial biopsy even if the TVUS was normal. However, comparing the results of both studies can be diagnostically helpful; for example, if you had an ultrasound that showed a thick stripe with some cystic spaces within it and yet the biopsy only showed atrophic endometrium, you would have to wonder about the discrepancy between those 2. In such a patient, further evaluation of the endometrium with either a repeat biopsy or with what some regard as the reigning gold standard-hysteroscopy-should be performed. ADVISORY BOARD How about in a postmenopausal woman on hormone replacement therapy (HRT) who had been doing fine but then developed a little spotting? Does a normal TVUS in this patient preclude the need for an endometrial biopsy?

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GOODMAN No. Taking HRT does not place her in a different category from anybody else. It is important to not forget that HRT does carry a risk of endometrial cancer, particularly in light of the current trend of using lower and lower doses of the progestin agent in HRT regimens. ADVISORY BOARD

more for fibroids, ovarian masses, and other forms of pelvic pathology that might be responsible for her bleeding. ADVISORY BOARD

What is the current thinking regarding the use of TVUS for monitoring women taking tamoxifen for endometrial neoplasia?
GOODMAN There have been a lot of changes in the thinking about tamoxifen. At one time we were screening all patients with TVUS. The only problem was that we began to see a lot of abnormally thickened endometrial stripes and consequently performed a lot of biopsies that proved to be negative. It turned out that there was a high percentage of false-positive thickened endometrial stripes in these patients as a result of tamoxifen causing subendometrial edema. A saline infusion sonography or sonohysterography can distinguish between an endometrial lesion and submucosal edema. The saline in the cavity provides you with sufficient contrast to determine that the true endometrial stripes in such patients are fine. ADVISORY BOARD

Is the criterion of a normal endometrial stripe being 54 mm in a postmenopausal woman applicable to women taking HRT?
GOODMAN First of all, it is important to be aware that different institutions may have different cutoffs for normal since there is some variability as to what is actually measured when determining the thickness of the stripe. Thus, it is important for clinicians to check with the ultrasonographer at the laboratory to which they refer their patients and find out what exactly has been established as normal. Second, although some investigators have published data suggesting that the endometial stripe can be thicker in women receiving HRT, Im a bit more conservative and apply the 4-mm criterion regardless of, whether a patient is taking hormones. ADVISORY BOARD

What then are the guidelines for screening in a patient receiving tamoxifen?
GOODMAN Screening is not generally indicated and an endometrial biopsy should be performed at the first sign of bleeding. However, if the patient has HNPCC or has risk factors for endometrial cancer in her medical or family history, I would favor getting annual endometrial biopsies? sonohysterograms, or both.

What is the role of TVUS in the premenopausal patient?

GOODMAN Since the thickness of the endometrial stripe in the premenopausal patient varies with the phase of the patients menstrual cycle, its determination does not have the same diagnostic value as it does in the postmenopausal patient. When I think of using ultrasound in a premenopausal woman, Im looking

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