[ Editorials | Letters | Selected Articles | Signature Series | Patient Handouts | Index ]

2002 Selected Articles

Abnormal Uterine Bleeding
Expanding the Role of Transvaginal Sonography

J. Kell Williams, MD and Anna Parsons, MD

Abnormal uterine bleeding (AUB) in nonpregnant women is a common problem. In fact, AUB accounted for almost 4 million outpatient visits (mostly to physicians’ offices) in the United States in 1996.¹ Indeed, this problem may prompt more than 20% of all visits to OB/GYNs,² and may account for more than one fourth of all hysterectomies.³ AUB refers to the symptom of excessive, prolonged, unexpected, or acyclic bleeding, regardless of diagnosis or cause, whereas dysfunctional uterine bleeding (DUB) is a diagnostic term for any abnormal bleeding from an essentially normal uterus.

Interpretation of clinical study findings regarding the frequency, diagnosis, and treatment of AUB may be compromised by a lack of consistency in the definition of normal and in the description of various patterns of AUB. Chimbira et al have defined the characteristics of a normal and abnormal menstrual cycle (Table 1).⁴ Various patterns of AUB are described in Table 2. Such “diagnostic” patterns have produced more words for vaginal bleeding than there are Inuit words for snow. These terms, each with its own ICD-9 code, are descriptive rather than diagnostic. The use of transvaginal sonography (TVS) to extend the physical examination to include inspection of the endometrium and ovaries has begun to change the approach to this problem.

AUB is rare in prepubertal females. Newborn girls occasionally have a slight bloody vaginal discharge secondary to withdrawal of placental estrogens. In the absence of puberty or evidence of estrogenization, vaginal bleeding may indicate trauma, presence of a foreign body, vaginitis, or rarely, sarcoma botryoides or other local malignancy.⁵

AUB is common in adolescents because of the 1- to 5-year delay in development of regular ovulatory menstrual cycles after menarche.⁶ Bacon offers a thorough description of the diagnosis and treatment of adolescents with dysfunctional uterine bleeding.⁷ AUB also tends to be more common during the fifth decade of life (the perimenopausal years). During this life stage, it is related to both dysfunction of the aging ovaries and to uterine abnormalities; this is reflected by the perimenopausal peak in hysterectomy rates for these indications.⁸ Initiation of hormone replacement therapy (HRT) during the sixth decade of life (just after menopause) leads to bleeding, requiring clinical evaluation in one third of women with an intact uterus for up to 2 years following HRT initiation.⁹

Unresolved AUB can have serious adverse consequences on women’s health and on their day-to-day living. They may develop acute or chronic anemia, or find themselves at increased risk for pregnancy (because of oral contraceptive [OC] discontinuation) or osteoporosis and degeneration of other hormone-sensitive tissues (because of HRT discontinuation¹⁰). Their quality of life may diminish because AUB can interfere with activities of daily living, marital relationships, social interactions, and work. Also, many women with improperly diagnosed or treated AUB may undergo hysterectomy, which has a mortality rate of 0.1% in whites and of 0.2% in African-Americans.¹¹ In the worst case, AUB may be a sign of atypical endometrial hyperplasia, which, if undiagnosed and untreated, can progress to uterine cancer—the most common female genital cancer. In 1998, an estimated 36,100 women were diagnosed with uterine cancer, which led to approximately 6300 deaths.¹² Uterine cancer accounts for 2% of all cancer deaths in women, with a disproportionate proportion occurring in African-American women, who are diagnosed at more advanced stages of the disease. Five-year survival rates for white women and Hispanic women diagnosed with uterine cancer are 86% and 81%, respectively,¹³ as compared with 55% in African-American women.¹⁴

CAUSES

Any of the following may trigger AUB:

• Pregnancy-related events: spontaneous, incomplete, threatened, or missed abortion; ectopic pregnancy; gestational trophoblastic disease
• Ovulatory dysfunction: excessive and/or erratic exposure to estrogen, with insufficient progesterone exposure and disorderly endometrial proliferation (common in women at the extremes of postmenarche or perimenopause)
• Exogenous hormone use or error in hormone use: common in women using OCs or HRT⁹ (erratic bleeding occurs with or without abnormal endometrial proliferation)
• Proliferative endometrial/myometrial lesions: polyps, hyperplasia, cancer, intracavitary or submucous myomas, adenomyosis, sarcoma (rare)
• Coagulopathy (acquired or inborn): von Willebrand disease, idiopathic thrombocytopenic purpura, thalassemia major, Fanconi anemia, or prothrombin deficiency
• Inflammation/infection of the cervix, vagina, fallopian tubes, or endometrium: may be the result of a sexually transmitted disease^15,16
• Systemic causes: thyroid, hepatic, or renal disease; thrombophilic disorder requiring anticoagulation; sepsis
• Trauma: accidental injury, coital trauma, sexual abuse
• Miscellaneous: estrogen-producing tumors, uterine vascular malformations, use of intrauterine device.

EVALUATION

The first step in identifying AUB is a thorough history, which includes a general health history, a detailed menstrual history (past and present), a history of past illnesses (eg, thyroid disorder), and use of medications, including herbal remedies. Weight changes, dietary/exercise habits, and stress management strategies may also be relevant. Specific laboratory tests may be indicated based on positive findings in the history. Figure 1 provides an algorithm for an ultrasonographic-based evaluation of AUB.

Patients should then undergo a complete physical examination, pelvic examination, pregnancy test (if indicated), and Papanicolaou smear, which is sometimes useful in detecting endometrial cancer.¹⁷ At this point, clinicians may perform further diagnostic testing, start patients on empiric hormone treatment, or institute “watchful waiting.” The choice usually depends on the patient’s age and presentation, as well as on the physician’s preferred approach and available equipment. For example, as most cases of AUB in younger women are secondary to ovulatory dysfunction, many clinicians forgo diagnostic testing and prescribe hormone therapy empirically to treat those at low risk for cancer. Until recently, however, this approach had not been studied for efficacy and safety. Davis et al demonstrated that a specific combination OC was significantly more effective than placebo in treating the dysfunctional component of AUB.¹⁸ However, OC use may not be helpful in treating other causes of AUB and, in fact, may delay diagnosis.

DIAGNOSTIC TECHNIQUES

Ideally, clinicians need a minimally invasive, accurate method of determining whether AUB is functional or structural. That way, they can quickly and easily determine whether endometrial biopsy is needed for diagnosis or whether surgery is needed for therapy. Needless to say, avoidance of unnecessary invasive diagnostic procedures and establishment of a diagnosis for which surgery is not required would reduce risk and cost for many women, and enable them to start medical treatment that would likely resolve the problem.

Endometrial Biopsy

Although many self-limited cases of AUB can be diagnosed based on the history and physical examination alone, persistent bleeding requires an endometrial diagnosis, by inspection and/or histologic analysis. Uterine cancer, the most serious cause of uterine bleeding, is diagnosed in fewer than 10% of endometrial biopsies performed in women presenting with AUB,^19-21 which means that more than 90% of endometrial biopsies reveal benign findings. Thus, this invasive technique is more useful in ruling out a relatively rare disease (ie, uterine cancer) than in identifying most causes of AUB.

Even dilation and curettage (D&C) under general anesthesia may miss 2% to 6% of cases of cancer or hyperplasia.^22-25 A study comparing specimens obtained by prehysterectomy D&C versus the hysterectomy itself showed that D&C sampled less than 50% of the uterine cavity in 60% of cases.²⁶ Once a mainstay of OB/GYN practice, D&C has given way to biopsy in the office using 3- to 4-mm sampling devices that usually do not require cervical dilation or anesthesia. Although office-based endometrial biopsy is the least expensive method for detecting endometrial cancer,²⁷ with a low false-negative rate,²⁸ it may fail to diagnose up to 90% of benign lesions (eg, focal hyperplasia, polyps, myomata).^29-31

Is there an alternative to endometrial biopsy that might spare thousands of women from a nondiagnostic invasive procedure and, at the same time, be more informative? Accumulated evidence to date indicates that visualization of the uterine cavity, by direct or sonographic technique, is more accurate for diagnosis than blind sampling methods.

Hysteroscopy

New methods of visualizing the endometrial cavity can help clinicians to determine whether biopsy is required, and, if so, to guide sampling. Hysteroscopy is an endoscopic technique used primarily for diagnosis in the office and for diagnosis and surgical therapy in the operating room.³² In the hands of skilled and experienced operators, hysteroscopy accurately detects most structural causes of AUB, including polyps and myomata. However, visualization is limited to the endocervical and endometrial surfaces. Also, this procedure has rare, but serious, complications including gas embolism, fluid overload, and death. Hysteroscopy has a low false-negative rate,^33,34 but it is the most costly diagnostic approach (requiring expensive dedicated instruments and surgical expertise), and is often performed under general anesthesia.³⁵ Some experts recommend that it be used only after a previous endometrial sample has been obtained.³⁶ When compared with hysterectomy, however, hysteroscopy is the therapeutic modality of choice for excision of focal intracavitary lesions because of its accuracy, minimal risk of injury to patients, and conservation of resources.

Transvaginal Sonography

In the past 10 years, TVS has become the most accurate imaging technique for the pelvis because of its ability to demonstrate structural resolution to within 1 mm.^37,38 A meta-analysis of 35 studies enrolling more than 5000 women revealed that TVS had a sensitivity of 96% in detecting cancer and of 92.5% in detecting any proliferative abnormality in postmenopausal endometrium (upper limit of normal, 5 mm).³⁹ The authors of this meta-analysis agreed with many other researchers over the past decade that women with postmenopausal bleeding and a well-imaged endometrium of &Mac178;5 mm could safely forgo endometrial biopsy, with a risk of missing a cancer of less than 1%.

Two factors limit applicability of TVS to the broad population of women with AUB: the sonographer’s expertise in obtaining an accurate image of the endometrial cavity, and the poor specificity of endometrial thickness alone in women with premenopausal levels of estrogen. Two studies showed that even when imaging was performed by very experienced or specially trained sonographers, 2.5% to 5% of images were inadequate for interpretation.^40,41 In a third study, when imaging was performed routinely by available sonographers during the Postmenopausal Estrogen/Progestin Intervention (PEPI) trial, which compared HRT regimens, 7% of images were considered to be inadequate for interpretation.⁴² In this study, poorly imaged uteri were at significantly greater risk of containing hyperplasia or cancer.

Two maneuvers can improve the accuracy of TVS diagnosis of abnormal endometrial proliferation. The first involves timing the study to follow spontaneous menses or induced withdrawal bleeding so that only the 1-mm thick basalis layer remains in the normal uterus.^43,44 The second method of enhancing specificity of the endometrial image thickness is saline infusion sonohysterography (SIS) (Figures 2 and 3). In this procedure, 2 to 30 cc of sterile, injectable-quality saline is infused through a 2-mm flexible plastic catheter into the uterine cavity during TVS.¹⁶ The only contraindications to SIS are suspected uterine pregnancy and infection. In more than 90 studies included in the MEDLINE database that compared SIS with hysteroscopy or hysterectomy, virtually all lesions visible by endoscopy or by inspection of the cavity after hysterectomy were visible by SIS.^45,46 Adding SIS to TVS is not only cost-saving⁴⁷ and easily mastered by experienced imagers of various specialities,⁴⁸ but it is also well tolerated by patients, who generally prefer it to office hysteroscopy.^49,50

FIGURE 2. Anterior Myoma

A retroverted uterus with an anterior myoma (M) and a completely normal uterine cavity with saline infusion sonohysterography (SIS). Expansion of the cavity with saline reveals a smooth surface. The fundus is on the reader’s right, the closed cervix (C ) is on the left, indicating retroversion. The catheter is not seen in this plane.

Finally, simultaneous imaging of the ovaries allows clinicians to make a definitive diagnosis of DUB due to ovulatory dysfunction. DUB no longer needs to be a diagnosis of exclusion after failed trials of hormone therapy, as experts once asserted.⁵¹

FIGURE 3. Submucous Myoma

A 55-year-old woman with postmenopausal bleeding, spotting for 2 years. TVU (not shown) showed a 3 cm submucous myoma (M). These 3 images are taken during SIS with three-dimensional ultrasonography in simultaneous orthogonal planes at the internal os (I) and the cervix (C). The arrows are placed at the edges of the 2.03 cm endometrial polyp (P), which was causing the bleeding. Two biopsies had previously yielded inactive tissue. The shadowing due to the deflection of the ultrasound by the dense cervix is best seen in the transverse image and it sets off the polyp in the horizontal plane. The catheter is seen in the cervical canal below the polyp (which contains 2 small cysts) in the sagittal plane. The uterus is anteverted.

RECOMMENDATIONS

Clinicians still lack a broadly accepted, standard approach to the differential diagnosis of AUB. Endometrial sampling tests, usually in combination with other diagnostic modalities, are performed at the discretion of individual clinicians, who then assemble the results to reach a diagnosis. However, data suggest that endometrial biopsy, which is relatively inaccurate in diagnosing benign causes of AUB, can be avoided in about 50% of postmenopausal women⁴⁰ and in 66% of premenopausal women if timed TVS reveals an endometrial thickness of less than 4 or 5 mm.⁴³ If TVS findings are suggestive of pathology or if they are equivocal, SIS can be added to distinguish between women who have focal causes of bleeding and those who have global thickening or normal cavities.³⁰ In fact, TVS can differentiate among women who:

• will benefit from operative hysteroscopy for excision and histologic diagnosis of a focal lesion
• should undergo office biopsy, with assurance that
• a midline or global abnormality will be accurately sampled
• can be observed or treated empirically with, requiring hormones.

Using this approach, researchers at a Danish sonography-based clinic completed a diagnostic evaluation and provided a definitive treatment plan for 98 (86%) of 114 women with AUB in one visit.⁵² Goldstein et al, using timed TVS, obviated the need for biopsy in 341 (79%) of 433 perimenopausal women with AUB (menorrhagia, metrorrhagia, or both).⁴³ The remaining 21% underwent additional diagnostic and/or therapeutic procedures, including SIS.

Use of these techniques has been impractical for many OB/GYNs because of cost concerns and logistics. As full-size machines range in cost from $30,000 to $250,000, their use is limited to a dedicated room in the offices of clinicians who have a particular interest in imaging. Even today, most gynecologic scans in the United States are performed by sonographers, not gynecologists, which means that patients must schedule another appointment at another site if they need to undergo TVS. Recently, however, miniaturization of sophisticated digital B mode and color Doppler energy TVS has made it possible to manufacture battery-powered units the size of a laptop computer but with high resolution. As expected, these machines are substantially less expensive than standard machines. This breakthrough has not only enabled most clinicians to afford this technology, but it has also allowed a single machine to serve several examination rooms or clinical sites. Now clinicians who wish to perform uterine imaging themselves can purchase or lease these machines and become trained in their use, thereby maximizing the technology’s potential to improve women’s health care.

CONCLUSION

Clinical research and experience suggest that use of TVS, when compared with other modalities, may enhance diagnostic accuracy and efficiency in women presenting with AUB. Potential benefits of routine inclusion of TVS in the initial evaluation include faster diagnosis (thereby reducing use of empiric treatment and hastening institution of proper treatment), less need for invasive procedures, and lower overall health care costs. Recent availability of less expensive, hand-carried ultrasound equipment that provides high-resolution images makes it feasible for TVS to become the standard for initial assessment of women with AUB by appropriately trained clinicians.

J. Kell Williams, MD, is director, Division of Gynecology, and Anna Parsons, MD, is director, Image-Based Gynecology, both in the Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa.

REFERENCES

1. Schappert SM. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1996 National Center for Health statistics. Vital Health Stat 13. 1998;134:1-37.
2. Long CA. Evaluation of the patient with abnormal uterine bleeding. Am J Obstet Gynecol. 1996;175:784-786.
3. Clarke A, Black N, Rowe P, et al. Indications for and outcome of total abdominal hysterectomy for benign disease: a prospective cohort study. Br J Obstet Gynaecol. 1995;102:611-620.
4. Chimbira TH, Anderson AB, Turnbull AC. Relation between measured menstrual blood loss and patient’s subjective assessment of loss, duration of bleeding, number of sanitary towels used, uterine weight and endometrial surface area. Br J Obstet Gynaecol. 1980;87:603-609.
5. Hill NCW, Oppenheimer LW, Morton KE. The aetiology of vaginal bleeding in children: a 20-year review. Br J Obstet Gynaecol. 1989;96:467-470.
6. Siegberg R, Nilsson CA, Stenman UH, Wilholm O. Endocrinologic features of oligomenorrheic adolescent girls. Fertil Steril. 1986;46:852-857.
7. Bacon JL. Dysfunctional uterine bleeding: diagnosis and treatment in the adolescent patient. The Female Patient. 2000(March suppl):21-27.
8. Wilcox LS, Koonin LM, Pokras R, et al. Hysterectomy in the United States, 1988-1990. Obstet Gynecol. 1994;83:549-555.
9. Ettinger B, Li DK, Klein R. Unexpected vaginal bleeding and associated gynecologic care in postmenopausal women using hormone replacement therapy: comparison of cyclic versus continuous combined schedules. Fertil Steril. 1998;69:865-869.
10. Hahn RG. Compliance considerations with estrogen replacement: withdrawal bleeding and other factors. Am J Obstet Gynecol. 1989;161:1854-1858.
11. Wingo PA, Huezo CM, Rubin GL, et al. The mortality risk associated with hysterectomy. Am J Obstet Gynecol. 1985;152:803-808.
12. Landis SH, Murray T, Bolden S, Wingo P. Cancer statistics 1998. CA Cancer J Clin. 1998;48:6-29.
13. Schiff M, Key CR, Gilliland FD, Becker TM. Ethnic differences in uterine corpus cancer incidence and mortality in New Mexico’s American Indians, Hispanics and non-Hispanic whites. Int J Epidemiol. 1997;26:249-255.
14. Parker SL, David KJ, Wingo PA, et al. Cancer statistics by race and ethnicity. CA Cancer J Clin. 1998;48:31-48.
15. Krettak JE, Arkin SI, Chaisilwattana P, Monif GR. Chlamydia trachomatis patients who used oral contraceptives and had intermenstrual spotting. Obstet Gynecol. 1993;81:728-731.Parsons AK, Lense JJ. Sonohysterography for endometrial abnormalities: preliminary results. J Clin Ultrasound. 1993;21:87-95.
16. Parsons AK, Londono J. Detection and surveillance of endometrial hyperplasia/carcinoma. In: Lobo RA, ed. Treatment of the Postmenopausal Woman: Basic and Clinical Aspects, 2nd ed. New York, NY: Lippincott Williams & Wilkins; 1999.
17. Van den Bosch T, Vandendael V, Wranz P, Lombard CJ. Cervical cytology in menopausal women at high risk for endometrial disease. Eur J Cancer Prev. 1998;7:149-152.
18. Davis A, Godwin A, Lippman J, et al. Triphasic norgestimate–ethinyl estradiol for treating dysfunctional uterine bleeding. Obstet Gynecol. 2000;96:913-920.
19. Ferrazzi E, Torri V, Trio D, et al. Sonographic endometrial thickness: a useful tool to predict atrophy in patients with postmenopausal bleeding. An Italian multicenter study. Ultrasound Obstet Gynecol. 1996;7:315-321.
20. Hoist J, Koseila O. Endometrial findings following curettage in 2018 women according to age and indications. Ann Chir Gynaecol. 1983:72:274-277.
21. Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding: a Nordic multicenter study. Am J Obstet Gynecol. 1995;172:1488-1494.
22. MacKenzie IZ, Bibby JG. Critical assessment of dilatation and curettage in 1029 women. Lancet. 1978;2:566-568.
23. Stovall TG, Solomon SK, Ling FW. Endometrial sampling prior to hysterectomy. Obstet Gynecol. 1989;73:405-409.
24. Grimes DA. Diagnostic dilation and curettage: a reappraisal. Am J Obstet Gynecol. 1982;142:1-6.
25. Smith JJ, Schulman H. Current dilation and curettage practice: a need for revision. Obstet Gynecol. 1985;65:516-518.
26. Stock R, Kanbour A. Prehysterectomy curettage. Obstet Gynecol. 1975;45:537-541.
27. Feldman S, Berkowitz RS, Tosteson ANA. Cost-effectiveness of strategies to evaluate postmenopausal bleeding. Obstet Gynecol. 1993;81:968-975.
28. Stovall TG, Ling FW, Morgan PL. A prospective randomized comparison of the Pipelle endometrial sampling device with the Novak curette. Am J Obstet Gynecol. 1991;165:1287-1290.
29. Goldschmit R, Katz Z, Blickstein I, et al. The accuracy of endometrial Pipelle sampling with and without sonographic measurement of the endometrial thickness. Obstet Gynecol. 1993;82:727-730.
30. Dubinsky TJ, Parvey HR, Gormaz G, et al. Transvaginal hysterosonography: comparison with biopsy in the evaluation of postmenopausal bleeding. J Ultrasound Med. 1995; 14:887-893.
31. Van den Bosch T, Vandendael A, van Schoubroeck D, et al. Combining vaginal ultrasonography and office endometrial sampling in the diagnosis of endometrial disease in postmenopausal women. Obstet Gynecol. 1995;85:349-352.
32. American College of Obstetricians and Gynecologists. ACOG Technical Bulletin 191. April 1994.
33. Gimpleson RJ, Rappold HO. A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. Am J Obstet Gynecol. 1988;158:489-492.
34. Fraser I. Hysteroscopy and laparoscopy in women with menorrhagia: a review of 276 cases. Am J Obstet Gynecol. 1990; 162:1264-1269.
35. Saidi MH, Sadler RK, Theis VD, et al. Comparison of sonography, sonohysterography, and hysteroscopy for the evaluation of abnormal uterine bleeding. J Ultrasound Med. 1997; 16:587-591.
36. American College of Obstetricians and Gynecologists. ACOG Criteria Set 16. May 1996.
37. Mendelson EB, Bohm-Velez M, Joseph N, Neiman HL. Gynecologic imaging: comparison of transabdominal and transvaginal sonography. Radiology. 1988;166:321-324.
38. Andolf E, Jorgensen C. A prospective comparison of transabdominal and transvaginal ultrasound with surgical findings in gynecologic disease. J Ultrasound Med. 1990;9:71-75.
39. Smith-Brindman R, Kerlikowske K, Felstein VA, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA. 1998;280:1510-1516.
40. Dijkhuizen FP, Brolmann HA, Potters AE, et al. The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities. Obstet Gynecol. 1996;87:345-349.
41. Di Naro E, Bratta FG, Romano F, et al. The diagnosis of benign uterine pathology using transvaginal endohysterosonography. Clin Exp Obstet Gynecol. 1996;23:103-107.
42. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. N Engl J Med. 1997;337: 1792-1798.
43. Goldstein SR, Zeltser I, Horan CK, et al. Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding. Am J Obstet Gynecol. 1997;177:102-108.
44. Parsons AK. Evaluation of postmenopausal endometrium. Ultrasound Obstet Gynecol. 1998;12:295-300.
45. Williams CD, Marshburn PB. A prospective study of transvaginal hydrosonography in the evaluation of abnormal uterine bleeding. Am J Obstet Gynecol. 1998;179:292-298.
46. Dijkhuizen FP, De Vries LD, Mol BW, et al. Comparison of transvaginal ultrasonography and saline infusion sonography for the detection of intracavitary abnormalities in premenopausal women. Ultrasound Obstet Gynecol. 2000;15: 372-376.
47. Shwayder JM. Hysterosonography as an alternative to office hysteroscopy. J Am Assoc Gynecol Laparosc. 1995;2:S77.
48. O’Connell LP, Fries MH, Zeringue E, Brehm W. Triage of abnormal postmenopausal bleeding: a comparison of endometrial biopsy and transvaginal sonohysterography versus fractional curettage with hysteroscopy. Am J Obstet Gynecol. 1998;178:956-961.
49. Widrich T, Bradley LD, Mitchinson AR, Collin RL. Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium. Am J Obstet Gynecol. 1996; 174:1327-1334.
50. Timmerman D, Deprest J, Bourne T, et al A randomized trial on the use of ultrasonography or office hysterography for endometrial assessment in postmenopausal patients with breast cancer who were treated with tamoxifen. Am J Obstet Gynecol. 1998; 179(1):62-70.
51. Bayer SR, DeCherney AH. Clinical manifestations and treatment of dysfunctional uterine bleeding. JAMA. 1993;269: 1823-1828.
52. Dueholm M, Laursen H, Knudsen UB. A simple one-stop menstrual problem clinic with the use of hysterosonography for the diagnosis of abnormal uterine bleeding. Acta Obstet Gynecol Scand. 1999;78:150-154.

back to top