Ultrasonography of the endometrium and endometrial pathology under tamoxifen treatment

PURPOSE: The estrogenic effects of tamoxifen on the endometrium and the vaginal epithelium are evaluated. METHOD: 211 postmenopausal women were examined (tamoxifen group: 176 estrogen-receptor positive breast cancer patients; control group I: 35 estrogen-receptor negative breast cancer patients; control group II: 50 women without breast cancer taking no hormones). We determined the endometrial thickness and the maturation index (MI). Person's chi-square-test and the t-test for independent samples were used. RESULTS: In the tamoxifen group, the mean endometrial thickness and the MI were significantly higher (p<0.0001) than in the control groups. No evidence of correlation in duration of tamoxifen intake and endometrial thickness was found (Pearson's correlation coefficient: 0.4773; p=0.0001). The maturation index significantly (p<0.0001) increased under tamoxifen therapy. There was no correlation in the maturation index and endometrial thickness (Pearson's correlation coefficient: 0.1649; p=0.169). The histological clarification (N=47; endometrial thickness greater than 8 mm) revealed 3 neoplasms, 9 endometrial polyps, 2 glandular-cystic hyperplasias and in 32 cases atrophic endometrium. CONCLUSION: An apparent increase of endometrial thickness and the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen was demonstrated.     

Recrudescent herpes labialis during and prior to early pregnancy

Objectives: To assess the experience of recrudescent herpes labialis (RHL) before and during early pregnancy. Methods: History of RHL prior to and during the first trimester of pregnancy was obtained from 3738 women attending at 10–15 weeks’ gestation. The influence of age, ethnicity, socioeconomic group, smoking behavior, and alcohol intake on RHL was assessed. Results: 1066 women (28.5%) reported a history of RHL lesions, with reduced incidence of RHL during pregnancy (0.111 lesions/subject per month) compared with outside pregnancy (0.19 lesions/subject per month) (P<0.0001). Those who did report lesions during pregnancy (n=296) experienced them at a higher monthly rate (0.41 lesions/subject per month) than before pregnancy (0.25 lesions/subject per month) (P<0.0001). RHL rate in early pregnancy was related solely to the previous rate of lesion recrudescence (P<0.001). Conclusion: Pregnant women with a history of RHL report reduced incidence of RHL during pregnancy.     

Maturation of Vaginal and Endometrial Epithelium in Postmenopausal Breast Cancer Patients Receiving Long-Term Tamoxifen

To assess the estrogenic effects of tamoxifen on vaginal and endometrial epithelium and to investigate whether these changes are associated with any pathological findings in the endometrium, 53 postmenopausal breast cancer patients receiving long-term tamoxifen and 52 control breast cancer patients without any hormonal treatment were examined. Pathological findings in the endometrium were evaluated by hysteroscopy and curettage. The main outcome measures were the maturation index in Papanicolaou (Pap) smears, estrogen-like epithelial changes in the endometrium, serum concentrations of gonadotropins, sex hormone-binding globulin (SHBG), estradiol (E2), and testosterone (T). Informative Pap smears showed estrogenic effects in 89% (41/46) of the tamoxifen group and in 49% (22/45) of the control group, and in endometrial aspiration samples in 71% (32/45) and in 41% (19/46), respectively. These changes were associated with increased concentrations of serum E2 in the control group but not in the tamoxifen group. All five patients (11%) with endometrial polyps in the control group showed estrogenic endometrial changes, whereas among 14 women with polyps in the tamoxifen group, 9 showed estrogenic changes and 5 endometrial atrophy. Endometrial adenocarcinoma was found in 3 patients in the tamoxifen group and in 2 in the control group. Pap smears showed atrophy in 2 patients in the former and in one in the latter group. These findings confirmed estrogen-like effects of tamoxifen on the vaginal and endometrial epithelium in postmenopausal breast cancer patients, but these were not closely associated with benign or malignant endometrial lesions.     

Meconium stained amniotic fluid in very low risk pregnancies at term gestation

Objective: To determine the prevalence and clinical significance of meconium stained amniotic fluid (MSAF) in a low risk population at term gestation and to investigate whether MSAF is a predictor for intrapartum and neonatal morbidity. Methods: A very low risk population including 37 085 consecutive deliveries at term composed the study population. A cross-sectional study was conducted and two groups of patients were identified according to the presence (n=6164) or absence (n=30 921) of meconium in the amniotic fluid at delivery and the outcomes of the two groups compared. Results: The prevalence of MSAF was 16.6%. The incidence of cesarean section (5.6% vs 2.3% P<0.01), instrumental deliveries (3.2% vs 1.8% P<0.01), fetal distress (6.5% vs. 2.1% P<0.01), clinical chorioamnionitis (0.2% vs. 0.1% P<0.01), post-partum infection (0.5% vs. 0.2% P<0.01), 1-minute Apgar score <3 (1.9% vs. 1.1% P<0.01), small for gestational age (7.4% vs. 6.4% P<0.01). was significantly higher in the MSAF compared with the clear amniotic fluid group. Intrapartum and neonatal mortality in this low risk population was significantly higher in the MSAF group ( ) compared with women with clear AF ( ). Conclusions: MSAF in a low risk population at term gestation is a predictor for adverse perinatal outcome and peripartum complications.     

Effect of long-term hormone replacement therapy on the bone in ovariectomized women with cancer

Objective: To evaluate longitudinally the effectiveness of long-term hormone replacement therapy (HRT) in preserving the bone mineral density (BMD) over a 5-year period in ovariectomized patients treated for gynecologic malignancies. Methods: A total of 70 pre-menopausal women ovariectomized for gynecologic malignancies at our hospital were divided non-randomly into two groups: HRT (+) group (n=59) and HRT (−) group (n=11). HRT was administered in a sequential regimen of 0.625–1.25 mg conjugated estrogen for 24 days and 5–10 mg medroxyprogesterone acetate for 10 days. Results: The BMD of the lumbar vertebrae decreased significantly in the HRT (−) group (pre-operative BMD was 91.8%, 91.0% and 91.3% at 1, 2 and 3 years post-ovariectomy), but no decrease in the BMD was observed in the HRT (+) group (pre-operative BMD was 98.4%, 99.0%, 99.4%, 98.8% and 98.7% at 1, 2, 3, 4 and 5 years post-ovariectomy); the difference in BMD between the two groups was statistically significant (P<0.01). Serum alkaline phosphatase levels were significantly lower in the HRT (+) group than in the HRT (−) group (P<0.01). There were four recurrences of cancer in the HRT (+) group. Conclusion: HRT appeared to have beneficial effects on bone metabolism by maintaining BMD for 5 years in ovariectomized patients for gynecologic malignancies.     

Dexamethasone compared with betamethasone for glucocorticoid treatment of postpartum HELLP syndrome

Objectives: To compare the efficacy of dexamethasone and betamethasone to ameliorate the course of postpartum hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: A prospective, mixed randomized/non-randomized clinical investigation of patients with postpartum HELLP syndrome. Treatment with either dexamethasone or betamethasone was continued until there was evidence of disease recovery. Results: Baseline characteristics of both the dexamethasone (n=18) and betamethasone (n=18) groups were similar. Although the time to discharge from the obstetrical recovery room was not statistically significant between groups, reduction in mean arterial blood pressure was more pronounced in the dexamethasone group as compared with the betamethasone group (−15.3±1.4 mmHg vs. −7.5±1.4 mmHg, respectively, P<0.01). Patients in the dexamethasone group required less antihypertensive treatment than the betamethasone group (6% vs. 50%, P=0.01) and also had a decreased need for readmission to the obstetrical recovery room (0% vs. 22%, P=0.03). Conclusion: This investigation supports the use of dexamethasone as the superior glucocorticoid to use for patients with postpartum HELLP syndrome.     

Hyaluronan in follicular fluids and fertilization of oocytes

Objective: To determine the concentrations of hyaluronan, E₂, and progesterone in follicular fluids (FFs) and the incidence of apoptotic granulosa cells. Also, to examine the relationship between the concentration of hyaluronan and follicular steroids, the incidence of apoptotic cells, and the fertilizability of the oocyte in the same follicle.

Design: Samples of 130 follicles were retrospectively analyzed for hyaluronan and steroids and the incidence of apoptotic cells.

Setting: The reproductive center in Yamagata University Hospital.

Patient(s): Forty women infertile because of tubal damage or unknown causes undergoing IVF treatment were selected.

Intervention(s): The samples were collected from follicle aspirations.

Main Outcome Measurement(s): The concentrations of hyaluronan and steroids in FFs, the incidence of apoptotic granulosa cells, and oocyte fertilizability.

Result(s): The levels of hyaluronan in FF were found to correlate positively with P (r=0.444, P<0.0001) and the incidence of apoptotic cumulus granulosa cells (r=0.387, P=0.002) and inversely with E₂ (r = −0.601, P<0.0001) and free T (r = −0.344, P=0.001). The concentration of hyaluronan in FFs containing a subsequently fertilized oocyte after insemination was significantly lower than that in FFs containing a subsequently unfertilized oocyte (P=0.0005) (fertilized, 50.0 ± 2.6 ng/mL; triploidy, 59.1 ± 6.8; and unfertilized, 66.9 ± 5.9).

Conclusion(s): The concentration of hyaluronan in FF is an indicator for estimation of oocyte viability for fertilization.     

Tamoxifen and giant endometrial polyps

Tamoxifen is a synthetic non-steroid anti-estrogen that has been used effectively for several years in the adjuvant treatment of breast cancer. Although its therapeutic effect is due to its anti-estrogenic properties, the drug also shows modest type B estrogen-receptor agonist activity during the menopausal period in which estrogens are at a low level. Owing to the fall in estrogen levels in menopause, tamoxifen provokes an up-regulation of both estrogen and progesterone receptors at an endometrial tissue is a direct consequence of this. This proliferation, which is the result of an inappropriate response of the basal layer and the basis for the onset of hyperplasia and polyps in the tissue. At standard therapeutic dosages, tamoxifen in postmenopausal women is associated with the onset of alterations in the vaginal and endometrial epithelium. Cases of endometrial hyperplasia, endometrial polyps, adenomyosis, endometriosis and fibromyomas are described in the literature. Endometrial polyps represent the most common pathology associated with TAM in women with previous breast cancer in menopause. The estrogenic stimulus to polyps following TAM treatment may be considerable, resulting in their growth to sizeable proportions, causing metrorrhagia and suspected neoplastic pathology. Two cases of patients receiving adjuvant treatment with tamoxifen for previous breast cancer, who presented two giant endometrial polyps of uncommon dimension, are reported.     

Efectos del tamoxifeno en el epitelio vaginal y los ovarios

Objective

To analyze the effects of tamoxifen on the vaginal epithelium and ovaries in patients treated with this drug for estrogen-dependent breast cancer.

Patients and method

We studied 92 women who received tamoxifen therapy for breast cancer from 2000 to 2003. The effects of tamoxifen on the vaginal epithelium and the association between this drug and the presence of ovarian cysts were analyzed.

Results

Although tamoxifen is an antiestrogenic drug, in postmenopausal women an estrogenic effect on the vaginal epithelium was found. Vaginal swabs showed estrogen stimulation in 87% of menopausal women receiving tamoxifen compared with 20.9% of the control group (menopausal women with breast cancer not receiving tamoxifen; p < 0.001).Ovarian cysts were found in 13% of the population studied, corresponding to women who were younger, premenopausal or with less than a year of menopause; the cysts resolved spontaneously. Only one patient underwent surgery due to abnormal Doppler findings corresponding to a hemorrhagic luteal cyst.     

Cancer of the endometrium caused by antiestrogens]

Tamoxifen is the most widely used non-steroidal antiestrogen compound for adjuvant treatment of postmenopausal breast cancer. Tamoxifen has both antiestrogen and estrogen-agonistic activity, which depends on the target tissue involved owing its systemic distribution. Upon the endometrium the agonistic estrogenic effect, so-called "paradoxical" effect, is suggested to induce proliferative changes such as hyperplasia or carcinoma. The authors report four cases of endometrial cancer developed in postmenopausal patients with breast cancer receiving tamoxifen. According to the literature data, the relationship of the tamoxifen to the endometrial remains uncertain: women with breast cancer are at increased risk for this neoplasm sharing common aetiologic hormonal factors and, in most published case reports, the uterine cavity has not been checked up before starting tamoxifen administration.     

Two different regimens of preinduction ripening of the uterine cervix with prostaglandin E2: a randomized clinical study

A randomized clinical study was designed to test the relative efficacy of preinduction cervical ripening with 0.25 mg prostaglandin E₂ (PGE₂), repeated if necessary (group 1) compared to a single maturation with 0.50 mg PGE₂ (group 2). In group 1 (n = 42), the ripening process was repeated every day until spontaneous onset of labor occurred or induction with oxytocin was decided (for improved Bishop score above 5, or maternal or fetal distress). In group 2 (n = 42) the patients who had not labored 12 h after the maturation procedure had labor induced with oxytocin, irrespective of their cervical status. In group 1, 28 patients experienced repeated maturations (from 2 to 9). Thirty patients had an induction of labor with oxytocin in group 2 and only 12 in group 1 (P < 0.0001). There were four failures of induction of labor in group 2 and none in group 1 (P < 0.05). Three episodes of myometrial hyperstimulation requiring an emergency cesarean section for acute fetal distress occurred in group 2 and none in group 1. There were 13 cesarean sections in group 2 and eight in group 1. The outcome of pregnancy was otherwise similar in both groups. In order to avoid failure of induction of labor, pre-induction cervical ripening with 0.25 mg PGE₂, repeated daily if necessary, is therefore recommended in high risk pregnancy unless a severe maternal or a fetal distress call for a prompt delivery irrespective of the cervical status.     

Transvaginal color Doppler ultrasonography for prediction of pre-cancerous endometrial lesions

Objective: To determine whether measurements of blood flow in endometrial and uterine vessels by transvaginal color Doppler ultrasonography was valuable in the diagnosis of a neoplastic endometrial pathology (hyperplasia and carcinoma) in women with abnormal bleeding. Methods: This is a prospective study and included 105 post-menopausal women and 33 pre-menopausal women with abnormal uterine bleeding. All subjects underwent transvaginal color Doppler ultrasonography. We investigated whether obtained results were correlated with histopathological findings. Results: There was no significant difference in the mean±S.D. RI of the left and the right uterine arteries, intramyometrial arteries and endometrial arteries between patients with neoplastic and non-neoplastic endometrium on histopathological examination. Doppler's velocity waveforms of small endometrial blood vessels could be detected in 9% of the women with non-neoplastic endometrium and in 42% of the women with neoplastic endometrium (P<0.05). The mean±S.D. of the endometrial thickness was significantly higher in the women with neoplastic endometrium than that of the women with non-neoplastic endometrium (16.6±6.1 mm vs. 9.5±4.7 mm, P<0.05). Conclusion: Doppler's velocity waveforms of uterine vessels coupled with transvaginal ultrasonography are not valuable enough to replace histopathological examination in the diagnosis of a neoplastic endometrial pathology. However, it may be helpful in cases in which invasive techniques are difficult to perform and in the differentiation of a certain group of patients at little risk of endometrial carcinoma.     

三苯氧胺对子宫内膜的影响

目的：观察乳腺癌患者服用三苯氧胺（TAM）后对子宫内膜的影响。方法：26例乳腺癌患者服用TAM（TAM组）后出现阴道异常出血或B超检查发现子宫内膜增厚而行宫腔镜检查及子宫内膜病理检查。另外以同时期无TAM服药史的非乳腺癌患者因绝经后阴道出血而行宫腔镜检查的78例作为对照组。结果：TAM组发生子宫内膜息肉和宫颈息肉共13例（50.0%）,而对照组为14例（17.9%),两组比较,差异有显著性（P＜0.05)。TAM组发生子宫内膜增生9例（34.6%),明显高于对照组的12例（15.4%,P＜0.05)。结论：乳腺癌患者长期服用TAM后子宫内膜病变增多,故对这些患者应进行B超监测子宫腔镜检查。     

Tamoxifen-induced endometrial changes in postmenopausal women with breast carcinoma.

OBJECTIVES: To assess the effects of tamoxifen (TAM) on the endometrium in postmenopausal women. METHODS: A case control study of postmenopausal women with breast carcinoma, who were undergoing treatment in the Department of Radiotherapy and Surgery at the Christian Medical College Hospital, Vellore, India was done. Thirty-five women who were on tamoxifen (20 mg/day) for a period of at least 6 months formed the study group. Thirty-three women who were not receiving tamoxifen, formed the control group. Subjects in both groups had a pelvic examination and transvaginal sonogram followed by endometrial biopsy. RESULTS: There was a statistically significant difference in the mean endometrial thickness between the study group and control group (7.8+/-6.4 mm vs. 4.0+/-2.0 mm, respectively) More women in the tamoxifen group had an endometrial thickness of >5 mm but the number of women with polyps or hyperplasia of the endometrium did not differ significantly between the two groups. There were no women with endometrial carcinoma in either group. CONCLUSION: All patients on tamoxifen need to be evaluated by clinical examination annually. A transvaginal sonogram and endometrial biopsy/hysteroscopy may be performed on patients with abnormal vaginal bleeding, bloody discharge, staining or spotting.     

Sonographic, hysteroscopic, and histologic evaluation of the endometrium in postmenopausal women with breast cancer receiving tamoxifen

STUDY OBJECTIVE: To evaluate the estrogenic effects of tamoxifen on the endometrium in postmenopausal women with breast cancer. DESIGN: Consecutive study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Thirty-three women. Interventions. All patients underwent transvaginal sonography (TVS) and color flow Doppler of endometrial vessels, hysteroscopy, and, if necessary, endometrial biopsy or other operative hysteroscopic procedures. MEASUREMENTS AND MAIN RESULTS: In four women the endometrium was thin on TVS and atrophic at hysteroscopic assessment. In 29 women with thick endometrium on TVS, hysteroscopy and endometrial biopsy showed atrophy (11 patients), hyperplasia (5), polyps (11), and well-differentiated adenocarcinoma (2). The two endometrial cancers were present in women with uterine bleeding. In women with positive histologic findings, the endometrium was significantly thicker (p = 0.04) and duration of tamoxifen therapy longer than in those with negative findings, although this was not statistically significant (p = 0.067). CONCLUSION: We believe regular assessment of the endometrium by TVS should be performed in postmenopausal patients at the start of the tamoxifen therapy, and hysteroscopy in women with a thick endometrium or postmenopausal bleeding. We believe that patients with thin endometrium on TVS at the beginning of tamoxifen therapy, who have no abnormal uterine bleeding should be screened with these examinations for 2 years.     

Transvaginal endometrial sonography in postmenopausal women taking tamoxifen

OBJECTIVE: To evaluate sonographic measurements of endometrial thickness in postmenopausal women taking adjuvant tamoxifen therapy for breast cancer, and to correlate sonographic and pathologic findings to symptoms and duration of tamoxifen therapy. METHODS: Medical records and sonograms of 80 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy were reviewed retrospectively. Endometrial thickness was recorded as a single-layer thickness and considered abnormal when greater than 2.5 mm for postmenopausal women. Sonographic endometrial thickness was correlated to histologic findings, symptoms, and duration of tamoxifen therapy. RESULTS: Fifty-seven of 80 postmenopausal women (69%) had single-layer endometrial thicknesses of 2.5 mm or greater, measured by transvaginal sonography, and 55 of 57 had endometrial biopsies or dilatations and curettage. Biopsies detected 24 cases of abnormal endometria, including endometrial carcinoma (two), breast carcinoma metastatic to the endometrium (one), endometrial polyps (13), tubal metaplasia (three), and benign endometrial hyperplasia (five). Using a single-layer endometrial thickness greater than 2.5 mm by transvaginal ultrasound, 21 of 24 (87.5%) women with abnormal endometria were detected. Women with abnormal pathologic findings had a significantly thicker mean single-layer endometrial thickness than those with normal findings, 7 mm versus 4 mm (P < .01). Twelve women had postmenopausal bleeding, all of whom had a single-layer endometrial thickness greater than 2.5 mm on transvaginal sonography. CONCLUSION: With a sensitivity of detecting endometrial abnormalities of 84%, transvaginal sonography was useful for studying postmenopausal tamoxifen-treated women.     

Drugs for the gynecologist to prescribe in the prevention of breast cancer: current status and future trends

Tamoxifen was approved for breast cancer prevention in October 1998. Thus, for the first time, we as gynecologists are being asked to prescribe this drug to healthy women. In the past each one of us has cared for women with breast cancer who have been treated with tamoxifen by oncologists or breast surgeons for the malignancy. Effects of tamoxifen on the uterus resulting in carcinomas, hyperplasia, and polyps are well known. Furthermore, tamoxifen has estrogenic properties in the venous system, increasing the incidence of deep vein thrombosis and pulmonary emboli. A new SERM (selective estrogen receptor modulator), raloxifene, has been approved for prevention and treatment of osteoporosis in postmenopausal women. It does not have stimulatory effects on the endometrium; however, it is estrogenic in the venous system. Preclinical data, as well as the breast cancer incidence reported in studies of the skeleton, seem to indicate that its effects in the breast are similar to those of tamoxifen. This article reviews tamoxifen and the new SERM, raloxifene, in an attempt to help gynecologists better understand each compound and what data are currently known, what we hope to learn from future studies, and what currently makes sense for clinical practice.     

Uterine effects of tamoxifen: a prospective study

The purpose of the study was to evaluate tamoxifen-associated changes in the vagina and uterus in postmenopausal breast cancer patients. Between June 1994 and December 1998, 45 patients enrolled in a prospective study before commencing tamoxifen therapy. Patients with endometrial thickness >5 mm or neoplasia were excluded. Transvaginal ultrasonography, vaginal maturation indexes (VMI), and endometrial biopsy were performed at baseline and repeated at 6 months (n= 42), 1 year (n= 39), 2 years (n= 32), 3 years (n= 26), 4 years (n= 19), and 5 years (n= 15). For the 39 patients followed for 1 year, VMI (% parabasal/intermediate/superficial) was 21/71/8 at baseline compared with 1/90/9 at 1 year (P value = 0.0008/0.001/0.78). At baseline, mean endometrial thickness and uterine volume were 2.6 mm and 64 cm(3), respectively, compared with 5.8 mm and 84 cm(3) at 1 year (P= 0.0002, 0.002). At baseline, 80% of patients had atrophic endometrium and 9% proliferative endometrium compared with 61% and 26% at 1 year, respectively (P= 0.04). No cases of endometrial hyperplasia or adenocarcinoma were detected. Findings observed at 6 months persisted through 5 years of follow-up. Tamoxifen exerts a weak estrogenic effect on the vagina and uterus in highly prescreened postmenopausal women without preexisting endometrial pathology.     

Expression of steroid receptors, Ki-67, and epidermal growth factor receptor in tamoxifen-treated endometrium.

Endometrial specimens of 34 (25 premenopausal and 9 postmenopausal) breast cancer patients receiving tamoxifen were immunohistochemically examined using estrogen receptor (ER), progesterone receptor (PR), Ki-67, and epidermal growth factor receptor (EGFR) antibodies. Proliferative (n = 6), secretory (n = 9), and postmenopausal (n = 6) endometria served as controls. The ER and PR expressions of the glandular cells in tamoxifen-treated patients did not differ from those of the glandular cells in the control women regardless of menopausal status. The Ki-67 index of glandular cells in tamoxifen-induced amenorrheic women was found to be lower than that of the proliferative glandular cells in the control women (p < 0.03), whereas the Ki-67 index of glandular cells in the tamoxifen-treated postmenopausal patients was higher than that of the glandular cells in the control women (p < 0.02). No EGFR overexpression was found in the glandular cells of the tamoxifen-treated premenopausal patients, but expression of EGFR was high in glandular cells of the tamoxifen-treated postmenopausal patients associated with a high Ki-67 index. In competition with ovarian estrogen secretion, tamoxifen may have an antiestrogenic effect on the endometrium, but tamoxifen probably has an estrogenic effect in the absence of ovarian estrogen secretion. This estrogenic effect of tamoxifen may be associated with an EGFR autocrine system.     

Endometrial histologic changes in post-menopausal breast cancer patients using tamoxifen.

OBJECTIVE: The aim of this study was to evaluate the effect of tamoxifen on the endometrium of post-menopausal women with breast cancer and to examine the relationship between ultrasonography, hysteroscopy and histopathologic changes. METHOD: Included in this longitudinal study were 303 post-menopausal women taking 20 mg daily of tamoxifen. Hysteroscopy was performed in 83 patients with an endometrial thickness of only >or=5 mm and 34 with vaginal bleeding also. Forty-five asymptomatic patients (control group) underwent hysteroscopies. RESULT: The most frequent outcome in patients with endometrial thickness of only >or=5 mm was an atrophic endometrium in an empty cavity (79.5%) whereas simple hyperplasia (35.3%) was found in women with vaginal bleeding. Carcinoma was diagnosed in seven cases (5.9%). In the control group, no endometrial cancer was found. CONCLUSION: This study suggests that patients with a thickness >5 mm should be offered a whole hysteroscopic evaluation, whenever bleeding is reported.