Liquid-based endometrial cytology in the management of sonographically thickened endometrium

Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.     

Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women

Objective: The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women. Methods: We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening. Results: In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma. Conclusion: Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue.     

Endometrial morphology after 12 months of vaginal oestriol therapy in post-menopausal women

The endometrial effect of long-term vaginal oestriol (E₃) therapy for urogenital atrophy was assessed in 23 post-menopausal women. Hysteroscopic and histological examinations were performed in each patient to assess endometrial atrophy before treatment and after 6 and 12 months of therapy (0.5 mg vaginal E₃ for 21 days, then 0.5 mg twice weekly). The primary atrophie picture was confirmed at the end of the 6th month in all but one of the patients. In one case, the histology showed an abnormal stromal reaction with no epithelial alterations. Treatment was continued and after the 12th month complete atrophy was confirmed both hysteroscopicaliy and histologically in all patients. Efficacy as regards vaginal and urogenital complaints was good. Our results demonstrate that in women with endometrial atrophy effective and well-tolerated treatment with vaginal E₃ can be safely continued for up to 12 months.     

Oral dexketoprofen for pain treatment during diagnostic hysteroscopy in postmenopausal women

Objective: To assess the efficacy of dexketoprofen (DEX) in reducing pain at different stages of the hysteroscopic procedure in comparison with local anaesthesia in menopausal women. Methods: Menopausal patients affected by uterine bleeding submitted to diagnostic hysteroscopy, were randomised to receive either 25 mg DEX tablet (n=148) or intracervical injection of 5 ml mepivacaine 2% (n=150). Pain suffered during the procedure itself and 30, 60, 120 min after, was scored on the 11 point Visual Analogic Scale, recorded and analysed. Results: No statistical difference were noted during the procedure itself in both groups of treatment. Patients treated with DEX has significantly less postoperative pain. Conclusions: DEX is not superior to mepivacaine in reducing the discomfort of the procedure but does significantly reduce postoperative pain.     

The significance of a thickened endometrial echo in asymptomatic postmenopausal patients

Objective

The purpose of this study was to evaluate the significance of a thickened endometrial echo in an asymptomatic, postmenopausal patient.Study design: A retrospective review was conducted of all women who underwent transvaginal ultrasonography between January 2003 and August 2008, were found to have an endometrial thickness of at least 5 mm and were subjected to endometrial sampling.

Results

Sixty-five postmenopausal women, without vaginal bleeding underwent ultrasonographic evaluation with subsequent endometrial sampling. The mean endometrial stripe thickness was 9.7 mm (range: 5.4–22). Four (6.2%) cases of simple/complex hyperplasia were identified and two (3.1%) cases of atypical hyperplasia were diagnosed. Zero (0%) specimens were identified as adenocarcinoma. Twenty-eight (43.1%) polyps and eleven (16.9%) leiomyomata were identified.

Conclusion

The use of transvaginal sonography as a screening tool in this population is not validated and need not trigger routine evaluation.     

The prevention of endometrial cancer in postmenopausal women with progestogens

Due to adverse publicity alleging an increased risk of endometrial cancer with estrogen therapy, a prospective study was begun in 1976 to determine the incidence of this disease in postmenopausal women. During 5,025 patient-years of observation in 1976–1977, 6 adenocarcinomas of the endometrium were diagnosed for an incidence of 1.2: 1,000 postmenopausal women per year. No endometrial malignancies were detected in 2,552 patient-years of therapy with estrogens and progestogens. In 1,028 patient-years of observation where estrogens only was the therapy, there were 3 endometrial cancers for an incidence of 2.9: 1,000. Adenocarcinoma of the endometrium was found in 2 of the untreated group, which gave an incidence of 3.0: 1,000. The sixth endometrial cancer occurred in a patient using estrogen vaginal cream. During this same period, 139 perimenopausal and postmenopausal women were treated with progestogens for endometrial hyperplasia. The hyperplasia was reversed to normal endometrium in 133 patients (95.7%). Hyperplasia is a precancerous lesion and should be treated with either progestogens or hysterectomy. All postmenopausal women with a uterus should be given the Progestogen Challenge Test and the progestogen continued each month as long as bleeding follows. These methods will prevent most endometrial cancers.     

阴道超声和宫腔镜对绝经后阴道出血的诊断价值

目的绝经后阴道出血(PMB)是老年妇女常见症状。及时地对PMB进行病因诊断很重要。本研究旨在通过比较阴道超声(TVS)和宫腔镜(HSC)对PMB的诊断,分析其优缺点。方法取2001年1月~2005年10月在我院妇产科住院的PMB患者117例进行TVS检查,测量其子宫内膜厚度,随后进行HSC检查并行内膜活检。将TVS和HSC检查结果与病理检查进行分析比较。结果萎缩性子宫内膜厚度3.26~4.39 mm,病变组的内膜厚度与萎缩性子宫内膜均有显著的统计学差异,以子宫内膜厚度6mm作为阴道超声判断绝经后子宫内膜有无病理改变的临界值,其敏感度为96.53%,特异度为91.53%,阳性预测值为90.32%,阴性预测值为96.32%。结论TVS和HSC对诊断PMB的敏感性都很高,但HSC的特异性高于TVS。PMB患者应常规进行TVS检查,如子宫内膜厚度超过6 mm,应行HSC检查。     

超声监测联合宫腔镜诊断不孕患者子宫内膜异常的价值

目的探讨阴道超声和宫腔镜检查对不孕患者子宫内膜病变的诊断价值。方法对在我中心不孕门诊进行阴道超声、宫腔镜检查的152例患者分为两组进行对照分析。自然周期超声监测内膜回声异常的105例为研究组,超声监测内膜正常的47例为对照组。结果研究组宫腔镜检查确诊内膜病变为84例（80.00%）,对照组为4例（8.51%）,两组比较差异有非常显著性意义（P〈0.001）。研究组中,子宫内膜息肉占30.48%（32/105）,内膜增殖36.19%（38/105）,粘膜下肌瘤0.95%（1/105）,输卵管阻塞8.57%（9/105）,内膜炎症3.81%（4/105）;对照组异常内膜为内膜粘连4.25%（2/47）,内膜炎症4.25%（2/47）。以宫腔镜结果为金标准,经阴道超声监测对子宫内膜病变诊断的敏感度95.45%（84/88）,特异度67.19%（43/64）。研究组确诊内膜异常者84例,妊娠率46.43%（39/84）,对照组确诊为内膜正常者43例,妊娠率74.41%（32/43）,两组比较差异有显著意义（P〈0.05）。结论阴道超声是诊断不孕症患者宫腔内病变的一种简便、廉价、无创伤、诊断率高的方法,可以作为不孕患者宫腔镜检查的初筛,而宫腔镜检查则为内膜病变提供准确的诊断。     

Neuroactive steroids after estrogen exposure in depressed postmenopausal women treated with sertraline and asymptomatic postmenopausal women

Neuroactive steroids (NAS) allopregnanolone (ALLO), Allotetrahydrodeoxycorticosterone (THDOC) and dehydroepiandrosterone (DHEA) are important in the regulation of mood and behavior. Knowledge about these steroids in postmenopausal depression and the effect of estrogen on NAS is lacking. We elected to determine if there were differences in NAS between postmenopausal depressed women and age matched controls. We also investigated the effect of estradiol on NAS in post menopausal depressed women receiving a selective serotonin reuptake inhibitor (SSRI), and in non-depressed postmenopausal controls. As part of a previously published double blind study on estrogen acceleration of antidepressant action, post menopausal women with major depression receiving sertraline and healthy non depressed controls were randomized to transdermal estrogen patch 0.1 mg or placebo. NAS were measured at baseline and after 10 weeks of treatment. Depressed subjects were treated with sertraline 50 mg/day to 100 mg/day for 9 weeks. At the baseline and after treatment ALLO and DHEA were significantly lower in depressed women compared to controls. Although all depressed subjects experienced a positive clinical response, estrogen administration was not associated with changes in NAS in either the depressed or the asymptomatic postmenopausal women. The lower ALLO and DHEA in postmenopausal depressed women suggests that symptoms of depression may be influenced by the synthesis or fluctuation of these NAS. Estradiol exposure did not alter ALLO, DHEA, or THDOC, implying these NAS are unlikely to play a role in any mood changes in post menopausal women given estrogen therapy.     

Transvaginal sonography of the endometrium in women with postmenopausal bleeding

Objective: The purpose of this study was to determine the value of screening transvaginal ultrasonography for the evaluation of endometrial abnormalities in women with postmenopausal bleeding. Materials and methods: 250 women with postmenopausal bleeding underwent transvaginal ultrasonographic examinations before undergoing dilatation and curettage. Women who had any pelvic symptoms or were on hormone replacement therapy were excluded. Results: In 151 women, the histologic diagnosis was atrophic endometrium. In these patients, the mean endometrial thickness was 3.4 ± 1.2 mm. In 24 patients with endometrial carcinoma, the mean endometrial thickness was 16.5 ± 6.2 mm. The measurement included both endometrial layers (i.e. double layer). Thirty six cases of other pelvic pathologic conditions were discovered on ultra sonography. Conclusions: We believe that is reasonable to have a cutoff limit for normal postmenopausal endometrium at 5 mm. Endovaginal ultrasound is a valuable diagnostic instrument, as sensitive as dilatation and curettage, for detecting pathological conditions in the uterine mucosa.     

卵泡晚期均质子宫内膜的容受性研究

目的探讨卵泡晚期超声下均质回声子宫内膜的容受性。方法收集卵泡晚期超声下均质子宫内膜妇女14例（实验组）,分别于排卵前和黄体中期取子宫内膜组织,测定白血病抑制因子（LIF）、整合素αvβ3、基质金属蛋白酶-9（MMP9）及血管内皮生长因子（VEGF）水平,其结果与14例卵泡晚期三线征回声内膜妇女（对照组）相比较。结果卵泡晚期对照组和实验组子宫内膜腺体VEGF水平分别为1.39±0.46和0.96±0.37,差别有显著性（P=0.010）。对照组平均LIF、整合素αv、β3水平分别为2.59±0.61、2.60±0.73和2.83±0.57,均高于实验组的1.58±.99、1.85±0.72和1.92±0.91,差别有统计学意义（P=0.003、P=0.011和P=0.004）。结论卵泡晚期均质内膜妇女的子宫内膜容受性低于三线征内膜妇女。     

The safety of 52 weeks of oral DHEA therapy for postmenopausal women

Objective

The aim of this study was to evaluate the safety of 52 weeks of DHEA 50 mg daily oral dose given to postmenopausal women with low libido to improve sexual function.

Method

93 postmenopausal women were enrolled in a 52-week randomised, double-blind, placebo-controlled trial and received either DHEA 50 mg or placebo (PL) daily. The effects of DHEA versus placebo on lipid profile, insulin–glucose homeostasis and the endomentrium were assessed over 52 weeks.

Results

Oral DHEA, 50 mg/day, was not associated with any effects on blood lipids or insulin resistance. The pattern of breakthrough bleeding did not substantially differ between the DHEA and PL groups and no significant adverse endometrial effects were apparent.

Conclusions

The use of 50 mg oral DHEA did not significantly alter lipid profile, insulin sensitivity or adversely affect the endometrium in postmenopausal women.     

Diagnostic evaluation of the endometrium in postmenopausal bleeding: an evidence-based approach

Postmenopausal bleeding (PMB) is a common complaint in general gynecological practice. Women with PMB have around a 10% chance of having endometrial carcinoma and therefore PMB always needs further evaluation. This article summarizes the reviews on the subject and provides an overview of the use of diagnostic tools in patients with PMB. Four types of diagnostic test are described: sonographic measurement of endometrial thickness, endometrial sampling, hysteroscopy and saline infusion sonography. All four have been independently shown to be accurate in excluding endometrial cancer. However, neither in systematic reviews nor in international guidelines is consensus found regarding the sequence in which these methods should be employed in women with PMB. For measurement of endometrial thickness in symptomatic women, a cut-off value of 3mm is recommended, but the cost-effectiveness of this strategy has yet to be shown. Research should now focus on the incorporation of individual patient characteristics and pre-test probabilities for cancer in algorithms for the investigation of PMB, and the most cost-effective sequenced combination of the four types of test.     

Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women

Objective: To evaluate the endometrial thickness in different periods of a continuous–sequential HRT regimen and to correlate the ultrasonographic findings with the histological patterns. Methods: The study was structured in two phases. In the 1st phase, 37 postmenopausal women (group A) treated by at least 6 months with a conventional continuous–sequential hormonal replacement therapy (cs–HRT) regimen were enrolled. In all patients, the endometrial thickness was measured at the 7th, 14th, 21st and 25th day of the cycle using transvaginal ultrasonography (TV-USG). In the 2nd phase of the study, other 41 postmenopausal women (group B) were enrolled and treated with the same sc-HRT regimen. At entry and after six cycles of cs–HRT, an endometrial biopsy was performed. The endometrial pattern was related with endometrial thickness. Either the evaluations were performed immediately after progestogen withdrawal bleeding, as showed by 1st phase results. Results: The results of the 1st phase of the study showed a mean endometrial thickness significantly lower at 7th day of the cycle compared to 14th, 21st and 25th day (4.3±1.2 versus 6.6±2.9, 7.8±4.2 and 7.4±4.6 mm±SD, respectively). After six cycles of cs–HRT (2nd phase of the study), the mean endometrial thickness was significantly increased in comparison with basal values (4.2±1.5 versus 2.8±1.2 mm±SD; P<0.05). Endometrial biopsies showed 13 cases (39.4%) of atrophy and 20 cases (60.6%) of proliferative endometrium. Mean endometrial thickness in case of atrophy was lower than in presence of a proliferative endometrium (3.7±1.2 versus 4.4±1.4 mm±SD; not significant). Endometrial thickness was <4 mm in 16 cases (11 of atrophic and five of proliferative endometrium), between 4 and 5 mm in 15 cases (13 of proliferative and two of atrophic endometrium) and between 5 and 6 mm in two cases (either case of proliferative endometrium). Conclusions: The best timing for monitoring endometrial thickness during cs–HRT regimens is the period immediately after withdrawal bleeding improving the reliability of the ultrasonographic exam to identify endometrial pathologies.     

Testosterone and 17β-oestradiol secretion of the human ovary. II. Normal postmenopausal women,postmenopausal women with endometrial hyperplasia and postmenopausal women with adenocarcinoma of the endometrium

A study of the concentration of testosterone and of 17β-estradiol in blood drawn from the ovarian and cubital veins of normal oestrogen-deficient postmenopausal women and of postmenopausal women with signs of oestrogen activity, and the subsequent computation of the ovarian production rates of these two hormones, show that in the latter group of women there is a high ovarian secretion of testosterone. The theory is advanced that this ovarian-secreted testosterone is rapidly converted into 17β-oestradiol, and that, by thus increasing the levels of circulating oestrogens, ovarian-secreted testosterone contributes, albeit indirectly, to endometrial hyperplasia and possibly to endometrial carcinoma.