Selective estrogen-receptor modulators (SERM's) in postmenopausal women]

Selective oestrogen receptor modulators (SERMs) constitute a group of new drugs which mimic oestrogen in some organs and tissues but have an oestrogen antagonistic mode of action in other tissues. In postmenopausal women these compounds have a favourable effect on lipoprotein cholesterol levels in the blood and bone mineral density, thereby reducing fracture risk, especially in the vertebral column. In contrast to oestrogen therapy SERMs reduce the risk of mammary carcinoma. Currently tamoxifen and raloxifene are the best known SERMs. Tamoxifen increases endometrial hyperplasia and the risk of endometrial carcinoma. Raloxifene inhibits uterine tissue proliferation and does not appear to influence the endometrium directly. Raloxifene appears to be finding a place for itself in the treatment and prevention of osteoporosis in postmenopausal women. At this moment it is not yet possible to foresee what the impact of SERMs will be in the treatment and prevention of cardiovascular diseases and breast cancer.     

Tamoxifen: does a wider range of indications require more careful monitoring?]

Two patients, premenopausal women aged 48 years and 37 years, who were treated with tamoxifen following a mammary carcinoma operation, experienced abdominal complaints, hot flushes, vaginal discharge, an irregular menstrual cycle and/or concern about the increased risk of ovarian carcinoma. Transvaginal ultrasonography of the ovaries and laboratory tests indicated ovarian overstimulation. Both patients temporarily stopped using tamoxifen; in one of the patients both ovaries were ablated. The range of indications for treatment with tamoxifen has in recent years been extended to premenopausal patient groups and the length of treatment has been increased from two to five years. We recommend more extensive checks when prescribing tamoxifen to premenopausal patients in view of the possible adverse effects of ovarian stimulation associated with this treatment.     

Prospects for the primary prevention of breast cancer.

In this paper, the rationale, stage of development, and known or potential adverse effects of three potential strategies for the prevention of breast cancer are reviewed. Two methods--the use of tamoxifen in postmenopausal women and the use of luteinizing hormone (LH)-releasing hormone agonists in premenopausal women--involve hormonal manipulation. In the premenopausal period, the goal is to reduce the number of ovulatory menstrual cycles a woman experiences in order to reduce her exposure to estrogen and progesterone. Physical activity during adolescence is proposed as a nonhormonal method of accomplishing this. The use of LH-releasing hormone agonists to produce a reversible menopause can also reduce a woman's cumulative exposure to ovarian steroid hormones. Tamoxifen, which is effective in breast cancer therapy, provides endocrine control of estrogen-regulated breast tumor growth. Breast cancer chemoprevention trials using tamoxifen among postmenopausal women have been proposed, and pilot studies are under way.     

Survival impact of tamoxifen use for breast cancer risk reduction: projections from a patient-specific Markov model.

The authors estimate tamoxifen's impact on life expectancy among healthy women. A Markov model compared the effects of 5 years of tamoxifen on survival among 50-year-old postmenopausal women. Scenarios were explored using alternative assumptions with regard to tamoxifen's long-term effects on breast and endometrial cancer. Postmenopausal women without a uterus had substantial life expectancy gains from tamoxifen (1 to 4 months), whereas women with a uterus had such gains only if they were at a very high breast cancer risk. If tamoxifen's impact on endometrial cancer persists after treatment is discontinued, women at high risk for endometrial cancer have life expectancy losses from tamoxifen unless they are at a very high risk for breast cancer. The authors conclude that tamoxifen use among postmenopausal women is associated with substantial life expectancy gains. However, this benefit is modulated in women at increased endometrial cancer risk and depends on assumptions concerning tamoxifen's lingering effects on breast and endometrial cancer.     

Ki67 ER及PR在乳腺癌患者服用他莫昔芬后子宫内膜的表达及其性激素水平的变化

目的:探讨乳腺癌患者服用他莫昔芬后子宫内膜的ER、PR和ki67表达特点及意义,子宫内膜厚度变化与时间、年龄的关系。方法:通过对48例服用他莫昔芬的乳腺癌患者,常规阴式B超检查子宫双附件的情况,B超提示子宫内膜>5 mm,做诊刮术,其中16例诊刮的内膜组织送病理,做免疫组化ER、PR和Ki67。设未用药组为对照组,对30例病理提示未见子宫内膜病变标本进行免疫组化染色,检测子宫内膜组织中ER、PR和Ki67表达,B超检测子宫内膜的厚度。结果:①乳腺癌患者的B超结果:子宫肌瘤23例(47.92%),卵巢囊肿9例(18.75%),子宫内膜息肉1例(2.08%),子宫肌腺症4例(8.33%)。②他莫昔芬组子宫内膜腺体上的ER表达要强于正常子宫内膜(分泌期)的表达。服用他莫昔芬组内膜PR表达强于分泌期内膜腺体上表达。③他莫昔芬组与对照组:PR腺体上的表达与Ki67的阳性率相关性最强。结论:ER、PR的表达与Ki67的表达呈现正相关。绝经后服用他莫昔芬乳癌患者子宫内膜易增厚。服用他莫昔芬后诊刮的子宫内膜ER、PR(+++)的比率很高,并与Ki67表达有关。B超提示发现服用他莫昔芬有子宫肌瘤、卵巢囊肿、子宫内膜息肉、子宫肌腺症等妇科并发症。绝经后乳癌患者内膜厚度更容易增厚。     

Tamoxifen effects on endometrium

BACKGROUND: To evaluate the effects on the endometrium of a long term treatment with Tamoxifen in postmenopausal patients, asymptomatic for gynecologic disorders, surgically treated for breast cancer. METHODS: Setting: Outpatient menopausal clinic and endoscopic unit. Patients and interventions: 45 patients (Group I) were treated with 20 mg of Tamoxifen daily for a mean of 23.4 months. Seven patients (Group II) represented the control group and did not receive Tamoxifen. A transvaginal ultrasonography and a hysteroscopic guided biopsy were performed in all patients. RESULTS: Sagittal sonograms showed abnormal endometrial thickening (range 8-32 mm, mean 13 mm) in 17 patients (35.4%) of Group I and in 1 patient of Group II. Pathology on endometrial tissue sampling obtained at the time of hysteroscopy showed hyperplastic endometrial polyps in 3 patients (6.25%), endometrial hyperplasia in 16 patients (33.4%), while 1 patient had an endometrial polyp cancer on a background of hyperplasia and 1 had a superficial endometrial cancer (4.1%). Out of the 7 patients of Group II, one had an endometrial polyp, while 6 had no relevant endometrial abnormalities. CONCLUSIONS: Our study confirms that Tamoxifen treatment is associated with an increased incidence of proliferative and neoplastic endometrial changes. No obvious correlation was found between the length of Tamoxifen exposure time and occurrence of endometrial pathologies. It is mandatory to undertake twice per year gynecological evaluations for patients treated with Tamoxifen to promptly identify and correctly manage endometrial changes.     

Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat

Background  

Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat.     

Genital and subjective sexual arousal in postmenopausal women: influence of laboratory-induced hyperventilation

The current study was aimed at comparing genital and subjective sexual arousal in pre- and postmenopausal women and exploring the effects of heightened sympathetic nervous system (SNS) activity on these parameters. Seventy-one women (25 young and premenopausal, 25 postmenopausal, and 21 age-matched premenopausal women) participated in two counterbalanced sessions consisting of genital arousal assessment with vaginal photoplethysmography and subjective arousal assessment with self-report questionnaires. SNS activity was enhanced using laboratory-induced hyperventilation. Results demonstrated no significant differences between pre- and postmenopausal women on genital and subjective measures of arousal in response to neutral and erotic films. SNS manipulation increased genital excitement only in young, premenopausal women. These data suggest that prior SNS enhancement can differentiate pre- from postmenopausal genital arousal. Data also revealed significant correlations between genital and subjective sexual arousal in older pre- and postmenopausal women, but not in young premenopausal women. These data are the first to directly compare genital-subjective correlations between pre- and postmenopausal women.     

绝经后阴道流血或流液超声检查的诊断价值

目的:探讨绝经后阴道不规则流血或流液患者的超声影像对绝经后子宫内膜癌患者的诊断价值。方法:对42例绝经后阴道不规则流血或流液患者的子宫内膜超声影像进行回顾,分析其子宫内膜的厚度。结果:其中子宫内膜厚度≥5 mm且病理诊断为子宫内膜癌的患者有27例,符合诊断率72.97%,50～59岁年龄段中子宫内膜癌的发病率较其他年龄段高。结论:超声检查可作为子宫内膜癌及诊断性刮宫前重要的筛查方法,对临床上制定个体化治疗方案提供重要依据。     

Effects of Chlorogenic Acids on Menopausal Symptoms in Healthy Women: A Randomized,Placebo-Controlled,Double-Blind,Parallel-Group Trial

A reduction in estrogen levels in the perimenopausal and postmenopausal periods causes various symptoms in women, such as hot flushes, sweats, depression, anxiety, and insomnia. Chlorogenic acids (CGAs), which are phenolic compounds widely present in plants such as coffee beans, have various physiological functions. However, the effects of CGAs on menopausal symptoms are unknown. To examine the effects of CGAs on menopausal symptoms, especially hot flushes, a randomized, placebo-controlled, double-blind, parallel-group trial was conducted in healthy women. Eighty-two subjects were randomized and assigned to receive CGAs (270 mg) tablets or the placebo for 4 weeks. After 4 weeks of intake, the number of hot flushes, the severity of hot flushes during sleep, and the severity of daytime sweats decreased significantly in the CGA group compared to the placebo group. The modified Kupperman index for menopausal symptoms decreased significantly after 2 weeks in the CGA group compared to the placebo group. Adverse effects caused by CGAs were not observed. The results show that continuous intake of CGAs resulted in improvements in menopausal symptoms, especially hot flushes, in healthy women.     

COX-2、ER和PR在绝经后妇女子宫内膜息肉中的表达及临床意义

目的:通过评价环氧合酶2(COX-2)、雌激素受体(ER)和孕激素受体(PR)的表达探讨绝经后妇女子宫内膜息肉的可能发生机制。方法:对16例正常绝经后妇女的子宫内膜及35例并发子宫内膜息肉的绝经后妇女的内膜息肉及其邻近内膜行COX-2、ER和PR免疫组化测定并行半定量分析。结果:COX-2蛋白在绝经后妇女子宫内膜息肉腺上皮和间质细胞的表达明显高于患者子宫内膜组及正常对照组,各组中ER的表达差异无统计学意义(P>0.05),息肉组腺体和间质内PR的表达明显低于其他两组的表达(P<0.05)。结论:绝经后妇女COX-2和PR的异常表达在子宫内膜息肉的发生中起重要作用。     

左炔诺孕酮宫内缓释系统预防乳腺癌患者服用他莫西芬所致子宫内膜息肉分析

目的:探讨左炔诺孕酮宫内缓释系统预防乳腺癌患者服用他莫西芬所致子宫内膜息肉效果。方法:随诊103例围绝经期及绝经后服用他莫西芬妇女随机分成2组,其中55例在服用他莫西芬前放置曼月乐环,48例作为对照组。治疗前及他莫西芬治疗12个月后分别行经阴道超声检查子宫内膜厚度及宫腔镜检查子宫内膜病理。结果:放置曼月乐环组发生子宫内膜息肉风险明显低于对照组(1.8%∶15.5%,P=0.02),发生子宫黏膜下肌瘤风险两组间差异无统计学意义(1.8%∶3.4%,P=1.0)。结论:左炔诺孕酮宫内缓释系统降低乳腺癌患者服用他莫西芬所致子宫内膜息肉的发生。     

Sexually and well-being in early menopause. Effect of transdermal estradiol therapy.

BACKGROUND: This study focus on the effect of 6 months transdermal estradiol therapy (TTS) on the sexual behaviour and the quality of life in early menopausal women, complaining of uncomfortable menopausal symptoms. METHODS: Three hundred and sixty-two postmenopausal women, aged 48-56, participated in this study. One hundred and seventy-one of them were given continuous solid matrix patch TTS 50 mg/day for 6 months. Sexual behaviour, menopausal symptoms and well-being were evaluated through a self-rating method. We used a structured questionnaire with three obligatory answers (less/same/more) for each question--sexual life, hot flushes, touchiness, insomnia, blood pressure, work willing, memory loss, well-being--filled in by the women themselves or by the medical equipe after a telephone interview. RESULTS: Seventy five per cent of women aged 51-53 and 84% aged 54-56, who had been treated for 6 months with TTS showed a fall of sexual drive, if compared with, respectively, 62% and 48% of untreated subjects. Relief of hot flushes, touchiness and insomnia occurred in 80% of treated women, with slight differences among the various groups while 61% showed increase of well-being. CONCLUSIONS: The results of our study demonstrate that continuous TTS for 6 months decreased sexual drive in 69% of women, improved menopausal symptoms in 80% women but increased well-being only in 61% of women. These differences suggest that women's well-being does not seem linked only to the relief of menopausal symptoms and the impairment of their sexual life can play a negative role.     

绝经后出血338例临床与病理分析

目的:分析绝经后出血的原因。方法: 对338例绝经后出血的患者进行临床及病理生理检查, 对结果进行统计学处理和分析。结果: 良性疾病引起的绝经后出血占40 .24%, 非器质性疾病占34 .02%, 恶性肿瘤占25. 74%。子宫内膜病理检查显示萎缩性内膜占44 .93%, 其次为增生、癌性内膜。结论: 出血来自子宫最多见; 恶性肿瘤以子宫内膜癌和宫颈癌为主;出血年龄大, 距绝经的年限长或子宫增大者, 恶性肿瘤的发生率高; 出血多与子宫内膜受卵巢或异源性性激素刺激, 使内膜局部充血或血管病变有关。     

ERα和ERβ在绝经后子宫内膜息肉中的表达及临床意义

目的：研究不同雌激素受体亚型（ERα,ERβ）在绝经后子宫内膜息肉中的表达及临床意义。方法：采用免疫组化方法对绝经后正常子宫内膜和子宫内膜息内中雌激素受体α和β进行叫定。结粜：免疫组化方法硷删ERα、ERβ在以上两组的阳性率,提示ERα在绝经后子宫内膜息内中呈高表达,ERβ在正常绝经后子宫内膜及子宫内膜息肉中均呈低表达。结论：绝经后局部雌激素受体表达失衡,尤其是ERα高表达,是造成子宫内膜息肉的重要原因之一。     

Tamoxifen treatment of bleeding irregularities associated with Norplant use

ObjectivesTo evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use.Material and MethodsRandomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception.ResultsThere was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group.ConclusionTamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.     

The benefits and costs of tamoxifen for breast cancer prevention

OBJECTIVE: To estimate the effects of key uncertainties on the effectiveness and cost-effectiveness of breast cancer prevention with tamoxifen. METHODS: The incremental cost-effectiveness ratio of tamoxifen therapy relative to placebo was estimated using decision analysis with Markov modelling of health states, outcomes and costs for a simulated cohort of women at high risk for breast cancer. Relative effects of tamoxifen's benefits and harms were estimated from meta-analyses of randomised controlled trials. Cost estimates were based on Australian treatment patterns and costs. The main outcome measure was cost per quality-adjusted life year (QALY) gained with costs and effects discounted at a 5% annual rate. RESULTS: Tamoxifen therapy over five years reduces the incidence of breast cancer by approximately 1.4%, which is offset by an increase in endometrial cancer of 0.7% and pulmonary embolism of 0.2%. If the reduction is permanent (preventing new breast cancers emerging over five years and no further treatment effect thereafter), the model estimates an increase in life expectancy of 0.057 QALYs and an extra cost of $2,193; or $38,271/QALY gained. A model assuming further treatment effects of tamoxifen preventing new breast cancers emerging for up to 10 years results in an incremental cost of $19,354/QALY. However, if five years of tamoxifen therapy merely delays when these breast cancers appear (such that by 10 years there is no longer a reduced incidence), the incremental cost per QALY saved is estimated to be $199,149. CONCLUSIONS: Tamoxifen is potentially cost-effective in preventing breast cancer in women at high risk. However, its cost-effectiveness as a preventive therapy is highly sensitive to whether these cancers are permanently prevented or their clinical presentation is only delayed. Long-term follow-up in randomised controlled trials is therefore crucial in forming health policy.     

宫腔镜对绝经后子宫出血的诊治价值

目的:探讨宫腔镜技术对绝经后子宫出血的临床应用价值。方法:对2009年8月～2011年8月在吉林市妇产医院就诊的125例绝经后子宫出血的患者给予宫腔镜检查,行取环术或活检、宫腔镜电切,并送病理检查。结果:未取出节育环12例,三苯氧胺或激素替代后患者5例;萎缩性子宫内膜43例,子宫内膜增生26例,子宫内膜息肉24例,黏膜下子宫肌瘤8例,子宫内膜癌6例,低度恶性子宫内膜间质肉瘤1例,病理符合率分别为90.7%、76.9%、83.3%、100.0%、100.0%、0.0%。结论:宫腔镜对绝经后子宫出血的诊治无可替代,病理符合率高。     

绝经后无症状子宫内膜增厚妇女256例临床分析

目的:探讨绝经后无症状子宫内膜增厚的临床处理。方法:对256例绝经后无症状、经阴道超声检查子宫内膜厚度≥5 mm妇女行孕激素试验(PCT)、宫腔镜检查或治疗、诊断性刮宫及病理检查。结果:171例妇女PCT阳性,活性内膜167例(97.66%),其中单纯性增生9例,复杂性增生5例,不典型性增生3例,子宫内膜癌1例,4者占总数的6.64%;85例PCT阴性,活性内膜19例(22.35%),无1例子宫内膜增殖症或子宫内膜癌,两组比较差异有统计学意义(P<0.05)。结论:绝经后无症状子宫内膜增厚妇女应行PCT检查,PCT阴性者可免于行诊断性刮宫,但应密切随访。     

雌激素对胰岛素抵抗的影响

目的：探讨雌激素对胰岛素抵抗的影响。方法：男、女冠心病及绝经前、后四组病人,分别测定其血糖、血胰岛素、葡萄糖耐量试验（ＯＧＴＴ）及胰岛素释放试验（ＩＲＴ）,并分别测定不同年龄组健康妇女的ＯＧＴＴ及ＩＲＴ。结果：育龄组ＯＧＴＴ及ＩＲＴ水平较低,与男、女冠心病组及绝经组比较均有显著差异（Ｐ＜０．０５或Ｐ＜０．０１）。年龄＜４０岁及绝经前妇女的ＯＧＴＴ及ＩＲＴ水平较绝经后妇女低,其间有显著差异（Ｐ＜０．０５或Ｐ＜０．０１）。结论：绝经前后妇女的ＯＧＴＴ及ＩＲＴ的显著差异,推测可能与雌激素增强胰岛素敏感性、降低胰岛素抵抗（ＩＲ）有关