Effects of hormone therapy on estrogen synthesis from E1S in the mammary gland of postmenopausal women

OBJECTIVES: To investigate the effect of hormone therapy (HT) on the expression of hormone receptors and the ex vivo estrogen biosynthesis in the breast. METHODS: Comparative studies were carried out in breast tissue from 28 postmenopausal women undergoing breast surgery due to breast cancer (BC). Glandular breast tissue at least 1cm distant from the tumor was analyzed. Groups included patients having received HT (n=18), and non-user of HT (controls, n=10) prior to BC diagnosis. Steroid sulfatase (STS) activity was evaluated by incubating homogenized breast tissue with [3H]-estrone sulfate. Thin layer chromatography was performed to separate the products estrone (E1) and estradiol (E2). Histomorphometry for breast tissue composition and immunohistochemistry for expression of estrogen receptor (ER) alpha and beta as well as progesterone receptor (PR) were performed. RESULTS: In all groups, significantly more E2 than E1 was produced. Local E2 formation was higher in women having been treated with estrogen and progestogen (p< or =0.05). Local EZ formation was positively correlated with ER alpha expression (r(s)=0.5; p=0.03). Histomorphometrical and immunohistochemical outcomes did not differ between groups. However, the amount of vessels was higher in women having been treated with HT compared to controls (p=0.09). CONCLUSIONS: Long-term HT increases local estrogen formation in normal human breast tissue.     

Obesity, estrone, and coronary artery disease in postmenopausal women

OBJECTIVES: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. METHODS: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at 1 and 2 years. Women were grouped according to their BMI (kg/m2) as normal (18.5< or =BMI<25), overweight (25< or =BMI<30) or obese (BMI > or =30), and by low and high estrone levels (<15 and > or =15pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. RESULTS: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p=0.074) of greater all cause mortality in women with low estrone levels (<15mL). In this model, adjusted for BMI, age [OR=1.08; p=0.03], C-reactive protein [OR=1.24; p=0.024] and hypertension [OR=6.22; p=0.003] were independent predictors of all cause mortality. CONCLUSIONS: Postmenopausal women with low estrone levels (<15pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed.     

Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts

Objective

To evaluate the effect of isoflavones derived from red clover extracts (MF11RCE) over anxiety and depressive symptoms among postmenopausal women.

Methods

One hundred and nine postmenopausal women aged 40 or more were randomly assigned to receive two daily capsules of MF11RCE (80 mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Anxiety and depressive symptoms were measured at baseline, 90 and 187 days with the Hospital Anxiety and Depression Scale (HADS) and Zung's Self Rating Depression Scale (SDS).

Results

After receiving the MF11RCE compound the total HADS (anxiety and depression subscale scores also) and the total SDS scores decreased significantly. This effect was equivalent to a 76.9% reduction in the total HADS score (76% for anxiety and 78.3% for depression) and an 80.6% reduction in the total SDS score. After placebo, total HADS (anxiety and depression subscale also) and total SDS scores also decreased significantly in comparison to baseline but only equivalent to an average 21.7% decline.

Conclusion

Red clover derived isoflavones (MF11RCE) were effective in reducing depressive and anxiety symptoms among postmenopausal women.     

Factors related to postmenopausal muscle performance: a cross-sectional population-based study

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm^–2 kg^–1 and N kg^–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.     

Hormone therapy and affect

This study investigated the influence of hormone therapy on affect in a double blind crossover trial. The sample consisted of 49 women who had previously undergone hysterectomy and bilateral oophorectomy. Therapy consisted of 3 mth each of ethinyl oestradiol — 50 μg/day, levonorgestrel — 250 μg/day, “Nordial” — a combination of these two substances, and placebo. Affect was measured by the Hamilton Depression Rating Scale, verbal reports by women and self-ratings on visual analogue scales. Ethinyl oestradiol was found to have a beneficial influence on aspects of affect such as Hamilton scores, anxiety, irritability and insomnia.

The influence of hormones on Hamilton scores could be partly but not fully explained by the alleviation of hot flushes. Norgestrel showed less favourable changes initially but these tended to diminish by the third therapy month. Most of the women studied were not clinically depressed. Anxiety symptoms were the major features exhibited in the group of women investigated. The results of this study suggest that visual analogue rating scales are of questionable validity in assessing affect in patients without any appreciable psychiatric morbidity.     

Efficacy and tolerability of estradiol 1 mg and drospirenone 2 mg in postmenopausal Korean women: a double-blind, randomized, placebo-controlled, multicenter study

Objectives

The aim of this study was to demonstrate that the therapeutic efficacy of an estradiol 1 mg/drospirenone 2 mg (E2/DRSP) preparation is superior to a placebo in postmenopausal Korean women with hot flushes and other climacteric symptoms, and to demonstrate that this treatment is both safe and tolerable.

Methods

This was a double-blind, randomized, placebo-controlled, multicenter study over four 28-day treatment cycles. A total of 158 subjects were screened and 90 women were randomized into two treatment groups (E2/DRSP group, n = 45; placebo group, n = 45). The primary efficacy parameter was the individual relative change of hot flushes. The secondary efficacy parameters such as other climacteric, urogenital symptoms and vaginal bleeding patterns were also evaluated, and the occurrence of any adverse events was noted. In addition, physical, gynecological examinations and laboratory analyses were performed at the beginning and end of the study.

Results

The mean number of hot flushes per week during treatment weeks 3–16 decreased by 48.1% during treatment with placebo, and by 84.4% during treatment with E2/DRSP (p < 0.001). The E2/DRSP combination also reduced the incidence and intensity of menopausal symptoms in postmenopausal women. Most of adverse events was mild or moderate degree of intensity. None of the parameters measured in the study, including laboratory analyses, physical and gynecological examinations, vital signs, and weight, led to any concerns of safety.

Conclusions

The E2 1 mg/DRSP 2 mg combination tested in the study was efficacious and safe in the treatment of hot flushes and other climacteric symptoms in postmenopausal Korean women.     

Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative

OBJECTIVE: To examine the prevalence and correlates of self-reported urogenital symptoms (dryness, irritation or itching, discharge, dysuria) among postmenopausal women aged 50-79. DESIGN: A cross-sectional analysis based on n=98,705 women enrolled in the US-based Women's Health Initiative observational study and clinical trials. Urogenital symptoms, symptom severity (mild, moderate, severe), and all covariates were self-reported through questionnaires at enrollment. Prevalence rates of each urogenital symptom were examined and logistic regression was used to identify potential correlates. RESULTS: Prevalence rates for each symptom were: dryness, 27.0%; irritation or itching, 18.6%; discharge, 11.1%; and dysuria, 5.2%. Four factors were correlated with two or more symptoms: Hispanic ethnicity (adjusted odds ratio (AOR)=2.1-3.1 versus white women across all symptoms), obesity (AOR=2.2 severe discharge versus none, AOR=3.6 severe irritation/itching versus none), treated diabetes (pills or shots) compared to no diabetes (AOR=2.4 severe dysuria versus none, AOR=3.2 severe irritation/itching versus none), and vaginal cream HRT/ERT compared to those who never used HRT/ERT (AOR=4.4 severe dryness versus none, AOR=4.6 severe irritation/itching versus none). Factors not associated with the symptoms included sexual activity, age, years since menopause, current smoking, marital status, gravidity, and natural versus surgical menopause. CONCLUSIONS: This is the first report to document urogenital symptoms by race/ethnicity among an exclusively postmenopausal population. We found an elevated prevalence of urogenital symptoms among women who are Hispanic, obese, and/or diabetic. Confirmation of our findings in these subgroups, and, if confirmed, analysis on why these populations are at greater risk, are areas for future research.     

绝经后子宫内膜增厚的研究进展

近年来,随着女性健康意识及超声检查技术的提高,超声发现绝经后妇女子宫内膜增厚的比例明显上升。根据有无阴道出血可将绝经后子宫内膜增厚分为绝经后子宫内膜增厚伴阴道出血及无症状的绝经后子宫内膜增厚。绝经后子宫内膜增厚的病因及病理类型复杂,早期无临床症状或仅表现为绝经后阴道出血(postmenopausal bleeding,PMB),诊断性刮宫或与宫腔镜检查联合是诊断子宫内膜病变的主要方式。目前子宫内膜厚度与子宫内膜病变的关系尚未明确,而对有无阴道出血的子宫内膜增厚的患者,对内膜增厚的评估的标准是不同的。根据子宫内膜厚度决定是否进一步检查以对子宫内膜病变做到早发现早治疗有重要意义。对绝经后子宫内膜增厚的发病原因、子宫内膜增厚的评估和诊疗进行阐述。     

阴道超声对行激素替代疗法的绝经后妇女子宫内膜形态变化的研究

目的 :探讨阴道超声观察绝经后行激素替代疗法 (HRT)妇女子宫内膜形态变化中的价值。方法 :对 1 0 2例绝经后行HRT妇女进行定期 (每年 3次 )经阴道超声检查 ,观察其子宫内膜厚度与形态并加以分析。结果 :HRT治疗后 1a内子宫内膜≤ 5mm的 71人 (占 6 9.6 %) ,6mm～ 8mm的 2 0人 (占 1 9.6 %) ,>8mm的 1 1人 (占 1 0 .8%) ,其中 4例伴阴道少量出血 ,诊刮结果 2例为萎缩性内膜 ,2例为内膜部分腺体上皮增生 ;第二年子宫内膜≤ 5mm的 89人 (占 87.3%) ,6mm～ 8mm的 1 3人 (占 1 2 .7%)。结论 :阴道超声对了解绝经后行激素替代疗法妇女子宫内膜形态变化有重要临床价值。当子宫内膜厚度 >8mm时 ,需进行进一步检查。     

宫腔镜在绝经后妇女子宫内膜病变中的诊治价值

目的探讨宫腔镜在绝经后子宫内膜病变中的诊治价值。方法回顾性分析2002年1月～2006年11月行官腔镜诊治的107例绝经后子宫内膜病变患者的临床资料，包括绝经后不规则阴道出血68例，B超检查子宫内膜增厚无阴道出血39例。并对手术时间、术中出血、并发症、术后病理和随访结果进行分析。结果106例顺利完成宫腔镜下检查及治疗，1例子宫穿孔，保守治愈。手术时间15～60min，（26．8±9．5）min，出血量10～60ml，（30．2±18．3）ml。术后病理结果：子宫内膜息肉69例（64．5％），黏膜下子宫肌瘤18例（16．8％），子宫内膜不典型增生12例（11．2％），子宫内膜癌2例（1．9％），正常子宫内膜6例（5．6％）。90例（84．1％）术后随访3～12个月，（6．0±3．8）月，其中8例子宫内膜息肉复发，再次宫腔镜手术治疗。结论官腔镜检查是绝经后子宫内膜病变首选的检查方法，可直视下观察子宫内膜的形态变化并取活检送病理；官腔镜治疗可以完整切除子宫内膜息肉、子宫黏膜下肌瘤等子宫内膜良性病变。