Withdrawal of Hormone Replacement Therapy is Associated with Significant Vertebral Bone Loss in Postmenopausal Women

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17β-estradiol given percutaneously or 50 μg/day of 17β-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 ± 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 ± 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (−1.64%± 1.3% vs −1.52 ± 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: −0.83%+ 1.35% in the study group vs −0.70%± 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (−0.13 vs −0.89, p<0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed. Received: 25 July 2000 / Accepted: 5 December 2000     

围绝经期与绝经后异常子宫出血原因的分析

目的探讨围绝经期与绝经后异常子宫出血的原因.方法结合B超检查、分段诊刮、宫腔镜检查及病理检查等多种方法,对394例围绝经期异常子宫出血及201例绝经后异常子宫出血患者进行回顾性分析,了解异常子宫出血的原因.结果围绝经期组异常子宫出血的病因构成比分别是:非器质性因素17.5%、良性病变68.8%、恶性肿瘤及癌前病变13.7%;绝经后组异常子宫出血的病因构成比分别是:非器质性因素28.4%、良性病变37.7%、恶性肿瘤及癌前病变34.3%.围绝经期组与绝经后组的病因构成比的差别具有统计学意义(P<0.01).结论围绝经期异常子宫出血以良性病变为主,绝经后异常子宫出血以良性病变、恶性肿瘤及癌前病变为主.结合B超检查、分段诊刮、宫腔镜检查及病理检查等检查手段能对围绝经期与绝经后异常子宫出血的患者做出病因诊断.     

阴道使用雌激素治疗绝经后妇女反复泌尿系统感染的初步观察

目的探讨阴道使用雌激素治疗绝经后妇女反复泌尿系感染的效果及可行性.方法将45例有反复泌尿系感染病史的绝经后妇女分成两组,分别使用结合雌激素(商品名倍美力),软膏30例(结合雌激素组),口服抗生素15例(抗生素组),疗程3个月.用药前、后分别行清洁中段尿尿常规检查、尿及阴道细菌培养,对阴道细胞成熟值及阴道健康情况进行评估.同时测定子宫内膜厚度及血清雌二醇水平.结果除结合雌激素组有3例自行停止治疗外,其余均完成治疗.治疗后结合雌激素组泌尿系感染的发生率(2/27)明显低于抗生素组(12/15),两组比较,差异有极显著性(P＜0.001).结合雌激素组阴道乳酸杆菌检出率达59.3%,抗生素组无乳酸杆菌出现.结合雌激素组阴道健隶评分(13.4±25)分;阴道细胞成熟值(74.6±14.1),分别明显高于抗生素组(5.2±0.4分;10.8±8.3),两项组问比较,差异均有显著性(P＜0.05).结论阴道局部使用雌激素,能有效减少绝经后妇女泌尿系感染的反复发作,较使用抗生素副反应轻,治疗效果明显提高.     

绝经后妇女腔内超声特点

目的通过腔内超声建立绝经后妇女正常子宫与卵巢体积的数值及形态图像,以便筛查异常子宫病变与异常卵巢体积与卵巢肿瘤.方法经阴道对绝经后3026例妇女进行TVS检查,测量子宫、卵巢的长、宽、厚三径.结果按具体公式计算出萎缩子宫三径之和＜11cm,卵巢体积应＜10cm3或8.8ml.结论经TVS检查是测量子宫与卵巢体积与形态的最佳方法,是筛查绝经后子宫病变与卵巢癌的首选方法.     

经阴道彩色多普勒超声对绝经后期子宫血流动力学的研究

目的 建立绝经后期子宫各段动脉血流参数的正常参考值范围,方法 应用经阴道彩色多勒对46例正常绝经后妇女的子宫动脉（UTA）,弓状动脉（AA）,放射动脉（RA）以及螺旋动脉（SA）的血流分别进行检测,66例正常生育期子宫和5例子宫内膜癌分别作为对照,结果 绝经后期正常子宫内膜面不见血流信号;UTA和RA的阻力指数（RI）随绝经时间的延长而增加。结论 绝经后期的子宫血流灌注减少,且随绝经后时间的延长而更为明显。     

绝经后妇女护骨素基因G1181C多态性与骨密度变化相关

目的　寻找护骨素基因(OPG)外显子中的单核苷酸多态性 (SNP),并分析其与绝经后妇女骨密度的关系。方法　在 205名绝经后妇女中,采用PCR和直接测序法确定OPG基因的SNP及基因型。应用双能X线骨密度仪测定腰椎和股骨颈骨密度 (BMD)。同时检测血清骨钙素 (BGP)、尿Ⅰ型胶原交联N端肽(NTx),以及血清护骨素(OPG)和核因子κB受体活化子配体 (RANKL)。结果　在OPG基因第一外显子中发现一个G1181C的SNP,该SNP的基因型频率分布依次为GG型占 0. 566、GC型 0. 346、CC型0. 088。去除年龄和体重的影响后,CC型的腰椎BMD明显高于GC和GG型 (P<0. 05),多元回归分析提示OPG基因型与绝经后妇女腰椎、股骨颈BMD相关 (P<0. 01)。Logistic回归分析显示OPG基因是绝经后妇女发生骨量减少和骨质疏松的独立危险因子,GG型发生骨量减少和骨质疏松的危险是CC型的 2. 83倍(P<0. 05)。结论　OPG基因的G1181C多态性与绝经后妇女BMD存在一定的关联,CC型对绝经后妇女腰椎BMD具有保护作用。     

北京地区9103例体检人群骨密度流行病学调查研究

目的调查北京地区9103例体检人群骨密度,探讨本地区原发性骨质疏松症流行病学情况。方法选择2012年3月-7月在我院体检的9103例汉族体检人群为研究对象,年龄16～93岁,采用韩国osteosys公司生产的ExA-3000型骨密度仪,检测受试者非受力侧前臂尺桡骨中远端1/3处骨密度,建立信息采集表,记录体检人群骨密度、身高、体重、体重指数(BMI)等情况,将检测结果以每10岁为一年龄段分组,分析每组骨密度、t、z评分、患病率及相关影响因素。结果北京地区男性、女性峰值骨量均发生在30～39岁年龄段,骨峰值分别为0.528±0.072、0.451±0.067,随着年龄的增长,骨密度逐渐降低,骨质疏松症发病率逐年增高;男性、女性30岁以前骨密度分别为0.47±0.107、0.436±0.060,骨质疏松症发病率分别为21.88%、1.33%;30～39岁骨密度分别为0.528±0.072、0.451±0.067,骨质疏松症发病率分别为7.31%、1.71%;40～49岁骨密度分别为0.52±0.071、0.445±0.065,骨质疏松症发病率分别为9.88%、2.3%;50～59骨密度分别为0.49±0.076、0.396±0.082,骨质疏松症发病率分别为20.83%、18.94%;60～69岁骨密度分别为0.463±0.085、0.328±0.071,骨质疏松症发病率分别为35.49%、52.21%;70～79岁骨密度分别为0.416±0.086、0.268±0.072,骨质疏松症发病率分别为57.31%、77.59%;80岁以上骨密度分别为0.384±0.091、0.222±0.059,骨质疏松症发病率分别为71.37%、95.24%。低BMI人群骨质疏松症发病率明显高于正常和高BMI人群,差距具有统计学意义(P0.05)。结论峰值骨量过后,随着年龄的增加,骨密度均呈下降趋势,骨质疏松症发病率显著上升,且女性绝经后骨量丢失明显加快,骨质疏松症发病率较同龄男性明显升高,差异具有统计学意义(P0.05)。值得关注的是,30岁以前的年轻男性骨密度状况也并不理想,可能跟工作繁忙,生活压力大,缺乏锻炼,生活方式不健康有关。因此,将骨密度检测作为中老年人体检的常规检查项目,早期发现,积极干预,同时加强年轻人群的健康宣教,倡导健康生活方式,提高峰值骨量,对于防治骨质疏松症具有重要意义。     

Nighttime melatonin secretion and sleep architecture: different associations in perimenopausal and postmenopausal women

BackgroundSleep quality typically decreases after menopause, but the underlying mechanisms are poorly understood. Concentrations of melatonin are lower and its secretion profiles different before and after menopause. However, whether and how melatonin and sleep architecture are associated in women of different reproductive states have not been examined to date.MethodsOvernight serum melatonin samples were taken from 17 perimenopausal and 18 postmenopausal healthy women. Sleep quality was measured with all-night polysomnography recordings.ResultsMelatonin concentrations tended to be the lowest during NREM sleep, and were associated with higher odds of transitions from wake to NREM sleep. The curves of predicted overnight melatonin values from linear mixed models varied according to sleep phases (NREM, REM, Wake) in perimenopausal, but not in postmenopausal women. In perimenopause higher melatonin area under curve (AUC) correlated with higher slow-wave activity (p = 0.043), and higher minimum concentrations with shorter slow-wave sleep (SWS) latency (p = 0.029). In postmenopause higher mean and maximum melatonin concentrations and AUC correlated with lower SWS percentage (p = 0.044, p = 0.029, p = 0.032), and higher mean (p = 0.032), maximum (p = 0.032) and minimum (p = 0.037) concentrations with more awakenings from REM sleep. In the age- and BMI- adjusted regression models, the association between higher maximum (p = 0.046) melatonin concentration and lower SWS percentage remained.ConclusionsThe relationship between melatonin and sleep architecture differed in perimenopausal and postmenopausal women. After menopause, high melatonin concentrations were associated with worse sleep. Whether these different patterns are related to aging of the reproductive system, and to decrease in menopausal sleep quality, remains to be elucidated.     

High Serum Osteopontin Levels Are Associated with Low Bone Mineral Density in Postmenopausal Women

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6±25.9 vs 26.3±18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.     

Association between Bone Mineral Density and Clinical Consequences: Cross-Sectional Study of Korean Postmenopausal Women in an Orthopaedic Outpatient Clinic

This study is to identify the characteristics of BMD and the related clinical consequences through a nationwide, consecutive, cross-sectional study. A total of 1,281 postmenopausal women was enrolled nationwide and underwent measurement for BMD using dual energy x-ray absorptiometry. Following the T-spine and L-spine plane radiography, they were evaluated for vertebral fracture by a semi-quantitative method using the Genant''s method. Relationship between BMD and osteoporotic fracture and a degree of deformity in vertebral fracture, treatment history in osteoporosis and the EQ-5D was analyzed. The distribution of the normal, osteopenia and osteoporosis group was 25.9%, 37.0%, and 37.2% in lumbar spine, and 31.4%, 45.3%, and 23.3% in femur neck, respectively. BMD in subjects with symptomatic or asymptomatic vertebral fracture was significantly lower than those without fracture. The femur neck and total hip BMDs were significantly lower in hip fracture group (0.646 g/cm² and 0.643 g/cm², respectively) and wrist fracture group (0.661 g/cm² and 0.712 g/cm², respectively) than in subjects without fracture (0.721 g/cm² and 0.712 g/cm², respectively). The BMD was significantly lower with more severe degree of deformity in vertebral fracture and lower scores in mobility, usual activities and pain/discomfort of the EQ-5D. In Korean postmenopausal women, the prevalence of osteoporosis and vertebral, hip and wrist fracture increase and quality of life decreases with lower BMD.

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