卵巢早衰与自然绝经妇女骨密度的对比观察

目的　比较卵巢早衰 (POF)与自然绝经妇女的骨密度 (BMD)。方法　 6 3例经DEXA确诊为骨质疏松的病人分为两组 :2 9例POF为A组 ,年龄 4 8～ 76岁 (6 2 1± 7 0 ) ;34例自然绝经妇女为B组 ,年龄 5 2～ 77岁 (6 3 4± 6 0 )。应用美国Hologic公司QDR4 5 0 0 W型双能X线骨密度仪测定A组和B组腰椎及股骨颈BMD。结果　A、B两组腰椎 2 4、股骨颈BMD相比 ,有显著性差异 (P <0 0 5 )。结论　POF比自然绝经妇女骨量丢失的早并且丢失的多 ,应及早应用HRT。     

福善美对绝经后妇女骨密度的影响

目的　评价福善美 (Fosamax)治疗绝经后骨质疏松症妇女的近期及中期疗效 ,以及改善骨量作用。方法　绝经 1年以上女性 80名 ,分成 4组 ,A组 :14例 ,年龄 5 4 . 97± 5. 5 1(47～ 6 2 )岁 ,绝经年限≤10年 ,疗程 6个月～ 1年 ;B组 :2 3例 ,年龄 5 5 . 5 5± 3. 6 6 (5 0～ 6 2岁 ) ,绝经年限≤ 10年 ,疗程 1年以上 ;C组 :18例 ,年龄 6 8. 18± 5 . 5 9(5 9～ 78岁 ) ,绝经年限 >10年 ,疗程 6个月～ 1年 ;D组 :2 5例 ,年龄6 7. 2 5± 6 .19(5 2～ 80岁 ,绝经年限 >10年 ,疗程 1年以上。患者每天接受口服福善美 10mg和元素钙5 0 0mg,疗程 6个月～ 2 8年。治疗前、后应用双能X线吸收仪 (HologicQDR 2 0 0 0型 )进行骨密度(BMD)测定。结果　 4组不论绝经年限长短 ,通过 6个月～ 2年以上福善美治疗 ,腰椎BMD平均增加百分率 3 74 %～ 5 4 5 % ,较基础值均有明显增加 (P <0 . 0 0 1) ,4组间差异无统计学意义 (P >0 . 0 5 )。股骨颈部位治疗后BMD平均增加百分率为 0 84 %～ 4 2 1% ,其中绝经年限相同时 ,疗程长者高于短者 ,即B组高于A组 ,D组高于C组 ;疗程相同时 ,绝经年限长者高于短者 ,即C组高于A组 ,D组高于B组 ,但 4组间差异无显著性 (P >0 . 0 5 )。大转子部位治疗后BMD增加平均变化百分率 1 4. 2 %～     

坤泰胶囊辅助治疗对绝经后骨质疏松症妇女骨密度、骨代谢和激素水平的影响

目的探讨坤泰胶囊辅助治疗对绝经后骨质疏松症患者骨密度、激素水平和骨代谢的影响。方法 150例绝经后骨质疏松症患者被随机分为治疗组、联合治疗组和对照组,每组50例。治疗组给予雷洛昔芬,联合治疗组给予雷洛昔芬加坤泰胶囊治疗,治疗12个月。检测治疗后两组患者髋部及腰椎的骨密度(bone mineral density,BMD)改变,同时测定血清雌二醇(estradiol,E2)、黄体生成素(luteinizing hormone,LH)、促卵泡剌激素(follicle stimulating hormone,FSH)、骨钙素(OC)和I型胶原交联C-末端肽(CTX-1)的水平,并记录治疗期间出现的药物不良反应。结果对照组的腰椎和髋部BMD在1年后较基线时有不同程度降低,比较差异有统计学意义(P0. 05);治疗1年后,治疗组和联合治疗组髋部及腰椎BMD都有不同程度的升高,且组间比较差异有明显的统计学意义(P0. 05);同时治疗组和联合治疗组血清CTX-1水平均降低,OC水平均升高,两组比较有明显的统计学意义(P0. 05);各组血清FSH和LH水平均降低,E2水平升高,两组比较有明显的统计学意义(P0. 05)。两组患者治疗时均未发现明显药物不良反应。结论坤泰胶囊辅助治疗有助于降低骨转换率,改善性激素水平,改善绝经后女性骨质疏松患者髋部及腰部的骨密度。     

应用小剂量利维爱对绝经后妇女的防治效果和意义

对绝经后妇女应用小剂量利维爱为期 3年的前瞻性研究。服药剂量每日 1 .2 5mg (1 / 2量组 ) 3 9例和每日 0 .62 5 mg (1 / 4量组 ) 1 2例。于用药前及用药后每 6个月随诊 ,分别观察骨密度、尿 Ca/ Cr比值、血脂 ,子宫大小、子宫内膜厚度 ,体重及副反应等。结果 :两组经 SPA、DXA和 QCT测量骨密度均有上升。以 QCT更为明显 ,其中 1 / 2量组治疗后上升 1 5 .4% ,与治疗前相比有显著差异 (P<0 .0 0 1 ) ,1 / 4量组治疗后上升 9.0 % ,与治疗前相比无显著差异 (P>0 .0 5 ) ;两组尿 Ca/ Cr比值相应的下降率分别为 1 1 .8%与8.6%。两组甘油三脂相应下降 1 6.5 %和 2 6.7% ;两组子宫内膜厚度虽有所增加 ,但平均厚度均未超过 0 .5 cm。以上各项两组相比均无显著差异 (P>0 .0 5 )。阴道出血率 2 6%(1 3 / 5 1 ) ,其中 77% (1 0 / 1 3 )为绝经 3年内开始服药 ,63 % (8/ 1 3 )为服药 1年内开始出血。体重在 1 / 2量组增加约 5 %而 1 / 4量组无明显增加 ,但两组相比也无明显差异 (P>0 .0 5 )。结论 :绝经后妇女应用 1 / 2量利维爱可提高骨密度 ,1 / 4量利维爱可维持骨量 ;甘油三脂均下降 ,参与保护心血管的作用 ,对子宫内膜无明显刺激作用。结果显示利维爱能有效地用于绝经后妇女激素替代治疗 ,但例数较少 ,年龄段有?     

微粉化17-β雌二醇阴道片治疗绝经后泌尿生殖道雌激素缺乏症状

目的 :验证微粉化 1 7β-雌二醇 ( E2 )阴道片剂治疗绝经后泌尿生殖道雌激素缺乏症状的疗效及安全性。方法 :61例主诉为泌尿生殖道雌激素缺乏症状的绝经后妇女 ,经阴道用微粉化 1 7-β E2 片剂 2 5μg,前 2周每日上药 1次 ,后改为每周 2次 ,疗程为 8周。分别于用药前、用药 2周及用药 8周评估症状及体征、阴道涂片成熟值 ( MV)及核致密指数( KPI)。阴道超声检查子宫内膜厚度 ,血 E2 、谷丙转氨酶 ( AL T)及血尿常规。结果 :经阴道给药后 ,阴道症状消失率为 84%～ 1 0 0 % ,泌尿道症状消失率为 62 %～ 95 % ;阴道健康评分、MV、KPI显著升高。阴道健康评分分别为用药前 7.3 0± 1 .60 ,用药 2周后 1 3 .90±1 .5 0 ,用药 8周后 1 4.1 0± 1 .3 5 ( P均 <0 .0 5 ) ;MV分别为 42 .3 0± 1 3 .0 0、5 3 .90± 4.1 0及5 1 .90± 4.70 ( P均 <0 .0 5 ) ;KP分别为 ( 0 .1 1± 0 .5 0 ) %、( 8.3 6± 9.2 1 ) %及 ( 5 .5 5±8.80 ) % ( P均 <0 .0 5 )。血 E2 水平显著上升 ,分别为 ( 1 3 .2 0± 6.2 0 )、( 2 8.80± 1 9.60 )及( 1 7.40± 1 0 .2 0 ) pg/ ml( P均 <0 .0 5 ) ,但仍处于绝经后水平 ,子宫内膜厚度无显著变化 ;AL T及血尿常规皆正常。结论 :微粉化 1 7β-E2 片剂能安全有效地治疗绝经后泌尿生殖道雌?     

促甲状腺素抑制对分化型甲状腺癌术后女性腰椎骨密度的影响

目的观察促甲状腺素抑制(thyroid-stimulating hormone suppression,TSHS)对分化型甲状腺癌(differential thyroid cancer,DTC)术后女性腰椎骨密度(bone mineral density,BMD)的影响。方法纳入225名2015～2016年期间DTC术后的绝经后妇女。将她们分为TSHS组[中位甲状腺素(TSH)0. 3μIU/mL]和绝经后对照组[中位甲状腺素(TSH)0. 3μIU/mL]。腰椎(L_(1～4))的BMD水平通过双能X射线吸收测定法(DXA)在基线和随访6、12和24个月检测。所有患者均补充钙和维生素D。骨量减少(-1 SDT≥-2. 5 SD)和骨质疏松症(T-2. 5 SD)的诊断根据WHO指南进行。结果 TSHS组有154名患者,未抑制的TSH组(绝经后对照组)有71名患者。在TSHS和未抑制TSH患者的治疗前后,基线和治疗前后6、12和24个月腰椎骨密度没有显著差异。与TSHS治疗前相比,2年随访时腰椎(L_(1～4))骨密度降低了1. 9%。TSHS组(103/152)和绝经后对照组(32/68)随访24个月时骨量减少和骨质疏松症患者数量发现有显著差异(χ~2=2. 88,P=0. 004)。TSHS不是骨丢失的重大风险,但会增加DTC绝经后妇女骨量减少的发生率。结论 2年的随访数据表明,TSHS对绝经后DTC女性的BMD几乎没有影响。     

脂肪因子Omentin-1、脂联素与中老年女性骨密度相关性研究

目的观察脂肪因子Omentin-1、脂联素与中老年女性骨密度之间的相关性。方法选取2017年3月至2018年4月在佛山市中医院就诊的338名女性,按照绝经状态分为围绝经期/绝经期组(n=194)和绝经后组(n=124)。将参研人员年龄、体质量指数(bone mass index,BMI)、腰围、吸烟状况、身体活动、脂联素、Omentin-1和激素进行多变量调整(ANCOVA),用于研究其脂肪因子和骨密度(bone mineral density,BMD)之间的潜在关系。结果与绝经后女性的腰椎BMD [(0. 69±0. 08)g/cm~2]相比,围绝经期女性的腰椎BMD[(0. 89±0. 09) g/cm~2]更高;在围绝经期/绝经期组女性中,脂联素和Omentin-1均与腰椎BMD无显著相关性(P0. 05);在绝经后组女性中,脂联素与腰椎BMD无相关性(P 0. 05);而在绝经后组女性中,Omentin-1与腰椎BMD呈显著负相关(P0. 05)。结论绝经后女性的Omentin-1与腰椎BMD呈负相关。     

雌孕激素连续联合替代疗法对绝经后妇女阴道流血及子宫内膜的影响

目的 :比较不同剂量倍美力与安宫黄体酮连续联合替代治疗对绝经后妇女子宫内膜的影响。方法 :绝经 1～ 4年的健康妇女 81名 ,年龄 43～ 59岁 ,随机入组 :I:倍美力 0 .62 5mg/ d、安宫黄体酮 2 mg/ d;II:倍美力 0 .3 mg/ d与安宫黄体酮 2 mg/ d(以上 2组均每日补充元素钙 60 0 mg) ;III:单纯补钙组。治疗时间为 2年 ,期间观察阴道出血、B超测量子宫内膜厚度并行子宫内膜病理检查。结果 :( 1 )治疗期间阴道无出血、少量出血、中等以上出血发生率 I组分别为 7%、1 9%、74% ,II组分别为 46%、3 6%、1 8,III组为85%、8%、8% ,差异显著 ( P<0 .0 0 1 ) ;3组出血月数分别为 7.5、1 .6及 0 .6月 ( P<0 .0 0 1 )。( 2 )各组治疗前后子宫内膜厚度无明显变化。 ( 3 )治疗 1年子宫内膜活检 ,I组增生、分泌、静止或萎缩内膜各 2例 ,2年后活检各为 1例 ,增生病例均为治疗前内膜厚度 >5mm、内膜活检为单纯增生者 ,无新的内膜增生病例发生 ;II及 III组内膜无增生。各组无复杂增生及不典型增生 ;阴道流血、子宫内膜厚度、子宫内膜病理之间无明确关系。结论 :倍美力 0 .62 5或 0 .3 mg/ d与安宫黄体酮 2 mg/ d连续联合治疗 2年对子宫内膜无明显致增生作用 ;倍美力 0 .62 5mg/ d与安宫黄体酮 2 mg/ d配伍不能完全逆转已增生     

绝经后妇女绝经年限、孕次、产次与腰椎骨密度的关系分析

目的 探讨绝经后妇女孕次、产次与腰椎骨密度(BMD)的关系。方法 调查204例健康的绝经后妇女年龄、绝经年限、孕次、产次、测量其身高、体重及正位腰椎BMD,并进行相关分析。结果 随着绝经年限的增加,腰椎各部位BMD逐渐降低。孕1-2次及产1次者的腰椎各部位BMD高于其他,并随着孕次和产次的增加BMD逐渐降低。单因素相关分析显示绝经年限与正位腰椎各部位BMD均呈显著负相关(P<0.01);孕次与第二腰椎(L2)、第三腰椎(L3)、第二腰椎至第四腰椎(L2-L4)呈显著负相关(P<0.05);产次与第二腰椎(L2)、第三腰椎(L3)、第二腰椎至第四腰椎(L2-L4)呈显著负相关(P<0.05)。但调整年龄、体重指数、孕次及产次后,绝经年限与正位腰椎各部位BMD均无显著相关(P>0.05)。调整年龄、体重指数、绝经年限后,孕次、产次与正位腰椎各部位BMD均无显著相关(P>0.05)。多元逐步回归分析显示绝经年限、孕次、产次与正位腰椎各部位BMD仍无显著相关(P>0.05)。结论 绝经后妇女绝经年限、孕次、产次与腰椎BMD的关系有待进一步研究。     

绝经前女性系统性红斑狼疮患者骨密度和骨代谢指标测定

目的 探讨绝经前女性系统性红斑狼疮(SLE)患者骨密度(BMD)和骨代谢指标的变化.方法 采用双能x线骨密度吸收仪(DEXA)测定178例绝经前女性SLE患者以及60例正常对照组的腰椎、股骨颈的骨密度以及T值,血钙、磷浓度,血清碱性磷酸酶(AKP)、血清骨钙素(BGP)、尿I型胶原交联氨基末端肽(NTX)水平,并将SLE组患者分为SLE初诊组与治疗组,分别对其数据进行统计分析.结果 SLE初诊组的腰椎BMD,股骨颈BMD及T值,血清AKP、尿NTX较正常对照组均无明显差异,而腰椎骨密度T值、血清BGP较正常对照组低(P＜O.05);SLE治疗组的腰椎BMD、T值和股骨颈1值,血清BGP低于正常对照组,但股骨颈BMD、血清AKP、尿NTX较正常对照组差异未达统计学意义;SLE治疗组的腰椎、股骨颈BMD与T值均显著低于SLE初诊组.SLE组的骨质疏松及骨量减少率分别为6.74%、16.85%.结论 绝经前SLE患者较同年龄正常女性易发生骨质疏松,血清BGP和腰椎骨密度可能较早反映骨质疏松的发生.     

Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.

Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. INTRODUCTION: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. MATERIALS AND METHODS: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. RESULTS: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. CONCLUSIONS: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.     

经皮用雌二醇凝胶预防绝经早期骨丢失用量的探索

探索经皮用雌激素凝胶对中国妇女预防绝经早期骨丢失的用量 ,进行 2年开放随机前瞻性研究。采用周期性联合应用雌孕激素 ,雌激素为经皮用雌二醇 (E2 )凝胶 ,孕激素为口服微粉化孕酮 (microprogesterone,MP)和醋甲羟孕酮 (MPA)。 60名妇女 ,身体健康 ,绝经 1～ 5年 ,随机进入 4组 :G1 :E2 1 .5 mg/ d+ MP1 0 0 mg/ d;G2 :E2 1 .5mg/ d+ MPA 2 mg/ d;G3 :E2 0 .75 mg/ d+ MP 1 0 0 mg/ d;G4:E2 0 .75 mg/ d+ MPA 2mg/ d。每日睡前应用 ,每月连用 2 5 d。用 SPA法测前臂骨密度 (CBMD) ;QCT法测腰椎松质骨骨密度 (TBMD) ;DEXA法测腰椎 (L 2 -4 )与髋部骨密度。分别在用药 0、 6、1 2、 1 8和 2 4个月时测量骨密度、骨代谢生化指标、评分绝经症状及骨质疏松症状及记录阴道出血。结果 :5 9名 (98% )完成 1年 ;5 6名 (93 % )完成 2年。用药 6个月时 4组症状平均缓解约 80 % ;2年时腰椎 TBMD平均升高 4.3 %～ 7.5 % ;L 2 -4升高 2 .7%～4.5 % ;股骨颈升高 2 .0 %～ 4.2 %。E2 1 .5 mg(G1 + G2 )与 E2 0 .75 mg(G3 + G4)比较 ,对骨密度的改善无显著性差异 (P=0 .0 7～ 0 .93 )。不规则阴道出血率 G2最高 (41 .3 % )、G3最低 (1 0 .2 % )。结论 :每日经皮用 0 .75 mg E2 凝胶可有效缓解绝经相关症状 ,预防绝经早期     

The Decrease in Serum Bone-Specific Alkaline Phosphatase Predicts Bone Mineral Density Response to Hormone Replacement Therapy in Early Postmenopausal Women

Hormone replacement therapy (HRT) prevents bone loss in postmenopausal women. Up to 20% of women demonstrate no increase in bone mineral density (BMD) on HRT. We examined whether early changes in serum bone alkaline phosphatase (B-ALP) predict long-term BMD changes in postmenopausal women on HRT. Ninety women within 1 year of menopause were randomly assigned to continuous or sequential estrogen/progestin (beta estradiol/norethisterone acetate) if naturally postmenopausal, or beta estradiol if within 1 month of surgical menopause. Spine, femoral neck BMD (DXA), and B-ALP were determined over 2 years. The mean percent BMD changes were 3.8%, 2.9%, 1.6% in the spine and 2.4%, 4.0%, 1.1% in the femoral neck in sequential, continuous, and estrogen alone treatment groups, respectively, significantly different from zero except for femoral neck BMD change in the estrogen alone group. HRT was associated with spine and femoral neck BMD loss in 17.4% and 25.3% of women, respectively. In estrogen/progestin-treated women, baseline B-ALP correlated with spine BMD change (r = 0.42, P < 0.01). At 3 months, B-ALP dropped significantly in the estrogen/progestin-groups with a maximal decrease at 12 months, but no change from baseline in the estrogen alone group. Using quartile analysis, women with the greatest drop in B-ALP (≥50%) at 6 months demonstrated the greatest gain in spine BMD at 2 years. A 40% decrease at 6 months in B-ALP had a 56% sensitivity, 83% specificity, 95% positive predictive value for spine BMD gain at 2 years. The decrease in B-ALP can be used to monitor BMD response to HRT. Received: 6 January 1999 / Accepted: 13 August 1999     

Long-Term Continuous Combined Hormone Replacement Therapy in the Prevention of Postmenopausal Bone Loss: A Comparison of High- and Low-Dose Estrogen–Progestin Regimens

We studied the effect of four continuous combined estradiol valerate (E₂V) and medroxyprogesterone acetate (MPA) dose combinations in six treatment groups (n= 70 per group) receiving regimens containing 1 mg or 2 mg E₂V combined to 2.5 mg or 5 mg MPA, on bone mineral density (BMD) and endometrium in 419 healthy postmenopausal women over 4 treatment years. In two groups the 1 mg dose of E₂V was increased to 2 mg after the first 6 months, while the MPA doses remained constant (2.5 mg or 5 mg). The remaining four groups received 1 E₂V + 2.5 mg MPA, 1 mg E₂V + 5 mg MPA, 2 mg E₂V + 2.5 mg MPA, or 2 mg E₂V + 5 mg MPA throughout the study. BMD at the spine and hip was measured by dual-energy X-ray absorptiometry and endometrial biopsy samples were taken at 6, 12, 24, 36 and 48 month follow-ups. Combinations containing the low dose of 1 mg of E₂V (with 2.5 mg or 5 mg MPA) resulted in a mean BMD increase of 6.2% at the spine and 2.9% at the femoral neck after 4 years of treatment. With 2 mg E₂V the corresponding increases were 7.4% and 2.9%, respectively. The largest increases in BMD were seen in women for whom the E₂V dose was doubled after the initial 6 months of treatment: 8.9% at the spine and 4.2% in the femoral neck. Both MPA doses (2.5 mg and 5 mg) effectively prevented estrogen-induced stimulation of the endometrium. No endometrial hyperplasia was observed in any of the treatment groups. Lower-dose combinations of continuous combined estrogen–progestin regimens are effective in increasing and maintaining BMD and provide a good endometrial safety profile for the long-term prevention of osteoporosis in postmenopausal women. Received: 15 February 2000 / Accepted: 3 May 2000     

Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women

Lower doses of conjugated estrogens (CE) alone or combined with lower doses of medroxyprogesterone acetate (MPA) increase mean bone mineral density (BMD) from baseline at the spine and hip in early postmenopausal women. However, not all women on therapy gain BMD. The incidence of continued bone loss (defined as a loss of BMD of >2% from baseline) among women using lower doses of CE and CE/MPA is unknown. This randomized, double-blind, placebo-controlled, multicenter substudy of the Womens Health, Osteoporosis, Progestin, Estrogen (Womens HOPE) trial investigated the incidence of continued bone loss with lower-dose CE and CE/MPA. Eight hundred twenty-two healthy postmenopausal women with intact uteri received CE 0.625, CE 0.625/MPA 2.5, CE 0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5, CE 0.3, CE 0.3/MPA 1.5 (all doses in mg/day), or placebo for 2 years along with 600 mg/day of calcium. Changes from baseline in spine and total hip BMD were compared among treatment groups in an intent-to-treat analysis. At 12 months, <10% of women on active treatment lost >2% of spinal BMD (except CE 0.3/MPA 1.5 [15.6%]), compared with 41.2% of women on placebo. At 24 months, the percentages of women on active treatment who lost >2% of spine BMD ranged from 4.5% with CE 0.45/MPA 1.5–15.6% with CE 0.3/MPA 1.5, compared with 55.2% of women taking placebo. More than 85% of women on active treatment did not experience continued BMD loss at the hip at 12 months and 24 months, in contrast to 30.6% of women on placebo at 12 months and 36.5% at 24 months. Women receiving active treatment who lost >2% of spine or hip BMD also had a lesser reduction in biochemical markers of bone turnover. In summary, continued bone loss among early postmenopausal women treated with lower doses of CE or CE/MPA is uncommon.This revised version was published online in January 2005 with corrections to Table figures.     

Endogenous estrogen levels and the effects of ultra-low-dose transdermal estradiol therapy on bone turnover and BMD in postmenopausal women.

In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment. INTRODUCTION: Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels. MATERIALS AND METHODS: We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) x 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to >or=80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI. RESULTS: Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels. CONCLUSIONS: The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment.     

Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1α-OH-vitamin D3 (alfacalcidol) for treatment of postmenopausal bone loss

We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women aged ≥60 years with low (T-score less than −1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day ± medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 μg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%–5.2%], 4.00% (95%CI 1.6%–6.4%), and 2.32% (95%CI −0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%–6.6%), 6.18% (95%CI 3.9%–8.5%), 7.17% (95%CI 4.3%–10.0%), and 8.75% (95%CI 6.0%–11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.     

Effects of Transdermal Estradiol Delivered by a Matrix Patch on Bone Density in Hysterectomized,Postmenopausal Women: A 2-year Placebo-Controlled Trial

This 2-year, double-masked, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy in preventing bone loss in postmenopausal women of two doses of transdermal 17β-estradiol (estradiol) delivered by a matrix patch, compared with placebo. One hundred and sixty healthy, hysterectomized postmenopausal volunteers aged 40–60 years with serum estradiol levels <20 pg/ml were started on treatment at four centers in The Netherlands. Every 6 months, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, non-dominant wrist and left hip, and markers of bone turnover were assessed in urine and serum. The treatment arms were: estradiol, 100 mg/day (E-100, n= 53), oestradiol, 50 mg/day (E-50, n= 54), placebo (P-100, placebo to E-100, n= 27 or P-50, placebo to E-50, n= 26). Treatment was continued for up to 2 years. After 24 months, BMD of the lumbar spine in the E-100 group differed by 7.7% [5.8–9.5%] (mean [95% confidence interval]) from the placebo group and showed a mean (s.e.m.) increase in BMD from baseline of 5.9% (0.69%). For the E-50 group the difference compared with placebo was 6.2% [4.4–8.0%] and the absolute increase was 4.5% (0.62%); in the placebo group, the absolute change was –2.3% (0.48%). In the total wrist, the changes were: E-100: difference compared with placebo 2.5% [1.5–3.6%], absolute increase 0.6% (0.3%); E-50: difference compared with placebo 2.9% [1.8–3.9%], absolute increase 0.7% (0.25%); and absolute change on placebo: –2.5% (0.35%). In the total hip, the changes were: E-100: difference compared with placebo 3.7% [2.2–5.2%], absolute increase 2.8% (0.5%); E-50: difference compared with placebo: 3.2% [1.8–4.7%], absolute change 2.4% (0.36%); and absolute change on placebo –1.4% (0.66%). Three markers of bone turnover – serum bone-specific alkaline phosphatase, serum osteocalcin and urinary CTX – fell significantly during the trial. Breast pain was reported by 8% of women on placebo, by 6% of women on E-50 and by 17% of women on E-100. Estradiol delivered by the E-50 matrix patch effectively reversed bone loss in hysterectomized postmenopausal women with few side-effects. The marginal additional gain in BMD with the higher dose may be offset by a more important side effect profile. Received: 9 May 2001 / Accepted: 29 August 2001     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Matrix Delivery Transdermal 17β-Estradiol for the Prevention of Bone Loss in Postmenopausal Women

A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17β-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1–4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7%± 0.7% with estradiol 25 mg/day, 7.3%± 0.7% with estradiol 50 mg/day and 8.7%± 0.7% with estradiol 75 mg/day (all values mean ± SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25–75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses. Received: 30 June 1998 / Accepted: 22 September 1998