去卵巢山羊腰椎骨计量学指标的变化

目的　探讨用山羊制作绝经后骨质疏松动物模型的可行性。方法　切除山羊的双侧卵巢 (OVX) ,制备腰椎不脱钙骨切片 ,应用骨组织形态计量学方法 ,观察正常对照组 (3只 ,无手术处理 )、假手术组 (3只 ,开腹后缝合切口 )、OVX术后 6个月组 (4只 )、术后 18个月组 (5只 )腰椎骨计量学指标的变化。结果　OVX术后 6、18个月组的骨小梁体积占全部骨组织体积的百分比 [(7 9± 1 7)与 (5 8± 0 7) % ]、骨小梁体积占海绵骨体积的百分比 [(12 7± 1 8)与 (9 9± 0 6 ) % ]、平均骨小梁板密度 [(1 0± 0 2 )与 (1 1± 1 1)个 /mm]显著减少 (P <0 0 1) ;平均骨小梁板厚度 [(12 9± 4 5 )与 (95± 15 ) μm]也显著减少 (P <0 0 5 ) ;骨小梁表面和体积之比 [(16 6± 4 6 )与 (2 1 4± 3 1)mm2 /mm3 ]与平均骨小梁板间隙 [(10 0 4± 2 33)与 (95 3± 10 3) μm]则显著增加 (P <0 0 1) ;四环素单标记、双标记、1/ 2单标记与双标记表面之和占全部骨小梁表面的百分比 [(19 5± 3 8)与 (17 5± 1 0 ) %、(16 4± 3 3)与 (13 9± 2 5 ) %、(2 6 2± 5 1)与 (2 2 7± 2 9) % ],平均类骨质宽度 [(11 6± 1 1)与(12 0± 1 0 ) μm]、骨矿化延迟时间 [(2 3 6± 8 2 )与 (2 3 0± 6 1)d]、组织水平的骨形成速率     

卵巢切除和雌激素补充治疗对大鼠膀胱功能及结构的影响

目的通过对不同雌激素水平大鼠进行膀胱功能、组织形态和超微结构的比较,探讨雌激素对膀胱功能的影响及其作用机制。方法30只雌性成年SD大鼠均分为3组:OVX+E组(切除双侧卵巢后补充戊酸雌二醇0·8mg·kg-1·d-1,溶于0·5%羧甲基纤维素钠,每日灌胃1次)、OVX组(切除双侧卵巢)、正常对照组(未切除卵巢),后两组大鼠每日给予0·5%羧甲基纤维素钠灌胃1次。3组大鼠用药12周后行膀胱压力容积测定,并用切除膀胱的石蜡切片分析胶原纤维和平滑肌的面密度及两者比值,透射电镜下观察逼尿肌的超微结构。结果(1)OVX组膀胱最大容量(0·32±0·20)ml、顺应性(0·012±0·006)ml/cmH2O(1cmH2O=0·098kPa)和最大收缩力(1·4±0·4)cmH2O,相对于正常对照组[分别为(1·11±0·09)ml、(0·026±0·003)ml/cmH2O和(4·4±0·3)cmH2O]明显减少,差异均有统计学意义(P<0·05)。OVX+E组膀胱最大容量为(0·83±0·10)ml,相对于正常对照组减少(P<0·05),而膀胱顺应性(0·029±0·003)ml/cmH2O、最大收缩力(4·8±1·4)cmH2O与正常对照组比较,差异无统计学意义(P>0·05)。(2)胶原纤维面密度、胶原纤维面密度/平滑肌面密度比值,OVX组分别为0·218±0·041和0·54±0·08,相对于正常对照组(0·160±0·039、0·32±0·09)明显增加,差异有统计学意义(P<0·05);而OVX+E组(0·178±0·027、0·38±0·06)与正常对照组比较,差异无统计学意义(P>0·05)。(3)电镜观察OVX组逼尿肌超微结构出现退行性改变,其他两组无类似变化。结论大鼠切除双侧卵巢后膀胱功能明显降低,补充雌激素有利于改善膀胱功能,这一作用可能是通过抑制胶原增生,保护细胞器来实现的。     

莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗(OVX+E2)组和OVX后ICR治疗(OVX+ICR)组,每组40只.所有大鼠术后恢复2周后,再用相应的药物分别治疗1,2,3,4周,麻醉,心脏灌注,取脑,制作冰冻切片.免疫组化法观察各组大鼠下丘脑视前区5-HT1AR和5-HT2AR的表达.结果:①OVX组1-4周时大鼠下丘脑视前区5-HT1AR阳性细胞数量和吸光度均较同期Sham组增加;ICR和戊酸E2治疗1-4周后,OVX+E2组和OVX+ICR组大鼠下丘脑视前区室周带表达5-HT1AR的阳性细胞数量和吸光度均较同期OVX组减少.②下丘脑视前区中间带和外侧区5-HT2AR阳性细胞数量和吸光度的变化:OVX组大鼠,1-4周均较同期Sham组增加;ICR和戊酸E2治疗1周和2周后,OVX+E组和OVX+ICR组较同期OVX组增加;治疗3周和4周后,OVX+E2组和OVX+ICR组均较同期OVX组减少.结论:5-HT1AR和5-HT2AR在去卵巢大鼠下丘脑视前区的表达量均增加;ICR和戊酸E2治疗后,5-HT1AR在大鼠下丘脑视前区的表达量减少,而5-HT2AR在下丘脑视前区的表达先增多后减少.ICR可能通过调节下丘脑视前区体温调节中枢的5-HT1AR和5-HT2AR的表达,以缓解围绝经期的潮热症状.     

替勃龙上调卵巢切除大鼠腰椎护骨素mRNA的表达

目的:建立绝经后骨质疏松(postmenopausalosteoporosis,PMOP)的大鼠模型,研究替勃龙对卵巢切除大鼠腰椎组织中护骨素(OPG)基因mRNA表达水平的影响,探讨其预防和治疗PMOP的作用机制。方法:6月龄未交配健康雌性SD大鼠40只,随机分为SHAM组,OVX组,OVX+戊酸雌二醇(E2)组和OVX+替勃龙(tibolone,TIB)组。灌胃13周后处死动物,第四腰椎行骨组织形态计量指标测定,第二腰椎采用RT-PCR方法,对OPGmRNA表达水平进行检测。结果:OVX组大鼠较SHAM组TBV%显著下降;OSV%明显升高(P<0·05);E2和TIB均可使OVX大鼠的TBV%明显升高,OSV%明显下降;OPGmRNA表达水平在OVX大鼠组织中下调,与SHAM组相比有显著性差异(P<0.05),E2和TIB均可上调OVX大鼠骨组织OPGmRNA表达水平(P<0.05)。结论:E2和TIB均通过抑制骨转换预防和治疗PMOP;PMOP的发生与OPG有关,TIB和E2一样,其抗骨吸收效应很可能是通过OPG介导的。     

GnRHa和避孕药保护化疗所致卵巢损伤的比较研究

目的:探讨促性腺激素释放激素激动剂(GnRHa)和口服避孕药(OC,达英-35)对注射环磷酰胺(CTX)大鼠卵巢功能的保护作用。方法:实验分为6组:空白对照组、CTX组、OC组、GnRHa组、OC保护组、GnRHa保护组,每组15只,分别接受生理盐水、CTX、达英-35、GnRHa、达英-35+CTX、GnRHa+CTX注射或灌胃。阴道涂片观察大鼠动情周期,以放射免疫法检测血清雌二醇(E2)和卵泡刺激素(FSH)浓度,每组在停药当天、15天及30天分别处死5只大鼠,观察卵巢重量、卵巢结构及各级卵泡数目。结果:停药后30天,OC保护组和GnRHa保护组的E2浓度分别为51.33±2.00pg/ml、44.38±5.98pg/ml,FSH浓度分别为3.69±0.28mIU/ml、3.35±0.22mIU/ml,两组比较及与空白对照组(51.76±2.57pg/ml、3.44±0.20mIU/ml)相比,差异均无统计学意义;与CTX组(21.78±2.11pg/ml、6.24±0.22mIU/ml)比较,差异有统计学意义。OC保护组和GnRHa保护组的卵巢重量、卵泡数量与空白对照组相比,差异无统计学意义,明显高于CTX组,两组间比较差异亦无统计学意义。结论:GnRHa和口服避孕药均能减轻化疗药物对卵巢功能的损伤,从而保护卵巢储备功能。     

替勃龙对卵巢切除大鼠膀胱功能及结构的影响

目的:通过比较正常、卵巢切除及卵巢切除后补充替勃龙大鼠的膀胱功能和组织形态,探讨替勃龙对膀胱的影响及其作用机制。方法:30只雌性成年SD大鼠分为3组:正常对照组、切除双侧卵巢组(OVX组)、切除双侧卵巢后补充替勃龙组(OVX+Tib组)。用药12周后测定膀胱压力容积,Masson染色膀胱石蜡切片分析胶原纤维(CF)和平滑肌(SM)的面密度及二者比值。结果:(1)OVX组膀胱最大容量(0.32±0.20m l)、顺应性(0.012±0.006m l/cmH2O)和最大收缩力(1.4±0.4cmH2O)相对于正常对照组(分别为1.11±0.09m l、0.026±0.003m l/cmH2O和4.4±0.3cmH2O)明显减少,有统计学差异(P<0.01)。OVX+Tib组膀胱顺应性(0.022±0.003m l/cmH2O)与正常对照组比较无统计学差异(P>0.05),膀胱最大容量(0.87±0.26m l)及最大收缩力(3.3±1.0cmH2O)比正常对照组减少(P<0.05),但比OVX组增加(P<0.01);(2)CF面密度、CF面密度与SM面密度比值:OVX组(0.2180±0.0407和0.5396±0.0837)比正常对照组(0.1598±0.0387、0.3199±0.0860)增加,有统计学差异(P<0.01)。OVX+Tib组此两值(0.1893±0.0251、0.4249±0.0646)介于OVX组与正常对照组之间。结论:大鼠切除双侧卵巢后膀胱功能降低,补充替勃龙在一定程度上改善了膀胱功能,这可能是与它对胶原的抑制有关。     

子宫内膜异位症保留生育功能术后GnRH-a联合不同反向添加方案的临床分析

目的探究Ⅲ~Ⅳ期子宫内膜异位症(EMT)保守术后应用促性腺激素释放激素激动剂(Gn RH-a)联合戊酸雌二醇或替勃龙反向添加方案的临床效果。方法回顾性分析腹腔镜保留生育功能手术后Ⅲ~Ⅳ期EMT且应用Gn RH-a治疗的88例患者,按照反向添加药物分为Gn RH-a+戊酸雌二醇组(Gn RH-a+E组)、Gn RH-a+替勃龙组(Gn RH-a+T组)和Gn RH-a组(对照组)。分析其效果、不良反应和术后1年复发率。结果 Gn RH-a+E组与Gn RH-a+T组更年期生活质量评分表(MRS)评分均低于对照组(P0.05),且雌二醇(E2)水平高于对照组(P0.05);两组潮热出汗的发生率明显低于对照组(P0.05);三组患者术后1年内复发率比较,差异无统计学意义(P0.05);Gn RH-a+E组与Gn RH-a+T组疼痛视觉模拟评分(VAS)评分、MRS评分、E2水平、不良反应和术后1年内复发率比较,差异均无统计学意义(P0.05)。结论Ⅲ~Ⅳ期子宫内膜异位症保守术后应用Gn RH-a联合戊酸雌二醇或替勃龙的反向添加方案不影响Gn RH-a的治疗效果,具有相似的临床效果及安全性。     

吗啡对雌性大鼠性腺轴和骨组织的影响

目的:研究吗啡对雌性大鼠性腺轴和骨组织的影响。方法:选取3月龄雌性大鼠45只,随机分为吗啡组30只和对照组15只。吗啡组采用剂量递增法皮下注射盐酸吗啡12周,对照组注射同等体积的生理盐水12周。放射免疫法测定血清FSH、LH、E2、P;免疫组织化学检测下丘脑、垂体、卵巢雌激素受体(ER)和β-内啡肽(β-EP)的表达;原位杂交方法测定下丘脑、垂体和卵巢的μ-阿片受体mRNA的表达;双能X线骨密度测量仪测量不同部位的骨密度值;测量骨代谢生化指标;对骨组织切片进行形态计量分析;并用RT-PCR方法检测骨组织中雌激素受体(ER)mRNA的变化。结果:(1)吗啡组FSH、LH、E2、P基础分泌较对照组降低(P<0·01,P<0·05,P<0·01,P<0·05);(2)吗啡组大鼠性腺轴各组织中ER平均光密度值均显著降低(P均<0·01);(3)吗啡组大鼠下丘脑、垂体β-内啡肽的含量下降,而μ-阿片受体mRNA表达增强;(4)吗啡组大鼠股骨远侧干骺端和胫骨近侧干骺端骨密度以及骨组织中ERmRNA表达均较对照组显著下降(P<0·05),组织切片观察显示,吗啡组大鼠骨小梁纤细、断裂、形态结构完整性差,骨髓腔大小不一,对照组大鼠骨小梁粗壮、饱满、形态结构完整,骨髓腔相对较小,计量分析显示,吗啡组骨小梁面积明显低于对照组(P<0·05);骨代谢生化指标结果显示,吗啡组大鼠血清钙和尿钙以及TRAP、HOP较对照组增加显著(P<0·05)。结论:长期使用吗啡对下丘脑-垂体-卵巢轴及骨组织会有不同程度的损伤。     

促性腺激素释放激素激动剂对化疗损伤卵巢功能保护作用的实验研究

目的研究促性腺激素释放激素激动剂(GnRHa)对注射环磷酰胺(CTX)大鼠的卵巢功能的保护作用。方法80只Fischer344大鼠分为4组,即空白对照组、GnRHa组、CTX组及联合治疗组,每组20只,分别接受生理盐水、CTX、GnRHa和CTX+GnRHα注射,采用酶联免疫吸附实验和化学发光法测定各组大鼠卵泡刺激素(FSH)和雌二醇浓度的变化,在实验开始后第60、90天,各组分别处死一半大鼠,观察卵巢重量、卵泡数量及卵泡直径的变化。结果实验第90天,CTX组大鼠血清雌二醇和FSH浓度分别为(148·3±16·5)pmol/L和(16·90±1·90)U/L,明显高于联合治疗组的(91·8±9·9)pmol/L和(7·60±0·30)U/L,两组分别比较,差异有统计学意义(P<0·05);CTX组大鼠卵巢重量为(37·0±3·0)mg,低于联合治疗组的(71·0±5·0)mg,两组比较,差异有统计学意义(P<0·05);CTX组大鼠卵泡总数为(550±50)个,而联合治疗组为(1250±160)个,两组比较,差异有统计学意义(P<0·05)。结论GnRHa能够降低CTX对大鼠卵巢功能的损伤,从而保护大鼠卵巢储备功能。     

雷洛昔芬和依普黄酮对去卵巢大鼠骨干力学的影响

目的:研究雷洛昔芬和依普黄酮对切除成熟卵巢大鼠骨干生物力学性能的影响,探讨此两种药物治疗绝经后骨质疏松症的疗效。方法:选用6月龄未交配健康雌性Sprague-Dawley大鼠50只,随机分为5组,每组10只:(1)假手术组(sham);(2)骨质疏松组(OVX);(3)OVX加戊酸雌二醇组(Valerate Estriol,E_2;0．8mg·kg~(-1)·d~(-1));(4)OVX加雷洛昔芬组(Raloxifene,RLX;5mg·kg~(-1)·d~(-1));(5)OVX加依普黄酮组(Ipriflavone,IPR; 100mg·kg~(-1)·d~(-1));于去势手术3周后开始按分组设计喂药(灌胃),治疗3个月后处死。取大鼠右股骨及第三腰椎测定骨密度;然后对右股骨中段进行三点弯曲试验,测定多个股骨干生物力学指标。结果:(1)骨密度:OVX组椎骨及股骨干骺端密度明显下降,使用E_2和RLX能够显著提升骨密度;但股骨干密度各组间差异无统计学意义;(2)骨干生物力学性能:三点弯曲实验结果显示,OVX组股骨干生物力学指标较sham组明显下降,用RLX和IPR治疗与E_2一样可阻止这种变化(P＜0．05)。结论:雷洛昔芬和依普黄酮能阻止卵巢切除所致的成熟雌性大鼠股骨干(皮质骨)生物力学性能受损。     

The effect of clomiphene citrate on osteoporosis in ovariectomized rats

OBJECTIVE: The aim of this study was to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contraindication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. STUDY DESIGN: This study was carried out in the Experimental Surgery Laboratory of the Brain Research Centre of the Medical Faculty of Ege University. Four-month-old Sprague-Dawley rats were used for the experiment. The study was carried out on six groups of animals each consisted of eight rats. Four groups of rats were ovariectomized and 2 groups of rats were used as control group. For 6 weeks every day, rats were injected physiological saline solution (1 ml/kg), clomiphene citrate (1 or 10 mg/1 ml/kg, Organon), 17beta-estradiol (50 microg/1 ml/kg, within susame oil, Sigma) or susame oil (1 ml/kg, Sigma). Drug administrations were carried out according to the weekly weight measurements. Group 1(PSS), n = 8, non-ovariectomized, were injected with physiological saline solution. Group 2(CC-1), n = 7, non-ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 3(OVX + CC-1), n = 7, ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 4(OVX + CC-10), n = 6, ovariectomized, were injected with CC (10 mg/1 ml/kg). Group 5(OVX + E), n = 8, ovariectomized, were injected with 17beta-estradiol (50 microg/1 ml/kg). Group 6(OVX), n = 8, ovariectomized, were injected with susame oil (1 ml/kg) Bone-specific serum alkaline phosphatase (ALP) levels were measured and statistical analyses were made by Kruskal Wallis test. Left femur bone histomorphometric studies were done. The uteri were dissected out to measure their weight and ANOVA was used to show the intergroup differences. RESULTS: The level of ALP in group 3 was significantly higher than the other five groups. Bone histomorphometric examination showed that total bone volume in group 3, 4, and 5 was higher than group 6, and group 4 had the highest level of bone volume compared to the rest of the groups. Uterus weights in group 1 were significantly higher than group 3 and 6 (P = 0.02, P = 0.01) and uterus weights in group 5 were significantly higher than group 3 and 4 (P = 0.00, P = 0.01) CONCLUSIONS: In ovariectomized rats, treatment with CC is seen as effective as estrogen treatment in preventing osteoporosis, without causing uterin hyperstimulation. Nevertheless, further investigations on more rats are needed to assess whether it is an alternative treatment method to estrogen.     

Progesterone stimulates cardiac muscle protein synthesis via receptor-dependent pathway

OBJECTIVE: To examine the effect of ovarian hormones on the regulation of cardiac growth. DESIGN: Ovariectomized rat model with replacement of 17beta-estradiol (E(2)) and progesterone (P). SETTING: University research laboratory. PATIENT(S): Female Sprague-Dawley rats (7-8 weeks old). INTERVENTION(S): Rats were separated into five groups: [1] sham-operated (S; n = 6), [2] ovariectomized plus placebo (OVX; n = 8), [3] OVX plus 17beta-E(2) (OVX+E(2); n = 8), [4] OVX plus P (OVX+P; n = 8), and [5] OVX+E(2)+P (n = 7). MAIN OUTCOME MEASURE(S): Cardiac muscle protein synthesis rates, steroid hormone receptor protein expression, and plasma volume. RESULT(S): Cardiac protein synthesis was greater in OVX+P (mean +/- SE; 11.4 +/- 1.5% per day) rats compared with S (5.9 +/- 0.6%/day), OVX (6.9 +/- 0.5%/day), OVX+E(2) (5.2 +/- 0.4%/day), and OVX+E(2)+P (6.8 +/- 0.3%/day) groups. Treatment of OVX+P rats with the P receptor antagonist RU 486 (n = 9) reduced protein synthesis rates to control levels (7.5 +/- 0.5% per day), indicating that P regulates cardiac protein metabolism through a receptor-dependent pathway. Both P and estrogen receptors were found in cardiac tissue homogenates, suggesting the possibility of direct effects of ovarian hormones on the heart. Progesterone replacement had an additional effect of increasing plasma volume. Rats in the OVX+P group had a 20% greater plasma volume compared with animals in the S group (5.24 +/- 0.22 vs. 4.19 +/- 0.26 mL/100 g). This effect of P replacement to increase plasma volume was not blocked by RU 486 (5.01 +/- 0.24 mL/100 g), suggesting that volume expansion was not solely responsible for the effects of P on cardiac protein synthesis. CONCLUSION(S): Our findings indicate a role for ovarian hormones in the regulation of cardiac growth in female rats.     

雌激素对去势兔血脂、内皮素及动脉粥样硬化形成的影响

目的 探讨雌激素对卵巢切除（ＯＶＸ）的去势兔的血脂、内皮素、动脉粥样硬化斑块形成的影响。方法 将４５只３月龄雌兔随机分为５组,每组９只,Ａ组为正常对照,Ｂ组为假手术＋胆固醇饮食,Ｃ组为ＯＶＸ＋胆固醇饮食,Ｄ组为ＯＶＸ＋胆固醇饮食＋苯甲酸雌二醇,Ｅ组为ＯＶＸ＋胆固醇饮食＋戊酸雌二醇。喂养１２周后取血,分别测定血脂、内皮素,处死动物并留取主动脉标本测量动脉粥样硬化斑块的面积。结果 ⑴Ｄ组和Ｅ组总胆固醇     

替勃龙联合更安宁对雌性去势大鼠血管内皮细胞的保护作用

目的:观察替勃龙联合补肾中药(更安宁)在雌性去势大鼠加高脂饮食状态下,对血管内皮细胞的保护作用。方法:9月龄雌性Sprague-Dawley大鼠50只,随机分为假手术组(SHAM)、卵巢切除组(OVX)、卵巢切除后药物联合治疗组(OVX+E)、高脂血症组(OVX+HC)、高脂血症药物联合治疗组(OVX+HC+E)。在卵巢切除术后14d起,OVX组、OVX+HC组给予生理盐水灌胃,OVX+E组、OVX+HC+E组予替勃龙+补肾中药更安宁溶液灌胃,OVX+HC组、OVX+HC+E组同时喂饲高脂饮食。12周后处死大鼠,测定血浆雌二醇(E2)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)、胆固醇(Tch)、甘油三脂(TG)、一氧化氮(NO)、血管性假性血友病因子(vWF),在光镜及电镜下观察主动脉管壁结构的改变。结果:OVX+E组与OVX组相比,OVX+HC+E组与OVX+HC组相比,均表现Tch、LDL-c明显降低,HDL-c明显升高,血浆NO含量增加;OVX组存在轻度动脉粥样硬化坏死,OVX+HC组动脉管壁损伤严重,伴随vWF明显升高;OVX+E组与OVX+HC+E组动脉管壁结构正常。结论:替勃龙联合补肾中药更安宁治疗能保护血管内皮细胞,对抗高脂血症对动脉管壁的损伤。     

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.     

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.     

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception

OBJECTIVE: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception. STUDY DESIGN: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment. RESULTS: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001). CONCLUSION: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.     

Effects of aromatase inhibitors letrozole and anastrazole on bone metabolism and steroid hormone levels in intact female rats.

AIM: The present study was designed to investigate the effects of two aromatase inhibitors on steroid hormone levels, bone mineral density (BMD) and bone turnover markers in intact female rats. METHODS: Letrozole and anastrazole at two different dose levels were investigated for their effect on serum levels of estradiol, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate, BMD of femur and dorsal spine, and osteocalcin and pyridinoline levels as bone turnover markers. Fifty intact female rats were randomly divided in five groups (group 1 (n = 10): control, 2 ml saline; group 2 (n = 10): letrozole 1 mg/kg; group 3 (n = 10): letrozole 2 mg/kg; group 4 (n = 10): anastrazole 0.1 mg/kg; group 5 (n = 10): anastrazole 0.2 mg/kg, and oral gavages were applied for a period of 16 weeks. RESULTS: Both doses of letrozole and anastrazole did not change femoral and vertebral BMD. Serum estradiol levels were reduced significantly at all dose levels by both agents (p < 0.001); all androgen levels were significantly elevated by letrozole (p < 0.05), although anastrazole increased only androstenedione (p < 0.05). The higher dose of letrozole increased osteocalcin levels (p < 0.05), while pyridinoline levels were increased (p < 0.05) by the higher dose of anastrazole. CONCLUSION: Our results indicate that short-term use of letrozole and anastrazole had no clear effects on BMD in intact rats. Further investigations are needed to understand their effects on bone metabolism in intact females.