甲基异炔诺酮对20例绝经期子宫肌瘤妇女的影响

子宫肌瘤组织中的雌、孕激素受体及其ｍＲＮＡ表达数量多于正常子宫肌纤维组织 ,因此患子宫肌瘤的妇女绝经期雌激素替代治疗 (ＨＲＴ)受到限制。我们对自然绝经一年以上的妇女 ,应用甲基异炔诺酮 (商品名利维爱 )行ＨＲＴ治疗 ,观察血浆内分泌素及子宫肌瘤的变化 ,以明确利维爱对绝经期合并子宫肌瘤的妇女行ＨＲＴ的可行性和安全性。1　资料与方法1.1　一般资料　对 1996年 1月至 1999年 12月四年间在我院及中国医大二院门诊就诊的 2 0例绝经期子宫肌瘤的妇女为治疗组 ,绝经前无明显症状 ,肌瘤单发或多发 ,直径最小在 2ｃｍ以上 ,最大为 4 5…     

长效孕激素炔诺酮庚酸酯及复方18甲基炔诺酮对血清性激素结合球蛋白的影响

24例妇女肌注炔诺酮庚酸酯200 mg,肌注前血清性激素结合球蛋白(SHBG)为53.32±23.23 nmol╱L。注射后5天为41.99±17.06nmol/L(P<0.05),21天降至最低值14.72±10.01 nmol/L,以后逐渐回升,直至注射后84天仍未回复到原来水平(34.46±20.39 nmol/L)。10例妇女单次口服18甲基炔诺酮6 mg+炔雌醚3 mg,服药前血清SHBG水平为42.76±13.89 n mol/L,服药后7天为62.53±10.90 nmol/L(P<0.01),14天达峰值为71.33±5.77 nmol/L,以后持续此高水平,直至服药后56天;8例连续3次口服18甲+炔雌醚,每次间隔23天,服药前血清SHBG水平为44.94±15.36 nmol/L,第1次服药后9天为83.46±10.08 nmol/L(P<0.01),16天达峰值为91.74±2.28nmol/L,以后持续高水平直至第3次服药后30天,第2、3次重复给药对业已升高的SHBG水平无影明显响。第2、3次服药后LNG峰值明显高于首次服药后峰值6倍。     

缓释左旋-18甲基炔诺酮皮埋避孕剂对骨密度和骨代谢的影响

对采用 Norplant R埋植剂和仿制 Norplant的国产埋植剂 型避孕的育龄妇女骨密度和骨代谢改变进行了 1年的随机前瞻性临床观察。 6 1例正常妇女被分为两组 :Norplant埋植剂组 30例 ,国产埋植剂组 31例。两组于埋植前和埋植后第 12个月时采用双能 X线骨密度测定仪 (DEXA)分别测定了腰椎 L2 ～ L4、股骨近端骨密度和骨矿含量。两组妇女埋植后第 12个月时腰椎 L2 ～ L4骨密度和骨矿含量均较埋植前明显增加 (P<0 .0 1) ,Norplant组骨密度平均增加2 .40 % ,骨矿含量平均增加 3.34 % ,国产埋植剂组分别增加 2 .75 %和 4.47% ;从年龄分析 ,以 2 5～ 2 9岁组腰椎 L2 ～ L4骨密度埋植后增加最为显著 ,Norplant组 P<0 .0 5 ,国产埋植剂组 P<0 .0 1。国产埋植剂组妇女埋植后第 12个月时股骨大粗隆骨密度和骨矿含量较埋植前明显增加 (P<0 .0 1) ;国产埋植剂组妇女空腹尿羟脯氨酸 /肌酐比值埋植后第 12个月时较埋植前明显下降 (P<0 .0 1) ;对使用妇女腰椎、股骨骨密度和骨代谢生化指标的影响 ,在两种埋植剂之间埋植前后比较均无显著差别 (P>0 .0 5 )。左旋 - 18甲基炔诺酮皮埋避孕剂对绝经妇女的骨骼是非有害的 ,对年轻妇女骨峰值的获得无明显影响。     

左旋18-甲基炔诺酮事后药对脂代谢的影响

本文报告10名健康,生育期妇女,口服左旋18甲基炔诺酮作为事后药,每个月经周期用药0.75mg×5次。于用药前,用药一与三周期后及停药后一周期,分别测定空腹血清甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、载脂蛋白A_Ⅰ、A_Ⅱ、B(apoA_Ⅰ、apoA_Ⅱ、apoB)水平。结果显示TG、HDL-C水平及apoA_Ⅰ/A_Ⅱ比率均显著降低,P<0.05～P<0.01,而预测心血管疾病较可靠的指标(HDL-C/TC比率,apoA_Ⅰ/B比率)则未见有显著改变,即使apoA_Ⅰ/A_Ⅱ比率在用药第三周期有显著降低,P<0.01,停药后一周期即见恢复。从而说明,由于机体的调节功能,可使已改变的脂质水平能很快地达到平衡状态。本研究提示,短期服用18-甲对脂代谢的影响是轻微的。     

缓释左旋-18甲基炔诺酮皮埋避孕剂

时采用NorplantR埋植剂和仿制Norplant的国产埋植剂I型避孕的育龄妇女骨密度和骨代谢改变进行了1年的随机前瞻性临床观察.61例正常妇女被分为两组Norplant埋植剂组30例,国产埋植剂组31例.两组于埋植前和埋植后第12个月时采用双能X线骨密度测定仪(DEXA)分别测定了腰椎L2～L4、股骨近端骨密度和骨矿含量.两组妇女埋植后第12个月时腰椎L2～L4骨密度和骨矿含量均较埋植前明显增加(P＜0.01),Norplant组骨密度平均增加2.40%,骨矿含量平均增加3.34%,国产埋植剂组分别增加2.75%和4.47%;从年龄分析,以25～29岁组腰椎L2～L4骨密度埋植后增加最为显著,Norplant组P＜0.05,国产埋植剂组P＜0.01.国产埋植剂组妇女埋植后第12个月时股骨大粗隆骨密度和骨矿含量较埋植前明显增加(P＜0.01);国产埋植剂组妇女空腹尿羟脯氨酸/肌酐比值埋植后第12个月时较埋植前明显下降(P＜0.01);对使用妇女腰椎、股骨骨密度和骨代谢生化指标的影响,在两种埋植剂之间埋植前后比较均无显著差别(P＞0.05).左旋-18甲基炔诺酮皮埋避孕剂对绝经妇女的骨骼是非有害的,对年轻妇女骨峰值的获得无明显影响.     

缓释18-甲基炔诺酮宫内节育器对大鼠子宫及主要脏器的影响

本文研究新制缓释18-甲基炔诺酮宫内节育器(LNGR-IUD)对大鼠子宫及主要脏器的影响。实验分四组:1.含药IUD组;2.不含药硅橡胶IUD组;3.手术对照组;4.正常对照组。结果表明,含药IUD组子宫内膜早期(15及30天时)有轻度炎症反应,60天时炎症反应逐渐消退,90天恢复正常。与不含药IUD组及手术对照组无差异。含药组子宫内膜呈乳头状增生与分泌,亦随时间延长而渐减轻。内膜血管仅早期呈现充血反应,30天后逐步消失。各组全身主要脏器皆未见病变,含药IUD组各期卵巢中见到正常卵泡发育及黄体形成。     

左旋18甲基炔诺酮皮下埋植避孕剂对血清中免疫球蛋白和细胞因子的影响

皮埋剂是一种高效、长效、简便、安全和可逆的新型节育技术,是目前国内外育龄妇女实施节育的主要措施之一,它所含的左旋１８甲基炔诺酮为孕激素类甾体避孕药物。不少研究报道了这类药物对于心血管系统、凝血、肿瘤发生、代谢、内分泌以及遗传等方面的影响及其安全性,但对机体免疫功能的影响国内外报道极少。为此我们对应用皮埋剂妇女血清中的免疫球蛋白分子ＩｇＧ、ＩｇＡ、ＩｇＭ和细胞因子ＩＬ－２、ＩＬ－６、ＴＮＦα、ＩＦＮ－γ的水平进行了测定,旨在了解皮埋剂对机体免疫功能的影响及其免疫安全性,并对变化产生的机制做初步的探…     

复方左旋18-甲基炔诺酮避孕片阴道持续和间断用药的临床比较

500例育龄妇女、志愿受试者，随机分为二组。阴道应用含左旋18－甲基炔诺酮0.25mg、炔雌醇0．05mg的避孕片。比较持续用药和间断用药的避孕效果、可接受性和副作用。间断用药组（249例）于每个月经周期的第5～25天，每天阴道塞药一片；连续用药组（251例）每天阴道塞药一片，二组的观察期都为一年。结果：两种给药法无一例因药物而失败。用药前后的血压、体重、血红蛋白含量、红细胞压积和红细胞数均无明显差异。月经周期在间断用药组与用药前比较无明显差异；但在连续用药组，多数对象在用药期间持续闭经，仅少数对象在头二个月中有月经。各种副作用的总发生率连续用药组高于间断用药组，主要副作用为恶心、乳房胀痛和腹痛等。用药后患宫颈炎的病例较用药前增加，但两组间无明显差别。两组相比，间断用药组的月经周期规则，点滴出血率低。因药物之故的停药率，两组间无明显区别。     

口服复方炔诺酮避孕片对脂质及脂蛋白的影响

20名健康育龄妇女口服复方炔诺酮避孕片,在月经周期的第五天开始服用,每日一片,22片为一周期,用药6个周期。于用药前,用药第1周期及第6周期及停药后第3个月经周期时,分别测定空腹血清甘油三酯(TG)、总胆固醇(Tc)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、载脂蛋白AⅠ、AⅡ、B(apoAⅠ,apoAⅡ,apoB)水平。结果显示用药6周期,所有各项参数都显著升高(p<0.01～0.001)。停药后三个周期,TG、TC及LDL-C水平均基本复原,其余各项虽呈下降趋势,但与用药前相比仍有显著差异(p<0.05～0.01)。在整个观察期间,各项比率的改变均无显著差异。     

Long-term effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity in healthy postmenopausal women

OBJECTIVE: To study the effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity. DESIGN: Prospective, randomized, controlled study. SETTING: Academic hospital. PATIENT(S): Healthy postmenopausal women with an intact uterus. INTERVENTION(S): For the first 12 months, the hormone replacement therapy group (n = 14) received oral E2, 1 mg daily, sequentially combined with 5 or 10 mg of dydrogesterone. Thereafter, they received oral E2, 2 mg daily, sequentially combined with 10 mg of dydrogesterone. The control group (n = 13) received no treatment. Data were collected at baseline and at 3, 12, and 15 months. MAIN OUTCOME MEASURE(S): Parameters of endothelial function and inflammatory activity. RESULT(S): During 12 months of follow-up, we observed decreases of 15% in plasma levels of endothelin-l, of 21% in soluble thrombomodulin, of 14% in von Willebrand factor, and of 12% in clottable fibrinogen in the hormone replacement therapy group compared with the control group. There was a 5% decrease in soluble E-selectin tevels. All significant changes were observed by 3 months and sustained after 15 months. Brachial artery flow-mediated vasodilatation and C-reactive protein levels did not change significantly. CONCLUSION(S): Long-term combined hormone replacement therapy with E2 and dydrogesterone in healthy women was associated with sustained improvement in some aspects of endothelial function and in clottable fibrinogen levels.     

The lipid and clinical effects of sequential transdermal estradiol and estradiol/norethisterone acetate in 674 women

Objective.

To measure lipid changes induced by patches delivering continuous estradiol (E₂) and sequential norethisterone acetate (NETA) in a large population of symptomatic menopausal women, compared with a non-symptomatic control group.

Patients and methods.

A total of 748 women recruited in 42 different hospital services and clinics in Spain were invited to participate in a prospective, open, controlled study for 48 weeks. Six hundred and seventy-four women were evaluated in the treatment group, and 74 in the control group. Treatment consisted of patches delivering 0.05 mg/day E₂ for the first 14 days of the cycle, and 0.05 mg/day E₂ plus 0.25 mg/day NETA for another 14 days.

Results.

Use of patches led to a slight, but significant decrease of 1.3% and 0.9% in concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C), respectively. A substantial 37.0% decrease in triglycerides concentration was observed in treated women. The treatment effectively reduced climacteric symptoms (Kupperman index) for the duration of the study. Compliance was acceptable, with 489 (72.6%) women completing the study. Adverse events were reported by 137 (20.3%) women.

Conclusions.

Transdermal administration of E₂ and sequential NETA for a period of 48 weeks (twelve 28-day cycles) was associated with beneficial changes, albeit of differing magnitudes, in the concentration of total cholesterol, LDL-C and triglycerides. This protective lipid profile, together with satisfactory clinical efficacy and acceptable safety and compliance, makes this system a good alternative in hormone replacement therapy.

     

The effects of a low-dose gestodene-containing oral contraceptive on endometrial histology in healthy women

Objective In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 Jig gestodene and 20 fig ethinylestradiol were assessed.

Method Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15–21 in cycle 6 for 13 subjects (Group A) and during days 15–21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B).

Results All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Predecidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6.

Conclusions With monophasic gestodene/ethinylestradiol 75 μ/20 μg, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.     

氨甲环酸与炔诺酮治疗排卵型月经过多的多中心前瞻性研究

目的 比较氨甲环酸与炔诺酮治疗排卵型月经过多患者的有效性和安全性.方法 2004年7月至2006年12月,自中国4个城市5个教学医院妇科门诊收集经筛查证实为排卵型月经过多的患者131例,按随机表法分为氨甲环酸组(70例)和炔诺酮组(61例),氨甲环酸组患者于月经周期第1～5天口服氨甲环酸1g,每天3次,炔诺酮组患者于月经周期第19～26天口服炔诺酮5mg,每天2次,均连续2个周期.两组患者停药后均随诊1个周期.观察两组患者治疗前后经期失血量[MBL,以绘图失血评估表(PBAC)评估]、经期长度、生活质量的变化及其安全性.结果 共128例患者完成研究,其中氨甲环酸组69例,炔诺酮组59例.两组患者第1、2个周期PBAC总分均显著降低,经期缩短,患者的生活质量显著改善,差异均有统计学意义(P＜0.05).氨甲环酸组第1、2个周期PBAC总分下降的百分率(分别为35%、44%)均高于炔诺酮组(分别为17%、34%),差异均有统计学意义(P＜0.05).第2个周期治疗有效率氨甲环酸组(41%,28/69)高于炔诺酮组(24%,14/59),差异有统计学意义(P=0.04).氨甲环酸组第1个周期生活质量的改善显著高于炔诺酮组,差异有统计学意义(P=0.03).两组之间血红蛋白含量变化比较,差异均无统计学意义(P＞0.05).氨甲环酸组至少出现1次不良反应患者的百分率(19%,13/69)显著少于炔诺酮组(35%,19/54),差异有统计学意义(P=0.04),第2个周期、随诊周期愿意继续用药患者的百分率氨甲环酸组分别为94%(63/67)、79%(48/61),均显著高于炔诺酮组[分别为79%(44/56)、59%(30/51)],差异均有统计学意义(P=0.01、0.02).结论 与黄体期口服炔诺酮相比,经期第1～5天口服氨甲环酸3 g/d能更有效地使排卵型月经过多患者的MBL减少,生活质量改善,患者的接受性较高.     

Effects of low-dose 17-beta-estradiol plus norethisterone acetate and tibolone on fasting plasma homocysteine levels in postmenopausal women

BACKGROUND: Many postmenopausal women currently receive hormone replacement therapy. The use of low-dose 17beta-estradiol plus norethisterone acetate and tibolone for hormone replacement therapy is not uncommon in postmenopausal women. Homocysteine, which is known to be an independent risk factor for the development of cardiovascular disease, is found in increased levels postmenopause. This study compared the effects of low-dose 17beta-estradiol plus norethisterone acetate and tibolone on the fasting plasma homocysteine level in healthy postmenopausal women. METHODS: Healthy postmenopausal women (n = 44) were enrolled in the study. Women randomly assigned received 1 mg of 17beta-estradiol plus 0.5 mg of norethisterone acetate or 2.5 mg tibolone during a period of 12 weeks. Fasting plasma homocysteine levels were measured at baseline, the 4th week, and the 12th week of therapy. RESULTS: In the 4th week there were no significant changes in plasma homocysteine levels in both groups (p > 0.05). However at the end of the 12th week the plasma homocysteine levels were reduced significantly in both groups (p < 0.05). CONCLUSION: Low-dose 17beta-estradiol plus norethisterone acetate and tibolone lower the fasting plasma homocysteine levels in healthy postmenopausal women.     

Effects of three low-dose oral contraceptive formulations on lipid metabolism

Three oral contraceptive preparations were studied in 60 healthy women. This randomized, comparative, baseline controlled study was designed to investigate the effects of the preparations on plasma lipids and lipoproteins. The following formulations were studied: a monophasic preparation containing ethinylestradiol and desogestrel (M-DSG) and two triphasic formulations containing ethinylestradiol and gestodene or levonorgestrel respectively (T-GSD and T-LNG). These preparations were studied for six treatment cycles. Total cholesterol and apoprotein B did not change in any group. Low density lipoprotein (LDL) cholesterol was significantly decreased in the groups of women treated with M-DSG and T-GSD respectively. No changes were observed in the T-LNG group. With M-DSG, significant increases were observed in high-density lipoprotein (HDL) cholesterol and HDL3 cholesterol, whilst HDL2 cholesterol did not change. With both T-GSD and T-LNG, no changes were observed in HDL cholesterol, whilst a significant increase in HDL3 cholesterol together with a trend to decrease in HDL2 cholesterol were observed. Apolipoprotein AI increased with the following ranking M-DSG greater than T-GSD greater than T-LNG. The LDL/HDL cholesterol ratio significantly decreased with both M-DSG and T-GSD. In the T-LNG group there was no change in this ratio. Triglycerides increased to the same extent in all treatment groups. As far as concerns the risk of arterial diseases, these three oral contraceptive formulations mostly induced negligible and/or partly favorable changes in plasma lipids and lipoproteins; however, the lipoprotein pattern during M-DSG treatment resulted better than during T-GSD, and the latter turned out to be better than during T-LNG.     

Piperazine oestrone sulphate and interrupted norethisterone in postmenopausal women: effects on bone mass, lipoprotein metabolism, climacteric symptoms, and adverse effects

Objective To compare the effects of two doses of piperazine oestrone sulphate combined with interrupted norethisterone, with that of oestradiol continuously combined with norethisterone acetate, and with placebo, in postmenopausal women.
Design A prospective randomised trial.
Participants Two hundred postmenopausal women.
Setting Monocentre study with expertise in osteoporosis.
Methods The participants were randomly assigned to two years of treatment with alternating three-day cycles of 1.5 mg of piperazine oestrone sulphate plus 0.7 mg of norethisterone (highEP), or alternating three-day cycles of 0.75 mg of piperaine oestrone sulphate plus 0.35 mg of norethisterone (lowEP), or 2 mg of 17β-oestradiol continuously combined with 1 mg of norethisterone acetate (E₂+NETA), or placebo.
Main outcome measures Change in bone mineral density, lipoprotein metabolism, climacteric symptoms, and adverse effects.
Results One hundred and twenty-one women completed the study. Spinal bone mineral density was increased about 9% over two years by E₂+NETA, about 6% by highEP, 4% by lowEP, but remained unchanged in the placebo group. The same pattern was seen in the hip and forearm. All hormone regimens decreased markers of bone turnover and alleviated climacteric symptoms. Serum lipoproteins decreased by about 10% in all hormone groups.
Conclusions All hormone regimens studied prevented bone loss completely and lowered serum lipids.     

Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women

In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.     

Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women

Background.?Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries.

Objectives.?To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate.

Subjects.?Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III).

Methods.?Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior® device, taken at baseline and after 12 weeks of treatment.

Results.?After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively).

Conclusions. PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.