甾体激素避孕药

<正> 五十年代中后期,由于生殖内分泌学研究的进展、以及大量甾体化合物的合成,促使甾体激素避孕药的研究成功。长期的临床实践表明,甾体避孕药的效果确切、安全性较高,是目前用于计划生育的主要的药物。一、分类甾体避孕药由不同类型的雌激素和孕激素化合物配伍组成。常用于避孕药制剂的雌激素     

甾体避孕药常见副反应及其处理

上一期(1卷3期)的“信箱”中,陈湫波医师就甾体激素避孕药所引起的月经紊乱的机理及处理方法作了解答,本期继续刊登有关甾体避孕药常见副反应的机理及防治。     

药物和口服甾体避孕药的相互作用

近年对于药物相互作用的兴趣日增,而有关药物与口服甾体避孕药相互作用的描述则是较近的事。这可能和早先使用者服用雌激素、孕激素量超过必需的高剂量有关。当炔雌醇剂量降到每天50μg或更低时,开始注意到其他药物可能影响口服甾体避孕药的效果问题。现在认识到,某些避孕失败乃由药物相互作用所致。一、其他药物对甾体避孕药的影响:1971年发现一些同时进行抗结核治疗的口服甾体避孕药妇女经间期出血率较高。之后,把镇痉药、抗菌素、止痛剂及作用中枢神经系统药物也与避孕失败联系起来。必须指出,将某类避孕药剂的结果引伸到另一类避孕药中去是错误的;而且,药物相互作用的个体差异又很大。此外,随着含炔雌醇剂量更低的避     

避孕药物的研究进展——常用女用避孕药的种类与选择

常用女用避孕药为甾体类，由人工合成的复方口服避孕药。甾体类激素的基本骨架为一甾环，亦称环戊烷多氢菲，是一个由17个碳原子组成的环形结构，由3个6碳环及1个5碳环相互连接构成。甾体激素来源于胆固醇裂解，胆固醇为产生所有性甾体激素的母体物质，有27个碳原子。人工合成的性激素比内源性激素有较强或较长时间的作用，因此，使用小剂量就能发挥效应。临床常用的是人工合成的甾体激素避孕药。     

甾体激素避孕药药代动力学与安全性

自从Ｐｉｎｃｕｓ于 195 6年首次报道女用甾体激素避孕药的临床试验结果以来 ,对甾体类激素的药理作用、药代动力学、临床有效性及长期使用安全性进行了极为广泛深入的研究。国内各种类型的甾体避孕药中应用最广、接受性最高的仍是口服复方甾体避孕药。国内外的研究均致力于降低雌激素及孕激素的含量。同时 ,继第 1、第 2代孕激素之后 ,更为安全的第 3代孕激素也上市应用。1　甾体激素的基本化学结构天然甾体激素均具有环戊烷多氢菲核的基本结构 ,由3个 6元环和 1个 5元环组成 ,共 17个碳原子。根据其Ｃ10 、Ｃ13上有无甲基及Ｃ17位上有无侧…     

剖宫产与围生期栓塞性疾病

栓塞性疾病通常指静脉血栓栓塞(venous thromboembolism,VTE),是由多种致病机制导致的一组血管性疾病,临床表现分为深静脉血栓栓塞(deep venous thrombosis,DVT)和肺栓塞(pulmonary embolism,     

常用女用避孕药的种类与选择

常用女用避孕药为甾体类 ,由人工合成的复方口服避孕药。甾体类激素的基本骨架为一甾环 ,亦称环戊烷多氢菲 ,是一个由 17个碳原子组成的环形结构 ,由 3个 6碳环及 1个 5碳环相互连接构成。甾体激素来源于胆固醇裂解 ,胆固醇为产生所有性甾体激素的母体物质 ,有 2 7个碳原子。人工合成的性激素比内源性激素有较强或较长时间的作用 ,因此 ,使用小剂量就能发挥效应。临床常用的是人工合成的甾体激素避孕药。1　短效口服避孕药是有效而可逆的避孕方法之一 ,它是以孕激素为主 ,由单方小剂量孕激素组成或辅以雌激素配伍构成复方避孕药 ,可减少突破…     

甾体避孕药进入人奶中

喂奶有暂时的避孕效果。但不是有效的避孕办法,因为哺乳妇女的排卵和行经的恢复有很大的个体差异。所以在哺乳期需要一种避孕方法,为此目的,多使用口服避孕药。不过关于外源的甾体避孕药在既定的哺乳期间进入人奶方面,最近才进行研究。外源的甾体避孕药进入人奶中的最初研究,是用标记的甾体来进行的。新近分娩和泌乳但未喂奶的妇女在4～6天内分泌到乳汁中的标记异炔诺酮(Norethynodrel)和双醋炔诺酮(Ethynodiol Diacetate)不到口服剂量的0.13%。以后用异炔诺酮进行的研究中,得到比前者略高的估计。每天进入600毫升奶汁中的标记的去氧炔诺酮(Lynestrenol)或甲地孕酮(Mestranol)及其代谢物约为母亲     

《中国实用妇科与产科杂志》第21卷（2005年）论文主题索引

(以下按汉语拼音字母顺序排列)B避孕药避孕药临床应用40年回顾与展望(吴熙瑞)(1):1常用女用避孕药的种类与选择(范光升)(1):5第三代孕激素口服避孕药的种类与应用(赵爽,郑建华)(1):6女用避孕药不良反应分型监测与预防(李瑛)(1):8女用避孕药的不良反应及其处理(孙敬霞,韩燕燕)(1):10皮下埋植避孕剂的避孕效果及不良反应处理原则(顾素娟)(1):11阴道药环的临床应用和前景(庄留琪)(1):13紧急避孕药的临床应用(吴尚纯,邹燕)(1):15避孕药长期应用的安全性(乌毓明)(1):17甾体避孕药对某些疾病的治疗作用(韩向阳)(1):19速效口服避孕药及其应用(刘福…     

现代口服避孕药的应用原则

激素避孕药已有40多年的历史,主要是甾体避孕药,大多数为人工合成复方制剂,由雌孕激素相配伍而成,少数为单方孕激素.近年甾体激素用于避孕的研究重点是:①激素减量而避孕效果不变;②研制新型避孕药;③给药途径多元化.     

Venous thromboembolism in relation to oral contraceptive use

The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.     

Oral contraceptives increase deep venous thrombosis in smoking women

There is consistent evidence that the use of oral contraceptives and is associated with increased risk of deep vein thrombosis. The study objective was to assess age specific incidence of deep venous thrombosis and pulmonary embolism in women 20 to 50 years of age associated with the use of oral contraceptives, and smoking habit. A case-control study of vein thrombosis was conducted in National Heart Hospital in Sofia. The study consists of studies for vascular events (peripheral vascular disease) during hormonal therapy. We found that cigarette smoking aggravates venous thromboembolism and pulmonary embolism the in women using oral contraceptives, v. The effect of smoking alone on venous tromboembolism was not found significant. Most probably different factors that increase the incidence of vascular narrowing or occlusion might explain the association between deep venous thrombosis, complicated pulmonary thromboembolism oral contraceptives use and smoking in women in pre-menopausal age.     

Interleukin-6 and antiphospholipid antibodies in women with contraceptive-related thromboembolic disease

OBJECTIVE: The aim of this study was to explore the possible (joint) contributing role of interleukin-6 (IL-6) and antiphospholipid antibodies to the occurrence of the venous thromboembolism in women using oral contraceptives. METHODS: Interleukin-6 and antiphospholipid antibodies (anti-beta2-glycoprotein I antibody-immunoglobulin M [IgM], G [IgG], and A [IgA]; anticardiolipin-IgM and IgG; antiphosphatidylserine-IgM and IgG) were measured in 30 women (median age 41, range 28-49 years) in the stable period (on average 3.5 years) after first venous thromboembolism. Sixteen patients used oral contraceptives during the episode of venous thromboembolism (oral contraceptives group), whereas 14 patients did not (non-oral contraceptives group). Thirty-seven age-matched, healthy women served as controls RESULTS: Compared with controls, the oral contraceptives group had elevated IL-6 (median interquartile range 2.3 [1.1-4.3] versus 1.4 [0-2.0] pg/mL, P <.05). The oral contraceptives group had elevated anti-beta2-glycoprotein I antibody-IgM in comparison with both the non-oral contraceptives group (median interquartile range 47.5 [2.0-77.0] versus 29.50 [11.00-45.50] OD(450), P <.06) and controls (47.5 [2.0-77.0] versus 17.5 [3.5-30.0] OD(450), P <.001). Interleukin-6 level in the non-oral contraceptives group was related to obesity, whereas such a relation was not found in the oral contraceptives group, suggesting the presence of another factor (oral contraceptive use), which stimulates IL-6 production. Of particular interest is our finding that elevated IL-6 levels correlated significantly positively with elevated anti-beta2-glycoprotein I antibody-IgG in patients who were users of oral contraceptives (but not overweight, n = 10) (r = 0.56, P <.05) CONCLUSION: The results suggest a new hypothesis that, in susceptible women, use of oral contraceptives induces production of IL-6, which stimulates production of anti-beta2-glycoprotein I. Thus, the prothrombotic profile is aggravated and could facilitate occurrence of venous thromboembolism. This remains to be elucidated in further studies.     

Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women.

BACKGROUND: The risk of cardiovascular disease associated with progestogen-only pills has rarely been studied so far. METHODS: In the Transnational case-control study we were looking for a potential cardiovascular disease risk with oral progestogen-only pills in women aged 16-44 years. A total of 1058 cases of myocardial infarction, thromboembolic cerebrovascular accident or venous thromboembolism, and 3808 controls unaffected by these diseases, were enrolled. The group of women who had either used oral progestogen-only pills or no oral contraceptives included 394 cardiovascular disease cases (123 cases of myocardial infarction, 90 cases of thromboembolic cerebrovascular accident and 181 cases of venous thromboembolism) and 2366 controls. RESULTS: The adjusted (matched) odds ratio (OR) for all cardiovascular diseases combined for women using progestogen-only pills compared with non-users of oral contraceptives was 0.84 (95% confidence interval (CI), 0.45-1.58). The adjusted ORs for myocardial infarction, thromboembolic cerebrovascular accidents and venous thromboembolism for users of progestogen-only pills were 0.94 (95% CI, 0.31-2.91), 1.60 (95% CI, 0.24-0.72) and 0.68 (95% CI, 0.28-1.66), respectively. Hence, there was no significant increase in cardiovascular disease risk associated with progestogen-only pill use. The association between cardiovascular disease and established risk factors (smoking and hypertension) was confirmed. CONCLUSION: Although limited by the small number of exposed cases, our data suggest that there is no convincing evidence for an increased risk of cardiovascular disease associated with progestogen-only pill use.     

The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives.

OBJECTIVES: To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates ofidiopathic venous thromboembolism among this population. METHODS: The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives. RESULTS: The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m2 and over, the association rising dramatically in women with a body mass index of 35 kg/m2 or more; smoking; general ill health; and asthma. CONCLUSION: We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.     

Contraceptive choices in women with coagulation disorders

When compared with older reports on the thromboembolic effects of high-dose oral contraceptives, new studies with low-dose oral contraceptives have a significantly reduced risk of thromboembolism. In the absence of risk factors such as smoking or inherited disorders predisposing to thrombosis, the modern low-dose oral contraceptive (< 50 μg of estrogen) is a safe and effective choice for contraception in women without symptoms who have family histories of sporadic thromboembolism. An intrauterine device or some form of barrier method is recommended for women who have a personal history of venous thrombus disease. The low-dose oral contraceptive may be a good choice in women taking oral anticoagulants because of the risk of teratogenic effects of anticoagulants and the risks of intraperitoneal bleeding associated with ovulation. In addition, oral contraceptives help diminish the excessive menstrual bleeding often seen in these women. (Am J Obstet Gynecol 1993;168:1990-3.)     

The effects of age,body mass index,smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives

Objectives To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates of idiopathic venous thromboembolism among this population.

Methods The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives.

Results The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100 000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m² and over, the association rising dramatically in women with a body mass index of 35 kg/m² or more; smoking; general ill health; and asthma.

Conclusion We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.     

Erroneous clinical diagnosis of leg vein thrombosis in women on oral contraceptives

Most studies demonstrating an increased risk of venous thromboembolism in women on oral contraceptives are based on clinical manifestations of the disease. Because of the fallibility of the clinical diagnosis of suspected leg vein thrombosis, Doppler ultrasonic evaluation (with a 93% accuracy compared to venography) was performed for clinical manifestations in deep vein thrombosis in 54 women taking birth control pills and 75 women of similar age who were not on contraceptives. The clinical diagnosis was confirmed by Doppler in only 16.7% of the women taking contraceptives and 30.7% of women not taking contraceptives (P = 0.052). This study suggests that the clinical diagnosis of leg vein thrombosis is frequently erroneous, particularly in women taking oral contraceptives. Future investigations reporting venous thromboembolism associated with oral contraceptives should be based on diagnoses validated by accurate objective techniques.     

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

BACKGROUND: Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more. OBJECTIVE: To replicate the reported risk estimates with a new population-based case-control study. METHODS: Eighty women with a diagnosis of venous thromboembolism were consecutively identified and compared with population-based controls (n = 406). Factor V Leiden mutation was identified by genotype analysis. The evaluation was performed with conditional logistic regression (matched for 5-year age group). RESULTS: Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism in women without and with the factor V Leiden mutation who used oral contraceptives were 4.1 (95% confidence interval (CI) 2.1-7.8) and 10.2 (95% CI 1.2-88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0 (95% CI 1.0-4.4). The OR for women with the factor V Leiden mutation and oral contraceptive use versus no factor V Leiden mutation and no oral contraceptive use was 10.2 (95% CI 3.8-27.6). CONCLUSION: The results confirm the increased relative risk of idiopathic venous thromboembolism for users of oral contraceptives and factor V Leiden carriers. However, we suspect that the true risk for women who are factor V Leiden carriers may be increased two- to four-fold rather than seven-fold or more, and that the risk for the combination of factor V Leiden and oral contraceptive use may be increased in the order often- to 15-fold rather than over 30-fold.     

Oral contraceptives and thromboembolism: A reassessment

The relationship between oral contraceptive usage and thromboembolism is controversial. Since thromboembolism is often undiagnosed, both clinically and at routine autopsy, most epidemiologic analyses rest on a very uncertain factual base. There are increases in blood coagulation factors in oral contraceptive users similar to, but less than, those seen in pregnancy, which isnot associated with increased thromboembolism. Hematologists emphasize that these changes do not define a “hypercoagulable” state, and they do not define or predict the occurrence of thrombosis. Intrinsic vascular wall changes, unrelated to drug use, may play a role in sporadic cases of thromboembolism. When the incidence of thromboembolism in very large Phase III trials of conventional oral contraceptives is compared to that in other populations (patients admitted to the hospital, women who visit a physician, pregnant women, or users of nonestrogenic oral contraceptives), no difference is seen. Epidemiologic studies by the “case-control” (“trohoc”) method consistently show an increased “relative risk” associated with oral contraceptive use in subjects with “idiopathic” thromboembolism but no increased risk in thromboembolism patients as a whole or in those with predisposing factors. This retrospective epidemiologic technique, its particular applications, and the inferences drawn are open to serious criticism, as are studies claiming a relationship between estrogen dose and thromboembolism incidence. An Australian prospective survey found no increased risk among users, and a large British study which initially reported an increased risk is currently undergoing recalculation. The only controlled clinical experiment (with random assignment of subjects to vaginal versus high-estrogen contraceptives) showed no increased incidence in the drug-treated group. Statistical associations derived from “trohoc” studies do not establish causal relationships; moreover, their risk estimates are in conflict with the findings of large Phase III clinical surveys including subjects using estrogen-free contraceptives, with at least one prospective clinical survey, and with a randomized, controlled clinical trial. The data relating estrogen dosage to thromboembolism incidence are ambiguous, at best. Thus, the claim of a causal relationship between oral contraceptive steroids and thromboembolism does not appear to be firmly founded, and the belief that predisposing factors increase the risk to contraceptive users is equally insubstantial.