10mg米非司酮与左炔诺酮用于紧急避孕的效果对比研究

通过米非司酮与左炔诺酮的临床效果对比,探讨米非司酮用于紧急避孕的最低有效剂量。选择接收无保护同房或避孕失败后72h内要求紧急避孕的健康育龄妇女400例,年龄29±6岁。米非司酮组200例,单次口服10mg(10mg/片);左炔诺酮组200例,首次口服0.75mg(0.75mg/片),间隔12h后再服0.75mg。以服药后月经来潮为成功标准,以Dixon表格计算避孕有效率。两组各妊娠2例,均明显低于预期妊娠数(15.46与10.84),有非常显著意义(P<0.01)。米非司酮组避孕有效率87.06％,与左炔诺酮组的81.55％相比无显著差异(P>0.05)。米非司酮组用药后副反应及对下次月经的影响均较轻微,且单次口服易于被接受,说明10mg米非司酮用于紧急避孕安全、有效、简便。     

Pharmacokinetics of single-dose levonorgestrel in adolescents

PURPOSE: The purpose of this study is to compare the pharmacokinetics of levonorgestrel, a drug used for emergency contraception between female adolescents and adults. METHODS: Twenty-two female subjects, aged 13-16 years, received a single 0.75-mg dose of the drug. Serial blood samples were collected for 72 h and used to measure plasma levonorgestrel concentrations. Previously published data from 16 adults, aged 18-45 years, served as comparison. RESULTS: There was a statistically significant higher total plasma clearance divided by the bioavailability (CL/F) of levonorgestrel in adolescents compared to adults, resulting in lower maximum and average total plasma concentrations. There was a trend for a larger volume of distribution divided by bioavailability (V/F), but there was no significant difference in the half-life of levonorgestrel in adolescents relative to adults (p=.098). CONCLUSION: The differences between adolescents and adults are unlikely to be clinically significant because specific changes in total concentrations suggest that unbound concentrations are probably not affected. Furthermore, empirically high doses of levonorgestrel are given for emergency contraception.     

Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration

Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.     

含铜IUD,小剂量米非司酮与单方左炔诺孕酮用于紧急避孕的临床？…

为观察米非司酮（Ｒｕ４８６）、左炔诺孕酮以及活性ＩＵＤ用于紧急避孕（ＥＣ）的临床效果、副反应、对月经的影响和活性ＩＵＤ的长期避孕效果，对１５０例身体健康、月经规律、未避孕或避孕失败１２０ｈ以内的妇女按自愿的方式分为放置ＩＵＤ组或服药组，服药组，服药组按随机方法给予口服Ｒｕ４８６或左炔诺孕酮。结果发现Ｒｕ４８６组和活性ＩＵＤ组有效率为１００％，左炔诺孕酮组为７６．８％（均按Ｄｉｘｏｎ方法计算），对月     

The pharmacokinetics of 750 microg levonorgestrel following administration of one single dose or two doses at 12- or 24-h interval

The administration of two tablets of 750 μg levonorgestrel at a 12- to 24-h interval has been shown to be a safe and effective means of emergency contraception, and Norlevo/Vikela (N/V) is a dedicated product for this indication. The aim of this study was to characterize the plasma pharmacokinetics of levonorgestrel following a single N/V tablet administration and following a second administration, 12 or 24 h after the first one in young, healthy, female volunteers under the same conditions as during clinical use. This was an open, observer-blind, randomized study with three parallel groups and three treatments performed in 24 white female volunteers randomized into three groups of eight participants, each receiving one of the following treatments: Group A, one tablet of 750 μg levonorgestrel at time −12 h and one tablet at time 0; Group B, one tablet of 750 μg levonorgestrel at time 0; Group C, one tablet of 750 μg levonorgestrel at time −24 h and one tablet at time 0. All treatments started between Day 2 and Day 6 of the menstrual cycle. Plasma levonorgestrel levels were measured at regular intervals from time 0 up to 36 h with a validated radioimmunoassay. The results of this study show that after either one single or two administrations of a tablet containing 750 μg levonorgestrel, levonorgestrel is rapidly absorbed. The absorption, distribution, and elimination profiles of levonorgestrel following the three different treatments were similar. It also indicates that 12 or 24 h after administration there remains a significant level of plasma levonorgestrel. In conclusion, this study reinforces clinical guidelines recommending that N/V tablets for emergency contraception be administered 12 to 24 h apart because levonorgestrel is present in plasma between the two administrations.     

Steroid hormones for contraception in men: systematic review of randomized controlled trials

Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so an "add-back" therapy is needed. We conducted a systematic review of all randomized controlled trials of male hormonal contraception and azoospermia. Few significant differences emerged from these trials. Levonorgestrel implants combined with injectable testosterone enanthate (100 mg im) were significantly more effective than was levonorgestrel 125 microg po daily combined with testosterone patches [10 mg/d; odds ratio (OR) for azoospermia with the oral levonorgestrel regimen, 0.03; 95% CI, 0.00-0.29]. The addition of levonorgestrel 500 microg po daily improved the effectiveness of testosterone enanthate 100 mg im weekly by itself (OR for azoospermia with the combined regimen, 4.0; 95% CI, 1.00-15.99). Several regimens, including testosterone alone and gonadotropin-releasing hormone agonists and antagonists, had disappointing results. In conclusion, no male hormonal contraceptive is ready for clinical use. All trials published to date have been small exploratory studies. As a result, their power to detect important differences has been limited and their results have been imprecise. In addition, the definition of oligospermia has been imprecise or inconsistent in many reports. To avoid bias, future trials need to pay more attention on the methodological requirements for randomized controlled trials. Trials with adequate power would also be helpful.     

The effects of levonorgestrel on various sperm functions

Two doses of 750-μg levonorgestrel at 12 h apart is one of the regimens for emergency contraception. The mechanism of action of this regimen is not fully known. We investigated whether levonorgestrel influences sperm functions and thereby, exerts contraceptive activity. The motility, acrosome reaction, zona binding capacity, and oocyte fusion capacity of human spermatozoa treated with 1, 10, and 100 ng/mL levonorgestrel for 3 h were evaluated. Levonorgestrel decreased the curvilinear velocity of the treated spermatozoa in a dose-dependent manner. A significant decrease in straight-line velocity, average path velocity and linearity were also found with 100 ng/mL levonorgestrel treatment. This concentration of levonorgestrel, but not others, also marginally decreased (p = 0.045) the zona binding capacity of the treated spermatozoa. The steroid had no effect on acrosome reaction but had a dose-dependent inhibition on spermatozoa-oocyte fusion. These data show that levonorgestrel affects sperm function only at high concentration and the contribution of these effects to emergency contraception is unlikely to be significant.     

Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel

A pharmaceutical and pharmacokinetic study was carried out on levonorgestrel tablets from two different sources (Hungarian- and Chinese-made). Both preparations contained 0.75 mg levonorgestrel and had been shown to have similar contraceptive efficacy and side effects when used for postcoital contraception. Absorption and bioavailability of the Hungarian-made tablets were greater as evidenced by higher serum concentrations of levonorgestrel, a greater area under the concentration-time curve during the first 24 hours, and a more marked suppressive effect on SHBG levels. These differences most probably reflect differences in their pharmaceutical formulation, in particular the extent of tablet dissolution and the degree of micronisation of levonorgestrel.     

Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians

Emergency contraception was introduced in Nigeria over two decades ago, but few women have used this method even in emergency situations because of the side effects. To find an acceptable levonorgestrel regimen for emergency contraception in our community, the two-dose regimen 0.75-mg levonorgestrel 12 h apart (group A) and the single dose 1.5-mg levonorgestrel (group B) were studied in 1118 volunteers. Mild side effects such as nausea, vomiting, lower abdominal pains, menorrhagia, dizziness, headache, and breast tenderness were reported. Significantly more women in the high-dose group reported headache, breast tenderness, and heavy menstrual flow. Eleven pregnancies (1.0%) were reported (7 in group A and 4 in group B). The crude relative risk of pregnancies was similar in the two groups (RR = 0.71, 95% CI = 0.32-1.55; p > 0.05) [corrected]. On the other hand, the estimated effectiveness rate of 86.80% in group A was significantly lower than the 92.99% for group B (p < 0.05). The pregnancy rates increased with delay in starting treatment and if further acts of unprotected sexual intercourse took place after treatment. It was concluded that both regimens were effective and safe.     

Norplant contraceptive implants: rods versus capsules

Norplant contraceptive implants are silastic implants containing levonorgestrel. When placed subcutaneously in the medial aspect of the upper arm, they release low levels of levonorgestrel in a constant manner over an extended period of time. Comparative studies of two silastic rods versus six capsules containing levonorgestrel were studied in 250 subjects for 4,464 months of use. Only one pregnancy occurred during the study. Side effect patterns were similar in both groups; the major side effect being irregular uterine bleeding. The bleeding, however, was well tolerated by subjects in both groups and discontinuation rate was very low. The two-rod system offers the advantages of easier insertion technique and shorter insertion time as well as ease of removal as compared to the six-capsule system. Norplant contraceptive implants offer a highly effective means of contraception which is particularly suited for women who are concerned about failure and compliance with oral contraceptives. This type of contraception should become well accepted, not only in underdeveloped countries, but in developed countries as well.     

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.     

Contraception by NORPLANT subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment

The contraceptive efficacy of progestin-only contraception was studied in epileptic patients using NORPLANT^R subdermal capsules. The effect of anticonvulsants on levonorgestrel plasma levels was determined. NORPLANT^R subdermal capsules were inserted into nine epileptic women, and ten control women using no medication. Venous blood samples were taken at 0, 1, 3, 6, 9 and 12 months after insertion and the concentration of levonorgestrel was determined by radioimmunoassay. At 3 to 12 months, the overall mean concentration of plasma levonorgestrel was significantly lower in the six epileptics taking phenytoin alone or in combination with other anticonvulsants (203 ± 128 pg/ml, mean ± SD) than in the controls (325 ± 135 pg/ml, p < 0.01). After one year, nine of the control patients continued the use of NORPLANT^R and no pregnancies occurred. Two of the nine epileptics became pregnant during contraception by NORPLANT^R. They both used phenytoin and their plasma concentrations of levonorgestrel were low near the time of conception. Levonorgestrel released from the capsules had no apparent harmful effects on epilepsy and none of the patients reported an increase in seizure frequency. The results show that contraception by the progestin levonorgestrel is not reliable in epileptic patients using anticonvulsants known to induce metabolizing enzymes of the liver.     

Emergency contraception

Emergency contraception is used after unprotected intercourse or a contraceptive accident to prevent unwanted pregnancy. It is thought to work by stopping or delaying ovulation or preventing implantation if fertilization has already taken place. Hormonal methods, mifepristone, and intrauterine device insertion are among the methods used worldwide. Combination estrogen-progestin birth control pills are the most commonly used form of emergency contraception in the United States. According to the Yuzpe method, combination pills are taken within 72 hours after intercourse, followed by a second identical dose 12 hours later. With this method, the number of unintended pregnancies is reduced by about 75%. Nausea and vomiting are the most troublesome adverse effects, but these can be controlled with antiemetic medication taken prior to the first dose. The Food and Drug Administration, Washington, DC, has approved an emergency contraception kit consisting of 4 combination pills, a urine pregnancy test, and a patient information book. Most recently, the Food and Drug Administration has approved a progestin-only formulation, which has fewer adverse effects and equal or improved efficacy compared with the combination formula. An intrauterine device can be inserted up to 5 days after unprotected intercourse and is a cost-effective option if it is used as ongoing contraceptive protection. The most readily available form of emergency contraception consists of 2 doses of estrogen-progestin combination birth control pills or 2 levonorgestrel pills taken 12 hours apart. Emergency contraception should not be considered as an alternative to ongoing contraceptive methods, but can prevent unwanted pregnancy.     

Mechanism of action of emergency contraception

A major barrier to the widespread acceptability and use of emergency contraception (EC) are concerns regarding the mechanisms of action of EC methods. Today, levonorgestrel (LNG) in a single dose of 1.5 mg taken within 120 h of an unprotected intercourse is the most widely used EC method worldwide. It has been demonstrated that LNG-EC acts through an effect on follicular development to delay or inhibit ovulation but has no effect once luteinizing hormone has started to increase. Thereafter, LNG-EC cannot prevent ovulation and it does not prevent fertilization or affect the human fallopian tube. LNG-EC has no effect on endometrial development or function. In an in vitro model, it was demonstrated that LNG did not interfere with blastocyst function or implantation.     

重复人工流产女性避孕态度及行为的调查分析

目的了解重复人工流产女性、避孕态度及避孕行为,为制定相应干预措施提供依据.方法 对2005年9月至2006年8月间,参与北京海淀区“早孕终止妊娠后避孕干预效果分析”项目的1098例早孕重复人工流产女性进行问卷调查,干预后6个月时进行随访,了解其避孕行为.结果 对于是否避孕及避孕方法的选择,仅65.0％的已婚者及57...     

A pilot clinical trial of ultrasound-guided postplacental insertion of a levonorgestrel intrauterine device

BACKGROUND: Postplacental intrauterine device (IUD) insertion is a safe, convenient and effective option for postpartum contraception. Few studies involve ultrasound-guided insertion, and none involve the levonorgestrel IUD or take place in the United States. STUDY DESIGN: The study was conducted to assess the safety and feasibility of ultrasound-guided postplacental insertion of the levonorgestrel IUD following vaginal delivery in a U.S. residency program. Levonorgestrel IUDs were inserted under ultrasound guidance within 10 min of placental delivery by hand or using ring forceps. Subjects were examined at 4 and 10 weeks postpartum for evidence of expulsion or infection. RESULTS: Thirty-four subjects were enrolled and 20 received an IUD. Follow-up data are available for 19 subjects over the 10-week follow-up period; 16 subjects returned for the 4-week follow-up, and 14 returned at 10 weeks. Two additional subjects could be contacted by telephone only. At 4 and 10 weeks postpartum, no subjects had evidence of infection. There were two expulsions (2/19, 10.5%) by 10 weeks postpartum. None of the subjects examined had a partial expulsion (intracervical location of the IUD). CONCLUSIONS: In this pilot study, ultrasound-guided postplacental insertion of the levonorgestrel IUD was feasible and not associated with infection. The risk of expulsion was acceptable. Ultrasound-guided postplacental insertion of the levonorgestrel IUD may be an alternative to delayed insertion but warrants further study.     

Fertility regulation in nursing women: V. Long-term influence of a low-dose combined oral contraceptive initiated at day 90 postpartum upon lactation and infant growth

The study was designed to test the long-term influence of a low-dose oral contraceptive upon lactation and infant growth when treatment was initiated at day 90 postpartum. The contraceptive tested contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. The control group was formed by women who chose non-hormonal contraception at the same postpartum time. Only cases who were in exclusive breast-feeding with a minimal infant daily weight increase of 20 g per day during the third month of age were included. The oral contraceptive group showed a significantly lower percentage of cases in full nursing from the 6th postpartum month and a significantly lower infant weight increase during the 4th month of age when compared to the control group. No differences were found in the absolute infant weight up to one year of age. No adverse side effects upon infant's health were detected. It was concluded that the oral contraceptive tested showed a moderate inhibitory influence upon lactation when treatment was initiated at day 90 postpartum.     

Serum lipids in Chinese patients using oral contraceptive pills

Eighty-four Chinese patients attending the Family Planning Association of Hong Kong for contraception with oral contraceptive pills were randomized into 2 groups. The first group received pills containing 0.15 mg levonorgestrel and 0.03 mg ethinyl oestradiol. The second group received pills containing 0.15 mg desogestrel and 0.03 mg ethinyl oestradiol. Blood was taken after overnight fast before the use of pills for assay of serum total lipids, triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-C). The tests were repeated at 1 month, 3 months and 6 months after the use of pills. There was a significant increase in the serum total lipids in the levonorgestrel group but not in the desogestrel group. The serum triglycerides showed a significant increase in the desogestrel group but not in the levonorgestrel group. There was no significant change in the serum total cholesterol levels in both groups. There was a significant decrease in the HDL-C in the levonorgestrel group but there was no significant change in the desogestrel group.     

A randomized, double-blind, noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria

Background

Unplanned pregnancies are common in Nigeria. Much of the unplanned pregnancies is due to low contraceptive prevalence and high contraceptive user failure rates. High user failure rates suggest the important role of emergency contraception to prevent unplanned pregnancy.

Study Design

Randomized, controlled, double-blind, multicenter, noninferiority trial comparing efficacy and side effects of two emergency contraceptive regimens up to 5 days after unprotected intercourse among 3022 Nigerian women: levonorgestrel administered in two doses of 0.75 mg given 12 h apart and levonorgestrel administered in a single dose of 1.5 mg.

Results

Efficacy was similar between the treatment groups; post-treatment pregnancy proportions were 0.57% in the two-dose regimen vs. 0.64% in the single-dose regimen (risk difference 0.07% (95% CI −0.50 to 0.64). The majority of women menstruated the first day of expected menses and the groups did not differ regarding reported side effects.

Conclusions

This study shows the simplified emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen among Nigerian women.