Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Will period-free hormonal contraception become the norm of the twenty-first century?

The feelings of women about their menstruations has been modified due to the use of hormonal contraception. Women using oestroprogestative pills know that menstruations are triggered by the cessation of their absorption rather than any other physiological phenomenon. They know that the amenorrhea which appears under progestative contraception is both non pathological and reversible. Consequently, a good many women, confident in terms of birth control by these very efficient contraceptive methods, wish also to space out those considered useless and unpleasant periods for 3 to 6 months and even for 1 year or more. The actual hormonal contraceptive methods theoretically allow this spacing out of the menstruations but often by dint of much metrorragia. Indeed, while the first studies on those "non-periods" contraceptive methods seem to show their harmlessness, they must be further evaluated in a more specific way. Additional studies must thus be pursued in this direction. This new request from women about their periods while being often undervalued by physicians, must now be taken into account for future contraceptive methods.

Accessibility and availability of abortion in six European countries.

OBJECTIVES: The accessibility and availability of abortion are a reflection of abortion law and the accessibility and availability of abortion services. Experiences from six European countries with different political, cultural, social and religious backgrounds (the Netherlands, France, Great Britain, Slovenia, Hungary and Turkey) are presented. RESULTS: Abortion laws in Europe range from complete prohibition to complete liberalization of abortion. Some countries demand a waiting period for the procedure, pre-abortion counseling, parental approval for minors, and in the others there are no mandatory requirements. Abortions are generally performed in authorized facilities by gynecologists or general practitioners. Abortion services are easily accessible, in terms of the law, availability of facilities and health insurance coverage of the procedure in the Netherlands, France and Slovenia. Abortion service is less accessible in United Kingdom, Hungary and Turkey, as a result of limited accessibility to abortion services or a relatively high abortion fee. In some Eastern European countries there has been a tendency in the last decade to limit the availability and access to abortion. CONCLUSIONS: In Europe abortion is generally well accessible in terms of abortion laws. There are differences in accessibility to abortion services between the countries, and in some countries, also between different areas of the country.

[Use of Misoprostol for medical abortion: a trial of the acceptability for home use]. / Enquête d'acceptabilité du misoprostol à domicile pour interruption volontaire de grossesse par méthode médicamenteuse.

OBJECTIVE: The object of this trial was to appreciate the acceptability of Misoprostol home use in medical abortion. PATIENTS AND METHOD: From 1 January 2001 to 28 February 2002, 120 voluntary patients were included in the study of medical voluntary pregnancy interruption with Misoprostol at home, and 289 patients were using the protocol "Misoprostol at hospital". RESULTS: The method was well tolerated by all patients. DISCUSSION AND CONCLUSION: The protocol "Misoprostol at home" is accepted under certain conditions: strict criteria selection, strict rules of security, good counseling of patients, and finally the availability at the telephone of the gynecologist to respond to any eventuality.

The Coraliance study: non-compliant behavior. Results after a 6-month follow-up of patients on oral contraceptives.

OBJECTIVES: This follow-up study was planned to establish the frequency with which women miss their contraceptive pill, and to observe their behavior when they forget it. In those women who changed from a continuous cycle to an interrupted type of cycle, or vice versa, the study also aimed to evaluate the impact of this change on the pattern of omission of pills. METHODS: The longitudinal, prospective cohort study included healthy women of child-bearing age for whom a change of pill was being prescribed by their gynecologist. Data were recorded during the 6 months preceding inclusion in the study, and for the 6 months of follow-up; the women were asked to complete a diary in which they recorded the number and exact times of pill omission, and their behavior at each omission. RESULTS: A total of 617 gynecologists included 3316 women into the study; of these, a group of 2418 (73%) revisited the same gynecologist at follow-up. The groups who either visited the same or a different gynecologist were similar with respect to age, oral contraception type, omission type and frequency. A large non-compliance rate and women's difficulties in maintaining safe contraception after missing a pill were observed in the group with follow-up. Women were never risk-free when they missed a pill; they turned to numerous sources for discordant or conflicting information; 15% of 'not-forgetting' women at the pre-inclusion cycle recorded at least one omission at the last cycle of the 6-month follow-up period. Omission fluctuations during the observational period make it difficult to designate 'forgetful' or 'non-forgetful' classes of women. Administration of the pill in a continuous cycle, and probably 'study' and 'auto-questionnaire' effects, contributed to an improvement in compliance. In the group taking the continuous cycle pill, the omission number slightly decreased, particularly on the first day and week of the cycle, irrespective of the initial cycle type. CONCLUSIONS: The importance of the phenomenon of non-compliance rate is confirmed as well as women's difficulties in knowing how to maintain contraceptive safety. The continuous cycle regimen is likely to improve women's compliance during the critical period of the cycle.

Oral contraception: patterns of non-compliance. The Coraliance study.

OBJECTIVES: To determine the number of times women failed to take their oral contraceptive medication and their behavior in response to a missed pill. Another objective was to determine the potential benefit provided by a continuously administered oral contraceptive compared with an oral contraceptive involving a pill-free interval during a 6-month period. METHODS: Healthy women were enrolled in a cohort study; their contraceptive practices were followed by their gynecologists. Data were collected at inclusion using cross-sectional method with retrospective data collection for the previous 6 months and, more specifically, on their previous or their current menstrual cycle. Women on the pill were asked to specify the number of times and precise time at which they missed one or more pills and what they did in response to missing a pill. RESULTS: A total of 617 gynecologists enrolled and followed 3316 patients from six geographic areas throughout France. The mean age of patients was 30 years. Duration of oral contraceptive use was 8 years. During their previous cycle, 23% of women (n = 737) missed a pill at least once. Among women on the pill involving a treatment-free interval, 42% of instances of missing a pill occurred during the first week following the treatment-free interval. In response to missing a pill, patients read the product information leaflet (39%) or asked someone's advice (28%), mainly their gynecologist (63%) or their family physician (18%). Almost one-third of women did not take any specific measures. CONCLUSIONS: Patients on a discontinuous oral contraceptive regimen tended to miss a pill during the first week of treatment. Prescription of a continuous regimen without a treatment-free interval may improve compliance.

A randomized comparison of mifepristone and self-administered oral or vaginal misoprostol for early abortion.

In France, mifepristone in association with orally administered misoprostol is widely used for the early termination of pregnancy (up to 49 days' gestation). In other centers, mifepristone in association with vaginally administered misoprostol has also been used. The aim of the present study was to compare the efficacy and tolerance of mifepristone in association with misoprostol administered orally or vaginally for the termination of pregnancy of up to 49 days' gestation. A total of 237 women were enrolled in the study. All women received 600 mg mifepristone administered orally and 400 microg misoprostol administered either orally (n = 119) or vaginally (n = 118). A second dose of 400 microg misoprostol was administered if women had not expelled the pregnancy within 3 h. Women were randomized into treatment groups according to the day of their admission. The overall success rate was 98.7% and there was no significant difference in efficacy between the two groups. There was one treatment failure in the group in which misoprostol was administered orally. Of those women who aborted within 3 h of administration of the first dose ofmisoprostol, the route of administration ofmisoprostol did not influence the time to abortion. Of the women who received a second dose ofmisoprostol, the time to abortion was shorter in those who received misoprostol orally (52 min versus 77 min). Tolerance was assessed by visual analog scales and was similar for both groups. In both groups, women preferred the oral route of administration.

Local spermicidal contraception: a comparative study of the acceptability and safety of a new pharmaceutical formulation of benzalkonium chloride, the vaginal capsule, with a reference formulation, the pessary.

OBJECTIVE: To evaluate comparatively the acceptability and safety of a new pharmaceutical form of benzalkonium chloride, the vaginal capsule, with the pessary form. METHODS: Eighty-nine women were randomized to receive either a benzalkonium chloride vaginal capsule or a benzalkonium chloride pessary prior to sexual intercourse according to an open cross-over design over a 2-month study period. RESULTS: The discomfort caused by delayed leakage or discharge was mild. The mean scores for subjective signs (burning, itching, vulvar pruritus) were also mild and were comparable for the two formulations. The capsule appeared to be slightly superior to the pessary regarding discomfort caused by immediate discharge or leakage, ease of use and acceptance by the woman's partner. Local safety was generally good. Adverse events consisted chiefly of vulvar pruritus and a vaginal or vulvar burning sensation, with a higher incidence being associated with the pessary than the capsule. All symptoms regressed spontaneously after the end of treatment. CONCLUSIONS: This study demonstrated good acceptability and good local safety for the benzalkonium chloride vaginal capsule. It is essential to take these parameters into consideration in the evaluation of any local spermicidal contraceptive, since they play a large part in compliance with, and thus in the efficacy of, the product under assessment.

[Trends since 1989, in France, of induced abortions by mifepristone (RU486) combined with a prostaglandin analogue]. / Evolution depuis 1989, en France, des interruptions volontaires de grossesse par mifépristone (RU 486) associée à un analogue de prostaglandine.

UNLABELLED: In 1989 the French Ministry of Health gave its agreement to the utilisation of the combination mifepristone + a prostaglandin analogue for abortion up to 49 DA. Since then, research activities have been carried out to improve this method. Research to define the best prostaglandin analogue: sulprostone and gemeprost were dropped out; misoprostol was authorized in 1992 following very convincing trials, it is now commonly used and has never generated any major problem. Research to extend the application time limit to 63 DA: it showed a significant drop in efficiency (86.8% instead of 95.4%) as well as an increase of the rate of haemorrhages (2.25% instead of 0.3%). Therefore the method currently used reads as follows. Day 1: mifepristone 600 mg, day 3: misoprostol 400 micrograms, day 10-15: control visit. The efficiency rate is 95.4%; an additional dose of 400 micrograms of misoprostol 3 hours after the first dose if no expulsion has occurred, increases the rate up to 98.5%. This method is well accepted by women as it enables an early abortion and avoids surgery and anesthies. The arrangements required to implement the method are not easy to make as they call for a change of habits by the institutions as well as by medical teams. CONCLUSION: Since the use of misoprostol, the abortion by mifepristone using. 400 micrograms + 400 micrograms of misoprostol has become a method which is safe, efficient and much appreciated by women, but it implies a change in the usual practice of abortion.

A multicenter European survey of the attitudes to contraception in women at high risk or with established cardiovascular disease.

OBJECTIVES: The survey was designed to study the attitudes of gynecologists from 11 European centers providing guidance in contraception to women at high risk and women with cardiovascular disease. METHODS: Attitudes were registered by means of a standard questionnaire. RESULTS: Most contributors reported that, in women with venous thrombosis (10/11), deep venous thrombosis (10/11), coagulation disorders (11/11) and stroke (8/11), they prefer to prescribe methods other than combined oral contraceptives (COCs). A history of myocardial infarction was considered a relative contraindication and some experts suggested that, in some cases, the use of third-generation COCs may be possible. COCs were not recommended in women with severe cardiovascular disease and in those over 35 years of age with light or moderate cardiovascular disease, heavy smokers (over 20 cigarettes per day), or those presenting with severe hyperlipidemia. CONCLUSION: The pill is not considered appropriate for women with clinically established cardiovascular diseases or in cases where more than two coronary risk factors exist. COCs may safely be given to women with elevated blood pressure as long as it is lower than 160/100 mmHg, in cases of light and moderate cardiovascular disease as long as the patient is less than 35 years of age, in women who are not heavy smokers, in the presence of a light or moderate degree of hyperlipidemia, and in uncomplicated diabetes mellitus provided that there are no additional risk factors. In these cases, third-generation COCs are preferred. The co-operation of the cardiologist is desirable in order to classify cardiovascular disease and for patient follow-up.

[RU 486. Contragestion, contraception]. / RU 486. Contragestion, contraception.

The word contragestion is used to name voluntary interruption of very early pregnancy. The RU associated with an analogue of prostaglandine E1 is used in this indication until 49 days of amenorrhea. Based on a study carried out by Roussel in 1993 on 488 patients, the rate of efficacy is 96.9%. Failures are: ongoing pregnancy 1.8%, hemostatic surgical procedure 0.4%, stopped but non expelled pregnancy 1.8%. Side effects are mainly pelvic pains but pain killers were necessary only for 20% of patients. The contraception with RU 486 has just started. The RU seems to be a very efficient post-coital contraceptive when taken within 72 hours after an unprotected intercourse. Two trials have had a rate of success of 100%. The RU in ordinary contraception could be used either just after ovulation or during all the cycle with very low doses. Trials have just started.

Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol [corrected].

The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.

Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol.

BACKGROUND AND METHODS: The combination of mifepristone (RU 486) and a prostaglandin analogue given either intramuscularly or intravaginally is effective in terminating early pregnancy, but the prostaglandin component of the regimen is cumbersome to administer and has side effects. We conducted two studies to determine the efficacy of 600 mg of mifepristone followed by a small dose of misoprostol, an orally active prostaglandin E1 analogue, for the same purpose. In the first study, 505 women who had had amenorrhea for less than 50 days received 400 micrograms of misoprostol 48 hours after receiving mifepristone, if the pregnancy was not terminated within that period. In the second study, 390 women initially received the same treatment, but if the pregnancy was not terminated within four hours after the administration of misoprostol, they were offered an additional 200-micrograms dose of misoprostol. RESULTS: In study 1, the rate of success (termination of pregnancy and complete expulsion of the conceptus) was 96.9 percent (95 percent confidence interval, 94.1 to 97.7 percent)--similar to the success rate of approximately 95 percent for mifepristone followed by the intramuscular or intravaginal administration of prostaglandin. Abortion occurred in 2.9 percent of the women within 48 hours after the administration of mifepristone, in 60.9 percent within 4 hours after the administration of misoprostol, and in 33.2 percent thereafter. The failures included ongoing pregnancies in four women (0.8 percent) and incomplete abortions in nine (1.8 percent); two other women (0.4 percent) required vacuum aspiration for prolonged uterine bleeding. In study 2, pregnancy was terminated in 5.5 percent of the women before the administration of misoprostol and within four hours after the first dose of misoprostol in 69.1 percent. Among the 71 women who received a second dose of misoprostol, 67 had complete abortions, 2 had partial retention of the conceptus, 1 had synechia with ongoing pregnancy, and 1 had an ectopic pregnancy. One ongoing pregnancy, which was terminated by vacuum aspiration, was recorded among the 27 women who declined to take the second dose of misoprostol. The overall rate of success of the regimen with the optional second dose of misoprostol was 98.7 percent (95 percent confidence interval, 96.8 to 99.5 percent). No woman had any serious adverse event. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for the termination of early pregnancy in terms of success, tolerance, safety, and practicality.

PIP: Between June and October 1991 health workers administered 1 dose of 600 mg mifepristone (RU-486) and a single oral dose of 400 mcg misoprostol on day 3 to at least 488 women at 25 centers in France to terminate pregnancy of less than 50 days duration. Pregnancy termination occurred within 48 hours in 2.9% of all women. They had only received RU-486. 1% vomited after taking the first dose of misoprostol, necessitating a second dose. The overall success rate for this regimen was 96.9%. 12 hours was the mean time between taking misoprostol and expulsion of the conceptus. The median time was 3 hours. The types of failure were incomplete expulsion of the conceptus (1.8%), ongoing pregnancy (0.8%), and prolonged bleeding (0.4%). Mean duration of bleeding following the regimen was 9 days. A second study occurred between March 1991 and March 1992 among at least 385 women at 1 center in France. They received RU-486 and misoprostol in the same manner as the women in study 1, but those who did not experience pregnancy termination within 4 hours after the initial dose received another 200 mcg dose of misoprostol. 5/5% experienced pregnancy termination before administration of misoprostol. 69.1% experienced termination within 4 hours. Pregnancy termination occurred within the first 3 hours in almost 90% of them. 27 women who did not abort within 4 hours did not take the additional dose and 26 of them aborted completely. The sole woman with a continued pregnancy underwent vacuum aspiration. 67 of the 71 women who took the second dose completely expelled the conceptus within 48 hours. Thus, 79.2% of all women aborted while being monitored at the center. The overall success rate was 98.7% . The leading side effects in both studies in order of frequency were uterine cramps and nausea, vomiting, and diarrhea. These results showed that oral administration of misoprostol is as effective and well tolerated as other prostaglandins administered parenterally or vaginally.