Woman-years Of Use Research Articles

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18–40 years.Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.Results: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.Conclusions: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique(®)): A Review of Its Use as an Oral Contraceptive.

A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30µg for 84days and ethinylestradiol 10µg for 7days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conventional 28-day regimens. Seasonique(®) was effective in preventing pregnancy in a large (n=1006), noncomparative trial of healthy, sexually active women. In this trial, the overall Pearl index (pregnancies per 100 woman-years of use) in women aged 18-35years (n=621) was 0.76 and the Pearl index for method-failure (compliant use) was 0.26. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with a mean of 2days of bleeding and 1day of spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting was highest during the first few cycles of use and decreased thereafter. Seasonique(®) was generally well tolerated, with a tolerability profile in line with that expected for OCs. Seasonique(®) extends the contraceptive options currently available to women, particularly in those who desire fewer withdrawal bleeding episodes.

Intrauterine contraception after cesarean section and during lactation: a systematic review.

BackgroundAll postpartum women, including those who are breastfeeding or have had a cesarean section, appear potentially suited to intrauterine contraception, a long acting reversible contraceptive (LARC). Like any other method used after delivery, it should not interfere with lactation or be affected by cesarean section.Study designWe searched the MEDLINE, PubMed, Popline, Google Scholar, and Clinicaltrials.gov databases from January 1968 through to December 2012. Studies were included if they reported event rates in women who had a cesarean section and event rates and clinical outcomes in lactating women or their infants in the breastfeeding group. Summary odds ratios were not calculated because of the diverse methods of reporting event rates in the cesarean section group and the heterogeneity of the results in the breastfeeding group.ResultsWe found 26 articles on event rates in interval and post-placental intrauterine device (IUD) use, and 18 on event rates and clinical outcomes in breastfeeding IUD users. Four prospective studies and one retrospective study showed an increased expulsion rate in interval insertion. There were 19 studies, of which five were controlled in post-placental IUD insertion after cesarean section. Four studies had expulsion rates of 10 or more per 100 woman-years of use and 15 expulsion rates below 10 per 100 woman-years of use. Three studies showed that event rates for lactating IUD users are the same as those for non-lactating users. Fifteen controlled studies showed that the IUD had no effect on milk production and seven of these showed no effect on infant growth. Pharmacovigilance databases report an increased rate of IUD perforations in lactating women, while the event rate studies report that insertion is generally easier and less painful than expected. These were uncontrolled reports.ConclusionThe IUD is a long-acting reversible method of contraception with expulsion rates of 5–15 per 100 woman-years of use when used as a post-placental method immediately after cesarean section. As an interval procedure (6 or more weeks after cesarean section) it appears to have a high expulsion rate (5% or higher) notably in older devices. The IUD does not affect breastfeeding and is easy to insert in these women, but appears to be associated with a higher perforation rate (>1 per 100). Providers should not be deterred from using this contraception method, especially in developing countries, but should be attentive to preventing these potential problems.

Contraceptive devices: intravaginal and intrauterine delivery systems

Substances with an antifertility activity can be delivered directly into the vagina and the uterus. Indeed, it has been known for decades that the vaginal mucosa is an excellent way through which to deliver a number of compounds to the general circulation. Research and development efforts have concentrated on rings delivering only progestins, or both an estrogen and a progestin. The only combined ring marketed so far releases 15 µg ethynyl estradiol and 120 µg etonogestrel, and has a failure rate between one and two per 100 women-years of use. It has a preset duration of action of 1 month, has to be inserted before day 5 of the cycle, irrespective of the presence of menstrual flow, and withdrawn after 21 days, thereby allowing proper cycle control. Among rings releasing only a progestin, one device releasing progesterone has been marketed; all others are still under development. Unlike other long-term methods, vaginal rings do not require the involvement of a healthcare professional and can be inserted and removed by the user. The first attempt at achieving contraception by inserting a device in the uterus is 100 years old. Half a century later, medicated intrauterine systems were investigated; they are superior to inert devices and today a number of active principles, such as copper and progestogens, have been incorporated and tested when released from an intrauterine device (IUD). Copper-releasing devices last more than 10 years, with cumulative pregnancy rates of between approximately 5 and 3, and cumulative expulsion rates between approximately 12 and 8. With all IUDs, bleeding and pain are the most common reasons for a request to withdraw a device. There is agreement that fertility after removal of a copper-IUD is not impaired. Finally, the overall risk of ectopic pregnancy is reduced in IUD users, compared with using no contraception. The first progestogen-releasing system contained progesterone, had 1-year duration of action and was marketed some 30 years ago; unfortunately, it was shown that failure caused an increase of extrauterine pregnancies. This potentially dangerous effect eventually led to the withdrawal of the device from the market. In the meantime, a device releasing the synthetic progestin levonorgestrel was being developed and has now been successfully marketed; it lasts for a minimum of 5 years and, although absorbed systemically, cyclic function is maintained. The system is one of the most effective methods of contraception available today: large clinical studies indicate a Pearl index of 0.1 per 100 woman-years. Although a postfertilization effect cannot be excluded, in a majority of cases, intrauterine systems act as true contraceptives, preventing fertilization.

Being strategic about contraceptive introduction: the experience of the Standard Days Method®

Background Many national and institutional family planning policies explicitly include fertility awareness-based methods among the method options that should be made available, but these methods are often not offered for a variety of reasons. After testing the efficacy of the Standard Days Method® (SDM), which is a fertility awareness-based method that identifies Days 8–19 of the menstrual cycle as fertile for women with cycles lasting between 26 and 32 days, pilot studies were conducted to introduce it into programs. Study Design Through 14 pilot studies around the world, ministries of health, family planning associations and community development organizations introduced the SDM. Follow-up interviews with users and other data collection methodologies were used to track user characteristics and experiences. Supervision data and simulated clients assessed the effects on service delivery. Results The SDM appeals to a broad range of women throughout the world. Clients report using abstinence or condoms to manage the fertile days. Both men and women report high levels of satisfaction with the method. The cross-study first-year failure rate of 14.1 pregnancies per 100 woman-years of use is similar to typical-use rates found in the SDM efficacy trial. Conclusions The results of the pilot studies offer guidance for scaling up service delivery of the SDM. Condom counseling can help many users manage the fertile window effectively. Because out-of-range cycles can lead to method failure, users must understand the importance of tracking cycle length and be willing to switch to another method when the SDM is contraindicated. Community providers can offer the method; within clinical settings, SDM counseling typically takes no more time than allowed in most program norms. Training providers to address alcohol use and gender-based violence improves SDM method use and contributes to better quality of care.

Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls

Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects. Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy. Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented. Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200,000 ovarian cancers and 100,000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30,000 per year.

Continuous-Use Ethinylestradiol/Levonorgestrel 20μg/90μg

▲ The continuous-use combination oral contraceptive ethinylestradiol/levonorgestrel 20μg/90μg suppresses gonadotropins, and subsequently ovulation and endometrial thickening, and suppresses breakthrough bleeding. ▲ Amenorrhoea and absence of breakthrough bleeding increase in incidence with extended administration. ▲ The pregnancy rate attributable to method failure in a large noncomparative trial of healthy, sexually active (aged 18–49 years) women during treatment with ethinylestradiol/levonorgestrel 20μg/90μg for 12 months was 15 per 2134 women (adjusted Pearl Index 1.26 per 100 women-years of use). ▲ There were no differences in pregnancy rates over 12 months between continuous-use ethinylestradiol/ levonorgestrel 20μg/90μg and cyclical ethinylestradiol/levonorgestrel 20μg/100μg in a smaller, randomised, nonblind trial. ▲ Adverse menstrual cycle-related symptoms were significantly improved with administration of continuous-use ethinylestradiol/levonorgestrel 20μg/ 90μg in a noncomparative trial. ▲ In small trials, hormonal and ultrasound changes indicative of reinstated ovulation occurred within a month of discontinuation of the drug, and menstruation began again in most women within 90 days. ▲ The incidence of adverse effects was similar in continuous-use and cyclical regimens of ethinylestradiol/levonorgestrel (20μg/90μg vs 20μg/100μg).

Low-Dose Ethinylestradiol/Levonorgestrel

Low-dose ethinylestradiol/levonorgestrel 20 microg/100 microg is a combined oral contraceptive that prevents pregnancy primarily by inhibiting ovulation. The Pearl index (pregnancies per 100 woman-years of use) with ethinylestradiol/levonorgestrel 20 microg/100 microg was 0.88 and the cumulative pregnancy rate was 1.9% at the end of a 3-year open-label trial (1708 women with 26 554 evaluable cycles). The contraceptive efficacy of ethinylestradiol/levonorgestrel 20 microg/100 microg was similar to that of other low-dose combined oral contraceptives containing ethinylestradiol 20 or 35 microg in a 6-cycle trial (463 evaluable women). Ethinylestradiol/levonorgestrel 20 microg/100 microg is well tolerated; adverse events were those commonly associated with combined oral contraceptives. Headache and metrorrhagia (2% of women) were the most common adverse events leading to treatment discontinuation in the 3-year trial. Cycle control in open-label trials in women receiving up to 36 cycles of ethinylestradiol/levonorgestrel 20 microg/100 microg was generally good, with the incidence of intermenstrual bleeding being highest during the first few cycles of use and decreasing thereafter.

Body Mass Index, Weight, and Oral Contraceptive Failure Risk

To estimate the effect of body mass index (BMI) and weight on risk of pregnancy while using oral contraceptives (OCs). We conducted a case-control study of 248 health maintenance organization enrollees who became pregnant while using OCs between 1998 and 2001 and 533 age-matched enrollees who were nonpregnant OC users during the same period. Using logistic regression we calculated adjusted odds ratios (ORs) to estimate the risk of pregnancy according to BMI and weight quartile. Among all OC users, when compared with women having a BMI of 27.3 or less, the risk of pregnancy was nearly 60% higher in women with BMI greater than 27.3 (OR 1.58, 95% confidence interval [CI] 1.11-2.24) and over 70% higher in women with BMI greater than 32.2 (OR 1.72, 95% CI 1.04-2.82). Among consistent users (women who missed no pills in reference month), the risk of pregnancy was more than doubled in women with BMI greater than 27.3 (OR 2.17, 95% CI 1.38-3.41) or BMI greater than 32.2 (OR 2.22, 95% CI 1.18-4.20). When compared with women weighing 74.8 kg or less, among consistent OC users the risk of pregnancy was over 70% higher in women weighing more than 74.8 kg (OR 1.71, 95% CI 1.08-2.71) and nearly doubled in women weighing more than 86.2 kg (OR 1.95, 95% CI 1.06-3.67). Our results suggest that being overweight may increase the risk of becoming pregnant while using OCs. If causal, this association translates to an additional 2-4 pregnancies per 100 woman-years of use among overweight women, for whom consideration of additional or effective alternative contraceptive methods may be warranted.

Oral contraceptive failures and body weight: Findings in a large cohort study

This report looks at data from 17 032 women who took part in the Oxford Family Planning Association contraceptive study. Thirty-eight first accidental pregnancies occurred during 6779 woman-years of use...

The pharmacokinetics and pharmacodynamics of Implanon®, a single-rod etonogestrel contraceptive implant

ABSTRACTThis paper reviews pharmacokinetic and pharmacodynamic studies with Implanon®, which provides serum etonogestrel levels sufficient to inhibit ovulation within 8 h of insertion. After a peak of 813 pg/ml at 4 days, levels reach steady state (200 pg/ml) after 4–6 months and remain sufficient to prevent ovulation for 3 years. Variability is lower than with Norplant®. Etonogestrel levels are similar in most ethnic groups, but 40% higher in women weighing < 50 kg. After implant removal, etonogestrel is not detectable within 1 week. Implanon® inhibits ovulation by preventing the mid-cycle luteinizing hormone peak. Although it initially suppresses follicular development and estradiol production, ovarian activity slowly increases after 6 months, and follicle stimulating hormone and estradiol levels are almost normal. Endogenous progesterone levels remain in the subovulatory range for > 3 yean in most subjects. In ovarian ultrasound studies, ovulation occurred in < 5% of users after 30 months of use. Ovulation was observed in most women within 3–4 weeks of implant removal. The pharmacokinetics and pharmacodynamics of Implanon® indicate that it has high contraceptive efficacy, as reflected in a zero pregnancy rate over 5629 woman-years of use. Its excellent reliability, ease of use, and reversibility make Implanon® a valuable addition to current contraceptives.

The Pharmacokinetics and Pharmacodynamics of Implanon®, a Single-Rod Etonogestrel Contraceptive Implant

This paper reviews pharmacokinetic and pharmacodynamic studies with Implanon®, which provides serum etonogestrel levels sufficient to inhibit ovulation within 8 h of insertion. After a peak of 813 pg/ml at 4 days, levels reach steady state (200 pg/ml) after 4–6 months and remain sufficient to prevent ovulation for 3 years. Variability is lower than with Norplant®. Etonogestrel levels are similar in most ethnic groups, but 40% higher in women weighing <50 kg. After implant removal, etonogestrel is not detectable within 1 week. Implanon® inhibits ovulation by preventing the mid-cycle luteinizing hormone peak. Although it initially suppresses follicular development and estradiol production, ovarian activity slowly increases after 6 months, and follicle stimulating hormone and estradiol levels are almost normal. Endogenous progesterone levels remain in the subovulatory range for > 3 years in most subjects. In ovarian ultrasound studies, ovulation occurred in < 5% of users after 30 months of use. Ovulation was observed in most women within 3–4 weeks of implant removal. The pharmacokinetics and pharmacodynamics of Implanon® indicate that it has high contraceptive efficacy, as reflected in a zero pregnancy rate over 5629 woman-years of use. Its excellent reliability, ease of use, and reversibility make Implanon® a valuable addition to current contraceptives.

Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly for contraception

We evaluated the efficacy and side effects of immediate postcoital administration of levonorgestrel 0.75 mg used repeatedly for contraception. A total of 295 healthy women with infrequent coitus were enrolled at 6 study sites. Each woman took levonorgestrel 0.75 mg by mouth immediately after intercourse during 6 months as her only method of contraception. We collected data on side effects and acceptability and calculated the Pearl index failure rates over 133 woman-years of use by standard methods. The Pearl index failure rate was 6.8 (95% CI 3.1–12.9) pregnancies per 100 woman-years of use. The overall probability of pregnancy per treated coital act was 1.4 per 1000. Approximately one-third of participants discontinued the study within 6 months (mainly for bleeding problems). Menstrual complaints were reported by 70% of women. Other complaints included (in decreasing order) nausea, breast tenderness, weakness, dizziness, headache, abdominal bloating, loss of libido, depression, and vomiting. High-dose levonorgestrel pills are unsuitable for regular postcoital contraception.

An open-label, multicenter, noncomparative safety and efficacy study of Mircette™, a low-dose estrogen-progestin oral contraceptive

OBJECTIVE: The primary efficacy and safety of Mircette™ (brand of desogestrel/ethinyl estradiol and ethinyl estradiol), an oral contraceptive containing 150 μg desogestrel and 20 μg ethinyl estradiol given for 21 days, followed by 2 days of placebo and then 5 days 10 μg ethinyl estradiol, was evaluated. STUDY DESIGN: In a large, open-label, 18-month, multicenter trial, a total of 1143 of 1250 healthy female subjects contributed to the determination of extent of exposure, for an equivalent of 1080.8 woman-years of use. RESULTS: Absence of withdrawal bleeding occurred in 5.5% of total cycles and intermenstrual bleeding occurred in 12.0% of total cycles. Breakthrough spotting was more common than breakthrough bleeding. The Pearl Index for total pregnancies during treatment was 1.02/100 woman-years. Fewer than 3% of subjects discontinued study participation, primarily because of menstrual problems, indicating that Mircette™ was an oral contraceptive acceptable to the women studied. Overall 73.6% of all subjects reported one or more adverse events, and a total of 43.9% of subjects reported drug-related adverse events. The most common drug-related adverse events reported included headache (8.5%), breast pain (7.3%), dysmenorrhea (4.2%), and menstrual disorder (4.2%). There were no reports of venous thromboembolic events or of significant changes in blood pressure, lipid metabolism, or serum glucose level. CONCLUSION: The study confirmed that Mircette™ is a safe and efficacious oral contraceptive that is well tolerated and acceptable to women who have previously used oral contraceptives, as well as first-time users. (Am J Obstet Gynecol 1998;179:S2-8.)

Oral contraceptive use in relation to smoking

Use of OC simultaneous with smoking in older women remains a concern for prescribing physicians, in light of current guidelines for OC use and evidence from recent studies about risks and benefits of different OC agents. It is useful to look at prevalence of OC use simultaneously with smoking after age of 35, as an indication of the effectiveness of these guidelines. Survey of OC use in relation to smoking on a representative sample of 1138 urban women aged 40-54, from Geneva, Switzerland. History of exposure to both OC and smoking is analyzed up to the age of 40. Seventy-six percent of women had ever used OC, and 49% had ever smoked by age 40. Fifty-four percent of women reported OC exposure simultaneous to smoking at some time, and simultaneous exposure accounted for 48% of woman-years of use. But simultaneous use decreased with age, such that simultaneous users during age 36-40 accounted for 37% of OC users during that age period, and for only 13% of all ever OC users. Similarly, woman-years of OC use simultaneous with smoking fell after age 25, and woman-years during age 36-40 accounted for 36% of woman-years during that age period, such that only 5% of woman-years of OC use overall. OC use simultaneous with smoking after age 35 is not typical. Results suggest that a physician today may prescribe a type of OC that fits a young woman's current risk profile, confident of being able to change OC use or smoking by the time the woman enters an older risk profile. Prescribing OC to a young smoker does not generally lead to simultaneous exposure at a later age.

Contraceptive efficacy and safety of a monophasic oral contraceptive containing 150 μg desogestrel and 30 μg ethinyl estradiol: United States clinical experience using a “Sunday start” approach

To report on experience in the United States with a monophasic oral contraceptive (OC) containing 150 micrograms desogestrel and 30 micrograms ethinyl E2 (EE). The results of a multicenter evaluation of efficacy, cycle control, and safety over 6 months of exposure using a "Sunday start" regimen is evaluated. Multicenter. Open noncomparative study. Study subjects were a mean age of 25 years, and the majority were educated, nonobese, white, nulliparous, and previously had used OCs. A total of 809 women were exposed to study medication for a total of 4,096 cycles (equivalent to 341.3 women-years of use). Efficacy was excellent. One user-failure pregnancy occurred (Pearl index 0.32); there were no method-failure pregnancies. Study medication was well tolerated; 6.6% of the subjects discontinued treatment because of drug-related adverse events. The study medication exhibited no adverse effects on blood pressure, body weight, or laboratory variables. Cycle control was evaluated in 697 subjects. In a total of 3,640 cycles, the incidences of intermenstrual bleeding, breakthrough bleeding, breakthrough spotting, and absence of withdrawal bleeding were 9.8%, 1.7%, 8.1%, and 1.4%, respectively, indicating appropriate cycle control. Patient acceptability was high; seven subjects (1%) discontinued the study because of menstrual irregularity (metrorrhagia). The results of this study, comparable to those demonstrated in a recent European multicenter study, add further documentation to the published data on the safety, efficacy, cycle control, and acceptability of this monophasic desogestrel-containing combined OC using a "Sunday start" approach.

A five-year evaluation of NORPLANT® II implants in China

A five-year study of NORPLANT II rod implants was undertaken in four large cities and metropolitan areas in eastern China. Designed to test the safety, efficacy and acceptability of these implants, the study involved 1,208 women and was conducted concurrently with a similar study of NORPLANT® capsule implants. At the end of five years, the gross pregnancy rate was 0.65 per 100, and the continuation rate was 65.3 per 100. Both these values were similar to and not statistically different from the rates of the capsule implant users. In 4,828 woman-years of use, there were few severe adverse events reported. Users and providers found the method to be an acceptable long-term contraceptive method of great reliability.

Safety and efficacy of a triphasic oral contraceptive containing desogestrel: Results of three multicenter trials

This report combines the data obtained in three multicenter efficacy studies with a new triphasic oral contraceptive combination containing desogestrel (DSG) and ethinyl estradiol (EE). The studies were conducted at 40 investigational sites in the United States (38 centers) and Canada (2 centers) in support of the FDA approval of the product. In total, 1,095 subjects were exposed to the study medication for 11,231 cycles, corresponding to approximately 864 woman-years of use. Of these subjects, 414 completed at least 13 cycles of treatment. Contraceptive efficacy was high; six pregnancies occurred during the in-treatment period (two due to method failure and four due to user failure), corresponding to Pearl Indices of 0.23 and 0.46, respectively. The incidence of irregular bleeding was low, and the acceptability was excellent as evidenced by the low incidence of drug-related drop-outs. No drug-related serious adverse experiences were reported, and the incidence of other drug-related adverse experiences was generally low and decreased with continued use. No effects were seen on blood pressure, body mass index, laboratory parameters, cervical cytology and breast nodularity. These studies demonstrate that triphasic DSG/EE is an effective and acceptable triphasic oral contraceptive preparation with excellent cycle control and no significant physiologic effects.

31781 cases of non-surgical female sterilisation with quinacrine pellets in Vietnam

The quinacrine method of non-surgical female sterilisation involves transcervical intrauterine insertion of 252 mg quinacrine as pellets during the proliferative phase of the menstrual cycle; the drug causes inflammation and fibrosis of the proximal fallopian tube. We have carried out a field trial of 31 781 cases in twenty-four provinces of Vietnam from Jan 2, 1989, until October, 1992. There were 818 pregnancies after the procedure, of which 80 were carried to term. Some women received only one dose of quinacrine; the majority received two doses with an interval of one month. Cumulative life-table pregnancy rates per 100 women at 1 year (for studies of at least 50 cases followed for 12 months) were 2·63 (SE 0·17) among 9461 women who received two doses and 5·15 (0·48) among 2225 who received only one dose. Failure rates (pregnancies) were strongly affected by the skill of the doctor or midwife. There were no deaths and only 8 serious complications were reported (0·03%); by contrast, in a similar series of women undergoing surgical sterilisation, 30 deaths and between 540 and 1812 serious complications would be expected. All reported side-effects were minor and of short duration. There were 19 ectopic pregnancies and the incidence was 0 89 per 1000 woman-years of use. There was one birth defect (anencephaly), in a fetus conceived 2·5 months after quinacrine insertions; however, we believe it is not related to the procedure. An estimated 242 maternal deaths will be averted by these 31 781 sterilisations. This method is safe and acceptably effective for female sterilisation.

Hormonal intrauterine devices.

Intrauterine administration of progestogens from an IUD was introduced more than 15 years ago in order to improve the contraceptive efficacy and to reduce side-effects. A device releasing 20 micrograms levonorgestrel daily (Levonova) with a life span of at least 5 years is now available and has been subjected to an extensive study including 1821 women followed during 5 years. The safety and efficacy were evaluated in comparison to Cu-T IUDs. The pregnancy rate (Pearl index) was 0.09. During the first two cycles after insertion intermenstrual bleeding was common, otherwise the frequency of side-effects was low. The results seem to justify the conclusion that intrauterine administration of progestogens represents a further development of IUDs and hormonal contraception. Furthermore, these devices have proven to be effective in treatment of heavy menstrual blood losses. In many menorrhagic women, use of these IUDs can replace more invasive surgical methods such as hysterectomy or endometrial resection. Intrauterine administration of progestogens is also effective in opposing the proliferative effect of oestrogen on the endometrium in women on hormonal replacement therapy.