Woman-years Of Use Research Articles

The safety and efficacy issues of progestin-only oral contraceptives — An epidemiologic perspective

Progestogen-only oral contraceptives (POCs) are generally considered a good contraceptive choice for brestfeeding women and for women who want to use an oral form of contraception, but are not suited for, or cannot tolerate the side effects of, estrogen-containing preparations. However, a number of POCs' safety, efficacy and other related issues remain to be addressed. This paper reviews recent literature and evaluates these issues from an epidemiologic perspective. The small number of users imposes severe limitations in designing epidemiologic studies to address POCs' long-term safety issues, but available information suggests POCs are at least as safe as, if not safer than, COCs. Compared to COCs, POCs are more likely to cause menstrual disturbances which, in turn, could affect their acceptability and lead to poor compliance and hence higher pregnancy rates. POCs' efficacy has been estimated to be between 1.4 and 4.3 pregnancies per 100 woman-years of use. Lower pregnancy rates approaching those of COCs have been reported in centers with good counseling. POCs' benefits outweigh their risks. However, more studies are needed to further address POCs' safety and efficacy issues.

Intrauterine devices and pelvic inflammatory disease: An international perspective

International Journal of Gynecology & ObstetricsVolume 39, Issue 3 p. 249-249 Citations from the literature infectious diseases Intrauterine devices and pelvic inflammatory disease: An international perspective TMM Farley, TMM FarleySearch for more papers by this authorMJ Rosenberg, MJ RosenbergSearch for more papers by this authorPJ Rowe, PJ RoweSearch for more papers by this authorJ-H Chen, J-H ChenSearch for more papers by this authorO Meirik, O MeirikSearch for more papers by this author TMM Farley, TMM FarleySearch for more papers by this authorMJ Rosenberg, MJ RosenbergSearch for more papers by this authorPJ Rowe, PJ RoweSearch for more papers by this authorJ-H Chen, J-H ChenSearch for more papers by this authorO Meirik, O MeirikSearch for more papers by this author First published: November 1992 https://doi.org/10.1016/0020-7292(92)90674-8Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume39, Issue3November 1992Pages 249-249 RelatedInformation

A multicenter efficacy and safety study of an oral contraceptive containing 150 μg desogestrel and 30 μg ethinyl estradiol

The study reported herein is the primary efficacy and safety study conducted to support U.S. registration of an oral contraceptive containing 150 μg desogestrel and 30 μg ethinyl estradiol. A large multicenter study enrolled 1,221 women at 50 centers in the United Kingdom. A total of 11,656 cycles of exposure was accumulated, corresponding to approximately 879 women-years of use. Contraceptive efficacy was high; no subject conceived as a result of method failure. The product was generally well tolerated with excellent cycle control, causing fewer than 2% of the subjects to discontinue because of bleeding irregularities. The study medication demonstrated no adverse effects on cervical cytology, blood pressure, body weight or laboratory variables, while pre-existing benign breast disease generally improved. The study did not identify any medication-related adverse experiences. This study confirmed that the monophasic oral contraceptive with 150 μg desogestrel and 30 μg ethinylestradiol is a safe and effective oral contraceptive with excellent cycle control and patient acceptability.

"Intrauterine devices and pelvic inflammatory disease: An international perspective."

The risk of pelvic inflammatory disease (PID) associated with use of an intrauterine device (IUD) has been an important concern that has dominated decisions on its use throughout the world, especially in the USA. Early research that suggested such an association led to both a dramatic decline in use of the method and its withdrawal from the US market by two manufacturers. However, factors other than use of an IUD are now thought to be major determinants of PID risk. To address these concerns, we have reviewed the World Health Organisation's IUD clinical trial data to explore the incidence and patterns of PID risk with use of an IUD. The overall rate of PID among 22 908 IUD insertions and during 51 399 woman-years of follow-up was 1·6 cases per 1000 woman-years of use. After adjustment for confounding factors, PID risk was more than six times higher during the 20 days after insertion than during later times (unadjusted rates, 9·7 vs 1 ·4 per 1000 woman-years, respectively); the risk was low and constant for up to eight years of follow-up. Rates varied according to geographical area (highest in Africa and lowest in China) and were inversely associated with age. PID rates were lower among women who had IUDs inserted more recently. Our findings indicate that PID among IUD users is most strongly related to the insertion process and to background risk of sexually transmissible disease. PID is an infrequent event beyond the first 20 days after insertion. Because of this increased risk with insertion, IUDs should be left in place up to their maximum lifespan and should not routinely be replaced earlier, provided there are no contraindications to continued use and the woman wishes to continue with the device. Lancet 1992; 339: 785-88.

Intrauterine devices and pelvic inflammatory disease: an international perspective

The risk of pelvic inflammatory disease (PID) associated with use of an intrauterine device (IUD) has been an important concern that has dominated decisions on its use throughout the world, especially in the USA. Early research that suggested such an association led to both a dramatic decline in use of the method and its withdrawal from the US market by two manufacturers. However, factors other than use of an IUD are now thought to be major determinants of PID risk. To address these concerns, we have reviewed the World Health Organisation's IUD clinical trial data to explore the incidence and patterns of PID risk with use of an IUD. The overall rate of PID among 22 908 IUD insertions and during 51 399 woman-years of follow-up was 1·6 cases per 1000 woman-years of use. After adjustment for confounding factors, PID risk was more than six times higher during the 20 days after insertion than during later times (unadjusted rates, 9·7 vs 1 ·4 per 1000 woman-years, respectively); the risk was low and constant for up to eight years of follow-up. Rates varied according to geographical area (highest in Africa and lowest in China) and were inversely associated with age. PID rates were lower among women who had IUDs inserted more recently. Our findings indicate that PID among IUD users is most strongly related to the insertion process and to background risk of sexually transmissible disease. PID is an infrequent event beyond the first 20 days after insertion. Because of this increased risk with insertion, IUDs should be left in place up to their maximum lifespan and should not routinely be replaced earlier, provided there are no contraindications to continued use and the woman wishes to continue with the device. Lancet 1992; 339: 785-88.

Developing Country Pill Users Experience Small Rise in Blood Pressure

According to the results of a multi-country study regarding the effects of oral contraceptives (OCs) on blood pressure pill users experience a small increase in blood pressure at the end of 1 year of use compared with IUD users. To analyze changes in blood pressure among OC users and IUD users researchers working with WHO collected data from 10 centers in three developed and six developing countries. Eligible study participants comprised 704 pill users and 703 IUD users. Overall results showed that hypertension was diagnosed in 4 women in the pill group; no women in the IUD group developed hypertension. The cumulative life-table rate of hypertension among pill users was 0.78 per 100 woman-years of use. The researchers conclude that OCs appear to cause a small transitory increase in both systolic and diastolic blood pressure but are unlikely to contribute substantially to hypertension and its sequelae. Consequently another study was conducted to examine whether the estrogen component of the pill is responsible for the apparent blood pressure increase. An overall comparison and a comparison within each center of blood pressure change among women taking the higher estrogen pill versus those taking the lower estrogen dose found no significant differences between the two groups. The researchers believe that the results provide some evidence against the hypothesis that estrogen or the estrogen/progestogen ratio cause pill-induced changes in blood pressure.

The WHO multicentre trial of the vasopressor effects of combined oral contraceptives: 1. Comparisons with IUD

Changes in blood pressure were measured at three-monthly intervals over one year in a prospective study of 704 women using an oral contraceptive (OC) containing levonorgestrel 250 ug with ethinyl estradiol 50 ug and 703 women using an intrauterine device (IUD). The study was conducted in 11 centres in seven developing and three developed countries. Women using OC developed systolic blood pressures which were 3.6–5.0 mmHg higher than those using IUDs; their diastolic pressures became 1.9–2.7 mm higher. The OC-induced change was not affected by climate, age, a family history of hypertension, stroke or heart disease or by a history of hypertension in pregnancy. The life-table rate of hypertension (BP 140/90 or more) in the first year of OC treatment was 0.6 ± 0.4 in the developing countries and 1.1 ± 0.8 in the developed ones, per 100 woman-years of use. The vasopressor response to OC varied widely between centres but was not obviously related to the economic development of the country.

International Experience with NORPLANT and NORPLANT-2 Contraceptives

Experience encompassing more than 20,000 woman-years of use of NORPLANT capsules and 6,000 woman-years of trials of NORPLANT-2 rods is reviewed. Implant contraception repeatedly has been associated with low pregnancy rates and high continuation rates through five full years of use. Weight has proved to be a factor related to effectiveness. Women weighing less than 50 kg experienced cumulative five-year pregnancy rates well below 1 per 100, whereas the overall cumulative rate has been 3.5 per 100. Medical events reported during use that have led to discontinuation are analyzed from four large data sets.

Two years of intrauterine contraception with levonorgestrel and with copper: A randomized comparison of the TCu 380Ag and levonorgestrel 20 mcg/day device

IUDs releasing 20 mcg/day of levonorgestrel (LNg20) were in randomized trial together with the Copper T, model TCu 380Ag, in seven centers involving 2244 women. Two-year (25 months) gross cumulative pregnancy rates were 0.2 ± 0.2 and 0.9 ± 0.3 for the levonorgestrel and copper releasing devices, respectively (P > 0.05). There were no ectopic pregnancies in more than 1600 woman-years of use of each device. Removal rates for bleeding and/or pain or for medical reasons other than menstrual problems did not differ significantly between devices. Oligomenorrhea or amenorrhea prompted 10.7 per hundred (gross rate, 8.4 net rate) women using the LNg 20 IUD to request removal in the two-year period, significantly above the 0.2 per hundred rate among women with the Copper IUD (P < 0.001). At the end of two years an estimated 59.4 per 100 women were continuing use of the LNg 20 IUD, and 67.5 per 100 (P < 0.001) with the TCu 380Ag. This difference is almost wholly ascribable to a marked reduction in bleeding episodes and days among women using the LNg 20 device with concomitant removal of device. Hemoglobin rose an average of 0.5g/dl (P < 0.001) for this group whereas women using the TCu 380Ag experienced a decline of 0.2g/dl compared with baseline values (P < 0.001).

Gynecological services utilization by contraceptive clients: a cost analysis.

A cost analysis of gynecological service use by students enrolled in a prepaid health plan at the University of Massachusetts revealed that pregnancy and abortion-related services account for almost half of total costs. The medical records of 495 randomly selected students who presented for diaphragm care during 1980-81 were reviewed and 78% of these women were interviewed. 27% had had at least 1 pregnancy; in 15% of these cases, the pregnancy was diaphragm-related, yielding a Pearl Index of 9.75 pregnancies/100 woman-years of use. Overall, 25% of students (33% of seniors) had an abortion while at college. Study subjects made a total of 1483 visits to the gynecological service and saw an average of 3.3 practitioners. 67% of contraception-related visits were for diaphragm fits, checks, or replacements; 24% involved a change to pills. The average cost per visit for diaphragm fit or method change was $31.20 if the provider was a physician ($22.60 for a nurse practitioner); the cost for diaphragm follow up by a physician was $23.60 ($16.60 for a nurse practitioner). For seniors, the average cost to the health plan over 3.4 years of visits was $83.10 for contraception, $47.43 for pregnancy-related care and abortion counseling, and $100.51 for other gynecological problems (e.g., vaginitis, menstrual disorders) and the annual examination. The $231.04 total cost/senior represents half of the $460 paid in direct premiums. Further analysis is recommended to determine whether increased resource allocation to contraceptive counseling would reduce pregnancy-related costs.

The Cervical Cap

The cervical cap may eventually prove to be a safe, satisfactory, noninvasive, and nonhormonal contraceptive alternative for women in the US. The cap is currently approved for investigational use only, and is available from a limited number of providers. The Prentif cavity rim cap is the most commonly used and is available in 4 sizes. The soft rubber device is thimble shaped, approximately 1 1/4 inches long, with a narrow groove along the inner surface that creates a suction seal when fitted over the cervix. The inability to match cap and cervical circumferences precisely is a recognized drawback. Theoretically, the cap alone should prevent sperm entry into the uterus, however, the use of a spermicide placed in the dome before insertion is recommended. The cap's effectiveness is not yet documented. Estimates from a 1953 study of 143 users were 92.4/100 women years of use for use effectiveness, and the theoretical effectiveness is believed to be more than 98%. Failures with the cap may result from a variety of reasons, particularly dislodgement. The advantage of the cap over other barrier methods is that it can be inserted any time prior to intercourse and left in place longer. The ideal safety period for placement has not been validated, but a range of 1-7 days has been recommended. The length of time the spermicide remains effective and the cervical effects of prolonged contact are of prime concern. The cap may be used by some women who cannot be properly fitted for a diaphragm due to vaginal or uterine anomalies. Sexual arousal and orgasmic response are reported by some cap users to be more pleasurable with the cap than with the diaphragm. Reported problems with use include discomfort during intercourse and improper fit during some days of the menstrual cycle. Contraindications for use include cervical inconsistencies, infection, allergy to the spermicide or the rubber, and inability to learn proper insertion and removal techniques. Insertion and removal may be difficult, and clients should be given sufficient time to practice. Cap placement needs to be checked manually after insertion and intercourse. With proper use, cleaning, and storage, the cap will last for several years. Instruction in use requires a significant amount of the practioner's time and methods must be sensitive to the client's needs. Attitudes of practitioners and other staff may impact on the acceptability of this method. Additional research is needed on the characteristics of cap users, partners' attitudes, the need to use spermicides, the length of time of spermicidal effectiveness and cap effectiveness rates. Further development of instructional methodologies is needed.

Effectiveness and risks of contraception.

At this time the ideal contraceptive, i.e., the safe, simple, inexpensive, totally effective, easily reversible contraceptive without side effects and not used at the time of the sexual act, has yet to be developed. This review highlights recent improvements in standard contraceptives and the views of these physicians concerning current risk benefit ratios. The benefits of tubal ligation are obvious, for few procedures offer more relief from anxiety and have such a high chance of success. Failure rates with tubal ligation range from 1 in 200 to 1 in 1000 cases, depending on the type of operation performed. Advances in laparoscopic technique, including the use of either silastic bands or spring loaded clips, have virtually eliminated the inadvertent "burns" associated with electrocautery. Due to the fact that clips and bands produce less tissue damage, it is anticipated that there will be a higher potential for reversibility. Recent literature has emphasized a specific syndrome that develops subsequent to tubal ligation; its major components are dysfunctional uterine bleeding and pelvic pain. The true incidence of this syndrome is difficult to establish but is estimated to be 10-33% in women who have had laparoscopic tubal fulguration. Vasectomy is simpler with less immediate morbidity, less expense, and easier reversibility than tubal ligation. The failure rate is slightly less with male sterilization. The most alarming recent report in relation to vasectomy is that it may be a surgical model for autoimmune disease. The theoretical effectiveness of steriodal contraceptives is 1 pregnancy/1000 woman years of use, and the actual use effectiveness is 5-8 pregnancies/1000 woman years of use. Many review articles document the various adverse effects that have been recorded in the literature. The mortality risk from oral contraceptive (OC) use in women under age 35 is 3 in 100,000. Few authors comment on the beneficial effects of OCs. These include fewer menstrual disorders, inhibition of the development of benign breast disease and a decrease in the incidence of functional ovarian cysts, and a decrease in some medical illnesses including peptic ulcers and rheumatoid arthritis. Liver adenomas are the most prominent complication of OCs that have been related to chronic use. The IUD has several benefits including a failure or pregnancy rate of 2-3/100 woman years of use. OCs are 3 times more dangerous than the IUD in regard to mortality, but the incidence of hospitalizations is 5-10 times higher with the IUD than with OCs. As effectiveness of barrier methods depends on high motivation, in studies of all forms of vaginal contraception and condoms there is a wide discrepancy between theoretical and use effectiveness. The lowest mortality rates are associated with barrier contraceptives with a back-up of early abortion when the method fails.

Clinical experience with a low dose oral contraceptive containing norethisterone and ethinyl oestradiol.

The results are presented of a clinical investigation of an oral contraceptive containing 0.5 mg norethisterone and 0.035 mg ethinyl oestradiol. The medication was administered orally as a 21-day cyclic regimen in 1,168 women. Duration of use was from 1 to 53 cycles with an overall total of 16,345 cycles. When the preparation was taken as directed, no pregnancies occurred. Three women conceived during the course of this study; however, these subjects missed 3, 2, and 1 prescribed tablets, respectively, and their pregnancies are thus judged due to patient failure. The overall pregnancy rate was 0.22 per 100 women years of use calculated as a Pearl Index. Intermenstrual bleeding (spotting and/or breakthrough bleeding) was noted primarily in the early cycles, soon tapering off to a lower and stable level. The overall cumulative cyclic incidence of amenorrhoea was 1.0%.

Letter: Epilepsy and the pill.

The possibility of increased oral contraceptive (OC) failure among epileptics is discussed. Data on 100 epileptics taking combined OCs showed 5 pregnancies, 4 of which were attributable to patient failure. Data from the entire study indicated 97 pregnancies over 48,350 women-years of use. The failure rate compared with that for epileptics was statistically significant (p less than .01) for total failures, but not for apparent method failures. It is concluded that epileptics are not as well protected by OCs as most women, though the protection is probably as good as that offered by other reversible methods.

Clinical efficacy, acceptability and metabolic effects of new low dose combined oral contraceptives.

Studies on the efficacy and acceptability of various low-dose combinations of ethinyl estradiol and either d-norgestrel lynestrenol or norethindrone acetate are reviewed. In all trials but 1 the pregnancy rate per 100 women years of use was less than 1. The lowest dose combination of ethinyl estradiol and d-norgestrel significantly reduced the incidence of nausea breast tenderness and leg cramps compared with side effects reported for the preparation containing 50 mcg ethinyl estradiol and .25 mg d-norgestrel (p less than .001 and p less than .01 respectively). The new combinations offer several advantages: good cycle control minimal side effects no alterations in serum cholesterol levels or other liver function tests little effect on carbohydrate metabolism and no effect on coagulation factor VII. The incidence of thromboembolic disorders is also expected to be reduced.

Minipill: Miniprotection from Ectopic Pregnancy

The progestogen-only minipill appears to offer only minimal protection against ectopic pregnancy according to 3 reports. In 1 report, 2 ectopic pregnancies occurred among 135 women taking .35 mg norethisterone for a total of 1024 woman-months, and 2 other ectopic pregnancies occurred in a group of women who completed 650 woman-months, yielding and approximate rate of 2/100 woman per year of use. In another report, 3 ectopic pregnancies were found among a group of 535 women using minipills for 4594 woman-months. Of these, 1 woman had used .5 mg chlormadinone acetate daily, another .35 mg norethisterone, and the third, .5 mg megestrol acetate. These failure rates ranged from .6 to 1.2 ectopic pregnancies per 100 woman-years of use. There were 35 pregnancies among these women, 8.6% of which were ectopic. In another report, there were 3 ectopic pregnancies among 73 pregnancies. This proportion, 4.1%, was similar to that reported for pregnancies among IUD users. It was noted that side effects of progestogen-only contraception, e.g., spotting and breakthrough bleeding, lengthened cycle, and amenorrhea, are also symptoms of ectopic pregnancy. Physicians should consider ectopic pregnancy when patients are taking minipill contraceptives.

Clinical results with a new low dose oral contraceptive utilizing norethindrone/ethinyl estradiol

A new oral contraceptive containing 0.5 mg norethindrone and 0.035 mg ethinyl estradiol (MODICON ∗ ∗ Trademark of Ortho Pharmaceutical Corporation. Tablets) was administered orally as a 21-day cyclic regimen to 613 clinic subjects for a total of 8,738 cycles. When taken as directed, there were no pregnancies reported. Two pregnancies occurred due to patient failure (missed tablets) and resulted in an overall pregnancy rate (Pearl Index) of 0.27 per 100 woman years of use or 0.42 per 100 women using Life-table analysis. Intermenstrual bleeding was noted primarily in the early cycles and decreased in subsequent cycles. The incidence of amenorrhea was 0.9%. Other clinical side effects were similar to those reported with other oral contraceptives.

Contraception by Injection

Clinical use of depot medroxyprogesterone acetate (DMPA) over a 10-year involving 43000 acceptors 320000 injections and 77500 woman-years of use is reported. In the Chiang Mai Thailand program 3 of every 4 new family planning acceptors elect this method. 150 mg has been injected in every 12 weeks. A safety period of an additional 3 weeks in most women results. Nursing mothers are considered especially suitable subjects. Quantity and quality of milk have not been affected. Injection of 450 mg DMPA effective for 24 weeks has been used for postpartum patients. Preferably injections should be started not later than 1 month after pregnancy termination. Women having regular periods may be started during the menstrual flow or within the first 7 days therafter. When given later other contraception methods should be used until the next cycle. Menstrual irregularities often follow Use of 50 mcg ethylestradiol once or twice daily for 10 days or injection of soluble estrogen such as 10 mg estradiol cyprionate may correct the condition. Normal menstrual cycles have returned in 93% of women by 9 months after the last injection. Pregnancy has followed in 6 months in 62% of those discontinuing the method to achieve pregnancy at 1 year in 77% and at 2 years in 88%. Physical examinations and Papanicolaou smears have usually been done before the 1st injection and yearly therafter. Of each 140 women using this method for 1 year 1 pregnancy has occurred. Other side effects ar comparable to those seen in women using combined contraceptives. This method is recommended.

Rhythm: Systematized Chance-Taking

The variations of the rhythm method of contraception and its inadequacy as a reliable method are discussed. Studies of women following the calendar method have shown a failure rate of 30 pregnancies per 100 women-years of use. Failure rates with the basal body temperature method have been observed to be lower than when the calendar method and basal body temperature method are combined (6.6 and 19.3 per 100 woman-years). Sufficient data does not yet exist to evaluate the cervical mucus method. The failure rates are higher than those found with oral contraceptives, IUDS, and occlusive methods. The development of methods to determine the post ovulatory phase of the menstrual cycle would enhance the rhythm method. It is concluded that methods which attempt to predict the ovulatory phase are not effective methods of birth control.

A two-man experience with the copper “T” intrauterine device

The contraceptive effectiveness and the incidence of side effects of the Copper T Model T Cu200 in 396 women was studied by a two-man team in a private clinic. There were six pregnancies, a rate of 2.7 per 100 woman years of use, which were associated with either expulsion or displacement of the IUCD. The expulsion-displacement was higher in the immediate postpartum insertions, and in the nulligravid group. The implications of these findings are discussed, and visible and invisible displacement of the IUCD are illustrated. Twenty IUCDs were removed for medical reasons primarily menorrhagia and/or metrorrhagia. There were 9 removals for non-medical reasons, mainly because of desired pregnancy. Menorrhagia and intermenstrual spotting were the most frequently reported side effects of the copper T. There was a drop in the incidence of reported side effects as the months of use increased with the exception of metrorrhagia in the gravid group. The significant advantages of the Cu T are its high acceptability in the nulligravid, the reduced bleeding, and the ease of insertion.