Michael J. Rosenberg

Use and misuse of oral contraceptives: Risk indicators for poor pill taking and discontinuation

The contraceptive efficacy of oral contraceptives (OCs) depends on their proper and continued use, particularly with lower estrogen preparations. However, few studies have examined why women miss pills or discontinue OCs, and those that do tend to be small and to focus on adolescents. To address the issues of poor OC compliance and early OC discontinuation, we analyzed OC use in a convenience sample of 6,676 women between the ages of 16 and 30 from Denmark, France, Italy, Portugal, and the United Kingdom. Logistic regression was used to examine the independent effect of each factor. Poor compliance was associated with a lack of established routine for pill-taking (relative risk [RR] = 3.3), failure to read and understand written materials that came with the OC package (RR = 2.2), not receiving adequate information or help about OCs from their health care provider (RR = 1.5), and occurrence of certain side effects, including hirsutism (RR = 2.1), nausea (RR = 1.4), bleeding irregularities (RR = 1.3), and breast tenderness (RR = 1.2). Women who were inconsistent OC users, missing one or more pills per cycle, were almost three times as likely to experience an unintended pregnancy while using OCs than were women who took their OCs consistently. Factors that predicted early discontinuation (women who wished to continue contraceptive protection but discontinued OC use) were primarily side effects, including nausea (RR = 2.1), bleeding (RR = 1.9), breast tenderness (RR = 1.8), mood changes (RR = 1.8), and weight gain (RR = 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone Receptor Modulator for Emergency Contraception A Randomized Controlled Trial

OBJECTIVE: Compare the efficacy and adverse effects of CDB-2914, a new progesterone receptor modulator, to levonorgestrel for emergency contraception. METHODS: We performed a randomized, double-blinded noninferiority trial, enrolling healthy women seeking emergency contraception within 72 hours of unprotected intercourse. Participants were randomly assigned to receive a single dose of 50 mg of CDB-2914, plus a placebo 12 hours later or two doses of 0.75 mg of levonorgestrel taken 12 hours apart. Follow-up was scheduled 5 to 7 days after the expected onset of the next menstrual period. Posttreatment pregnancy was established by a positive urine test at follow-up and confirmed by quantitative serum &bgr;-hCG. Daily diaries were used from the time of emergency contraception use until next menses to record adverse effects and sexual activity. RESULTS: Product efficacy was evaluable in 775 of CDB-2914 users and 774 of levonorgestrel users. Pregnancies occurred in 7 (0.9%, 95% confidence interval 0.2–1.6%) and 13 (1.7%, 95% confidence interval 0.8–2.6%) women, respectively. Based on the estimated cycle day of unprotected intercourse, 85% and 69% of anticipated pregnancies, respectively, were averted. Nausea was reported by a somewhat greater percentage of CDB-2914 than levonorgestrel users (29% compared with 24%, P=.03), but the distribution of other adverse effects was similar in both groups. Women in both groups experienced considerable variation in menstrual cycle length as compared with their reported individual normal cycle lengths. CONCLUSION: CDB-2914 is at least as effective as levonorgestrel in preventing pregnancies after unprotected intercourse and has a similar side effect profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00271583 LEVEL OF EVIDENCE: I

Causes and consequences of oral contraceptive noncompliance

Compliance difficulties are more common among oral contraceptive users than is generally appreciated. Inconsistent use and method discontinuation are estimated to account for approximately 20% of the annual 3.5 million annual unintended pregnancies in the United States. In the past research focused on adolescents, for whom predictors of poor oral contraceptive compliance include multiple sex partners, low evaluation of personal health, low degree of concern about pregnancy, and previous abortion. More recent research confirms that compliance problems are common among all age groups, with 47% of women missing >/=1 pill per cycle and almost a quarter (22%) missing >/=2 pills per cycle. Good compliance has been linked to patient satisfaction with the clinician, the absence of certain side effects, establishing a regular daily routine to take oral contraceptives, and reading information distributed with oral contraceptive packaging. Clinicians are the focal point for improving oral contraceptive compliance. They should focus counseling on the transience of most side effects, instructions on dealing with a missed pill, provision of a backup method, and establishment of a daily pill-taking routine. Easy-to-understand literature should be given to patients to take home.

Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives : A randomized trial of 20 μg and 35 μg estrogen preparations

Abstract Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 μg preparations are available. To address this issue, we conducted a randomized, open-label multicenter clinical trial comparing Alesse® (20 μg ethinyl estradiol [EE]), Mircette® (20 μg EE), and Ortho Tri-Cyclen® (35 μg EE) among 463 OC starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 μg EE as compared to 20 μg EE preparations. Cycle control was similar in all products, although during the first two cycles among starters; users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 μg EE users.

Compliance and oral contraceptives: A review

Compliance difficulties are more common among oral contraceptive (OC) users than generally appreciated by clinicians, in part because unintended pregnancy is a relatively infrequent consequence and in part because more common manifestations such as spotting and bleeding may not be recognized as resulting from poor compliance. While improving compliance is a shared responsibility of patients, clinicians, and manufacturers, the clinician is the focal point for these efforts. Counseling must be individualized, which requires knowledge of factors that predict compliance and an understanding of the patients decision-making process as it relates to medications. Most OC compliance research has focused on adolescents, where predictors of poor compliance include multiple sex partners, low evaluation of personal health, degree of concern about pregnancy, and previous abortion. Good compliance has been linked with patient satisfaction with the clinician, the absence of certain side effects, establishing a regular daily routine to take OCs, and reading information distributed with OC packaging.

Weight change with oral contraceptive use and during the menstrual cycle: Results of daily measurements

Although weight gain is among the most common complaints of women using oral contraceptives (OC) and a frequent reason for discontinuation, studies demonstrate little basis for this perception. We explored this issue by analyzing the daily weights of 128 women during four cycles of triphasic OC use. The mean weight at the end of the fourth cycle of use was the same as baseline weight (average weight change, 0.0 pounds). The largest proportion of women, 52%, remained within 2 pounds (0.9 kg) of their starting weight, and 72% of women had either no weight change or a loss. Over each menstrual cycle, regular but minor weight shifts were observed, with the mean weight rising by one-half pound (0.2 kg) during the first weeks of each cycle and falling by the same amount during the last few days. These results emphasize the lack of association of OC use with weight gain but OC may be blamed at least in part, based on cyclic fluctuations. Counseling should emphasize weight gain as a misperception and stress the fact that a highly effective and safe form of contraception should not be ruled out or discontinued because of concern about weight.

Contraceptive Efficacy of a Novel Spermicidal Microbicide Used With a Diaphragm : A Randomized Controlled Trial

OBJECTIVE: Women need products that protect against both pregnancy and sexually transmitted infections, including human immunodeficiency virus (HIV). The acid buffering gel is a nondetergent spermicide that may provide this dual protection by reinforcing normal vaginal acidity to inactivate both sperm and acid-sensitive sexually transmitted pathogens. The objective of this study was to assess the gel’s contraceptive effects, safety, and acceptability. METHODS: We conducted a multicenter, randomized, double-masked, noninferiority study at 11 centers, comparing 621women who used an acid buffering gel plus diaphragm with 300 women who used a nonoxynol-9 spermicide plus diaphragm for 6 months. A double-masked study extension followed 234 women for an additional 6 months of use. RESULTS: The 6-month pregnancy rate per hundred women was 10.1% (95% confidence interval [CI] 7.1–13.1%) for acid buffering gel and 12.3 (95% CI 7.7–16.9) for nonoxynol-9 spermicide users. The difference in rates was –2.2% with a 95% CI –7.7 to 3.3%. Consistent and correct use 6-month pregnancy rates were 4.7% for acid buffering gel and 6.1% for nonoxynol-9 spermicide users, calculated from those cycles where diary entries indicated such use. Adverse events and acceptability were similar between the two groups. Pregnancy probabilities were similar between groups participating in the 12-month study extension. CONCLUSION: An acid buffering gel used with a diaphragm is a safe, acceptable contraceptive with efficacy comparable to that of a common commercial spermicide with diaphragm. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00065858 LEVEL OF EVIDENCE: I

The effect of desogestrel gestodene and other factors on spotting and bleeding.

Spotting and bleeding are among the most common side effects associated with oral contraceptive (OC) use and their occurrence is a prime determinant of whether a new user will continue to use OCs. Desogestrel and gestodene are two new progestins that were developed in part to minimize the occurrence of these side effects. Assessing the effect of these progestins is difficult, however, in part because their effects may be subtle, requiring a large sample size and possibly being overshadowed by other factors. To address these issues, we analyzed data from two comparative multicenter clinical trials that included 15,421 cycles among 2767 women. One study compared 75 micrograms gestodene + 30 micrograms ethinyl estradiol (EE) with 150 micrograms desogestrel + 30 micrograms EE, the other compared the same gestodene preparation with 150 micrograms desogestrel + 20 micrograms EE. Both studies found a higher risk of spotting or bleeding in all cycles among users of the desogestrel-containing preparation, with the differences ranging between 20% and 70% higher for the first study and 40% and 140% in the second. These differences were statistically significant in four of six cycles in each study and persisted after controlling for consistency and recency of OC use as well as smoking. After pooling the data and controlling for estrogen dose, the desogestrel-containing preparation was significantly associated with more frequent spotting or bleeding in five of six cycles. Smoking and consistency and recency of OC use were also independent predictors of spotting or bleeding.

Performance of the TCu380A and Cu-Fix IUDs in an international randomized trial.

To compare the clinical performance of the TCu380A, the most widely used copper IUD in the world today, and a new frameless device, the Cu-Fix, we report results from a randomized international two-year clinical trial involving 874 parous women followed for an average of fourteen months. Event rates at the end of two years (per 100 women) for pregnancy were 0.0 for the TCu380A and 1.5 for the Cu-Fix. Termination due to expulsion was significantly less for TCu380A as compared with Cu-Fix users (2.0 and 11.4 per hundred women, respectively); other medical reasons for termination (bleeding/pain, pelvic inflammatory disease (PID), and other) did not differ significantly. PID incidence rates at two years were 1.0 per hundred women for the TCu380A and 1.6 for the Cu-Fix (equivalent to 6.0 and 8.3 per 1,000 woman-years, respectively). The net cumulative continuation rates at two years per hundred women were 78.8 for TCu380A, and 71.9 for the Cu-Fix. Both IUDs provide highly effective protection against pregnancy, but the TCu380A has a lower expulsion rate. The low rate of PID indicates that it is an in-frequent occurrence in appropriately selected candidates.

The male polyurethane condom: A review of current knowledge

Condoms are one of the oldest form of contraceptive and the best recognized form of protection against sexually transmitted diseases. Their use, however, is limited by both behavioral factors and device-related factors, including complaints about decreased sensitivity and sexual enjoyment. To address these limitations, a male condom made of polyurethane was developed. Polyurethane is a strong impermeable material with good heat transfer characteristics that is less susceptible to deterioration during storage than latex. Because little information is available comparing polyurethane and latex condoms in terms of consumer preferences as well as breakage and slippage, we reviewed four pre-marketing studies of polyurethane condoms, one of which included comparison to latex. No significant differences in slippage and breakage rates between latex and polyurethane condoms were reported in the study that included a latex comparator, and other studies of polyurethane condoms alone resulted in rates in the same range as published for latex condoms. Subjectively, consumers expressed significantly greater preference for the polyurethane condom over latex in regard to appearance, lack of smell, likelihood of slippage, comfort, sensitivity, natural look, natural feel, and overall. While additional testing is needed, these preliminary results suggest that the male polyurethane condom reviewed performed at least as well as latex condoms and is preferred by consumers. If preference translates to greater use, the male polyurethane condom may address important barriers that have been linked with inadequate condom use in the past. These results, however, may not be generalizable to other brands of polyurethane condom currently under development.