A catalogue of reporting guidelines for health research.

Growing evidence demonstrates widespread deficiencies in the reporting of health research studies. The EQUATOR Network is an international initiative that aims to enhance the reliability and value of the published health research literature. EQUATOR provides resources, education and training to facilitate good research reporting and assists in the development, dissemination and implementation of robust reporting guidelines. This paper presents a collection of tools and guidelines available on the EQUATOR website (http://www.equator-network.org) that have been developed to increase the accuracy and transparency of health research reporting.

Immediate start of hormonal contraceptives for contraception.

BACKGROUND: Health care providers often tell women to wait until the next menses to begin hormonal contraception. The main intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was first introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. How immediate start compares to conventional menses-dependent start is unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception. OBJECTIVES: This review examined randomized controlled trials of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability. SEARCH STRATEGY: We searched MEDLINE, CENTRAL, POPLINE, EMBASE, and LILACS for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. SELECTION CRITERIA: We included randomized controlled trials that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated. MAIN RESULTS: Five studies were included. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77).A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. For satisfaction, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22). AUTHORS' CONCLUSIONS: We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, that is, immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.

Strategies for communicating contraceptive effectiveness.

BACKGROUND: Knowledge of contraceptive effectiveness is crucial to making an informed choice. The consumer has to comprehend the pros and cons of the contraceptive methods being considered. Choice may be influenced by understanding the likelihood of pregnancy with each method and factors that influence effectiveness. OBJECTIVES: To review all randomized controlled trials comparing strategies for communicating to consumers the effectiveness of contraceptives in preventing pregnancy. SEARCH STRATEGY: We searched the computerized databases MEDLINE, POPLINE, CENTRAL, PsycINFO, and EMBASE for studies of communicating contraceptive effectiveness. We also examined references lists of relevant articles, and wrote to known investigators for information about other published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials that compared methods for communicating contraceptive effectiveness to consumers. The comparison could be usual practice or an alternative to the experimental intervention. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the weighted mean difference (WMD) was computed. MAIN RESULTS: Five trials met the inclusion criteria. In one study, knowledge gain favored a slide-and-sound presentation versus a physician's oral presentation (WMD -19.00; 95% CI -27.52 to -10.48). Another trial showed a table with effectiveness categories led to more correct answers than one based on numbers [ORs were 2.42 (95% CI 1.43 to 4.12) and 2.19 (95% CI 1.21 to 3.97)] or a table with categories and numbers [ORs were 2.58 (95% CI 1.5 to 4.42) and 2.03 (95% CI 1.13 to 3.64)]. One trial examined contraceptive choice: women in the expanded program were more likely to choose sterilization (OR 4.26; 95% CI 2.46 to 7.37) or use a modern contraceptive method (OR 2.35; 95% CI 1.82 to 3.03). No trial had an explicit theoretical base, but each used concepts from common theories or models. AUTHORS' CONCLUSIONS: We have limited evidence about what works to help consumers choose an appropriate contraceptive method. For presenting pregnancy risk data, one trial showed that categories were better than numbers. In another trial, audiovisual aids worked better than the usual oral presentation. Strategies for communicating information should be examined in clinical settings and assessed for effect on contraceptive choice and retention of knowledge. To expand the knowledge base of what works in contraceptive counseling, randomized trials could intentionally use and test theories or models.

Skin patch and vaginal ring versus combined oral contraceptives for contraception.

BACKGROUND: The delivery of combination contraceptive steroids from a skin patch or vaginal ring offers potential advantages over the traditional oral route. The skin patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. OBJECTIVES: To compare the contraceptive effectiveness, cycle control, compliance, and safety of the skin patch or the vaginal ring versus combination oral contraceptives (COCs). SEARCH STRATEGY: We searched MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for trials of the contraceptive patch or the vaginal ring. We contacted manufacturers and researchers to identify other trials. SELECTION CRITERIA: All randomized controlled trials comparing the skin patch or vaginal ring with a COC. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the weighted mean difference was computed. MAIN RESULTS: We found three trials of the skin patch and eight of the vaginal ring. Contraceptive effectiveness was similar for the patch or ring and the comparison COC. Patch users reported more compliant cycles than COC users; ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24) in two trials. One crossover ring trial had more noncompliance for the ring users. Satisfaction with method was higher for ring users than COC users in two studies. More patch users discontinued early than COC users: OR 1.58 (95% CI 1.25 to 1.99) and 1.45 (95% CI 1.11 to 1.90) in two trials. Patch users also had more discontinuation due to adverse events (AEs). The ring trials generally showed similar discontinuation for ring and COC users. Compared to COC users, patch users were more likely to report breast discomfort, dysmenorrhea, nausea, and vomiting. Ring users reported less nausea, irritability, and depression than COC users in single trials. However, ring users had more vaginitis and leukorrhea. Bleeding problems were generally similar or less common for the ring versus COC. AUTHORS' CONCLUSIONS: Effectiveness rates were similar for the methods compared. The patch group had better compliance than the COC group. Compared to COC users, patch users had more side effects. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge. The patch could lead to more discontinuation while the vaginal ring showed little difference. High losses to follow up can affect the validity of the results.

Steroid hormones for contraception in men.

BACKGROUND: Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed. OBJECTIVES: To summarize all randomized controlled trials of male hormonal contraception. SEARCH STRATEGY: We searched the computerized databases CENTRAL, MEDLINE, EMBASE, POPLINE, and LILACS (each from inception to March 2006) for randomized controlled trials of hormonal contraception in men. We wrote to authors of identified trials to seek unpublished or published trials that we might have missed. SELECTION CRITERIA: We included all randomized controlled trials in any language that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups. All trials identified included only healthy men with normal semen analyses. DATA COLLECTION AND ANALYSIS: Azoospermia (absence of spermatozoa on semen examination) was the primary outcome measure. Data were insufficient to examine pregnancy rates and side effects. MAIN RESULTS: We found 30 trials that met our inclusion criteria. The proportion of men who achieved azoospermia varied widely in reports to date. A few important differences emerged from these trials: levonorgestrel implants combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 microg daily combined with testosterone patches; levonorgestrel 500 mug daily improved the effectiveness of TE 100 mg injected weekly; desogestrel 150 mug was less effective than desogestrel 300 mug (with testosterone pellets); testosterone undecanoate (TU) 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants); norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks; four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. Several trials showed promising efficacy in terms of percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel (metabolite of desogestrel) and testosterone, and two examined levonorgestrel and testosterone. AUTHORS' CONCLUSIONS: No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. As a result, their power to detect important differences was limited and their results imprecise. In addition, the definition of oligozoospermia has been imprecise or inconsistent. To avoid bias, future trials need more attention to the methodological requirements for randomized controlled trials. More trials with adequate power would also be helpful.

Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus.

BACKGROUND: Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised with progestin-only contraceptives as well as contraceptives containing estrogen. Such potential effects could influence recommendations for, and use of, these widely used and effective contraceptives. OBJECTIVES: To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight. SEARCH STRATEGY: We searched the computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. The latest search was conducted in March 2006. We wrote to investigators for information about other published or unpublished trials. SELECTION CRITERIA: All randomized controlled trials (RCTs) were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Interventions included comparisons of a hormonal contraceptive with a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin levels, which were generally reported as fasting value or response to an oral glucose tolerance test. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts identified during the literature searches with no language limitations. The data were abstracted and the information was entered into RevMan. Studies were examined for methodological quality. For continuous variables, the weighted mean difference was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated. MAIN RESULTS: A total of 39 trials met the inclusion criteria. No study stratified by body weight (normal-weight versus overweight women). Results for desogestrel were often favorable regarding carbohydrate metabolism but inconsistent overall. Glucose and insulin means were more favorable for norethisterone in studies of progestin-only contraceptives. For other progestins, little or no difference was noted across trials. AUTHORS' CONCLUSIONS: Current evidence suggests that hormonal contraceptives have limited effect on carbohydrate metabolism in women without diabetes. Strong statements cannot be made, though, due to having few studies that compared any particular types of contraceptives. Many trials had small numbers of participants and some had large losses to follow up. Most studies had poor reporting of methods. No information was available regarding the effects among women who were overweight.

Steroid hormones for contraception in women with sickle cell disease.

BACKGROUND: Whether steroid contraceptives are appropriate for women with homozygous sickle cell (SS) disease remains unresolved. Historically, women with SS disease have experienced difficult pregnancies, characterized by high rates of maternal mortality and morbidity and poor infant outcomes. Unresolved questions about steroidal contraceptives in women with SS disease include whether using them may promote blood clots. OBJECTIVES: To assess the safety of steroid hormones in this setting, we retrieved and analyzed all randomized controlled trials that examined steroid hormones for contraception in women with SS disease. SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE and EMBASE (each from its inception to November, 2005) for randomized controlled trials of steroid hormone use for contraception in women with SS disease. We examined the reference list of each trial as well as that of review articles. SELECTION CRITERIA: We included any randomized controlled trial in any language that compared steroid hormones for contraception with another contraceptive or placebo. Frequency or intensity of sickle pain crises must have been reported as an outcome. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts found. We evaluated the methodological quality of the trial found for potential biases by qualitatively assessing the study design, randomization method, allocation concealment, blinding, premature discontinuation rates, and loss to follow-up rates. We entered trial results in RevMan and reported Peto odds ratios with 95% confidence intervals for dichotomous outcomes, such as occurrence of sickle pain crises. MAIN RESULTS: Only one trial met the inclusion criteria. Twenty-five patients were randomized to three monthly depo-medroxyprogesterone acetate (DMPA) or intramuscular saline placebo injections in a crossover design. A six-month washout period was implemented before the crossover; however, pharmacological evidence indicates that levels of DMPA may be detected for more than 200 days after the injection. During DMPA use, women were less likely to experience painful sickle episodes (OR 0.23; 95% CI 0.05 to 1.02). No trial involved estrogen products. AUTHORS' CONCLUSIONS: The limited available data suggest that DMPA is a safe contraceptive option for women in SS disease. In addition to providing effective contraception, DMPA may reduce sickle pain crises.

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women SEARCH STRATEGY: We searched MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of fracture or bone health and hormonal contraceptives. We wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The weighted mean difference (WMD) was computed with 95% confidence interval (CI) using a fixed-effect model. MAIN RESULTS: No trial had fracture as an outcome. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Non-steroidal anti-inflammatory drugs for heavy bleeding or pain associated with intrauterine-device use.

BACKGROUND: Heavy bleeding and pain are the most common reasons why women discontinue IUDs. Non-steroidal anti-inflammatory drugs, which inhibit prostaglandin synthesis, have been shown to be effective in reducing menstrual bleeding and pain in women without IUDs. OBJECTIVES: This review summarizes all randomized controlled trials studying use of nonsteroidal anti-inflammatory drugs for treatment of bleeding or pain associated with IUD use. Trials of prophylactic use of these drugs around the time of IUD insertion were also included. SEARCH STRATEGY: We performed searches of PubMed, CENTRAL, POPLINE, EMBASE, LILACS, and CINAHL for relevant trials. We also wrote to the authors of all trials identified to seek other published or unpublished trials. SELECTION CRITERIA: We included all randomized controlled trials in any language that tested one or more nonsteroidal anti-inflammatory drugs for treatment or prevention of bleeding or pain associated with IUD insertion or use. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data from relevant trials, and we entered data into RevMan for analysis. MAIN RESULTS: We found 15 trials from 10 countries; the total number of participants was 2702. Nonsteroidal anti-inflammatory drugs (naproxen, suprofen, mefenamic acid, ibuprofen, indomethacin, flufenamic acid, alclofenac, and diclofenac) were effective in reducing menstrual blood loss associated with IUD use. This held true for women with and without complaints of heavy bleeding. Similarly, these drugs were effective in reducing pain associated with IUD use. In contrast, prophylactic use of nonsteroidal anti-inflammatory drugs had mixed results; studies with ibuprofen found no effect on pain after insertion on IUD discontinuation. No important differences emerged in the one trial comparing the effect of different NSAIDs on bleeding. AUTHORS' CONCLUSIONS: Nonsteroidal anti-inflammatory drugs reduce bleeding and pain associated with IUD use. NSAIDs should be considered first-line therapy; if NSAIDs are ineffective, tranexamic acid may be considered as second-line therapy. Prophylactic ibuprofen administration with the first six menses after insertion appears unwarranted.

Oral contraceptives for functional ovarian cysts.

BACKGROUND: Functional ovarian cysts are a common gynecological problem among women of reproductive age worldwide. When large, persistent, or painful, these cysts may require operations, sometimes resulting in removal of the ovary. Since early oral contraceptives were associated with a reduced incidence of functional ovarian cysts, many clinicians inferred that birth control pills could be used to treat cysts as well. This became a common clinical practice in the early 1970s. OBJECTIVES: This review examined all randomized controlled trials that studied oral contraceptives as therapy for functional ovarian cysts. SEARCH STRATEGY: We searched the computer databases of CENTRAL, PubMed, POPLINE, and EMBASE for randomized controlled trials. We also examined the reference lists of articles and wrote to authors of all studies identified to seek articles we had missed. SELECTION CRITERIA: We included randomized controlled trials in any language that included oral contraceptives used for treatment and not prevention of functional ovarian cysts. Criteria for diagnosis of cysts were those used by authors of studies. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data from the articles and entered them into RevMan 4.2. We used Peto odds ratios with 95% confidence intervals for dichotomous outcomes. MAIN RESULTS: We identified four randomized controlled trials from three countries; the studies included a total of 227 women. Treatment with combined oral contraceptives did not hasten resolution of functional ovarian cysts in any trial. This held true for cysts that occurred spontaneously as well as those that developed after ovulation induction. Most cysts resolved without treatment within a few cycles; persistent cysts tended to be pathological (e.g., endometrioma or para-ovarian cyst) and not physiological. AUTHORS' CONCLUSIONS: Although widely used for treating functional ovarian cysts, combined oral contraceptives appear to be of no benefit. Watchful waiting over several cycles is appropriate. Should cysts persist, surgical management is often indicated.

Biphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. OBJECTIVES: To compare biphasic with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective than monophasic oral contraceptives in preventing pregnancy; (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates. SEARCH STRATEGY: We searched the computerized databases MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. In addition, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic with any monophasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the various literature searches for possible inclusion and assessed their methodology using Cochrane guidelines. We contacted the authors of all included studies and possibly randomized studies for supplemental information about methodology and outcome. We entered the data into RevMan, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith 1990 examined 533 user cycles of a biphasic pill (500 microg norethindrone/35 microg ethinyl estradiol for 10 days, followed by 1000 microg norethindrone/35 microg ethinyl estradiol for 11 days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (1500 microg norethindrone acetate/30 microg ethinyl estradiol daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. AUTHORS' CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Biphasic versus triphasic oral contraceptives for contraception.

BACKGROUND: Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. A suggested disadvantage of biphasic compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. OBJECTIVES: To compare biphasic with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. We searched the reference lists of relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic with any triphasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the searches for possible inclusion and assessed methodological quality using Cochrane guidelines. We contacted the authors of included studies and of possibly randomized studies for supplemental information about the methods and outcomes. We entered the data into RevMan. We calculated Peto odds ratios for incidence of discontinuation due to medical reasons, intermenstrual bleeding, and absence of withdrawal bleeding. MAIN RESULTS: Only two trials of limited quality met our inclusion criteria. Larranaga 1978 compared two biphasic pills and one triphasic pill, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival-Smith 1990 compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and with another triphasic containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95% CI 1.3 to 2.2) for the biphasic compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95% CI 3.1 to 13). In contrast, cycle control with the biphasic pill was comparable to that of the triphasic containing the same progestin (norethindrone). AUTHORS' CONCLUSIONS: The available evidence is limited and the internal validity of these trials is questionable. Given the high losses to follow up, these reports may even be considered observational. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. The choice of progestin may be more important than the phasic regimen in determining bleeding patterns.

Triphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects of oral contraceptive pills (OCs) discourage adherence to and continuation of OC regimens. Strategies to decrease adverse effects led to the introduction of the triphasic OC in the 1980s. Whether triphasic OCs have higher accidental pregnancy rates than monophasic pills is unknown. Nor is it known if triphasic pills give better cycle control and fewer side effects than the monophasic pills. OBJECTIVES: To compare triphasic OCs with monophasic OCs in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched the computerized databases of MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. Additionally, we searched the reference lists of relevant articles and book chapters. We also contacted researchers and pharmaceutical companies in Europe and the U.S. to identify other trials not found in our search. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any triphasic OC with any monophasic pill used to prevent pregnancy. Interventions had to include at least three treatment cycles. DATA COLLECTION AND ANALYSIS: We assessed the studies found in the literature searches for possible inclusion and for their methodological quality. We contacted the authors of all included studies and of possibly randomized trials for supplemental information about the methods and outcomes studied. We entered the data into RevMan 4.2 and calculated odds ratios for the outcome measures of efficacy, breakthrough bleeding, spotting, withdrawal bleeding and discontinuation. MAIN RESULTS: Of 21 trials included, 18 examined contraceptive effectiveness: the triphasic and monophasic preparations did not differ significantly. Several trials reported favorable bleeding patterns, i.e. less spotting, breakthrough bleeding or amenorrhea, in triphasic versus monophasic OC users. However, meta-analysis was generally not possible due to differences in measuring and reporting the cycle disturbance data as well as differences in progestogen type and hormone dosages. No significant differences were found in the numbers of women who discontinued due to medical reasons, cycle disturbances, intermenstrual bleeding or adverse events. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether triphasic OCs differ from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates. Therefore, we recommend monophasic pills as a first choice for women starting OC use. Large, high-quality RCTs that compare triphasic and monophasic OCs with identical progestogens are needed to determine whether triphasic pills differ from monophasic OCs. Future studies should follow the WHO recommendations on recording menstrual bleeding patterns and the CONSORT reporting guidelines.

Continuous versus cyclic use of combined oral contraceptives for contraception: systematic Cochrane review of randomized controlled trials.

BACKGROUND: With the recent US Food and Drug Administration approval of a combination oral contraceptive that causes a withdrawal bleed every 3 months instead of monthly, avoidance of menstruation through extended or continuous administration (>28 days of active pills) of combined oral contraceptives may become more commonplace for reasons of personal preference rather than limited to treatment of menstrual-associated medical disorders. METHODS: The review aimed to compare contraceptive efficacy, compliance, continuation, satisfaction, bleeding profiles, and menstrual symptoms of combined oral contraceptives with continuous dosing (>28 days of active pills) versus traditional cyclic dosing (21 days of active pills and 7 days of placebo). We searched five computerized databases as well as reference lists of relevant articles for randomized controlled trials (RCT) using continuous or extended combined oral contraceptives for contraception. Two reviewers independently extracted data from eligible articles. RESULTS: Six RCT met inclusion criteria and were of good quality. Contraceptive efficacy and compliance were similar between groups. Discontinuation overall, and for bleeding problems, was not uniformly higher in either group. When studied, participants reported high satisfaction with both dosing regimens. Five out of the six studies found that bleeding patterns were either equivalent or improved with continuous-dosing regimens. The continuous-dosing group had greater improvement of menstrual-associated symptoms (headaches, genital irritation, tiredness, bloating, and menstrual pain). CONCLUSIONS: The variations in pill type and time-interval for continuous dosing make direct comparisons between regimens unfeasible. To allow for comparisons, future studies should choose a previously researched pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

Non-latex versus latex male condoms for contraception.

BACKGROUND: The male condom, which consists of a thin sheath placed over the glans and shaft of the penis, is designed to prevent pregnancy by providing a physical barrier against the deposition of semen into the vagina during intercourse. Beginning in the 1990s, nonlatex male condoms made of polyurethane film or synthetic elastomers were developed as alternative male barrier methods for individuals with allergies, sensitivities or preferences that prevented the consistent use of condoms made of latex. OBJECTIVES: The review sought to evaluate nonlatex male condoms in comparison with latex condoms in terms of contraceptive efficacy, breakage and slippage, safety, and user preferences. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of nonlatex condoms. We also wrote to the manufacturers of nonlatex condoms and known investigators in an attempt to locate any other trials not identified in our search. SELECTION CRITERIA: The review included all randomized controlled trials identified in the literature search that evaluated a male nonlatex condom made of polyurethane film or synthetic elastomers in comparison with a latex condom. DATA COLLECTION AND ANALYSIS: We evaluated all titles and abstracts located in the literature searches for inclusion. Two authors independently extracted data from the identified studies. We analyzed data with RevMan. The Peto odds ratio (Peto OR) with 95% confidence interval (CI) was calculated for each outcome of contraceptive efficacy, condom breakage and slippage, discontinuation of use, safety, and user preference. Contraceptive efficacy, early discontinuation, and safety outcomes were also measured with survival analysis techniques. MAIN RESULTS: While the eZ.on condom did not protect against pregnancy as well as its latex comparison condom, no differences were found in the typical-use efficacy between the Avanti and the Standard Tactylon and their latex counterparts. The nonlatex condoms had significantly higher rates of clinical breakage than their latex comparison condoms: the Peto OR for clinical breakage ranged from 2.6 (95% CI 1.6 to 4.3) to 5.0 (95% CI 3.6 to 6.8). Few adverse events were reported. Substantial proportions of participants preferred the nonlatex condom or reported that they would recommend its use to others. AUTHORS' CONCLUSIONS: Although the nonlatex condoms were associated with higher rates of clinical breakage than their latex comparison condoms, the new condoms still provide an acceptable alternative for those with allergies, sensitivities, or preferences that might prevent the consistent use of latex condoms. The contraceptive efficacy of the nonlatex condoms requires more research.

Combination contraceptives: effects on weight.

BACKGROUND: Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. OBJECTIVES: The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. SEARCH STRATEGY: We searched the computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of combination contraceptives. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. SELECTION CRITERIA: All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, and/or study length. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan, and a second author verified the data entered. Depending on the data available, the weighted mean difference using a fixed effects model with 95% confidence intervals (CI) was calculated for the mean change in weight between baseline and post-treatment measurements or the Peto odds ratio with 95% confidence intervals was calculated using the proportion of women who gained or lost more than a specified amount of weight. MAIN RESULTS: The three placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied. AUTHORS' CONCLUSIONS: Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident.

Spermicide used alone for contraception.

BACKGROUND: Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository. OBJECTIVES: This review examined all known randomized controlled trials of a spermicide used alone for contraception. SEARCH STRATEGY: We searched the following computerized databases from inception to July 2004 for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, LILACS, and EMBASE. We examined the reference list of each trial found as well as that of review articles and textbook chapters. SELECTION CRITERIA: We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates. We located reports from 14 trials. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow-up. We entered the data into tables and presented the results descriptively. MAIN RESULTS: In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials. AUTHORS' CONCLUSIONS: The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.