Biomedical subjects

D A Grimes

Publications and source records attributed to D A Grimes.

At least 19 recordsLinked to original sources

PubMed2006

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.

Bone Density↗

PubMed2006

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.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

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.

Contraceptives, Oral, Combined↗

PubMed2006

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.

Chemistry, Pharmaceutical↗

PubMed2006

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.

Contraception↗

PubMed2006

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.

Contraception↗

PubMed2006

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.

Condoms↗

PubMed2006

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.

Body Weight↗

PubMed2006

Strategies to improve adherence and acceptability of hormonal methods for contraception.

BACKGROUND: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives in current use. Despite their high theoretical effectiveness, typical use results in much lower effectiveness. In large part, this disparity reflects difficulties in adherence to the contraceptive regimen and low rates for long-term continuation. OBJECTIVES: To determine the effectiveness of ancillary techniques to improve adherence to, and continuation rates of, hormonal methods of contraception. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials (RCTs) comparing client-provider interventions with standard family planning counseling. Sources included CENTRAL, MEDLINE, EMBASE, POPLINE, LILACS, and PsycINFO. SELECTION CRITERIA: Randomized controlled trials (RCTs) of an intensive counseling technique or client-provider intervention versus routine family planning counseling. Interventions included group motivation; structured, peer, or multi-component counseling; and intensive reminders of appointments. Outcome measures were discontinuation, reasons for discontinuation, number of missed pills and on-time injections, and pregnancy. DATA COLLECTION AND ANALYSIS: The primary author evaluated all titles and abstracts from the searches to determine eligibility. Two authors independently extracted data from the included studies. With RevMan 4.2, we calculated the odds ratio for all dichotomous outcomes and the weighted mean difference for continuous data. The studies were so different that we could not conduct a meta-analysis. MAIN RESULTS: We found six RCTs; only one showed a statistically significant benefit of the experimental intervention. In that trial, women who received repeated, structured information about the injectable contraceptive depo-medroxyprogesterone acetate (DMPA) were less likely to have discontinued the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than were women who had routine counseling. The intervention group was also less likely to discontinue due to menstrual disturbances. In another study, the intervention group was less likely to discontinue due to dissatisfaction with the contraceptive method, but overall continuation was not affected. AUTHORS' CONCLUSIONS: Most studies to date have shown no benefit of strategies to improve adherence and continuation. These trials have important limitations, however. Two had small sample sizes, several had high losses to follow-up, and the intervention and its intensity varied across the studies. High-quality research is a priority, since adherence and continuation are fundamentally important to the successful use of hormonal contraceptives.

Contraception↗

PubMed2006

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.

Adult↗

PubMed2005

Intra-uterine insemination versus timed intercourse for cervical hostility in subfertile couples.

BACKGROUND: The postcoital test has poor diagnostic and prognostic characteristics. Nevertheless, some physicians believe it can identify scanty or abnormal mucus that might impair fertility. One way to avoid 'hostile' cervical mucus is intrauterine insemination. With this technique, the physician injects sperm directly into the uterine cavity through a small catheter passed through the cervix; the theory is to bypass the "hostile" cervical mucus. Although most gynaecological societies do not endorse use of intrauterine insemination for hostile cervical mucus, some physicians consider it an effective treatment for women with infertility thought due to cervical mucus problems. OBJECTIVES: The aim of this review was to determine the effectiveness of intrauterine insemination with or without ovarian stimulation in women with cervical hostility who failed to conceive. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), POPLINE (to June 2005) and LILACS (to June 2005). In addition, we contacted experts and searched the reference list of relevant articles and book chapters. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing intrauterine insemination with intercourse timed at the presumed fertile period. Participants were women with cervical hostility who failed to conceive for at least one year. DATA COLLECTION AND ANALYSIS: We assessed the titles and abstracts of 386 publications and two reviewers independently abstracted data on methods and results from five studies identified for inclusion. The main outcome is pregnancy rate per couple. MAIN RESULTS: We did not pool the outcomes of the included five studies in a meta-analysis due to the methodological quality of the trials and variations in the patient characteristics and interventions. Narrative summaries of the outcomes are provided. Each study was too small for a clinically relevant conclusion. None of the studies provided information on important outcomes such as spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. AUTHORS' CONCLUSIONS: There is no evidence from the published studies that intrauterine insemination is an effective treatment for cervical hostility. Given the poor diagnostic and prognostic properties of the postcoital test and the observation that the test has no benefit on pregnancy rates, intrauterine insemination (with or without ovarian stimulation) is unlikely to be a useful treatment for putative problems identified by postcoital testing.

Biomarkers↗

PubMed2005

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.

Contraception↗

PubMed2005

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.

Algestone↗

PubMed2005

Continuous or extended cycle vs. cyclic use of combined oral contraceptives for contraception.

BACKGROUND: The avoidance of menstruation through extended or continuous administration (greater than 28 days of active pills) of combination oral contraceptives (COCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through continuous use of COCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school. OBJECTIVES: To determine the differences between COCs dosed continuously (greater than 28 days of active pills) compared with traditional cyclic dosing (21 days of active pills and 7 days of placebo). Our hypothesis was that continuously administered COCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with cyclic COCs. SEARCH STRATEGY: We searched computerized databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, POPLINE, LILACS) for trials using continuous or extended COCs during the years 1966 to 2005. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references. SELECTION CRITERIA: All randomized controlled trials in any language comparing continuous (greater than 28 days of active pills) versus traditional cyclic administration (21 days of active pills and 7 days of placebo) of COCs for contraception. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 4.2. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow-up, and early discontinuation. Because the included trials did not have a standard treatment (type of pill and time length for continuous dosing), we could not aggregate data into meta-analysis. MAIN RESULTS: Six randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended cycles in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group in most studies. The few studies that reported menstrual symptoms found that the extended cycle group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Five out of the six studies found that bleeding patterns were either equivalent between groups or improved with continuous-dosing regimens. Endometrial lining assessments by ultrasound were done in a small number of participants but all endometrial stripe measurements were less than 5 mm. AUTHORS' CONCLUSIONS: Evidence from existing randomized control trials comparing COCs given continuously (greater than 28 days of active pills) to traditional monthly cyclic dosing (21 days of active pills and 7 days of placebo) is of good quality. However, the variations in type of pill and time length for continuous dosing make direct comparisons between regimens impossible. Future studies should choose a previously described type of pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

Contraceptives, Oral, Combined↗

PubMed2005

20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception.

BACKGROUND: Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety also could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns. OBJECTIVES: To test the hypothesis that COCs containing </=20 mcg ethinyl estradiol (EE) perform similarly as those containing >20 mcg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects. SEARCH STRATEGY: We searched computerized databases (CENTRAL, MEDLINE, EMBASE, and POPLINE) from their inception to November 2003, searched the references of eligible trials, and wrote to oral contraceptive manufacturers to identify eligible trials. SELECTION CRITERIA: English-language reports of randomized controlled trials that compare a COC containing </=20 mcg EE with a COC containing >20 mcg EE were eligible. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts located in the literature searches to determine whether they met the inclusion criteria. Two reviewers independently extracted data from the studies identified for inclusion. We wrote to the authors when clarifications or additional data were needed. Data were entered and analyzed with RevMan 4.2. MAIN RESULTS: No differences were found in contraceptive effectiveness for the 11 COC pairs for which this outcome was reported. Several COCs containing 20 mcg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea/infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting) than their higher-estrogen comparison pills. AUTHORS' CONCLUSIONS: While COCs containing 20 mcg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose.

Contraceptives, Oral, Combined↗

PubMed2005

Neurofilament M gene in a French-Canadian population with Parkinson's disease.

BACKGROUND: Recently, a single base pair substitution (G1747A) mutation of the neurofilament M (NF-M) gene was reported in a French-Canadian patient with early onset Parkinson's disease (PD). Three unaffected siblings were found to be heterozygotes for the NF-M Gly336Ser mutation but, to date, no other affected PD individuals have been found with a similar mutation. No other individuals with Parkinson's disease and of similar ethnic background have been screened for this mutation. METHODS: We screened 102 French-Canadian patients with definite PD and 45 French-Canadian controls for this substitution in the NF-M gene using a PCR-restriction enzyme digestion method. RESULTS: None of the patients or controls carried this mutation. CONCLUSION: Our results would indicate that this mutation is not common even in a PD population of similar ethnic background and suggest this change represents a rare variant. However, these results do not exclude the possibility that other mutations in this gene could be present.

Aged↗

PubMed2004

Fertility awareness-based methods for contraception.

BACKGROUND: "Fertility awareness-based methods" (FAB) of family planning "involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature, or by monitoring cycle days. FAB methods can be used in combination with abstinence or barrier methods during the fertile time" (WHO 2000). Several names have been used to describe this approach to contraception, including "rhythm," "natural family planning" and "periodic abstinence." Fertility awareness-based methods can be used with abstinence from sexual intercourse. Alternatively, they can be used with barrier contraceptives or withdrawal during presumed fertile times. OBJECTIVES: We retrieved and analyzed all randomized controlled trials that examined any fertility awareness-based methods used for contraception. SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its inception to January, 2004) for randomized controlled trials of fertility awareness-based methods. We examined the reference list of each trial as well as that of review articles. SELECTION CRITERIA: We included all randomized controlled trials in any language that compared any fertility awareness-based methods for contraception with a placebo; another method, including an alternative fertility awareness-based method; or fertility awareness-based methods used in conjunction with another contraceptive. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts found for inclusion. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design; randomization method; allocation concealment; blinding; premature discontinuation rates; and loss to follow-up rates. Because of methodological weaknesses, we could not enter the trial results in RevMan, calculate measures of association, or aggregate data. MAIN RESULTS: Because of poor methods and reporting, pregnancy rates could not be determined. A trial in Colombia found similar numbers of pregnancies among women randomized to the ovulation and symptothermal methods. In contrast, a companion trial in Los Angeles observed more pregnancies in the group assigned to the ovulation method. In the two U.S. trials, recruitment of participants was unexpectedly difficult; this aspect was not mentioned in the report from Colombia. Continuation rates were poor. In the two larger trials, most participants discontinued their assigned method before entering the observation phase of the trial. REVIEWERS' CONCLUSIONS: The comparative efficacy of fertility awareness-based methods of contraception remains unknown. Despite intensive training and ongoing support, most participants in these trials discontinued prematurely. Contraceptive methods should be properly evaluated, preferably in randomized controlled trials, before adoption and dissemination.

Awareness↗

PubMed2004

Combined oral contraceptive pills for treatment of acne.

BACKGROUND: Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women. OBJECTIVES: To determine the effectiveness of COCs for the treatment of facial acne compared to placebo or other active therapies. SEARCH STRATEGY: We searched the computerized databases Cochrane Skin Group trial register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, Biological Abstracts and LILACS for randomized controlled trials of COCs and acne. We wrote to authors of identified trials to seek any unpublished or published trials that we might have missed. SELECTION CRITERIA: All randomized controlled trials reported in any language that compare the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women were eligible. DATA COLLECTION AND ANALYSIS: We extracted data on total and specific (i.e. open or closed comedones, papules, pustules and nodules) facial lesion counts; acne severity grades; global assessments by the clinician or the participant and discontinuation due to adverse events. Data were entered and analyzed in RevMan 4.2. MAIN RESULTS: The search yielded five placebo-controlled trials that made three different comparisons and 14 trials that made nine comparisons between two COC regimens. An additional trial compared a COC to an antibiotic. COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo. Differences in the comparative effectiveness of COCs containing varying progestin types and dosages, though, were less clear. COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel although this apparent advantage was based on limited data. A COC with cyproterone acetate might result in better acne outcomes than one with desogrestrel; however, the three studies comparing these COCs produced conflicting results. Likewise, levonorgestrel showed a slight improvement over desogestrel in acne outcomes in one trial, but a second trial found no difference between the COCs. REVIEWERS' CONCLUSIONS: The three COCs evaluated in placebo-controlled trials are effective in reducing inflammatory and non-inflammatory facial acne lesions. Few differences were found in acne effectiveness between COC types. How COCs compare to alternative acne treatments is unknown since limited data were available regarding this question.

Acne Vulgaris↗