Entity

Time filter

Source Type

Östermalm, Sweden

Lopez L.M.,Clinical science
Cochrane database of systematic reviews (Online) | Year: 2012

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 primarily with contraceptives containing estrogen. To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight. In February 2012, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE. All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be 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 measures. We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated. We found 31 trials that met the inclusion criteria. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome.Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36).Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38).Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73).Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly. Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods.We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).


Lopez L.M.,Clinical science
Cochrane database of systematic reviews (Online) | Year: 2012

Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception. To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms. We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials. We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined. Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated. We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95% CI -11.16 to -4.67). The drospirenone group had greater mean decreases in impairment of productivity (MD -0.31; 95% CI -0.55 to -0.08), social activities (MD -0.29; 95% CI -0.54 to -0.04), and relationships (MD -0.30; 95% CI -0.54 to -0.06). Side effects more common with the use of the drospirenone COC contraceptive were nausea, intermenstrual bleeding, and breast pain. The respective odds ratios were 3.15 (95% CI 1.90 to 5.22), 4.92 (95% CI 3.03 to 7.96), and 2.67 (95% CI 1.50 to 4.78). Total adverse events related to the study drug were more likely for the drospirenone COC group (OR 2.36; 95% CI 1.62 to 3.44). Three trials studied the effect of drospirenone 3 mg plus ethinyl estradiol 30 μg on less severe symptoms. A placebo-controlled six-month trial had insufficient data for primary outcome analysis. Another six-month study used levonorgestrel 150 μg plus ethinyl estradiol 30 μg for the comparison group but did not provide enough data on premenstrual symptoms. In a two-year trial, the drospirenone COC group had similar premenstrual symptoms to the comparison group given desogestrel 150 μg plus ethinyl estradiol 30 μg (OR 0.87; 95% CI 0.63 to 1.22). The groups were also similar for adverse events related to treatment (OR 1.02; 95% CI 0.78 to 1.33). Drospirenone 3 mg plus ethinyl estradiol 20 μg may help treat premenstrual symptoms in women with severe symptoms, that is, premenstrual dysphoric disorder. The placebo also had a large effect. We do not know whether the combined oral contraceptive works after three cycles, helps women with less severe symptoms, or is better than other oral contraceptives. Larger and longer trials of higher quality are needed to address these issues. Trials should follow CONSORT guidelines.


Lopez L.M.,Clinical science
Cochrane database of systematic reviews (Online) | Year: 2012

Providing contraceptive education is now considered a standard component of postpartum care. The effectiveness is seldom examined. Questions have been raised about the assumptions on which such programs are based, e.g., that postpartum women are motivated to use contraception and that they will not return to a health center for family planning advice. Surveys indicate that women may wish to discuss contraception both prenatally and after hospital discharge. Nonetheless, two-thirds of postpartum women may have unmet needs for contraception. In the USA, many adolescents become pregnant again within a year a giving birth. Assess the effects of educational interventions for postpartum mothers about contraceptive use In May 2012, we searched the computerized databases of MEDLINE, CENTRAL, CINAHL, PsycINFO, and POPLINE. We also searched for current trials via ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE. In addition, we examined reference lists of relevant articles, and contacted subject experts to locate additional reports. Randomized controlled trials were considered if they evaluated the effectiveness of postpartum education about contraceptive use. The intervention must have started postpartum and have occurred within one month of delivery. We assessed for inclusion all titles and abstracts identified during the literature searches with no language limitations. The data were abstracted and entered into RevMan. Studies were examined for methodological quality. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI) was calculated. For continuous variables, we computed the mean difference (MD) with 95% CI. Due to varied study designs, we did not conduct meta-analysis. Ten trials met the inclusion criteria. Of four trials that provided one or two counseling sessions, two showed some evidence of effectiveness. In a study from Nepal, women with an immediate postpartum and a session three months later were more likely to use contraception at six months than those with only the later session (OR 1.62; 95% CI 1.06 to 2.50). However, most comparisons did not show evidence of effectiveness. In a trial conducted in Pakistan, women in the counseling group were more likely than those without counseling to use contraception at 8 to 12 weeks postpartum (OR 19.56; 95% CI 11.65 to 32.83). The assessments were short-term. The remaining two studies were from the USA; one did not provided sufficient data and one had too small a sample to detect differences.Six trials provided multifaceted programs with many contacts. Three showed evidence of effectiveness. Of those, two USA studies focused on adolescents. Adolescents in a home-visiting program were less likely to have a second birth in two years compared to adolescents who received usual care (OR 0.41; 95% CI 0.17 to 1.00). In the other trial, adolescents receiving enhanced well-baby care were less likely to have a repeat pregnancy by 18 months compared to those with usual well-baby care (OR 0.35; 95% CI 0.17 to 0.70). In an Australian study, teenagers in a structured home-visiting program were more likely to use contraception at six months than those who had standard home visits (OR 3.24; 95% CI 1.35 to 7.79). The trials without evidence of effectiveness included two for adolescents in the USA (computer-assisted motivational interviewing and cell phone counseling) and a home-visiting program for women in Syria. The overall quality of evidence was moderate. Half of these postpartum interventions led to fewer repeat pregnancies or births or more contraceptive use. However, the evidence of intervention effectiveness was of low to moderate quality. Trials with evidence of effectiveness included two that provided one or two sessions and three that had multiple contacts. The former had limitations, such as self-reported outcomes and showing no effect for many comparisons. The interventions with multiple sessions were promising but would have to be adapted for other locations and then retested. Researchers and health care providers will have to determine which intervention might be appropriate for their setting and level of resources.


Lopez L.M.,Clinical science
The Cochrane database of systematic reviews | Year: 2013

The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. 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 mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group. Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.


Lopez L.M.,Clinical science
The Cochrane database of systematic reviews | Year: 2013

Obesity has reached epidemic proportions around the world. Effectiveness of hormonal contraceptives may be related to metabolic changes in obesity or greater body mass or body fat. Hormonal contraceptives mainly include oral contraceptives, injectables and implants, the transdermal patch, and the vaginal ring. We systematically reviewed the evidence on the effectiveness of hormonal contraceptives among overweight and obese women. To examine the effectiveness of hormonal contraceptives in preventing unplanned pregnancies among women who are overweight or obese versus women of lower weight or body mass index (BMI). Through January 2013, we searched MEDLINE, CENTRAL, POPLINE, ClinicalTrials.gov, and ICTRP. The previous search also included EMBASE. We contacted investigators to identify other trials. All study designs were eligible. Any type of hormonal contraceptive could have been examined. Reports had to contain information on the specific contraceptive method(s). The primary outcome was pregnancy. Overweight or obese women must have been identified by an analysis cutoff for weight or BMI (kg/m(2)). Data were abstracted by two authors. Life-table rates were included where available. For dichotomous variables, we computed an odds ratio with 95% confidence interval (CI). We used reported pregnancy rates or relative risk (RR) when those were the only results provided. The main comparisons were between overweight or obese women and women of lower weight or BMI. We assessed the quality of evidence for this review. We found nine reports with data from 13 trials that included a total of 49,712 women. Five reports from 2002 to 2012 compared BMI groups; of those, one reported a higher pregnancy risk for overweight or obese women. In that trial, women assigned to an oral contraceptive containing norethindrone acetate 1.0 mg plus EE 20 μg and having a BMI at least 25 had greater pregnancy risk compared to those with BMI less than 25 (reported RR 2.49; 95% CI 1.01 to 6.13). The comparisons reported in the other four studies were not significantly different for pregnancy. These included studies of a combined oral contraceptive (COC), a transdermal patch, an implant, and an injectable. The COC study showed no trend by BMI or weight. With the transdermal patch, body weight was associated with pregnancy (reported P < 0.001) but BMI was not. The implant study had one pregnancy and the injectable study reported no pregnancies.Four studies from the 1990s used weight alone rather than BMI. Results were mixed. Studies of a vaginal ring (never marketed) and a six-rod implant showed higher pregnancy rates for women weighing at least 70 kg versus those weighing less than 70 kg (reported P values: 0.0013 and < 0.05, respectively). However, two implant studies showed no trend by body weight. The evidence did not generally show an association of BMI with effectiveness of hormonal contraceptives. However, the evidence was limited for any individual contraceptive method. Studies using BMI (rather than weight alone) can provide more information about whether body composition is related to contraceptive effectiveness. The efficacy of subdermal implants and injectable contraceptives may be unaffected by body mass. The contraceptive methods examined here are among the most effective when the recommended regimen is followed.The overall quality of evidence was low for this review. More recent reports provided moderate quality evidence, while the older studies provided evidence of low or very low quality for our purposes. Investigators should consider adjusting for potential confounding related to BMI. Trials should be designed to include sufficient numbers of overweight or obese women to adequately examine effectiveness and side effects of hormonal contraceptives within those groups.

Discover hidden collaborations