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Hormonal contraceptives for contraception in overweight or obese women

  1. Laureen M Lopez1,*,
  2. David A Grimes2,
  3. Mario Chen3,
  4. Conrad Otterness4,
  5. Carolyn Westhoff5,
  6. Alison Edelman6,
  7. Frans M Helmerhorst7

Editorial Group: Cochrane Fertility Regulation Group

Published Online: 30 APR 2013

Assessed as up-to-date: 4 FEB 2013

DOI: 10.1002/14651858.CD008452.pub3


How to Cite

Lopez LM, Grimes DA, Chen M, Otterness C, Westhoff C, Edelman A, Helmerhorst FM. Hormonal contraceptives for contraception in overweight or obese women. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD008452. DOI: 10.1002/14651858.CD008452.pub3.

Author Information

  1. 1

    FHI 360, Clinical Sciences, Research Triangle Park, North Carolina, USA

  2. 2

    University of North Carolina, School of Medicine, Obstetrics and Gynecology, Chapel Hill, North Carolina, USA

  3. 3

    FHI 360, Division of Biostatistics, Research Triangle Park, North Carolina, USA

  4. 4

    FHI 360, Program Sciences, Research Triangle Park, North Carolina, USA

  5. 5

    Columbia University, Dept of Obstetrics and Gynecology, New York, New York, USA

  6. 6

    Oregon Health & Science University, Dept. of Obstetrics and Gynecology, Portland, Oregon, USA

  7. 7

    Leiden University Medical Center, Department of Gynaecology, Division of Reproductive Medicine and Dept. of Clinical Epidemiology, Leiden, Netherlands

*Laureen M Lopez, Clinical Sciences, FHI 360, P.O. Box 13950, Research Triangle Park, North Carolina, 27709, USA. llopez@fhi360.org.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 APR 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Description of the condition

Obesity has reached epidemic proportions around the world. In the United States (US), the prevalence among adults doubled from 1980 to 2004 (Ogden 2007). More than a third of US adults were estimated to be obese during 2009 and 2010, and more than two-thirds were considered to be either overweight or obese (Flegal 2012). In many European countries, the prevalence of obesity has tripled since the 1980s (WHO 2012). The epidemic has also affected less developed countries, particularly among people in urban areas (Prentice 2006).

Overweight and obesity are generally determined with the body mass index (BMI), which is based on weight and height [BMI = weight (kg) / height (m)2] (CDC 2012). The BMI does not distinguish between lean and fat body mass, but for most people (other than highly trained athletes) a higher BMI reflects more body fat (CDC 2012). Frequently used BMI categories are 25 to 29.9 (kg/m2) for overweight and 30 or higher for obesity. Older cutoffs still in use were derived from the National Health and Nutrition Examination Survey II (NHANES II), conducted from 1976 to 1980 in the US. With the NHANES II criteria, women with a BMI greater than 27.3 are overweight, and those with a BMI greater than 32 are considered obese.

Overweight and obese women may have a higher risk for failure of hormonal contraceptives (Grimes 2005a). Some studies have suggested an association between higher body weight or BMI and unintended pregnancies while using oral contraceptives (Holt 2005) or implants (Sivin 2001). However, survey research has suggested little association, especially after adjusting for demographics or socioeconomic factors (Brunner 2005; Brunner Huber 2007). The risk of oral contraceptive failure among overweight or obese women may depend on whether the assessment is based on 'perfect use' or 'typical use' (Trussell 2009).

 

Description of the intervention

Hormonal contraceptives mainly include oral contraceptives (OCs), injectables and implants, the transdermal patch, and the vaginal ring. Oral contraceptives are the most commonly used reversible method in more developed countries (UN 2011), and include combined oral contraceptives (COCs) as well as progestin-only pills (POPs) (Grimes 2010a). IUDs lead in less developed countries, most of which are non-hormonal. Hormonal IUDs are not widely used. Next in usage are injectables (combined or progestin-only) (UN 2011).

 

How the intervention might work

Effectiveness of hormonal contraceptives may be related to metabolic changes in obesity or greater body mass or body fat (Grimes 2005a; Trussell 2009). However, we know little about how overweight women metabolize hormonal contraceptives, since many studies exclude overweight women (Edelman 2009a; Lopez 2012). Recent pharmacokinetic studies have shown differences between obese versus normal-weight women using a COC (Edelman 2009b) or a vaginal ring (Westhoff 2012b). However, ovarian suppression appears to be similar for the two groups (Westhoff 2009; Westhoff 2012b). Other small studies have showed pharmacokinetic differences that may not be clinically significant between obese and normal-weight users of the injectable depot medroxyprogesterone acetate (Segall-Gutierrez 2010) or the etonogestrel implant (Mornar 2012), as well as differences by body weight for users of a levonorgestrel implant (Sivin 2001).

 

Why it is important to do this review

We wanted to identify what was known about the relationship between excess body weight or mass and the effectiveness of hormonal contraceptives. Given the prevalence of overweight and obesity, the public health impact of any effect on contraceptive efficacy could be substantial. The results may inform researchers in the field, as well as help healthcare providers assist women in making contraceptive choices.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

The primary purpose was to examine the effectiveness of hormonal contraceptives in preventing unplanned pregnancies among women who are overweight or obese versus women in a lower weight or BMI group.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We included studies of hormonal contraceptive effectiveness among overweight or obese women. Reports had to contain information on the specific contraceptive method(s). Treatment duration must have been at least three cycles. We did not anticipate finding randomized controlled trials stratified by body weight. Therefore, we searched for and included all study designs. All languages of publication were eligible for inclusion.

We eliminated studies focused on women with specific health problems, such as HIV or diabetes. We also excluded studies of contraceptives as treatment for specific disorders, e.g., acne, hirsutism, or polycystic ovary syndrome.

 

Types of participants

Participants were the women in the studies who used the hormonal contraceptive for contraception. Overweight or obese women must have been identified by an analysis cutoff for weight or body mass index. The comparison group could have been women in a lower weight or BMI group. As noted above, several criteria for defining overweight or obese are still commonly used, including a BMI (kg/m2) >= 25 for overweight and >= 30 for obesity (CDC 2012) as well as the NHANES II cutoff of greater than 27.3 for overweight and greater than 32 for obesity (Burkman 2009). Some researchers may analyze the outcome by body weight quartiles or deciles or by body weight groups, e.g., less than 70 kg or >= 70 kg. We included studies with differing criteria, as practices differ across time periods and by country and we anticipated finding few studies. The weight or BMI cutoff points must have been reported.

 

Types of interventions

The use of one or more hormonal contraceptives must have been studied. Any hormonal contraceptive could have been examined, such as an oral contraceptive, a transdermal skin patch, a vaginal ring, an injectable contraceptive, a subdermal implant, or a hormonal intrauterine system. Due to the limited number of studies of overweight or obese women using contraceptives, we included non-comparative studies as well as comparative trials. The main comparisons for this review were between overweight or obese women and women of lower weight or BMI. Therefore, the comparisons of interest were possible in single-arm studies, i.e., those having only one intervention.

 

Types of outcome measures

 

Primary outcomes

The main outcome was pregnancy. Studies must have assessed pregnancies to be considered.

 

Secondary outcomes

Other outcomes include side effects such as bleeding and rare events such as venous thromboembolism. We also looked for adherence data, by weight or BMI groups, to determine if study groups differed in contraceptive use patterns.

Weight gain was not an outcome of interest for this review, as weight was being examined as a potential predictor of contraceptive effectiveness. The effect of combination contraceptives on weight gain was the focus of a separate review (Gallo 2011).

We did not include ovulation, since it is not a useful surrogate endpoint for pregnancy. A valid surrogate marker captures the effect of the treatment on the true outcome (Grimes 2010b), i.e., pregnancy.

 

Search methods for identification of studies

 

Electronic searches

Through January 2013, we searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and POPLINE. We also searched for current trials through ClinicalTrials.gov and ICTRP. The 2012 search strategies are given in Appendix 1. The 2009 search included EMBASE and is shown in Appendix 2.

 

Searching other resources

We examined reference lists of relevant articles and contacted investigators in the field to seek additional unpublished trials or published trials.

 

Data collection and analysis

 

Selection of studies

We assessed for inclusion all titles and abstracts identified during the literature searches with no language limitations. One author reviewed the search results and identified reports for inclusion or exclusion. A second author also examined the reports for appropriate categorization according to the criteria in this Protocol.

All study designs were included. Studies could have been randomized controlled trials (RCTs), prospective single-arm or multi-arm studies, case-control studies, or observational studies of contraceptive users. We considered post hoc analysis from any of these types of studies as long as the studies met the Criteria for considering studies for this review.

 

Data extraction and management

One author abstracted the data and entered the information into RevMan. Another author conducted a second data abstraction and verified correct data entry. Any discrepancies were resolved by discussion or with a third author if necessary. For studies conducted within the last 10 years, we attempted to contact researchers for missing data and clarification of issues related to participants and methods.

 

Assessment of risk of bias in included studies

The randomized controlled trials were examined for methodological quality, according to recommended principles (Higgins 2011). The randomization was unrelated to the weight or BMI groups, but provides an indicator of study quality. Methodology considered included randomization method, allocation concealment, blinding, and losses to follow up and early discontinuation. Adequate methods for allocation concealment include a centralized telephone system and the use of sequentially-numbered, opaque, sealed envelopes (Schulz 2002). In addition, high losses to follow up threaten validity (Strauss 2005).

We recorded whether pregnancies and body weight were measured or self-reported. Pregnancies may be underreported when relying on self-reports from interviews or questionnaires rather than testing. Such underreporting is unlikely to differ by study group. However, body weight is frequently underestimated by a few pounds (Holt 2005). The result would be categorizing more women in a lower weight group, which would bias the effect estimate toward no difference.

To assess the nonrandomized studies, we followed recommended principles (Higgins 2011, section 13.5) and used the Newcastle-Ottawa Quality Assessment Scale (NOS) for assessing the quality of nonrandomized studies (Wells 2011). We adapted the NOS items for the interventions and outcomes in this review according to the developers' suggestions (Wells 2011). The scale has two versions, i.e., for case-control and for cohort studies. Each version has eight items within three domains: selection (representativeness), comparability (due to design or analysis), and outcomes (assessment and follow-up). We treated the studies in this review as cohort studies and used that NOS version (Appendix 3). We developed a summary table, using headings appropriate to the NOS.

A study can receive one star (✸) for meeting each NOS criterion. The exception is comparability, for which a study can receive a maximum of two stars (for design and for analysis). In this review, assessment of analysis included adjustment for potential confounding factors related to weight. For one star under comparability, the study would have controlled for socioeconomic status. For two stars under comparability, the study would have controlled for other important variables such as other demographics or health conditions. We added analysis of BMI, rather than weight alone, as a criterion for quality of evidence.

Limitations in design and analysis were presented in Risk of bias in included studies and considered when interpreting the results.

 

Measures of treatment effect

The main comparisons for this review were between overweight or obese women and women of lower weight or BMI. Therefore, the comparisons were possible in single-arm studies, i.e., those having only one intervention. For example, for the primary outcome of pregnancy, we compared pregnancies among 'overweight' women with those of 'normal' or 'healthy' women who used Contraceptive A. Definitions of overweight and normal, or the cutoffs for weight or BMI, depended on the analytic methods used for the study reports. For two-arm studies, we planned to compare the weight or BMI groups within Contraceptive A (overweight or obese versus normal weight women) and then within Contraceptive B. Burkman 2009 combined the COC groups for examining risk by BMI. Within COC groups, the researchers reported the results but provided insufficient data for analysis in this review. Zieman 2002 only used data from those assigned to the skin patch. Two of the three trials had a COC comparison group.

Oral contraceptive studies tend to have relatively high discontinuation rates. Time-to-event measures such as life-table or incidence rates are most commonly used, as they are based on actual exposure to the contraceptive and prevent an imbalance in discontinuations from distorting the comparisons. In this review, we extracted life-table rates (actuarial or continuous) where available. We had intended to use the rate difference as the effect measure but the available data were insufficient. Pregnancy by weight or BMI group was not the primary interest for these studies. Six reports either lacked pregnancy counts by weight group (Grubb 1995; Gu 1995) or woman-years for the weight or BMI groups (WHO 1990; Sivin 1997a; Zieman 2002; Burkman 2009). Jain 2004 detected no pregnancies.

Where only the crude number of events was published for dichotomous outcomes, we computed an odds ratio (OR) with 95% CI. An example is the proportion of women that reported bleeding or spotting problems.

 

Dealing with missing data

If reports were missing data needed for analysis, we wrote to the study researchers. Responses and any data provided are shown in the Notes section of Characteristics of included studies. We limited our data requests to studies less than 10 years old. Researchers are unlikely to have access to data for older studies.

 

Assessment of heterogeneity

As expected, we found study populations, designs, and interventions to be heterogeneous. We described the clinical and methodological diversity (or heterogeneity) of the studies. We did not pool data from studies that had different contraceptive methods (e.g., vaginal ring or COC), different doses of the same method, or different criteria for reporting body weight. Therefore, we did not conduct formal meta-analysis due to the few studies available and the range of contraceptive methods examined. Heterogeneity is not an issue when a comparison has a single study.

 

Data synthesis

Following GRADE principles, we assessed the quality of evidence and addressed confidence in the effect estimates (Balshem 2011). When a meta-analysis is not viable due to varied interventions, a summary of findings table is not feasible. Therefore, we did not conduct a formal GRADE assessment with an evidence profile and summary of findings table (Guyatt 2011).

We assessed the quality of evidence with the Newcastle-Ottawa Quality Assessment Scale (NOS) as described earlier (Assessment of risk of bias in included studies). The NOS version for cohort studies was appropriate. The evidence was initially considered high quality since participants could not be randomized by BMI or weight (our comparison groups), though the sample could have been stratified. Studies were downgraded for not analyzing BMI, i.e., using weight alone; not controlling for any confounding, i.e., not having any stars for comparability; and meeting fewer than five of the remaining seven NOS criteria. Our assessment of the body of evidence was based on the quality of evidence from the individual studies. For each major comparison, we examined the evidence for the primary outcome of pregnancy.

 

Sensitivity analysis

From the available data, we conducted sensitivity analysis by examining only those studies that had confirmed pregnancies and measured body weight (rather than self-reported).

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

 

Results of the search

The 2012 searches produced 421 references: 395 from the database searches, 8 from other sources such as reference lists, and 18 trials from searches of clinical trials sites. Two new studies were included (with four reports) (Westhoff 2012a; Xu 2012). Another study was added to 'Additional studies of interest' (Dinger 2011;  Table 1). Six were excluded (with seven reports) after examining the full text (Excluded studies). A conference presentation is awaiting classification due to limited data (Kaunitz 2012; Characteristics of studies awaiting classification). After reviewing the abstracts, we retained 22 references for background information and discarded 366 for not meeting the eligibility criteria.

 

Included studies

Nine studies representing 13 trials met our inclusion criteria and had a total of 49,712 women. The median sample size was 3319. The hormonal contraceptives studied varied as follows:

  • Combination oral contraceptives containing
    • Norgestimate (NGM) 180-215-250 µg plus ethinyl estradiol (EE) 25 µg or norethindrone acetate (NETA) 1.0 mg plus EE 20 µg (Burkman 2009);
    • Levonorgestrel 100 µg plus EE 20 µg (extended regimen) (Westhoff 2012a).
  • Transdermal contraceptive patch (Zieman 2002) releasing norelgestromin 150 µg plus EE 20 µg daily;
  • Vaginal ring (WHO 1990) releasing levonorgestrel (LNG) 20 µg daily and intended for 90-day use;
  • Implants:
  • Subcutaneous formulation of the injectable depot medroxyprogesterone acetate (DMPA-SC) containing 104/0.65 mL (Jain 2004).

The treatment duration varied. Three studies lasted one year (WHO 1990; Jain 2004; Westhoff 2012a) and two had durations of 6 and 13 cycles within the same study (Zieman 2002; Burkman 2009). Four implant studies had the following durations: three years (Xu 2012), five years (Grubb 1995), and seven years (Gu 1995; Sivin 1997a).

Three reports used data from RCTs (Sivin 1997a; Zieman 2002; Burkman 2009). The main comparisons were between contraceptive methods, and the randomization was not stratified by weight. Burkman 2009 was a post-hoc analysis. Zieman 2002 pooled data from three trials; two were RCTs and one was uncontrolled. The other four reports were from prospective non-comparative trials (WHO 1990; Grubb 1995; Gu 1995; Jain 2004). Grubb 1995 used data from two protocols and Jain 2004 had data from two trials.

BMI cutoffs for overweight or obesity were used by four studies (Jain 2004; Burkman 2009; Westhoff 2012a; Xu 2012). However, Burkman 2009 and Westhoff 2012a also used a body weight dichotomy at 70 kg. In addition, Westhoff 2012a examined deciles for BMI and for weight. The results for cycle control under Burkman 2009 came from Hampton 2008; the researchers used quartiles of body weight in pounds (lb): below the 25th percentile (123 lb or less); 25th to 75th percentile (124 to 155 lb); above the 75th percentile (155 lb or more). Four older studies only used body weight groups of 10 kg each (WHO 1990; Grubb 1995; Gu 1995; Sivin 1997a). Zieman 2002 used body weight and BMI in the analyses, and presented results by body weight deciles as well as a dichotomy at 90 kg.

 

Excluded studies

Six studies (seven reports) were newly excluded (Du 2000; Berenson 2011; Casey 2011; Glasier 2011; Moreau 2012; Mornar 2012). Four did not have pregnancy outcome data and two studies of emergency contraception did not meet our criteria for duration of treatment. Details are in Characteristics of excluded studies. A number of studies were discarded earlier due to not assessing pregnancy; most of these were pharmacokinetic studies.

 

Risk of bias in included studies

Many of these criteria were not applicable for our review. Even though we had some RCTs, we were not comparing the randomized groups but rather weight or BMI groups. In addition, several studies were not RCTs. Therefore, we also used Newcastle-Ottawa Scale to assess the quality of evidence for this review, as noted in Assessment of risk of bias in included studies.  Table 2 summarizes the results, which are discussed in Quality of the evidence.

 

Allocation

The three reports using data from RCTs provided information on how the randomization sequence was generated, and all had allocation concealment. As noted earlier, the randomization methods indicate overall study quality, but were unrelated to our comparisons of interest (overweight or obese versus not overweight).

 

Blinding

 

Incomplete outcome data

Two reports had some evidence of incomplete outcome data. Burkman 2009 used an inappropriate definition of intent-to-treat (CONSORT 2009); the researchers excluded from the analysis cycles with incorrect pill intake as well as cycles lacking data on dosing and bleeding. In WHO 1990, women were dropped from study if they had three expulsions in one week or more than five within four weeks.

Losses to follow-up were greater than 20% for one year in Jain 2004; Xu 2012 lost 7% in one year but 23% by three years. Losses were not reported in Grubb 1995 and Sivin 1997a. Across the three trials in Zieman 2002, non-completers ranged from 19% to 31%. Westhoff 2012a had early discontinuations of 29%, besides those lost to follow-up.

 

Other potential sources of bias

None of the studies adjusted for potential confounding related to the condition of interest here (overweight or obesity). Zieman 2002 provided adjusted analysis that could account for confounding effects. For two studies, pregnancy rate by weight or BMI group was not a main outcome (Grubb 1995; Gu 1995). For others, the report focused on an outcome by weight or BMI group even if the original study did not emphasize weight (WHO 1990; Sivin 1997a; Burkman 2009; Westhoff 2012a; Xu 2012). Confounding was not an issue for the comparison in Jain 2004, as no pregnancies were detected.

Four of the nine reports specified that pregnancy was tested and weight was measured (Jain 2004; Burkman 2009; Westhoff 2012a; Xu 2012). In addition, Zieman 2002 tested for pregnancy and Grubb 1995 mentioned objective assessment of pregnancy. WHO 1990 recorded weight during the clinic visits. Details can be found in the Characteristics of included studies.

 

Effects of interventions

 

Contraceptive method

 

Combined oral contraceptives

Within contraceptive methods in Burkman 2009, one significant difference was reported between BMI groups from six Cox proportional hazards models. In the group assigned to NETA/EE, women with a BMI of 25 or more had a higher reported risk versus those with a BMI less than 25 (reported relative risk 2.49; 95% CI 1.01 to 6.13;  Analysis 1.1). When the BMI cutoff of 27.3 was used, the reported risks were similar for the BMI groups ( Analysis 1.1). An earlier publication from Burkman 2009 reported on cycle control (Hampton 2008). Of eight comparisons for breakthrough bleeding or spotting, three showed a difference. Within the NGM/EE group, women above the 75th percentile for weight (more than 155 lb) were less likely to report breakthrough bleeding or spotting at cycle 13 than those below the 25th percentile (123 lb or less) ( Analysis 1.4) or those in the 25th to 75th percentiles (124 to 155 lb) ( Analysis 1.5). Within the NETA/EE group, women above the 75th percentile (more than 155 lb) were less likely to report breakthrough bleeding or spotting at cycle 6 than the women below the 25th percentile (123 lb or less) ( Analysis 1.6). We did not include the analyses in which the two COC groups were combined, since we intended to examine specific contraceptive methods.

Pregnancy rates did not differ significantly in Westhoff 2012a for the BMI groups of normal (or healthy) weight versus overweight or obese ( Analysis 2.1;  Analysis 2.2). Similarly, when 70 kg was used as the cutoff for weight, pregnancy rates did not differ significantly ( Analysis 2.3;  Analysis 2.4). The investigators also examined deciles for weight and BMI and found no trends in the crude pregnancy rates.

 

Transdermal contraceptive patch

Zieman 2002 reported 15 pregnancies in 3319 women over one year in the pooled data from three trials ( Analysis 3.1). The top three deciles of women weighed 69 kg or more (about 30% of the sample). Of the 15 pregnancies detected among the patch users, 7 were in the top decile of women weighing 80 kg or more. Five of those seven pregnancies were among a subgroup of women weighing 90 kg or more (198 lb), who comprised 3% of the study population. The researchers reported baseline body weight was significantly associated with pregnancy risk in a proportional hazards model (reported P < 0.001) in which potential prognostic variables were also assessed (i.e., age, race, BMI, and body surface area). However, pregnancies were reportedly not clustered in any BMI subgroup (no data provided).

 

Implants

Four studies examined various implants. Grubb 1995 and Gu 1995 studied a six-rod implant that contained levonorgestrel 216 mg. Sivin 1997a examined a two-rod implant containing levonorgestrel 150 mg; this included an implant in current use ('original') and a similar implant with a new elastomer. Xu 2012 studied a single-rod implant that released etonogestrel. More detail can be found in Characteristics of included studies.

Outcome data by weight group for Grubb 1995 were shown in a figure without specific rates or counts. Reportedly, contiguous weight groups differed in their fifth-year pregnancy rates (life-table method). The group weighing 40 to 49 kg apparently had a lower rate than the group that weighed 50 to 59 kg, which had a lower rate than the group weighing 60 to 69 kg. The P value was reported as < 0.01. The group of women who weighed 70 kg or more had seven pregnancies, and the rate was reportedly similar to that of the group weighing 60 to 69 kg. The numbers of women in each weight group were not reported.

In Gu 1995, weight was associated with pregnancy rate; the P value was reported as < 0.05. The cumulative pregnancy rate for the group weighing 70 kg or more was 4.58 at Years 5 and 6 and 6.62 at Year 7. The women in this highest weight group represented about 3% of the study sample. These life-table rates were nearly twice those of the group weighing 60 to 69 kg ( Analysis 5.1). Annual pregnancy rates were also provided ( Analysis 5.2).

In Sivin 1997a, no pregnancies were noted in the first three years ( Analysis 6.1). In a follow-up study of the newer two-rod implant, five pregnancies were reported. Only one occurred in the group that weighed 70 kg or more ( Analysis 6.1), which represented 16% of the study population.

Over three years in Xu 2012, one pregnancy was found in 1377 women-years of use. Her baseline BMI was 30.7. Of the implant users, 28% were overweight and 35% were classed as obese. We did not report pregnancies among the IUD users, as the analysis grouped both hormonal and non-hormonal IUDs.

 

Depot medroxyprogesterone acetate, subcutaneous (DMPA-SC)

In two trials, Jain 2004 examined a subcutaneous form of depot medroxyprogesterone acetate (DMPA-SC) containing 104 mg/0.65 mL. No pregnancies were detected in the one-year trials ( Analysis 8.1). Overweight or obese women were 27% of the sample in the European and Asian trial, but only 6% had a BMI greater than 30. In contrast, 44% of the women in the 'Americas' trial were overweight or obese with nearly 18% having a BMI higher than 30.

 

Progestin-only vaginal ring

The experimental ring in WHO 1990 was never marketed. The group weighing 70 kg or more had a cumulative discontinuation rate for pregnancy of 8.2 ( Analysis 4.1), and represented about 10% of the sample. The rates for the other three weight groups were 1.8 (49 kg or less), 2.6 (50 to 59 kg), and 5.3 (60 to 69 kg). From the chi-square test across groups, the reported P value was 0.0013. The researchers also fitted a Cox proportional hazards model to examine the relationship between body weight and pregnancy. Based on that model, they estimated pregnancy risk increased by 61% with a 10 kg increase in body weight. The risk of pregnancy more than doubled with a 20 kg increase (e.g., from 60 kg to 80 kg). The estimated hazards ratio is 2.60 for this increase in body weight; however, statistical significance was not reported. The researchers also estimated the cumulative life-table pregnancy rates. The pregnancy rate for a woman weighing 80 kg was 9.8 or more than twice the 4.4 rate for a woman weighing 60 kg ( Analysis 4.2).

 

Sensitivity analysis

Our criteria for the sensitivity analysis from 2010 included having tested for pregnancy and measured weight. The four studies meeting those criteria examined COCs (Burkman 2009; Westhoff 2012a), DMPA-SC (Jain 2004), and an implant (Xu 2012). These studies provided moderate-quality evidence, based on the quality assessment in 2013 ( Table 2). Jain 2004 had no pregnancies in one year and Xu 2012 had one in three years. Within contraceptive method in Burkman 2009, the groups were generally not significantly different for pregnancy at one year. Women with higher body weights had fewer bleeding problems (not reported by BMI group). Westhoff 2012a did not show any trend associated with weight or BMI at one year.

We also examined studies that met one of the criteria; they either 1) tested for pregnancy (Grubb 1995; Zieman 2002) or 2) measured weight (WHO 1990). The results varied. The heaviest women did not have an increased risk in Grubb 1995 but they did in WHO 1990. In Zieman 2002, the difference in pregnancies for the heavier women was not apparent when the analysis was conducted with BMI rather than weight.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Summary of main results

Of nine studies, the five most recent used body mass index to categorize overweight or obesity while the earlier reports used weight alone. One of the five studies that used BMI found a higher pregnancy risk for overweight (or obese) women by BMI. That trial examined two COCs and reported one higher risk of six comparisons for a specific COC (Burkman 2009).The investigators used two different cutoffs for BMI (25 and 27.3), but the reported risks were similar. The four studies that did not find a significant difference by BMI studied an extended-regimen for a COC (Westhoff 2012a), a single-rod implant (Xu 2012), an injectable (Jain 2004) and a transdermal skin patch (Zieman 2002). Pregnancy rates did not differ significantly in Westhoff 2012a for the BMI groups of normal (or healthy) weight versus overweight or obese nor when 70 kg was used as the cutoff for weight. The investigators did not see any trends when they examined deciles for weight and BMI. In an implant study, Xu 2012 used BMI for analysis and found only one pregnancy in three years. For the injectable trials, Jain 2004 used BMI but found no pregnancies; 27% to 44% of the women were overweight or obese in those studies. Zieman 2002 examined three studies of the transdermal skin patch and reported an association for body weight but not for BMI. About 30% of the women in Zieman 2002 weighed 69 kg or more.

The four older studies used weight alone. Two showed a higher risk for pregnancy among the heaviest women. WHO 1990 examined a progestin-only vaginal ring and Gu 1995 was an implant study. In contrast, two implant studies did not report a significant difference by weight. In Grubb 1995, with more than 16,000 implant users, the heaviest group did not have a significantly higher risk, although the lower weight groups differed from each other. In the implant studies of Sivin 1997a, few pregnancies were reported with no trend by body weight group.

As noted earlier, a higher BMI generally reflects more body fat, except in highly trained athletes. Body weight alone indicates total body mass, but does not help determine whether the person is overweight for a particular height. For example, a woman weighing 70 kg (154 lb) and 1.65 meters (65 inches) in height would have a BMI of 25.7 and be considered slightly overweight (CDC 2012). If she were 1.5 meters tall, her BMI would be 31.1, obese by current standards.

The studies using body weight groups implicitly addressed a different issue than those using BMI. A study of body weight may examine whether a different dose was needed for larger women. On the other hand, studying BMI might inform whether body composition (amount of fat in particular) plays a role in effectiveness.

 

Overall completeness and applicability of evidence

The variety of contraceptive methods examined limits the conclusions about specific types. Most of the studies showed no major trends: two COC trials, three implant studies, and an injectable study. Higher risk for heavier women (by weight) came from three reports that examined the transdermal patch, an older implant, and an early experimental ring. We found no studies of the currently available vaginal ring or the hormonal IUD that met our inclusion criteria. In Xu 2012, the investigators grouped IUD types in the analysis. One study reported cycle control data, but that was provided by weight group not by BMI group.

Risk of unintended pregnancy depends on regimen adherence, often presented as method failure versus user failure (Trussell 2009). Adherence is less of a concern for long-acting methods such as implants rather than for COCs or a transdermal patch. Burkman 2009 had adherence data from daily diaries, but only reported method failures per COC group not for the BMI groups. Zieman 2002 examined adherence for the overall report but not for the post-hoc analysis by weight and BMI. In other work, noncompliance in a COC trial was associated with poverty level, which is related to female obesity and low education (in the USA); those factors were also associated with noncompliance in the trial (Westhoff 2012c).

Contraceptive studies often restrict weight to 115% or 120% of ideal weight (Lopez 2012) but these studies varied in their eligibility criteria. The trials included in Zieman 2002 limited weight to 135% of ideal body weight. Many obese women were likely to have been excluded with that cutoff. Burkman 2009 reported that women with a BMI greater than 32.4 were excluded from participation. However, the reported cutoff for BMI may have been an error, as the authors noted elsewhere that the highest BMI of enrollees was 47.6. In contrast, Westhoff 2012a and Xu 2012 had no restrictions on body weight. Half of the women in Westhoff 2012a were at least overweight, having a BMI greater than 25, and more than 20% had a BMI over 31. In Xu 2012, 28% were overweight and 35% were classed as obese. Xu 2012 recruited in the community as well as in clinics; therefore, the participants may have been more representative of the community. However, most of the studies did not specify their recruitment methods. For Jain 2004, nearly 44% were reportedly overweight or obese in one trial and 27% were reportedly overweight or obese in the other.

 

Quality of the evidence

RCTs are generally considered the gold standard for experimental research. Study design is usually stronger for RCTs than for other types of studies. Three of the eight reports in this review used data from RCTs. However, the main comparisons in this review were not the contraceptive methods but the weight or BMI groups, which were not used for stratification. Allocation concealment and blinding seem less relevant when the comparisons are not the contraceptive methods, and were not applicable to the single-arm studies. Further, while one study provided adjusted analysis, confounding factors for overweight may differ from those for a contraceptive method. None of the studies adjusted for potential confounding related to weight or BMI, which lowered the ratings for all studies. The older studies used only body weight rather than BMI, which we also used for rating the quality of evidence.

We considered the overall quality of evidence to be low for this review, based on assessing the evidence from each study ( Table 2). The reports published since 2002 provided moderate quality evidence, while those from the 1990s provided evidence of low or very low quality.

 

Agreements and disagreements with other studies or reviews

Several relevant studies did not meet the inclusion criteria ( Table 1). Most of them analyzed data on any oral contraceptive rather than one specific contraceptive method. One abstract did not report the duration of use; the data were from multiple trials of the vaginal ring. However, many of these reports have been cited in reviews of body weight and COC effectiveness (Edelman 2009a; Trussell 2009) and are worth examination. Most used BMI rather than body weight for constructing the comparison groups.

Once the models in these additional studies were adjusted for potential confounding, overweight or obese women had similar pregnancy risk to women of normal BMI (Brunner 2005; Brunner Huber 2006; Brunner Huber 2007; Dinger 2009) or weight (Vessey 2001). One with adjusted analysis showed some difference when obese women were compared to all other women. Two studies with unadjusted rates showed no relationship of weight to pregnancy risk (Westhoff 2005; Westhoff 2008). Two often-cited studies using adjusted models were the exceptions: in Holt 2002, heavier women by body weight had a higher risk; in Holt 2005, women with a higher BMI had greater risk but the body weight groups had similar risks.

We excluded the implant data of Sivin 1988, since half appeared to overlap those in Gu 1995. The report also included data from several other countries. The researchers examined pregnancies by four weight groups (< 50, 50 to 59, 60 to 69, and >= 70 kg). The gross cumulative rates at 60 months were 0.2, 3.5, 3.5, and 7.6, respectively, suggesting an association of weight with pregnancy risk. Graesslin 2008 provided post-marketing surveillance data on implant use. By body weight (10 kg groups), the frequency of method failures was reportedly similar to the distribution of users. However, nearly half of the reported pregnancies had insufficient documentation for classification and inclusion.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

 

Implications for practice

The evidence did not generally show an association of BMI with effectiveness of hormonal contraceptives. Studies using body mass index, rather than body weight alone, can provide more information about whether body composition (especially fat) is related to contraceptive effectiveness. Of five recent studies using BMI, only one showed a higher pregnancy risk for overweight or obese women when comparing oral contraceptives. The efficacy of implants and an injectable may not be affected by body mass. The contraceptive methods examined here are among the most effective when the regimen is followed.

 
Implications for research

The evidence was limited for any particular contraceptive method. The quality of evidence was moderate for recent studies and low for older ones. Many reports represented secondary analysis of data from studies not necessarily planned to compare BMI groups. Investigators should consider adjusting for potential confounding when comparing nonrandomized groups. 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.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Carol Manion of FHI 360 developed the search strategies for several databases.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
Download statistical data

 
Comparison 1. COC: norgestimate 180/215/250 µg/ EE 25 or norethindrone acetate 1mg/EE 20 µg)

 
Comparison 2. COC (extended regimen): levonorgestrel 100 µg + EE 20 µg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Crude pregnancy rate by BMI groupOther dataNo numeric data

 2 Pregnancies by BMI group11734Odds Ratio (M-H, Fixed, 95% CI)0.87 [0.45, 1.68]

 3 Crude pregnancy rate by weight groupOther dataNo numeric data

 4 Pregnancies by weight group11736Odds Ratio (M-H, Fixed, 95% CI)1.13 [0.58, 2.18]

 
Comparison 3. Skin patch: norelgestromin 150 µg + EE 20 µg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pregnancies by body weight decileOther dataNo numeric data

 
Comparison 4. Vaginal ring: levonorgestrel 5 mg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Discontinuation rate due to pregnancy at 12 months by body weightOther dataNo numeric data

 2 Pregnancy life-table rates by body weightOther dataNo numeric data

 
Comparison 5. Implant: 6-rod levonorgestrel 216 mg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Cumulative pregnancy rates per 100 women by body weightOther dataNo numeric data

 2 Annual pregnancy rates per 100 women by body weightOther dataNo numeric data

 
Comparison 6. Implant: 2-rod levonorgestrel 150 mg (original or with new elastomer)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pregnancies by body weightOther dataNo numeric data

 
Comparison 7. Implant: single-rod etongestrel 68 mg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pregnancy rate per 100 woman-years by BMI group (3 years)Other dataNo numeric data

 
Comparison 8. Injectable: DMPA-SC 104 mg/0.65 mL

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pregnancies at 1 year by BMIOther dataNo numeric data

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Appendix 1. 2012 to 2013 search strategies

 

MEDLINE via PubMed (01 Jan 2009 to 01 Feb 2013)

(Contraceptive Agents, Female[MESH] OR Contraceptive Devices, Female[MESH] OR contraception[MeSH] OR contracept*[tiab]) AND (obesity[tiab] OR obese[tiab] OR weight[tiab] OR body mass index[MeSH] OR body weight[Mesh]) NOT (cancer*[ti] OR polycystic[ti] OR exercise[ti] OR physical activity[ti] OR postmenopaus*[ti] OR body weight changes)

 

CENTRAL (2009 to 20 Nov 2012)

overweight OR obese OR obesity OR weight OR body mass index OR BMI in Abstract
AND contracept* in Abstract
NOT premenstrual OR dysmenor* OR endometr* OR *androgen* OR HIV OR polycystic OR PCOS OR cancer OR exercise OR anorexia OR bulimic in Record Title
NOT postmenopausal OR post-menopausal OR hormone therapy OR male hormonal in Record Title

 

POPLINE (2009 to 20 Nov 2012)

global: contracept* AND (efficacy OR effectiveness OR "contraceptive failure") AND (obesity OR obese OR overweight OR "body weight" OR "body mass index" OR BMI) NOT (spermicid* OR "weight changes" OR "barrier methods" OR cancer OR polycystic OR exercise OR postmenopausal OR "hormone therapy" OR "hormone replacement")

Limited to research reports

 

ClinicalTrials.gov (01 Jun 2009 to 20 Nov 2012)

Search terms: (overweight OR obese OR obesity OR weight OR body mass index OR BMI) NOT (child OR children OR infant)
Condition: NOT (diabetes OR tuberculosis OR acne OR HIV OR postmenopausal OR polycystic OR PCOS OR cancer OR anorexia)
Intervention: contraceptive OR contraception

 

ICTRP (01 Jun 2009 to 26 Nov 2012)

Title: overweight OR obese OR obesity OR weight OR body mass index OR BMI
Condition: contraceptive OR contraception

 

Appendix 2. 2009 search strategies

 

MEDLINE via PubMed (23 Aug 2009)

1. Search for clinical trials:
(Contraceptive Agents, Female[MESH] OR Contraceptive Devices, Female[MESH] OR contraception[MeSH] OR contracept*[tiab]) AND (obesity[tiab] OR obese[tiab] OR weight[tiab] OR body mass index[MeSH] OR body weight[Mesh]) NOT (cancer*[ti] OR polycystic[ti] OR exercise[ti] OR physical activity[ti] OR postmenopaus*[ti] OR body weight changes) AND (Clinical Trial[ptyp] OR Randomized Controlled Trial[ptyp])

2. Search for other types of studies:
(Contraceptive Agents, Female[MESH] OR Contraceptive Devices, Female[MESH] OR contraception[MeSH] OR contracept*[tiab]) AND (obesity[ti] OR obese[ti] OR overweight[ti] OR weight[ti] OR body mass index[ti] OR BMI[ti]) NOT (cancer*[ti] OR polycystic[ti] OR exercise[ti] OR physical activity[ti] OR postmenopaus*[ti] OR body weight changes) NOT (Editorial[ptyp] OR Letter[ptyp] OR Practice Guideline[ptyp] OR Review[ptyp])

 

POPLINE (29 Aug 2009)

(contraceptive agents, female/contracept*/oral contraceptives/contraceptive methods/vaginal rings/injectables/contraceptive implants/contraceptive patch*/skin patch*/vaginal contraceptive ring*/IUD, hormone releasing/(IUD & hormon*) & (efficacy/effective*/contraception failure) & (obesity/obese/overweight/body weight/weight/body mass index/ BMI) !(spermicid*/vaginal spermicides/barrier methods/weight changes/cancer/polycystic/exercise/postmenopaus*/hormone therapy/hormone replacement therapy/HRT)

 

CENTRAL (22 Oct 2009)

overweight OR obese OR obesity OR weight OR body mass index OR BMI in Abstract
AND contraceptive OR contraception in Abstract
NOT premenstrual OR dysmenor* OR endometr* OR *androgen* OR HIV OR polycystic OR PCOS OR cancer OR exercise OR anorexia OR bulimic in Record Title
NOT postmenopausal OR post-menopausal OR hormone therapy OR male hormonal in Record Title

 

EMBASE (20 Oct 2009)

1) s contraceptive agents or contraceptive device or contraception or female contraceptive device or contracept?
2) s obesity or obese or weight
3) s weight, mass and size
e weight, mass and size
4) s e3
5) s body()mass()index or BMI
6) s s2 or s4 or s5
7) s s1 and s6
8) s cancer or polycystic or exercise or physical()activity or postmenopaus? or body()weight()change?
9) s s7 not s8
10) s efficacy or effective?
11) s s9 and s10
12) s clinical trial or clinical study or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial or randomized controlled trial or controlled clinical trial
13) s s11 and s12

 

ClinicalTrials.gov (10 Sep 2009)

Search terms: overweight OR obese OR obesity OR weight OR body mass index OR BMI
Condition: NOT (HIV OR polycystic OR PCOS OR cancer OR anorexia)
Intervention: contraceptive OR contraception

 

ICTRP (15 Sep 2009)

Title: overweight OR obese OR obesity OR weight OR body mass index OR BMI
Condition: contraceptive OR contraception

 

Appendix 3. Newcastle-Ottawa Quality Assessment Scale

 

Cohort studies

Note: A study can be awarded a maximum of one star (✸) for each numbered item within the Selection and Outcome categories. A maximum of two stars can be given for Comparability.

 

Selection

1) Representativeness of the exposed cohort

a) truly representative of the average _______________ (describe) in the community ✸

b) somewhat representative of the average ______________ in the community ✸

c) selected group of users eg nurses, volunteers

d) no description of the derivation of the cohort

2) Selection of the non exposed cohort

a) drawn from the same community as the exposed cohort ✸

b) drawn from a different source

c) no description of the derivation of the non exposed cohort       

3) Ascertainment of exposure

a) secure record (eg surgical records) ✸

b) structured interview ✸

c) written self report

d) no description

4) Demonstration that outcome of interest was not present at start of study

a) yes ✸

b) no

 

Comparability

1) Comparability of cohorts on the basis of the design or analysis

a) study controls for _____________ (select the most important factor) ✸

b) study controls for any additional factor ✸  (This criteria could be modified to indicate specific control for a second important factor.)           

 

Outcome

1) Assessment of outcome

a) independent blind assessment ✸

b) record linkage ✸

c) self report           

d) no description

2) Was follow-up long enough for outcomes to occur

a) yes (select an adequate follow up period for outcome of interest) ✸

b) no

3) Adequacy of follow up of cohorts

a) complete follow up - all subjects accounted for ✸

b) subjects lost to follow up unlikely to introduce bias - small number lost - > ____ % (select an adequate %) follow up, or description provided of those lost) ✸

c) follow up rate < ____% (select an adequate %) and no description of those lost

d) no statement

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Last assessed as up-to-date: 4 February 2013.


DateEventDescription

4 February 2013New citation required but conclusions have not changedTwo new studies were included (Westhoff 2012a; Xu 2012). Added one 'additional study'  Table 1 (Dinger 2011) and one report to Studies awaiting classification (Kaunitz 2012).
We summarized the quality assessment of the evidence ( Table 2).

1 February 2012New search has been performedSearches were updated. An earlier ongoing trial was excluded (Mornar 2012).



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

LM Lopez reviewed the search results, conducted the first data extraction and drafted the review. For the 2013 update, LM Lopez and C Otterness reviewed search results, conducted the data extractions, and incorporated the new studies. For the initial review, DA Grimes conducted the second data extraction and verified correct data entry. M Chen reviewed the statistical reporting of the included studies and provided guidance on presentation and interpretation of the statistics. All authors reviewed and commented on the manuscript.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Some of the trials in Grubb 1995 were conducted at Family Health International (now known as FHI 360), where LM Lopez, M Chen, and C Otterness are employed. DA Grimes was employed at FHI 360 when the initial review was conducted. The authors were not involved in the Grubb 1995 trials.

DA Grimes has consulted with the pharmaceutical companies Bayer Healthcare Pharmaceuticals and Merck & Co, Inc.

C Westhoff conducted Westhoff 2012a and studies listed in  Table 1. She has consulted with Bayer, Merck (previously Schering-Plough), and Duramed.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Internal sources

  • No sources of support supplied

 

External sources

  • National Institute of Child Health and Human Development, USA.
    For conducting the review and update: LML, CO, MC (2009 to 2013); DAG (2009 to 2010)

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Burkman 2009 {published and unpublished data}
  • Burkman RT, Fisher AC, Wan GJ, Barnowski CE, LaGuardia KD. Association between efficacy and body weight or body mass index for two low-dose oral contraceptives. Contraception 2009;79(6):424-7.
  • Hampton RM, Short M, Bieber E, Bouchard C, Ayotte N, et al. Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20. Contraception 2001;63(6):289-95.
  • Hampton RM, Zhang HF, Barnowski C, Wan GJ. Bleeding patterns with monophasic and triphasic low-dose ethinyl estradiol combined oral contraceptives. Contraception 2008;77(6):415-9.
  • Zhang H, LaGuardia K, Creanga D. Higher body weight and body mass index are not associated with reduced efficacy in Ortho Tri-Cyclen Lo users (abstract). Obstetrics and Gynecology 2006;107(4 Suppl):50S.
Grubb 1995 {published data only}
Gu 1995 {published data only}
Jain 2004 {published data only}
Sivin 1997a {published data only}
Westhoff 2012a {published data only}
  • Kroll R, Reape KZ, Margolis M. The efficacy and safety of a low-dose, 91-day, extended-regimen oral contraceptive with continuous ethinyl estradiol. Contraception 2010;81(1):41-8.
  • Westhoff CL, Hait HI, Reape KZ. Body weight does not impact pregnancy rates during use of a low-dose extended-regimen 91-day oral contraceptive. Contraception. 2011/11/10 2012; Vol. 85, issue 3:235-9.
WHO 1990 {published data only}
  • World Health Organization, Task Force on Long-Acting Systemic Agents for Fertility Regulation. Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. Contraception 1990;41(2):105-24.
  • World Health Organization, Task Force on Long-Acting Systemic Agents for Fertility Regulation. Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. II. Expulsions and removals. Contraception 1990;41(2):125-41.
  • World Health Organization, Task Force on Long-Acting Systemic Agents for Fertility Regulation. Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Contraception 1990;41(2):143-50.
Xu 2012 {published data only}
  • Secura GM, Allsworth JE, Madden T, Mullersman JL, Peipert JF. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. American Journal of Obstetrics and Gynecology. 2010/06/15 2010; Vol. 203, issue 2:115 e1-7.
  • Xu H, Wade JA, Peipert JF, Zhao Q, Madden T, Secura GM. Contraceptive failure rates of etonogestrel subdermal implants in overweight and obese women. Obstetrics and Gynecology. 2012/06/09 2012; Vol. 120, issue 1:21-6.
Zieman 2002 {published data only}
  • Audet MC, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. Journal of the American Medical Association 2001;285(18):2347-54.
  • Smallwood GH, Meador ML, Lenihan JP, Shangold GA, Fisher AC, Creasy GW. Efficacy and safety of a transdermal contraceptive system. Obstetrics and Gynecology 2001;98(5 Pt 1):799-805.
  • Urdl W, Apter D, Alperstein A, Koll P, Schonian S, Bringer J, et al. Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005;121(2):202-10.
  • Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertility and Sterility 2002;77(2 Suppl 2):S13-8.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Banerjee 1984 {published data only}
  • Banerjee SK, Baweja R, Bhatt RV, Chatterjee A, Choudhury SD, Coyaji B, et al. Comparative evaluation of contraceptive efficacy of norethisterone oenanthate (200 mg) injectable contraceptive given every two or three monthly. Indian Council of Medical Research Task Force on Hormonal Contraception. Contraception 1984, issue 6:561-74.
Berenson 2011 {published data only}
  • Berenson AB, van den Berg P, Williams KJ, Rahman M. Effect of injectable and oral contraceptives on glucose and insulin levels. Obstet Gynecol. 2010/12/22 2011; Vol. 117, issue 1:41-7.
Casey 2011 {published data only}
  • Casey PM, Long ME, Marnach ML, Bury JE. Bleeding related to etonogestrel subdermal implant in a US population. Contraception. 2011/04/12 2011; Vol. 83, issue 5:426-30. [1879-0518: (Electronic)]
Cirkel 1990 {published data only}
  • Cirkel U, Schneider HPG. [Incidence of side effects caused by a three-stage preparation administered to 10,034 women] [[Nebenwirkungsinzidenz eines Dreistufenpräparates unter der Anwendung bei 10.034 Frauen]]. Geburtshilfe und Frauenheilkunde 1991;50(12):969-73.
Du 2000 {published data only}
  • Du MK, Chow LP, Zheng HM, Chen CH. A 10-year follow-up study of contraceptive Norplant implants. International Journal of Gynaecology & Obstetrics. 2000/03/04 2000; Vol. 68, issue 3:249-56.
  • Du MK, Zheng HM, Chen HC, Chow LP. Study of Norplant implants in Shanghai: three-year experience. International Journal of Gynaecology & Obstetrics. 1990/12/01 1990; Vol. 33, issue 4:345-57.
Glasier 2011 {published data only}
  • Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011/09/17 2011; Vol. 84, issue 4:363-7.
Graesslin 2008 {published data only}
  • Graesslin O, Korver T. The contraceptive efficacy of Implanon®: a review of clinical trials and marketing experience. European Journal of Contraception and Reproductive Health Care 2008;13(Suppl 1):4-12.
Moreau 2012 {published data only}
  • Moreau C, Trussell J. Results from pooled Phase III studies of ulipristal acetate for emergency contraception. Contraception. 2012/07/10 2012.
Mornar 2012 {published data only}
  • Mornar S, Chan L-N, Mistretta S, Neustadt A, Martins S, Gilliam M. Pharmacokinetics of the etonogestrel contraceptive implant in obese women. American Journal of Obstetrics and Gynecology August 2012; Vol. 207, issue 110:e1-6. [: NCT00724438]
  • Neustadt A, Gilliam M. Pharmacokinetics of Implanon in obese women. http://clinicaltrials.gov/ct2/show/NCT00724438 (accessed 15 Sep 2009). [: NCT00724438]
Sivin 1988 {published data only}
Sivin 1997b {published data only}
  • Sivin I, Viegas O, Campodonico I, Diaz S, Pavez M, Wan L, et al. Clinical performance of a new two-rod levonorgestrel contraceptive implant: a three-year randomized study with Norplant implants as controls. Contraception 1997;55(2):73-80.
Sivin 2000 {published data only}
  • Sivin I, Mishell DR, Diaz S, Biswas A, Alvarez F, Darney P, et al. Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study. Contraception 2000, issue 3:187-94.
Weisberg 1999 {published data only}

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Kaunitz 2012 {published data only (unpublished sought but not used)}
  • Kaunitz A, Archer DF, Foegh M. Increased compliance with a low-dose combination contraceptive patch (AG200-15) compared with a low-dose combination oral contraceptive (COC) in a Phase 3 clinical trial (abstract). Contraception 2012;86(2):178.
  • Kaunitz A, Foegh M, Mishell D. Increased compliance independent of patient demographics with a low-dose combination contraceptive patch (AG200-15) compared with a low-dose combination oral contraceptive in a Phase 3 clinical trial (abstract). Contraception 2012;86(3):314.
  • Kaunitz AM, Mishell DR, Foegh M. Comparative Phase 3 study of AG200-15, a low-dose estrogen and levonorgestrel contraceptive patch. http://www.agiletherapeutics.com/Clinical_support.html (accessed 26 Sep 2012).

Additional references

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
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