Combined Oral Contraceptives Users Research Articles

Side effects unrelated to disease activity and acceptability of highly effective contraceptive methods in women with systemic lupus erythematosus: a randomized, clinical trial

ObjectivesTo assess the side effects unrelated to disease activity and the acceptability of combined oral contraceptives (COCs), progestin-only pills (POPs) and copper-releasing intrauterine devices (IUDs) in women with systemic lupus erythematosus (SLE). Study designA randomized clinical trial including 162 women with SLE, assigned to COC (n=54), POP (n=54) or IUD (n=54). Follow-up visits were conducted after 1, 2, 3, 6, 9 and 12 months of treatment to monitor the presence of symptoms, changes in body weight and blood pressure as well as the development of health problems other than those relating to lupus. Reasons for discontinuation and satisfaction with the use of the assigned method were recorded at the end of treatment. Statistical analysis included descriptive statistics, repeated measure analyses and Kaplan–Meier curves. ResultsSignificantly different discontinuation rates due to any reason [35%, 55%, 29% (p<0.01)] or nonmedical reasons [(11%, 31%, 4% (p<0.05)] were observed among the COC, POP and IUD groups. Nausea was most frequent among COC users, dysmenorrhea among IUD users and acne and hirsutism among POP users. Mean blood pressures remained unchanged. Mild increases in body weight were observed over time in all treatment groups. Most women were satisfied with the use of the assigned contraceptive method. ConclusionsOral contraceptives and IUD are acceptable birth control methods for patients with lupus, when counseling and specialized health attention are provided; however, the acceptability of POP appears to be inferior. Side effects unrelated to lupus disease activity are not frequent reasons to discontinue the contraceptive methods. ImplicationsThis study delves into an area that has not been explored among patients with lupus. Our findings on the associated side effects and reasons for discontinuing COCs, POPs or copper-bearing IUDs may be useful in improving contraceptive counseling for women with lupus. Furthermore, they also heighten our knowledge on the reasons that may preclude the widespread use of effective contraceptives among lupus patients.

Amelioration of lipid abnormalities by vitamin therapy in women using oral contraceptives

ObjectiveCombined oral contraceptives (COCs) have some adverse effects on the serum lipid profile. Because hyperlipidemia is one of the risk factors in cardiovascular diseases, lipid abnormalities should be evaluated in women consuming COCs. Vitamins E and C are known to have beneficial effects on serum lipid profiles. Therefore, in this study, we evaluated the effects of vitamins E and C on serum lipids in women using COCs.MethodsThe study compared changes in lipid parameters with and without vitamin therapy in women consuming COCs compared to those of a control group (40 non-contraceptive users or NCU) for 4 weeks. Total cholesterol and triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels along with HDL/LDL ratios were measured for all participants.ResultsCOC users experienced significantly higher increases in the levels of triglycerides and LDL than non-users (p<0.05). However, no significant differences were noted in the total cholesterol and HDL levels. In the treated COC group receiving vitamins E and C, the HDL level and the HDL/LDL ratio increased and the LDL and triglycerides levels decreased significantly compared with those of the other groups.ConclusionThe results of our study indicate that supplementation with antioxidant vitamins E and C restores a normal lipid profile in COC users.

Use of prescription contraceptive methods in the UK general population: a primary care study

To determine prescription contraceptive use in the UK. Observational study using a primary care database. The Health Improvement Network (THIN). Women in THIN aged 12-49 years in 2008, registered with their primary care doctor for at least 5 years, and with a prescription history of at least 1 year were included. THIN was searched using the Read and MULTILEX codes for the following methods: combined oral contraceptives (COCs), progestogen-only pills (POPs), copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS), progestogen-only implants, progestogen-only injections, and contraceptive patches. Prevalence, switching, and duration of prescriptions. A cohort of 194 054 women was identified. The prevalence of contraceptive use was: COCs, 16.2% (95% confidence interval, 95% CI 16.1-16.3%); POPs, 5.6% (95% CI 5.5-5.6%); Cu-IUD, 4.5% (95% CI 4.4-4.5%); LNG-IUS, 4.2% (95% CI 4.1-4.2%); progestogen-only implants, 1.5% (95% CI 1.5-1.6%); progestogen-only injections, 2.4% (95% CI 2.3-2.4%); and contraceptive patches, 0.1% (95% CI 0.1-0.2%). Within 1 year, 9.8% of new COC users switched to alternative COCs, and 9.0% changed to a different method. Among new COC users who did not switch method, 34.8% did not continue use beyond 3 months, and were no longer using a prescription contraceptive. Among users of oral contraceptives who did not switch method, over one-third did not continue use beyond 3 months. This supports current UK guidelines recommending a follow-up consultation with a healthcare professional 3 months after the first prescription of COCs.

Oral contraceptive use and impact of cumulative intake of estrogen and progestin on risk of ovarian cancer

Oral contraceptive use decreases the risk of ovarian cancer, but no previous studies have assessed the impact of cumulative intake of estrogen and progestin on ovarian cancer risk. We used data from a population-based case–control study conducted in Denmark in 1995–1999 among women aged 35–79 years; 554 women with epithelial ovarian cancer and 1,564 age-matched controls were included in the analyses. Data were analyzed in multiple logistic regression models. The use of combined oral contraceptives only and the mixed use of combined and progestin-only pills decreased the risk of ovarian cancer, while no association was found with exclusive use of progestin-only pills. No major differences in risk were found for users of combined oral contraceptives with high- and low-potency estrogen and progestin. There was no effect of cumulative progestin intake, but decreased risks of ovarian cancer with increasing cumulative intake of estrogen (OR = 0.82; 95 % CI 0.67–0.99, per 100 mg estrogen) and increasing duration of oral contraceptive use (OR = 0.95; 95 % CI 0.92–0.98, per year of use) were found. No effect of cumulative estrogen intake was found, however, after adjustment for duration of oral contraceptive use. The protective effect of oral contraceptives against ovarian cancer may be sufficiently explained by duration of anovulation. This suggests that if the estrogen and progestin doses are sufficient to cause anovulation, a higher intake of estrogen or progestin confers no extra protection against ovarian cancer.

Attitudes, knowledge and prescribing habits of Brazilian gynecologists regarding extended-cycle oral contraceptives

Extended-cycle and continuous use combined oral contraceptives (COC) have been widely investigated; however, gynecologists’ prescribing habits are largely unknown. This study evaluated the opinions and prescribing habits of Brazilian gynecologists regarding extended/continuous COC. Gynecologists caring for reproductive-age women and used to prescribing COC were recruited to an online survey. Overall, 1097 physicians were included. Of these, 93.0% stated that patients requested extended/continuous COC, with 93.9% of the physicians having already prescribed these regimens at least once. Only 67 physicians reported never having prescribed extended/continuous COC. The most common reasons for prescribing extended/continuous COC were “dysmenorrhea”, “endometriosis” and “convenience of menstrual suppression”. Physicians reported prescribing extended/continuous regimens for 20.7 ± 17.2% of their patients with an indication for COC, postgraduate degree holders being more likely to prescribe extended/continuous regimens than physicians without postgraduate degree (23.6 ± 19.1% versus 20.0 ± 16.7%; p = 0.014). In conclusion, the vast majority of gynecologists prescribe extended/continuous COC. Women often request information from their doctors on the subject. “Convenience of menstrual suppression” is a common reason given for prescribing extended/continuous COC. According to the physicians, the great majority of extended/continuous COC users are satisfied or very satisfied with the regimen prescribed.

The Effect of Low-dose Combined Oral Contraceptive Pills on Brachial Artery Endothelial Function and Common Carotid Artery Intima–Media Thickness

Combined oral contraceptives (COCs) are considered for their thrombogenicity and the risk of premature atherosclerosis and the stroke caused by them. The aim of this study was to evaluate the relationship between chronic use of low-dose COCs (ethinyl estradiol 30 mcg + levonorgestrel 150 mcg) and endothelial dysfunction and intima-media thickness. In a cross-sectional study, in 2011-2012, 60 healthy premenopausal women (30 cases of COC consumers and 30 controls as nonconsumers), aged between 25 and 45 years, participated in this study. They were current users for at least a 3-year period. Brachial artery flow-mediated dilatation (FMD) and common carotid artery intima-media thickness (CCA-IMT) were measured for the patients. The mean duration of COC consumption was 54.03 ± 27.27 months in the case group. There was a significant FMD% difference between 2 groups of cases and controls: 11 ± 3.53 versus 15.80 ± 9.22 (P = .01). In addition, a significant mean CCA-IMT thickness difference was detected: .53 ± .07 versus .44 ± .08 (P = .00). However, after multiple regression analysis and adjusting for body mass index (BMI), in COC users, no significant association between COC consumption duration and FMD% and mean CCA-IMT was observed. Prolonged used of low-dose COCs may cause changes in both endothelial function (measured by FMD%) and endothelial structure (measured by CCA-IMT). There was a nonsignificant inverse relationship between the duration of COC ingestion and FMD% and a nonsignificant positive relationship with CCA-IMT. Our results are in favor of early atherosclerotic changes in prolonged users of COCs.

P3.221 Oral and Injectable Hormonal Contraception Decrease Risk of Bacterial Vaginosis But Oral Contraception May Increase Risk of Vaginal Candidiasis: A Systematic Review of Published and Unpublished Data

BackgroundA recent World Health Organization (WHO) technical consultation concluded that combined oral contraception (COC) does not increase HIV acquisition in women, but the evidence for depot medroxyprogesterone acetate (DMPA) is...

Randomized trial of the effect of tailored versus standard use of the combined oral contraceptive pill on continuation rates at 1 year

BackgroundThere is growing interest from women and clinicians in extended or tailored use of the combined oral contraceptive (COC) pill. Potential advantages include less bleeding, greater contraceptive efficacy and user satisfaction. We examined the effect of a tailored pill regimen, compared with the standard regimen, on continuation and satisfaction rates at 1 year and associated bleeding patterns. Study DesignThis was a randomized controlled trial with 503 women aged 18–45 years. Women were randomized to either the standard regimen (21 daily pills followed by a 7-day pill-free interval) or tailored regimen (daily pills until three consecutive days bleeding triggers a 3-day pill-free interval) of Microgynon 30® (ethinyl oestradiol 30 mcg, levonorgestrel 150 mcg). Primary outcome was COC continuation at 12 months; secondary outcomes included satisfaction with pill regimen regarding contraception and bleeding pattern. Daily electronic diaries were used to record women's pill use, switching to other contraceptive methods, menstrual bleeding patterns and satisfaction levels. ResultsEighty-three percent of women were already taking the COC at recruitment, 13% were restarting the COC and 4% were first time COC users. Seventy-one percent of all women were followed up at 12 months. Continuation rates at 1 year were 82% in the tailored arm versus 80% in the standard arm [odds ratio (OR)=1.13; 95% confidence interval (CI)=0.67–1.91]. Satisfaction with contraceptive regimen was 86% (tailored) versus 94% (standard) (OR=0.37; 95% CI=0.17–0.79), and satisfaction with bleeding pattern was 79% versus 87%, respectively (OR=0.53; 95% CI=0.30–0.93). Median number of bleeding days per month was 2.4 (tailored) and 4.9 (standard). Incidence, duration and intensity of bleeding episodes were significantly lower in the tailored arm. ConclusionsIn women familiar with standard use of the COC, switching to tailored COC use or continuing with standard use were both associated with high COC continuation rates and high satisfaction with contraceptive regimen and bleeding pattern. While significant differences tended to favor the standard group, tailored COC use was associated with significantly less bleeding, suited some women very well and can provide a suitable alternative to standard use.

Can a meta-analysis that included articles with high heterogeneity appropriately evaluate the risk of venous thromboembolism in users of combined hormonal contraceptives containing drospirenone or desogestrel?

The authors suggest that the authors of the systematic review reassess the meta-analyses which demonstrated high diversities. The reanalysis of the cohort studies comparing venous thromboembolism (VTE) risk in users of combined oral contraceptives (COCs) containing desogestrel with that of women taking a COC containing levonorgestrel brought no substantial change to light with regard to the aforementioned author’s findings. On the contrary when reassessing the cohort studies comparing users of COCs containing drospirenone with women taking a COC containing levonorgestrel unlike the review authors they found no significant difference in VTE risk between these two groups. The authors’ meta-analysis of nested case control studies did show a higher VTE risk associated with the use of drosperinone-containing pills. Future studies of higher quality and longer duration are needed to determine whether the risk of VTE associated with the use of COCs containing drosperinone is greater than with those containing levonorgestrel.

Contraceptive failures in overweight and obese combined hormonal contraceptive users.

To estimate weather contraceptive failure rates among combined oral contraceptive pill (OCP), patch, and vaginal ring users was associated with increasing body mass index (BMI). Females enrolled in a large contraceptive study offering the reversible method of their choice at no cost were followed-up for 2-3 years. We compared the failure rates (pregnancy) among users of the OCP, transdermal patch, and contraceptive vaginal ring stratified by BMI. Among the 7,486 participants available for this analysis, 1,523 chose OCPs, patch, or ring at enrollment. Of the 334 unintended pregnancies, 128 were found to be a result of OCP, patch, or ring failure. Three-year failure rates were not different across BMI categories (BMI less than 25 8.44%, 95% confidence interval [CI] 6.1-11.5; BMI 25-30 11.03%, 95% CI 7.5-16.0; BMI more than 30 8.92%, 95% confidence interval 7.6-11.5). Increasing parity (hazard ratio [HR] 3.06, CI 1.31-7.18) and history of a previous unintended pregnancy (HR 2.82, CI 1.63-4.87), but not BMI, were significant risk factors for unintended pregnancy. Overweight and obese females do not appear to be at increased risk for contraceptive failure when using the OCP, patch, or vaginal ring.

The influence of combined oral contraceptives on female sexual desire: A systematic review

ABSTRACTObjectives To determine the relationship between the use of combined oral contraceptives (COCs) and sexual desire based on a systematic review of the literature.Methods MEDLINE Complete, Google Scholar and the Cochrane Library were searched for articles published between 1975 and 2011, reporting the effects of oral contraceptives on sexual desire. Reports fully meeting all the predefined criteria were analysed and included in a final reference list. In addition, a review of the reference list of selected articles was carried out.Results We evaluated 36 studies (1978–2011; 13,673 women). Of the COC users (n = 8,422), 85% reported an increase (n = 1,826) or no change (n = 5,358) in libido and 15% reported a decrease (n = 1,238). We found no significant difference in sexual desire in the case of COCs with 20–35 μg ethinylestradiol; libido decreased only with pills containing 15 μg ethinylestradiol.Conclusions The majority of COC users report no significant change in libido although in most studies a decline in plasma levels of free testosterone and an increase in those of sex hormone binding globulin were observed.

Immediate start of hormonal contraceptives for contraception

Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. At the time of the initial review, how immediate start compared to conventional menses-dependent start was unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception. This review examined randomized controlled trials (RCTs) of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability. In August 2012, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. Earlier searches also included EMBASE. We included RCTs that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other. Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated. Five studies were included. No new eligible studies have been found since the review was initially conducted. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77). A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. Also, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22). We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, i.e., immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.

Is lipid profile determination necessary in women wishing to use oral contraceptives?

IntroductionAlthough coronary heart disease in users of combined oral contraceptives (COCs) is rare, one of the principal risk factors for its occurrence is dyslipidemia. ObjectiveTo evaluate the prevalence of dyslipidemia in women wishing to use COCs, and its association with known clinical risk factors in order to evaluate the need to determine the lipid profile in this population. Study DesignCross-sectional study involving 516 women aged 18–40 years, 54% nulligravid, who wished to use COCs and presented no contraindications. Dyslipidemia was classified according to the National Cholesterol Educational Project Adult Treatment Panel III guidelines, which define levels of total cholesterol ≥200 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, triglycerides >150 mg/dL, and low-density lipoprotein cholesterol ≥160 mg/dL as an abnormal lipid profile. The lipid profile was determined, and the association between clinical risk factors and the presence of dyslipidemia was evaluated by the chi-squared test and logistic regression. The receiver operating characteristic curve was constructed to compare body mass index (BMI) and smoking relevance for dyslipidemia. ResultsThe prevalence of dyslipidemia was 33.9%. Smoking and BMI were significantly associated with the presence of dyslipidemia, with sensitivity of 31.3–54% and specificity of 41.9–67.7% for diagnosis of dyslipidemia, respectively. ConclusionThe high prevalence of dyslipidemia could justify lipid profile evaluation before prescribing a COC. BMI and smoking represent modest predictive markers for the presence of dyslipidemia in candidates for the use of combined oral contraceptives.

Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill—A double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis

There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown. We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 18-46 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS. The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41-3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10-2.19). We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS.

Effects of combined oral contraceptives containing levonorgestrel or chlormadinone on the endothelium

BackgroundAlthough the use of combined oral contraceptives (COCs) is associated with an increased risk of arterial and venous thromboembolic events, less is known about the impact of COCs on endothelial function. The present study evaluated the effects on the endothelium of healthy women of combinations of 30 mcg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA) and 30 mcg EE/150 mcg levonorgestrel (LNG). Study DesignSixty-four healthy women were evaluated, 21 using a nonhormonal contraceptive method (control) and 43 using COCs, randomized to EE 30 mcg /CMA 2 mg or to EE 30 mcg/LNG 150 mcg. Anthropometric parameters, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), ultrasound markers of endothelial function, flow-mediated dilation (FMD) of the brachial artery, intima–media thickness (IMT) and common carotid artery stiffness were measured at randomization and 6 months later. ResultsRelative to baseline, EE/CMA users showed a significant reduction in mean DAP at 6 months (p=.02), and EE/LNG users showed a significant increase in mean IMT (p=.02) and a significant reduction in mean FMD (p=.01) at 6 months. DAP at 6 months was significantly lower in COC users than in controls (p=.01). Intergroup evaluations showed that, at 6 months, mean SAP (p=.02) was significantly lower in EE/LNG users than in controls (p=.02) and that mean DAP was significantly lower in EE/CMA (p<.01) and EE/LNG (p=.01) users than in controls. EE/LNG users experienced a mean FMD reduction almost threefold greater than that of EE/CMA users. Compared to controls, EE/LNG users experienced a 7.5-fold greater reduction in mean FMD. ConclusionsCOC containing LNG is associated with more pronounced changes in the FMD and IMT of healthy women than a COC containing CMA and nonhormonal contraception. Further studies are needed to determine whether these differences may lead to higher risk of arterial thromboembolic events.

Venous Thrombosis in Users of Non-Oral Hormonal Contraception: Follow-Up Study, Denmark 2001-10

Conclusion: Women who use transdermal patches or vaginal rings for contraception have approximately a six to seven times increased risk of venous thromboembolism (VTE) compared to women who do not use hormonal contraception. Summary: It is well known oral contraceptive agents increase the risk of VTE. There are, however, little to no data regarding the effects of methods other than pills to deliver hormonal contraceptive agents. Such methods include transdermal patches, subcutaneous implants, and vaginal rings. The authors used a historic national registry in a cohort study design to assess absolute and relative risk of VTE in Danish women using nonoral hormonal contraception. This national registry-based cohort study used four national registries from Denmark. All Danish nonpregnant women aged 15 to 49 years (n = 1,626,158), who were free of previous VTE or cancer, were followed up from 2001 to 2010. The main outcome measures were incidence rates of VTE in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception. Relative risk of venous thrombosis was compared with nonusers of hormonal contraception, and rate ratios of venous thrombosis in current users of nonoral products were compared with the standard reference of an oral contraceptive with levonorgestrel and estrogen (30-40 μg). A diagnosis of VTE was considered confirmed if there was at least 4 weeks of anticoagulation therapy after the initial VTE diagnosis. There were 5,287 first ever VTE events recorded within 9,429,128 women-years of observation. Of these VTE events, 3,434 were confirmed. The rate of confirmed VTE events was 2.1/10,000 years in nonusers of hormonal contraception. After adjustment for age, calendar year, and education, the relative risks and 95% confidence interval (95% CI) of confirmed VTE in users of transdermal combined contraceptive patches and vaginal ring compared with nonusers of hormonal contraception were 7.9 (3.5-17.7) and 6.5 (7.4-8.9), respectively. Corresponding incidence events per 10,000 exposure-years were 9.7 and 7.8 events. The relative risk (95% CI) was increased in women who used subcutaneous implants (1.4 [0.6-3.4]) but not in those who use the levonorgestrel intrauterine system (0.6 [0.4-0.8]). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk (95% CI) of VTE was 2.3 (1.0-5.2) in users of transdermal patches and 1.9 (1.3-2.7) in users of the vaginal ring. Comment: In the last paragraph of the discussion portion of this article the authors succinctly point out the implications of their study, “if the incidence rate of venous thrombosis in women using combined oral contraceptives containing levonorgestrel is 6 per 10,000 exposure years, that of the vaginal ring is 11 per 10,000 exposure years, and that of the transdermal patch is 14 per 10,000 exposure years, then 2000 women using the vaginal ring, and 1250 using the transdermal patch should shift to combined oral contraceptives with levonorgestrel to prevent 1 event of VTE in one year. A risk of 10 per 10,000 years implies a risk of VTE more than 1% over a 10 year user period. Therefore, women are generally advised to use combined oral contraceptives with levonorgestrel or norgestimate, rather than to use transdermal patches or vaginal rings.”

Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women.

While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women. Thirty-four, obese (body mass index, BMI > 30 kg m(-2)) women of reproductive age (18-35 years old) were placed on a COC pill containing 20 µg ethinylestradiol/100 µg levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non-compartmental method. Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h(-1) vs. 53.9 l h(-1), P < 0.05). A median decrease of 5.6 l h(-1) (95% CI -4.1, 13.3 l h(-1)) was observed. However, the magnitude of change was similar to that reported in women with normal BMI. Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug-drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs.

User characteristics and out-of-pocket expenditures for progestin-only versus combined oral contraceptives

BackgroundLittle is known about the proportion of oral contraceptive pill (OCP) users that use progestin-only pills (POPs), factors associated with POP use, and whether out-of-pocket expenditures and dispensing patterns are similar to combined oral contraceptives (COCs). Study DesignObservational cohort using 1996–2008 Medical Expenditure Panel Surveys. ResultsAmong all OCP users, 4% used POPs and changed little between 1996 and 2008. Women were more likely to use POPs if they received postpartum care (p<.001), had a diagnosis of hypertension (p<.001) or resided in the West (p<.01). POP users, compared to COC users, were more likely to pay $15 and more (p<.01) and less likely to obtain more than one pack per purchase (p<.001), controlling for age, race/ethnicity and insurance coverage. ConclusionPOP use is very low in the United States. POP users obtained fewer packs per purchase compared with COC users, suggesting that POP may be used as transitional OCPs, particularly during the postpartum period.

Types of combined oral contraceptives used by US women

BackgroundWe sought to estimate the prevalence of types of combined oral contraceptives (COCs) used among US women. Study DesignWe analyzed interview-collected data from 12,279 women aged 15–44 years participating in the National Survey of Family Growth, 2006–2010. Analyses focused on COC use overall, by pill type, across sociodemographics and health factors. ResultsThe prevalence of current COC use (88 different brands) was 17%. The majority of COC users used earlier-formulation COCs: ≥30 mcg (67%) versus <30 mcg estrogen (33%), monophasic (67%) versus multiphasic (33%) dosages and traditional 21/7 (88%) versus extended/other cycle regimens (12%) regimens. Norgestimate (32%) and norethindrone (20%) were the most commonly used progestins. Sociodemographic, gynecological and health risk factors were associated with type of COC use. ConclusionFurther investigation of specific COC use and of the factors associated with types of pills used among US women at the population level is needed.