Combined Oral Contraceptives Group Research Articles

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18–40 years.Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.Results: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.Conclusions: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

Acceptance and Continuation of Contraceptive Methods Immediate Postabortion

Background/Aims: Providing preabortion contraceptive counseling for the method of contraception may reduce the incidence of repeat abortions. This study aimed to compare the acceptance and continuation rates of intrauterine devices (IUDs), combined oral contraceptives (COCs), and condom use after abortion in women who received preabortion contraceptive counseling. Methods: Women seeking a first-trimester abortion prospectively received preabortion contraceptive counseling and the choice of method of contraception was based on the counseling and not related to prior methods of birth control. Outcomes included continuation of postabortion contraceptive use and repeat abortions over a 6-month follow-up period. Results: Four hundred and fifty-five women (IUD group: n = 161; COC group: n = 149; condom group: n = 135) completed 6-month follow-up after the abortions. At the sixth month follow-up, patients continued using the IUD, COC, and condoms for contraception were 64.2, 10, and 51.5%, respectively. Higher age, being married, parity ≥1, and previous abortion were factors that were associated with more frequent selection of an IUD, while a higher education level was associated with a more frequent selection of COC and condoms. Conclusion: The continued use of COCs after abortion is low even with preabortion contraceptive counseling. The IUD offers reliable birth control with a lower discontinuation rate than COCs or condoms.

A Randomised Controlled Trial Comparing the Efficacy and Side-Effects of Intravaginal Ring (Nuvaring(®)) With Combined Oral Hormonal Preparation in Dysfunctional Uterine Bleeding.

Combined Oral Contraceptive (COC) pills are being used in patients of abnormal uterine bleeding, especially adolescents and reproductive age women considering their need for contraception. It decreases the blood loss due to haemostatic effect of estrogen and also regularizes the cycle. Intravaginal route has been found to be effective and acceptable; Gastrointestinal absorption and hepatic first-pass metabolism is avoided and steady, uniform blood concentration is achieved. Bioavailability of estrogen and progestogen through oral and vaginal route are same. The convenience of once-a-month administration is another major advantage. Sixty women fulfilling inclusion criteria were randomised into 2 groups in 1:1 ratio. In one group (n=30), monthly insertion of Nuvaring(®)) was done for three consecutive months. Nuvaring(®) releases 15μg ethinyl estradiol and 120 μg etonogesterol daily. The other group (n=30) received COC pill containing 30μg EE and 150 μg levonorgestrel for three consecutive months. Primary outcome measures were change in menstrual cycle pattern and pictorial Blood Loss Assessment chart (PBAC) score. Other Parameters included side effects, change in haemoglobin and weight. Data was analyzed by statistical software SPSS 20. Both Nuvaring(®) and COC were found to significantly decrease blood loss in each cycle. Decrease in PBAC score was more in Nuvaring(®) group compared to COC, however difference was not significant. Ideal bleed (IB) was frequently higher for Nuvaring(®) group than COC in all 3 cycles, although no statistically significant difference was observed between groups (p-value=0.286). Late withdrawl, intermenstural spotting was higher in COC group. Compliance was better and women were more satisfied in Nuvaring(®) group compared to COC group. Minor side effects like headache, mastalgia, nausea and mood changes were seen in both groups, which were not significant. Continuation rate was significantly higher in Nuvaring® group. 30% women discontinued treatment in OCP group after 3 month compare to 10% in Nuvaring(®) group. Present study shows Nuvaring(®) to be as effective as COC in controlling heavy menstural bleed, better cycle control, with minor acceptable systemic side effects.

Different Effects of Myoinositol plus Folic Acid versus Combined Oral Treatment on Androgen Levels in PCOS Women.

Recently, myoinositol (myo-ins) and folic acid combination has gained an important role for treating Polycystic Ovary Syndrome (PCOS), in addition to combined oral contraceptives (COC). We aimed to examine myo-ins effects on anti-Mullerian hormone (AMH) levels and compare them with those ones obtained administering COC. In this prospective study, 137 PCOS patients, diagnosed according to Rotterdam criteria and admitted to the Reproductive Endocrinology and Infertility Outpatient Clinic at Dokuz Eylul University (Izmir, Turkey), were included. After randomization to COC (n = 60) and myo-ins (n = 77) arms, anthropometric measurements, blood pressure, Modified Ferriman Gallwey scores were calculated. Biochemical and hormonal analysis were performed, and LH/FSH and Apo B/A1 ratios were calculated. Data analysis was carried out in demographically and clinically matched 106 patients (COC = 54; myo-ins = 52). After 3-month treatment, increase in HDL and decreases in LH and LH/FSH ratio were statistically more significant only in COC group when compared with baseline (in both cases p > 0.05). In myo-ins group, fasting glucose, LDL, DHEAS, total cholesterol, and prolactin levels decreased significantly (for all p < 0.05). Progesterone and AMH levels, ovarian volume, ovarian antral follicle, and total antral follicle counts lessened significantly in both groups (for all p < 0.05). In PCOS treatment, MYO is observed more effective in reductions of total ovarian volume and AMH levels.

Levonorgestrel-releasing intrauterine system versus low-dose combined oral contraceptive for treatment of adenomyosis uteri: a randomized clinical trial

Introduction: This study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding. Materials and methods: A randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs. Results: Both treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm. Conclusion: Both LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance. © 2015 Elsevier Inc. All rights reserved.

Effect of a combined oral contraceptive on patency of arterial anastomosis in a female rat model.

Oral contraceptives, which may lead to thrombotic events, are widely used drugs by women in reproductive age, some of whom might need emergent or elective microsurgical intervention. This study was planned to investigate the effects of combined oral contraceptives (COC) on arterial anastomosis patency in female rat model. A third generation COC (ethinyl estradiol and desogestrel) was used in this study. A total of 50 female Wistar albino rats were included. The rats were divided into two groups. Experimental group received 0.03 mg ethinyl estradiol/0.15 mg desogestrel with gastric catheter for 20 days before the surgery. Afterward, the femoral arteries of all rats were divided and anastomosed. The patency of the anastomoses were assessed surgically (at 15 min, 7th day) and radiologically with Doppler ultrasonography (at 3rd and 7th days). The samples were examined using light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The early patency assessed in the 15th min showed arterial flow in all rats. But at the 7th day 68% of the anastomosis were patent in the COC group while 100% of the anastomosis were patent in the control group as demonstrated surgically and radiologically (P = 0.004). Microscopic examination showed an increase in cytoplasmic organelles and activation of endothelial cells in all rats in the experimental group that received COCs. The present study demonstrated the negative effects of the use of COCs on anastomosis patency in rats.

Hormonal and intrauterine methods for contraception for women aged 25 years and younger.

Women between the ages of 15 and 24 years have high rates of unintended pregnancy; over half of women in this age group want to avoid pregnancy. However, women under age 25 years have higher typical contraceptive failure rates within the first 12 months of use than older women. High discontinuation rates may also be a problem in this population. Concern that adolescents and young women will not find hormonal or intrauterine contraceptives acceptable or effective might deter healthcare providers from recommending these contraceptive methods. To compare the contraceptive failure (pregnancy) rates and to examine the continuation rates for hormonal and intrauterine contraception among young women aged 25 years and younger. We searched until 4 August 2015 for randomized controlled trials (RCTs) that compared hormonal or intrauterine methods of contraception in women aged 25 years and younger. Computerized databases included the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS. We also searched for current trials via ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We considered RCTs in any language that reported the contraceptive failure rates for hormonal or intrauterine contraceptive methods, when compared with another contraceptive method, for women aged 25 years and younger. The other contraceptive method could have been another intrauterine contraceptive, another hormonal contraceptive or different dose of the same method, or a non-hormonal contraceptive. Treatment duration must have been at least three months. Eligible trials had to include the primary outcome of contraceptive failure rate (pregnancy). The secondary outcome was contraceptive continuation rate. One author conducted the primary data extraction and entered the information into Review Manager. Another author performed an independent data extraction and verified the initial entry. For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). Because of disparate interventions and outcome measures, we did not conduct meta-analysis. Five trials met the inclusion criteria. The studies included a total of 1503 women, with a mean of 301 participants. The trials compared the following contraceptives: combined oral contraceptive (COC) versus transdermal contraceptive patch, vaginal contraceptive ring, or levonorgestrel intrauterine system 20 µg/day (LNG-IUS 20); LNG-IUS 12 µg/day (LNG-IUS 12) versus LNG-IUS 16 µg/day (LNG-IUS 16); and LNG-IUS 20 versus the copper T380A intrauterine device (IUD). In the trials comparing two different types of methods, the study arms did not differ significantly for contraceptive efficacy or continuation. The sample sizes were small for two of those studies. The only significant outcome was that a COC group had a higher proportion of women who discontinued for 'other personal reasons' compared with the group assigned to the LNG-IUS 20 (OR 0.27, 95% CI 0.09 to 0.85), which may have little clinic relevance. The trial comparing LNG-IUS 12 versus LNG-IUS 16 showed similar efficacy over one and three years. In three trials that examined different LNG-IUS, continuation was at least 75% at 6 to 36 months. We considered the overall quality of evidence to be moderate to low. Limitations were due to trial design or limited reporting. Different doses in the LNG-IUS did not appear to influence efficacy over three years. In another study, continuation of the LNG-IUS appeared at least as high as that for the COC. The current evidence was insufficient to compare efficacy and continuation rates for hormonal and intrauterine contraceptive methods in women aged 25 years and younger.

Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial

IntroductionThis study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding. Materials and methodsA randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs. ResultsBoth treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm. ConclusionBoth LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance.

Combined hormonal versus nonhormonal versus progestin-only contraception in lactation

Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production. To determine the effects of hormonal contraceptives on lactation and infant growth We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators. We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval. For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis. In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information.For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year.For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant.Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS. Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.

Progesterone-based intrauterine device use is associated with a thinner apical layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression.

Currently, whether hormonal contraceptives affect male to female human immunodeficiency virus (HIV) transmission is being debated. In this study, we investigated whether the use of progesterone-based intrauterine devices (pIUDs) is associated with a thinning effect on the ectocervical squamous epithelium, down-regulation of epithelial junction proteins, and/or alteration of HIV target cell distribution in the human ectocervix. Ectocervical tissue biopsies from healthy premenopausal volunteers using pIUDs were collected and compared to biopsies obtained from two control groups, namely women using combined oral contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining and image analysis were used to measure epithelial thickness and the presence of HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction markers were measured by quantitative PCR. The epithelial thickness displayed by women in the pIUD group was similar to those in the COC group, but significantly thinner as compared to women in the no hormonal contraceptive group. The thinner epithelial layer of the pIUD group was specific to the apical layer of the ectocervix. Furthermore, the pIUD group expressed significantly lower levels of the tight junction marker ZO-1 within the epithelium as compared to the COC group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC-SIGN, and Langerin were observed in the three study groups. Thus, women using pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced ZO-1 expression as compared to control groups. These data suggest that pIUD use may weaken the ectocervical epithelial barrier against invading pathogens, including HIV.

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study

Objective(s)The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). Study designIn this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18–45 years (smokers aged 18–35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. ResultsMean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Conclusion(s)Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. Implications statementThe findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women.

Can Extracorporeal Magnetic Innervation Be a Treatment Modality for Primary Dysmenorrhea

Background/Aims: To evaluate the efficacy of extracorporeal magnetic innervation (ExMI) as a treatment for primary dysmenorrhea compared with nonsteroidal anti-inflammatory drugs (NSAIDs) and combined oral contraceptives (COCs). Methods: The cases were randomized into three groups (NSAID = 51, ExMI = 53, COC = 54). ExMI was applied for a total of 10 sessions. Women in the NSAID group used an oral NSAID at the start of each menstruation. Women in the COC group were given combined pills. Of the treatment options, ExMI was applied for only a single period, whereas NSAID and COC use continued for 12 months. Results: At the first menstruation, visual analog scale (VAS) scores improved significantly in all groups (p < 0.001). NSAIDs and COCs continued to show efficacy over the entire study period (p < 0.05). However, in the ExMI group, VAS values increased from the first menstruation until 12 months. The VAS score at the 12th month was significantly higher in the ExMI group than in the other groups (p < 0.05), but markedly lower than the pretreatment value (49.9 ± 8.3 vs. 71.1 ± 10.1, p < 0.001). Conclusions: ExMI therapy might be a promising novel noninvasive option for primary dysmenorrhea. Efficacy began to decline after 3 months, but continued for 12 months.

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.

Investigation of the Hemostatic Effect of a Transdermal Patch Containing 0.55 mg Ethinyl Estradiol and 2.1 mg Gestodene Compared with a Monophasic Oral Contraceptive Containing 0.03 mg Ethinyl Estradiol and 0.15 mg Levonorgestrel: An Open-Label, Randomized, Crossover Study

BackgroundTransdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch.ObjectiveThe objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel.MethodsIn this single-center, open-label, randomized, crossover study, 30 women (aged 18–35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and d-dimer.ResultsFor both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in d-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or d-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects.ConclusionA COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

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.

Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence

The aim was to evaluate changes of bone mineral density (BMD) and markers of bone turnover in healthy adolescents, and in adolescent users of combined oral contraceptives (COCs) with different ethinylestradiol (EE) contents. In this prospective crossover study, 56 healthy females (15-19.5 years) with desire to use hormonal contraception were randomized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order. Nonusers of the same age (n=28) served as controls. BMD at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months. In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). In the crossover design, a difference between the low- and very low-dose COC users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months. Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC, especially those containing very low dose of EE.

Hormonal contraception and the risk of HIV acquisition among women in South Africa

To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa. We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16-24 years) in particular. Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI 0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96-2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users. In this study conducted among South African women, hormonal contraception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies.

Oral contraceptives containing drospirenone for premenstrual syndrome.

Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception. To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms. We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials. We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined. Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated. We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95% CI -11.16 to -4.67). The drospirenone group had greater mean decreases in impairment of productivity (MD -0.31; 95% CI -0.55 to -0.08), social activities (MD -0.29; 95% CI -0.54 to -0.04), and relationships (MD -0.30; 95% CI -0.54 to -0.06). Side effects more common with the use of the drospirenone COC contraceptive were nausea, intermenstrual bleeding, and breast pain. The respective odds ratios were 3.15 (95% CI 1.90 to 5.22), 4.92 (95% CI 3.03 to 7.96), and 2.67 (95% CI 1.50 to4.78). Total adverse events related to the study drug were more likely for the drospirenone COC group (OR 2.36; 95% CI 1.62 to3.44). Three trials studied the effect of drospirenone 3 mg plus ethinyl estradiol 30 μg on less severe symptoms. A placebo-controlled six-month trial had insufficient data for primary outcome analysis. Another six-month study used levonorgestrel 150 µg plus ethinyl estradiol 30 µg for the comparison group but did not provide enough data on premenstrual symptoms. In a two-year trial, the drospirenone COC group had similar premenstrual symptoms to the comparison group given desogestrel 150 µg plus ethinyl estradiol 30 µg (OR 0.87; 95% CI 0.63 to1.22). The groups were also similar for adverse events related to treatment (OR 1.02; 95% CI 0.78 to1.33). Drospirenone 3 mg plus ethinyl estradiol 20 μg may help treat premenstrual symptoms in women with severe symptoms, that is, premenstrual dysphoric disorder. The placebo also had a large effect. We do not know whether the combined oral contraceptive works after three cycles, helps women with less severe symptoms, or is better than other oral contraceptives. Larger and longer trials of higher quality are needed to address these issues. Trials should follow CONSORT guidelines.

Combined contraceptive ring versus combined oral contraceptive (30-μg ethinylestradiol and 3-mg drospirenone)

Objectives To compare the adverse effects, cycle control, and metabolic effects of NuvaRing and a combined oral contraceptive (COC). Methods Women seeking contraception received NuvaRing (n = 300) or a COC (n = 300) for 12 cycles in a randomized, open-label trial. Results The total number of women with adverse effects did not differ significantly between the 2 groups. Leucorrhea, vaginitis, decreased libido, and ring-related problems were more common with NuvaRing, whereas weight increase, acne, and emotional lability were more common with the COC. Breakthrough bleeding occurred in 11.3% of women receiving NuvaRing and in 14.7% of women receiving the COC; 2.1% and 2.9% of women, respectively, had no withdrawal bleeding. Differences in blood pressure, blood sugar levels, lipid profile, liver enzyme activity, and anticoagulant activity were not statistically significant, with the exception of low-density lipoprotein levels measured at 6 and 12 months, which were significantly lower in the NuvaRing group than in the COC group. Conclusions NuvaRing is a good alternative to a COC. It is associated with a slightly reduced incidence of breakthrough bleeding and there were no clinically relevant adverse effects or changes in blood pressure, blood sugar levels, lipid profile, or anticoagulant activity when compared with the COC.