Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism. Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. Effects of two low-dose oral contraceptives containing ethinylestradiol and either desogestrel or levonorgestrel on serum lipids and lipoproteins with particular regard to LDL size. Contraception in perimenopausal women with diabetes mellitus. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Efficacy and safety of the combined oral contraceptive ethinylestradiol/drospirenone (Yasmin) in healthy Chinese women: a randomized, open-label, controlled, multicentre trial. Comparison of cycle control and side effects between transdermal contraceptive patch and an oral contraceptive in women older than 35 years. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use. Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables.
This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-microg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.
                Copyright 2002 Elsevier Science Inc. The primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17β-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE).
                Women (aged 18-50 years) were randomised to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=1591) or DRSP/EE (3 mg/30 μg) in a 21/7-day regimen (n=535) for 13 cycles.
                Estimated Pearl Indices for NOMAC/E2 and DRSP/EE were 0.38 and 0.81 in women aged≤35 years and 0.31 and 0.66 for all women (18-50 years), respectively. Scheduled withdrawal bleedings were shorter and lighter among users of NOMAC/E2 and were sometimes absent altogether. Intracyclic bleeding/spotting was infrequent in both groups, and decreased over time. Type and frequency of adverse events were similar to those typically reported for COCs.
                These data show that NOMAC/E2 provides high contraceptive efficacy with acceptable cycle control as well as an overall adverse event profile similar to that of DRSP/EE. This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 microg of ethinyl estradiol (EE) and 3 mg of drospirenone.
                In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC.
                One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC.
                NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone. User acceptability of both methods was high. This study was designed to determine the effects of two low-dose oral contraceptives, most frequently given in our area, monophasic desogestrel/ethinylestradiol (DG/EE) and triphasic levonorgestrel/ethinylestradiol (LNG/EE), on lipoprotein parameters, especially LDL particle size and HDL subclass distribution (determined by lipid-stained 2%-20% polyacrylamide gradient gel electrophoresis) in 37 healthy normolipidemic women aged 19 to 27 years. Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use. Results reflected the estrogen-progestin balance. As compared with baseline values, with both formulations, plasma total cholesterol, phospholipids, and HDL3 cholesterol increased, and LDL-predominant peak size decreased, with a translation of LDL pattern A towards pattern I. With DG/EE, plasma triglycerides, apolipoproteins AI and B increased. With LNG/EE, LDL cholesterol increased, and HDL2 cholesterol decreased. All these modifications were moderate, within threshold limits. Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE, since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol. To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women.
                The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception.
                Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems.
                Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices. This open-label, randomized, Phase III study compared the efficacy and tolerability of and compliance with NuvaRing, a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel daily, with those of and with a combined oral contraceptive (COC) containing 150 microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was randomized and started treatment (intent-to-treat [ITT] population). The percentage of women in the ITT population who completed the trial was 70.9% for the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC. Compliance with both treatments was excellent and both were well tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing. To evaluate and compare the contraceptive efficacy, bleeding pattern, side effects and other positive effects of a combined oral contraceptive (COC) containing drospirenone (DRSP) [Yasmin] with those of a COC containing desogestrel (DSG) in healthy Chinese women. This was a randomized, open-label, controlled, multicentre study of 768 healthy Chinese women requiring contraception. The subjects were randomized to ethinylestradiol (EE) 30 microg/DRSP 3 mg (n = 573) or EE 30 microg/ DSG 150 microg (n = 195), at a ratio of 3 : 1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment. Weight, height and body mass index were evaluated at each visit. The Menstrual Distress Questionnaire (MDQ) was administered at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). Baseline characteristics were similar between the two groups (p > 0.05). The Pearl Index (method failure) for EE/DRSP was 0.208 per 100 women-years, which was lower than that for EE/DSG (0.601 per 100 women-years). There were no significant differences between the treatment groups with regard to bleeding patterns. According to the MDQ subscale, improvements in water retention and increases in appetite during the intermenstrual period and in water retention and general well-being during the menstrual period in the EE/DRSP group (-0.297, -0.057, 0.033 and 0.150, respectively) were significantly improved compared with the EE/DSG group (-0.108, 0.023, 0.231 and -0.023, respectively) [all p < 0.05]. Other values that improved in both groups, particularly improvement in breast pain and tenderness and skin condition, were more evident in the EE/DRSP group (18.0%, 89/494; 12.6%, 62/494) than in the EE/DSG group (11.3%, 19/168; 5.4%, 9/168). Mean weight increased in the EE/DSG group (0.57 kg) while there was a significant decrease in mean weight (-0.28 kg) in the EE/DRSP group (p < 0.01). Both EE/DRSP and EE/DSG have good contraceptive efficacy and a comparable bleeding pattern. EE/DRSP had a more favourable effect on weight and premenstrual symptoms than EE/DSG. To compare menstrual patterns and side effects between transdermal contraceptive patch and oral contraceptive use in Thai women over 35 years old.
                Open labeled randomized control trial.
                Family Planning Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
                Ninety-six women above the age of 35 years old were randomized to receive either transdermal contraceptive patch (n = 48) or oral contraceptive (n = 48). The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive contained with ethinyl estradiol (EE) 30 microg and levonorgestrel 150 microg.
                There were no statistically significant differences between the two groups in terms of cycle length. The mean duration in the transdermal contraceptive group was longer than the COC group with statistically significant difference. More patients in the COC group experienced spotting than the transdermal contraceptive group. Neither amenorrhea nor pregnancies occurred in both groups.
                Transdermal contraceptive patch provides reliable contraceptive efficacy. It also provides good cycle control equal to COC in Thai women aged above 35 years old. However, a higher incidence of minor adverse effects such as breast tenderness and nausea were demonstrated when compared to oral contraceptive containing with ethinyl estradiol (EE) 30 microg and levonorgestrel 150 microg. To compare the effects of a combined oral contraceptive (COC) containing nomegestrol acetate and 17β-oestradiol (NOMAC/E2) on haemostasis, lipids, carbohydrate metabolism, C-reactive protein (CRP) and sex hormone-binding globulin (SHBG) with those of a COC containing levonorgestrel and ethinylestradiol (LNG/EE).
                In a randomised, open-label study, 121 healthy women, 18-50 years of age, were randomly assigned to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n=61) for six cycles. The primary outcome was the change from baseline to cycle 6 for all indices.
                All parameters were similar at baseline between the two groups. Over six cycles, NOMAC/E2 had less effect on most haemostatic indices than LNG/EE. Lipids were essentially unchanged with NOMAC/E2, whereas with LNG/EE high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol and triglycerides slightly increased. NOMAC/E2 induced negligible changes in glucose and insulin parameters, in contrast to LNG/EE. A much smaller increase in CRP was observed with NOMAC/E2 than with LNG/EE. NOMAC/E2 was associated with a greater increase in SHBG.
                The monophasic COC NOMAC/E2 had less influence on haemostasis, lipids and carbohydrate metabolism than the COC LNG/EE. To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG).
                Randomised, open-label, multicentre, comparative substudy of a larger phase 3 trial involving 147 healthy women (age 18-49 years). Participants received the COC either continuously (levonorgestrel [LNG] 90 μg/ethinylestradiol [EE] 20 μg) or cyclically (21/7 days pattern; LNG 100 μg/EE 20 μg).
                After 13 pill packs, changes in total cholesterol (+0.23 vs. -0.06 mmol/l), low-density lipoprotein cholesterol (+0.25 vs. -0.12 mmol/l), and high-density lipoprotein cholesterol(3) (-0.06 vs. -0.15 mmol/l) differed significantly (p<0.05) between the continuous and cyclic regimens, respectively. Increases were significantly greater (p <0.05) for protein C antigen (+11.8% vs. +6.1%) and SHBG (+791 vs. +565 nmol/l), and significantly smaller (p <0.05, ranks) for D-dimer (+19 vs. +37 μg FE/l).
                Overall, the continuous and cyclic regimens affected metabolic variables similarly. The larger increase in SHBG with the continuous COC is consistent with a higher net oestrogenic effect due to a lower daily dose of LNG. Prospective studies are required to determine the long-term effects of this continuous COC regimen. The aim of this study was to compare effects of the transdermal contraceptive patch, a desogestrel/ethinyl estradiol (EE)-containing, monophasic combination oral contraceptive (COC) and a levonorgestrel/EE-containing, triphasic COC on hemostasis variables.
                This was a randomized, open-label study of 104 young women who received six cycles of treatment. Blood was collected at baseline and on treatment; changes by Day 20/Cycle 6 in baseline hemostasis markers [prothrombin fragment 1+2 (F 1+2), plasmin-plasmin inhibitor complex (PAP) and fibrin degradation products (D-dimer)] were assessed.
                All contraceptives induced similar increases in F 1+2 and D-dimer. Patch-induced PAP increases were less than with the monophasic and similar to the triphasic COC. Decreases in protein S and increases in sex hormone-binding globulin were greater with the patch than with either COC. Patch-induced increases in activated protein C resistance were greater than with the triphasic and similar to the monophasic COC.
                These contraceptives appeared to accelerate baseline procoagulation processes to a similar extent and to change coagulation potency variables differently.
While COCs containing 20 μg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. Higher follow-up rates are essential for meaningful interpretation of results.