A 1-year study to compare the hemostatic effects of oral contraceptive containing 20 microg of ethinylestradiol and 100 microg of levonorgestrel with 30 microg of ethinylestradiol and 100 microg of levonorgestrel

OBJECTIVES: To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol (EE) and 100 microg of levonorgestrel (LNG) was compared with a reference preparation containing 30 microg of EE and 150 microg of LNG. One-year data were obtained from 48 volunteers. RESULTS: The direction and magnitude of the changes (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. The majority of changes of all investigated variables remained within the reference ranges of variation. The procoagulatory variables increased to some extent from baseline to treatment cycle 13, while the anticoagulatory variables slightly decreased. In particular, thrombin turnover measured by prothrombin fragments 1+2 increased during treatment by 35% in the 20 microg of EE group and by 38% in the 30 microg of EE group. Statistically significant differences between the two treatment groups were found only for TAT. For the profibrinolytic variables, plasminogen was increased by 42% (20 microg of EE) and 49% (30 microg of EE). While the plasma levels of tPA antigen were reduced during treatment, the levels of its activity were increased by 54% (20 microg of EE) and 20% (30 microg of EE). For PAI, both antigen and activity were decreased, somewhat more pronounced with 20 microg of EE. D-Dimer remained virtually unchanged. Finally, the median FbDP levels were elevated by 30% (20 microg of EE) and 38% (30 microg of EE).     

An open label, randomized study to evaluate the effects of seven monophasic oral contraceptive regimens on hemostatic variables: Outline of the protocol

Complementary to the epidemiological knowledge on the association between oral contraceptive use and the occurrence of venous thromboembolism, a study was designed to obtain more conclusive data regarding the effect of estrogen dose and progestogen type of oral contraceptives on risk markers for the occurrence of venous thromboembolism. The protocol for this multicenter, randomized, open label, parallel group, comparative study is outlined in the present article. A total of 730 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested in this study. The effects of progestogen type (desogestrel, gestodene, levonorgestrel, and norgestimate) and the effects of ethinyl estradiol dose (50, 30, and 20 μg) on various hemostatic variables was assessed, including the key components of the anticoagulant and fibrinolytic system, as well as the coagulation system. The primary outcome variables in the study were prothrombin fragment 1+2 and -dimer.     

Third-generation progestogen type influences hemostatic changes caused by oral contraceptives in Brazilian women

We compared the effects of two third-generation progestogens, desogestrel (DSG) and gestodene (GSD), on coagulation and fibrinolysis in Brazilian users of oral contraceptives (OCs). Forty-six women were evaluated before treatment and after six cycles of treatment. The coagulation, anticoagulant, and fibrinolytic systems were investigated. During the use of the DSG-containing OC, the activity of factors VII, VIII, IX, X, and XII increased significantly whereas the GSD-containing OC caused no changes in coagulation parameters. Concerning the anticoagulant pathways, the DSG-containing OC increased protein C levels and decreased total protein S levels, and the GSD-containing OC only decreased total protein S. Both OCs increased plasminogen activity, although the DSG-containing OC increased fibrin degradation products levels and decreased the tissue plasminogen activator antigen. In conclusion, we have found that in Brazilian women the effects of DSG and GSD on hemostatic parameters are different and, therefore, third-generation progestogens may not contribute equally to the thrombotic risk.     

A 13-month multicenter clinical experience of a low-dose monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene in Latin American women

This prospective, multicenter study was conducted to evaluate the contraceptive reliability, cycle control and tolerability of a 21-day oral contraceptive regimen containing 20 μg ethinylestradiol and 75 μg gestodene in four Latin American countries (Mexico, Argentina, Brazil and Colombia). Participants took trial medication daily for 21 days. Contraceptive efficacy, cycle control and tolerability were evaluated over a period of 13 cycles. Efficacy data gathered from 5,109 treatment cycles were obtained from 393 participants. The trial medication proved to be an effective contraceptive and provided good cycle control. One pregnancy because of poor compliance was recorded. This resulted in a study Pearl index of 0.25. Forty-six percent of Latin American women reported one intracyclic spotting bleeding episode and 37.6% reported one intracyclic breakthrough bleeding (medium/excessive bleeding) episode during cycles 2-4 (primary target). Overall, intracyclic bleeding was reported in 41%. Overall, there was a trend towards a lower incidence of spotting in all the countries and this difference had statistical significance between Argentina and the others three countries (p < 0.05) during cycles 2-4. This trend was also apparent with respect to breakthrough bleeding, but again the difference did not achieve statistical significance. The discontinuation rate because of adverse events was low (3%); no serious adverse events were reported. More than 78% of the women in the four countries maintained constant body weight or lost weight (2 kg) during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study.     

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel

OBJECTIVES: To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. RESULTS: We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. CONCLUSION: Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.     

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers.In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.     

Effect of four oral contraceptives on hemostatic parameters

This is the first double-blind, controlled, randomized study comparing the effect of different estrogen components in oral contraceptives (OCs) on hemostasis variables. Four groups of 25 women each were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). Blood samples were taken on Days 21-26 of the control cycle and on Days 18-21 of the first, third and sixth treatment cycle. Treatment with all four OCs caused an increase in levels of fibrinogen, prothrombin fragment 1+2, D-dimer, plasminogen, plasmin-antiplasmin complex and an increase in protein C activity, a decrease in antithrombin activity, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), and a slight decrease in the sensitivity to activated protein C, but no significant change in that of the thrombin-antithrombin complex. In users of the DNG-containing OCs, the reduction in total and free protein S, and in t-PA and PAI was dependent on the EE dose, while factor VII activity was elevated, but not significantly different from EE/LNG. The results are in agreement with those of previous studies. The effects of EE/EV/DNG on total and free protein S and on t-PA and PAI were lower than those of 20EE/DNG, suggesting that the impact of 2 mg EV on several hemostasis variables is less than that of 10 microg EE. The results show an antagonistic effect of LNG on the EE-induced rise of factor VII activity and fragment 1+2 and on the EE-dependent reduction of total and free protein S.     

A randomized study on the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on lipid and lipoprotein metabolism over a period of 13 cycles

In this open-label, randomized study we compared the influence of a new oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (EE + DRSP = Yasmin), with a reference preparation containing 30 microg ethinylestradiol and 150 microg desogestrel (EE + DSG = Marvelon) on the lipid profile. The primary target variables were total high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol and low-density lipoprotein (LDL) cholesterol. These and additional lipid and lipoprotein fractions were measured at baseline and in the 3rd, 6th and 13th treatment cycles in a total of 50 volunteers, and also assessed after density gradient ultracentrifugation. A slight increase in mean total HDL cholesterol vs. baseline was found for the DRSP group (+12.8%) and the DSG group (+11.8%) after 13 treatment cycles. HDL2 cholesterol did not change remarkably in both groups. The mean LDL cholesterol values increased by 10.6% vs. baseline in the DSG group and remained nearly stable in the DRSP group (+1.8%). All measured values remained within the reference ranges. No statistically significant differences were found between the two treatment groups for those primary endpoints. A slight rise in mean total cholesterol was found for all cycles after the initiation of treatment. The mean increase after 1 year of treatment was approximately 8% in both treatment groups. Mean triglyceride levels increased for both treatment groups without leaving the reference range. The increase for total triglycerides was +73.6 % in the DRSP group and +61.3% in DSG group. For total phospholipids, an increase of +13.6% (DRSP) and +18.5% (DSG) over 13 cycles was measured. The apolipoproteins Apo A-I, Apo A-II and Apo B increased slightly more during DRSP treatment than during DSG treatment. The reduction of Apo E was similar in both groups. Lipoprotein (a) remained stable in the DRSP group, whereas it increased by +10.8% in the DSG group. In conclusion, the combined low-dose oral contraceptive Yasmin, with 30 microg ethinylestradiol and 3 mg of the novel progestogen drospirenone, as well as the reference preparation, had little impact on the lipid profile. While both preparations displayed a favorable lipid profile with increased total HDL cholesterol, the antiandrogenic or missing androgenic activity of Yasmin may be regarded as responsible for the stable LDL cholesterol levels. As a result, the ratio of total HDL:LDL was increased, a pattern that is usually considered clinically beneficial with respect to cardiovascular disease risk.     

An open-label randomized comparative study of oral contraceptives between medications containing 3 mg drospirenone/30 microg ethinylestradiol and 150 microg levonogestrel/30 microg ethinylestradiol in Thai women

This study was conducted to compare the cycle control, efficacy and adverse events of a new low-dose oral contraceptive pill regimen containing 3 mg drospirenone (DRSP)/30 microg ethinylestradiol (EE), with a widely prescribed 150 microg levonogestrel (LNG)/30 microg EE. The results of this comparative trial demonstrated that the two preparations had no statistically significant difference in terms of cycle control, efficacy and adverse events. The occurrence of spotting and breakthrough bleeding was low and was not different between the two regimens. There was neither amenorrhea nor pregnancies reported in either group. The most common adverse events in both groups were nausea, headache and breast tenderness. Also statistically significant changes were found in body weight and blood pressure in both groups at the end of the study. In conclusion, the 3 mg DRSP/30 microg EE regimen provides good cycle control with reliable contraceptive efficacy and a low incidence of adverse events equal to the 150 microg LNG/30 microg EE preparation. Compared with the 150 microg LNG/30 microg EE preparation, the 3 mg DRSP/30 microg EE preparation demonstrated a more favorable effect on body weight and blood pressure, with the mean body weight and mean blood pressure remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in blood pressure.     

Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: a randomized trial

The purpose of this study is to compare bleeding patterns and acceptability of a contraceptive regimen of combined 20 microg ethinyl estradiol/100 microg levonorgestrel taken with and without a hormone-free interval. Thirty-two women desiring oral contraception were randomized to six 28-day cycles (standard group) or 168 days without a pill-free interval (continuous group). Participants kept a daily bleeding calendar documenting bleeding events (none, spotting or required sanitary protection) and side effects (headache, nausea, breast tenderness, depression, premenstrual syndrome and bloating). Primary outcome was number of bleeding days. Secondary outcomes included bleeding days requiring sanitary protection, amenorrhea, patient acceptability of bleeding patterns, method satisfaction and affective side effects. There were no differences in the baseline characteristics of the two groups. Although total bleeding days were fewer in the continuous group (mean = 25.9 vs. 34.9 days), this result did not reach statistical significance. However, women in the continuous group reported significantly fewer bleeding days that required protection (18.4 vs. 33.8 days, p < 0.01), and were more likely to have amenorrhea. Although both groups reported a high level of satisfaction with bleeding patterns and side effect profiles, women in the continuous group reported significantly fewer days of bloating (0.7 vs. 11.1 days, p = 0.04), and menstrual pain (1.9 vs. 13.3 days, p < 0.01). Continuous use of 20 microg ethinyl estradiol/100 microg levonorgestrel is associated with less bleeding requiring protection, and more amenorrhea than standard administration. Taken with or without a hormone-free interval, this oral contraceptive formulation is highly acceptable with regard to bleeding patterns and side effect profile. The continuous group had fewer light and moderate bleeding days, less bloating and menstrual pain. For patients who are seeking these results, this method may be more desirable.     

A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism

In this open-label, randomized study we compared the influence of a new oral contraceptive containing 30 μg ethinylestradiol and 3 mg drospirenone (Yasmin™) with a reference preparation containing 30 μg ethinylestradiol and 150 μg desogestrel (Marvelon™) on variables of carbohydrate metabolism by means of oral glucose tolerance tests at baseline and in the 6th and 13th treatment cycle. The mean levels of fasting glucose and insulin were similar at baseline and after 13 treatment cycles, whereas C-peptide and free fatty acid levels decreased slightly in both groups. All blood glucose and insulin values measured in the oral glucose tolerance tests were within normal ranges, despite a slight increase in the mean areas under the curves of 0–3 h [AUCs (0–3 h)] of both variables from baseline to treatment cycle 13. Differences between both treatments were not statistically significant. The mean AUCs (0–3 h) for C-peptide were not markedly changed in any treatment group. Free fatty acid levels decreased by 42% in the drospirenone group and increased by 48.9% in the desogestrel group, in terms of means of individual changes. Both preparations were well tolerated and equally efficacious regarding contraception and cycle control. The mean body weight was slightly decreased in most cycles during treatment with the drospirenone combination, as compared to baseline, while it was slightly increased versus baseline in all cycles during treatment with the desogestrel combination. The combination with drospirenone had less impact on blood pressure than the combination with desogestrel. In conclusion, Yasmin, a combined low-dose oral contraceptive with 30 μg ethinylestradiol and 3 mg of the novel progestogen drospirenone, as well as the reference Marvelon, containing 30 μg ethinylestradiol and 150 μg desogestrel had little impact on carbohydrate metabolism when used for 1 year. The observed changes were small and not suggestive of a clinically relevant deterioration of carbohydrate metabolism.     

A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 microg or 30 microg ethinylestradiol in combination with levonorgestrel on bone mineral density

In this first prospective, double-blind, randomized, parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density (BMD) and metabolic bone parameters. One dose-reduced preparation contained 20 microg ethinylestradiol (EE) in combination with 100 microg levonorgestrel (LNG) (20/100) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48 volunteers aged 20-35 years were obtained over an observation period of 36 treatment cycles. The direction of the change (increase or decrease) in all investigated bone-related variables was similar in both treatment groups. As compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not significantly different between the two treatment groups (p = 0.902). For bone-specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100 group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments did not differ statistically significantly (p = 0.522). With respect to cross-linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did not significantly differ between the two treatments (p = 0.613). Both study treatments were safe and well-tolerated by all volunteers participating in the study. In conclusion, BMD did not change during the 3-year observation period. Thus, both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women. There is no reason to assume that the EE dose reduction had any negative impact on BMD. Because there were no differences in BMD between the treatment groups, it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection. Biochemical markers provided evidence for a reduced bone resorption.     

Effects of conventional or extended-cycle regimen of an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on various hemostasis parameters

Background

The study was conducted to investigate the effect of a combined oral contraceptive (COC) containing 30 mcg ethinylestradiol and 2 mg dienogest with two different regimens on various hemostasis variables.

Study Design

Hemostatic parameters were measured in 59 women treated with a monophasic COC containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or with an extended-cycle regimen (4 extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle or on Days 82-84 of the first and fourth extended cycle.

Results

After 3 and 12 months, significant increases in fibrinogen (20%), factor VII antigen (50-60%), factor VII activity (45%), activated factor VII (30-45%) and factor VIII activity (10-20%) occurred in both treatment regimens. In both groups, there was a small but significant decrease in the level and activity of antithrombin, a 20-25% decrease in total and free protein S and a 15-20% rise in the level and activity of protein C, but no significant change of the thrombin-antithrombin complex. A significant over-time rise by about 25% of prothrombin fragment 1+2 occurred only in the extended-cycle group, but this effect did not differ significantly from that observed during conventional treatment. Plasminogen was elevated by 50% in both groups, while tissue-plasminogen activator (t-PA) activity rose by 15% in the conventional group and by 25-30% in the extended-cycle group. In both groups, t-PA antigen was reduced by about 30% and plasminogen activator inhibitor-1 by 40-60%. The levels of the plasmin-antiplasmin complex rose by 30-40% and those of D-dimers by 20-55%. The prothrombin time was slightly increased and the activated partial thromboplastin time was slightly decreased.

Conclusion

In general, these results were in agreement with those observed during treatment with other COCs. The study demonstrated that during conventional and extended-cycle treatment with EE/DNG, a steady-state in the effects on hemostasis variables was reached within 3 months, and that the effects observed after 3 and 12 months of treatment did not substantially differ between conventional and extended-cycle regimen.     

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background

The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (OC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women.

Study Design

Eighty-eight women (23±2.1 years old) were divided into four groups — active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) — and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min⁻¹ increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%.

Results

The OC use effect for the variables relative and absolute oxygen uptake V?O₂ mL kg−¹ min⁻¹; V?O₂, L min⁻¹, respectively), carbon dioxide output (V?CO₂, L min⁻¹), ventilation (VE, L min⁻¹), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables V?O₂, V?CO₂, VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4.

Conclusions

Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests.     

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol

PURPOSE: In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. METHODS: Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. RESULTS: Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. CONCLUSION: The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.     

Effects of two different oral contraceptives on total body water: a randomized study

Purpose

This open-label, randomized study evaluated the effect of two different oral contraceptives on body weight and composition during one cycle of treatment.

Method

Eighty women (mean age, 24.6 years) were randomized into three groups and given one of the following contraceptive methods: ethinylestradiol 15 μg/gestodene 60 μg (EE/GST, n=25), ethinylestradiol 30 μg/drospirenone 3 mg (EE/DRS, n=29) or male condom (control group, n=26). Bioelectric impedance analysis (BIA) was carried out on the first, 10th and 21st days during the use of oral contraceptives or in the menstrual cycle (control group), and total body water (TBW), fat mass (FM) and fat-free mass (FFM) were measured.

Results

No significant variations in TBW, FM or FFM were observed in the three groups during the cycle. Intergroup analysis showed no differences in TBW or FM; however, users of EE/GST showed a statistically significant increase in FFM compared to the control group.

Conclusion

The different doses of ethinylestradiol associated with gestodene or drospirenone showed no statistically significant effects on TBW or FM during one cycle of observation.     

Clinical comparative study of oral contraceptives containing 30 microg ethinylestradiol/150 microg levonorgestrel,and 35 microg ethinylestradiol/250 microg norgestimate in Thai women

The study was conducted to compare cycle control, efficacy and side effects of two oral contraceptives containing 30 μg ethinylestradiol (EE)/150 μg levonorgestrel (LNG) and 35 μg ethinylestradiol (EE)/250 μg norgestimate (NGM). An open-label, randomized, comparative study was conducted in which 140 healthy women received the 30 μg EE/150 μg LNG or 35 μg EE/250 μg NGM preparation for six treatment cycles. There were no significant statistical differences between both groups in terms of cycle length and amount of withdrawal bleeding. The mean duration in the 35 μg EE/250 μg NGM group was longer than 30 μg EE/150 μg LNG group with significant statistical difference. More patients in 35 μg EE/250 μg NGM group experienced BTT at each cycle compared with the 30 μg EE/150 μg LNG group, but was not statistically significant. There was no amenorrhea nor pregnancies occurring in either group. No significant changes in body weight or blood pressure were found in both groups. The incidence of adverse events in both groups was low and tended to decrease with time. Statistically significant differences were observed for headache and dizziness, which occurred more in the 30 μg EE/150 μg LNG group. In conclusion, 35 μg EE/250 μg NGM provides reliable contraceptive efficacy. It also provides good cycle control equal to 30 μg EE/150 μg LNG with a lower incidence of minor adverse effects such as headache and dizziness compared to 30 μg EE/150 μg LNG.     

The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study

This open-label, nonrandomized study compared changes in hemostatic variables during NuvaRing® and oral levonorgestrel 150 μg/ethinylestradiol 30 μg (LNG/EE) use for six cycles. Eighty-seven women started the study, 44 with NuvaRing and 43 with the LNG/EE oral contraceptive. For most procoagulation variables, there was no difference between NuvaRing and oral LNG/EE; only Factor VII levels increased in the NuvaRing group and decreased in the LNG/EE group. The majority of assessed variables show that anticoagulation and fibrinolytic activity was comparable between the NuvaRing and oral LNG/EE groups. Antithrombin activity and protein C activity both tended to be higher with NuvaRing. Levels of tissue plasminogen activator decreased in both groups but the reduction was smaller with NuvaRing. There were no significant differences in fibrin turnover between the treatment groups. The data show that both NuvaRing and oral LNG/EE are associated with a minimal effect on hemostatic variables.     

The combined contraceptive vaginal ring (NuvaRing) and lipid metabolism: a comparative study

This study compared the lipid profile after three and six cycles of treatment with NuvaRing delivering 15 microg ethinylestradiol and 120 microg etonogestrel daily with a combined oral contraceptive (COC) containing ethinylestradiol 30 microg and levonorgestrel 150 microg. In the NuvaRing group 40 women were treated and 43 in the COC group. Compared with baseline, total cholesterol did not change in either group. NuvaRing did not affect HDL, but HDL, HDL2 and HDL3 levels decreased with the COC. In contrast, HDL2 increased with NuvaRing at cycle 3. LDL increased after cycles 3 and 6 with COC, and decreased after three cycles of NuvaRing treatment. Apolipoprotein A-1 levels increased with NuvaRing, but decreased with COC; apolipoprotein B and triglycerides increased, and lipoprotein(a) decreased in both groups. Sex hormone-binding globulin increased markedly more with NuvaRing, whereas corticosteroid-binding globulin levels increased less. These changes reflect the lower androgenicity of etonogestrel versus levonorgestrel and show that NuvaRing has a minimal effect on lipid profile.     

One versus multiple packs for women starting oral contraceptive pills: a comparison of two distribution regimens

Background

Despite World Health Organization and International Planned Parenthood Federation recommendations to provide multiple pill cycles to new users, many programs in developing countries still give only one pill cycle to new acceptors.

Study Design

To compare provision of a single versus multiple packs of pills, new pill users in 20 matched public sector clinics in Jamaica were assigned to one of two pill regimens in which they received either one (then subsequently three) or four pill cycles at method initiation. The primary outcome was the proportion of women who used pills beyond 4 months.

Results

Among 655 women, those receiving one cycle of pills at initiation, followed by counseling and a three-pack resupply, were no more likely to be using pills after 4 months than women who received four packs at initiation (odds ratio=1.33; 95% confidence interval=0.88-2.0). In both pill regimen groups, returning late to the clinic for resupply was a problem. However, more women in the 1+3-pack regimen group returned late to study clinics to obtain their fifth cycle of pills than their counterparts in the 4-pack regimen group (53% vs. 28%).

Conclusion

Our findings support the recommendation that pill users should be given more than one cycle to start, because an extra visit for resupply contributes to clinic and provider costs. Moreover, providing more pill cycles at initiation would decrease the likelihood that women experience a gap in pill use between cycles.