The effect on blood pressure of a monophasic oral contraceptive containing ethinylestradiol and gestodene

To obtain an overview of the effect of monophasic gestodene on blood pressure and to determine the frequency of “OC elevated BP/hypertension,” the results of blood pressure monitoring from four clinical studies of contraceptive efficacy and safety have been retrospectively analyzed. A total of 1930 women took part in the studies, which recorded BP for up to 24 cycles. Analysis of results revealed that 97 women (5.0%) showed an increase in blood pressure from previously normal to elevated values while taking monophasic gestodene, with only 26 (1.35%) fulfilling the criteria of “OC elevated BP/hypertension.” Only four women dropped out of the trials due to hypertensive blood pressure values, while 67 women (3.5%) experienced a normalization of previously elevated blood pressure measurements. In conclusion, this analysis has confirmed that gestodene has a negligible effect on blood pressure, with increased BP a relatively rare event.     

A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet (gestodene75/EE20) on body fat

This open-label study evaluated the effects on body fat of the use of a low-dose oral contraceptive (gestodene75/EE20) in a group of 61 women (OC-U group) as compared to a nonuser group (OC-N group) of 51 women who did not receive an oral contraceptive. Weight, body mass index (BMI), waist-over-hip ratio and body composition data, obtained by bioelectrical impedance [percentages of body fat (%FAT), water (%TBW) and lean mass (%FFM)], were assessed before and after six treatment cycles. Baseline OC-U group weight, BMI, %FAT, %TBW and %FFM did not differ from the OC-N group, either at baseline or at the end of the study, and did not significantly change within each group during the study. Also, there was no modification of fat distribution in either group. Among women in the OC-U group, there was a slight increase in total cholesterol levels and a trend towards higher triglycerides levels. No changes were detected in blood pressure. In conclusion, this low-dose oral contraceptive did not affect weight or body composition. Thus, our data suggest that gestodene75/EE20 represents an appropriate OC choice and may enhance compliance of women who mistakenly believe that the use of oral contraceptives always leads to weight gain.     

Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism

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 μg ethinyl estradiol (EE) and 75 μg gestodene (GSD) or 20 μg ethinyl estradiol and 150 μg 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-μg 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.     

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel on lipid and lipoprotein metabolism

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) on lipid and lipoprotein metabolism was conducted on 45 Singapore women under the WHO Special Programme of Research in Human Reproduction. The women were randomly allocated to one of the two pill groups--a triphasic preparation containing low doses of LNG and EE in various proportions and a monophasic preparation of 150 micrograms LNG and 30 micrograms EE, and an additional 18 women, choosing to use IUDs, were recruited as controls. Blood samples were taken at admission, 3 and 12 months thereafter. For both pill groups, total cholesterol decreased with duration of use, while HDL cholesterol decreased slightly at 3 months and thereafter increased. LDL cholesterol decreased slightly at 3 months, returning to baseline at 12 months for the monophasic group, while remaining unchanged at 12 months for the triphasic group. The monophasic preparation appeared to lower total, LDL and HDL cholesterols to a greater extent at 3 months than the triphasic preparation. Compared with IUD users, for the monophasic group, both total and HDL cholesterols were significantly lower at 3 months and HDL and LDL cholesterols were lower at 12 months. In addition, ratios of HDL cholesterol/LDL cholesterol and HDL cholesterol/total cholesterol were significantly lower at 12 months. Changes in triglycerides were minimal for both pill groups. However, at 3 months, triglycerides for the triphasic group were significantly higher than the IUD users, but this observation was not of any clinical importance since comparison of changes with their respective pretreatment values were not statistically significant. These results indicate that these changes are related to the dosage and estrogen-progestogen ratio of the preparation. Furthermore, the monophasic preparation may have a disadvantage over the triphasic preparation since it appears to cause more disturbance in lipid metabolism. However, it is noted that these changes in lipids and lipoproteins were minimal and did not appear to be of any clinical significance.     

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.     

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.     

A comparative study on the effects of a monophasic pill containing desogestrel plus 20 micrograms ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulatory factors.

The changes in haemostasis during oral contraception are related to the ethinylestradiol dose present in the formulation taken by the patient. An open, randomized longitudinal study was performed to evaluate and compare the effects that low-dose oral contraceptives (OCs) containing different doses of ethinylestradiol exert on the haemostatic system. Eighty-nine healthy women, aged 18-45 years, were randomly assigned to treatment with 3 different OCs: a monophasic pill containing 30 micrograms of ethinylestradiol plus 75 micrograms of gestodene (GSD/30) (30 subjects), a triphasic pill containing levonorgestrel (TRI/LNG) (28 subjects), a monophasic pill containing 20 micrograms ethinylestradiol plus 150 micrograms of desogestrel (DOG/20) (31 subjects). From every woman, blood samples were collected before treatment and at the 3rd and 6th cycle of pill intake. The number of platelets significantly increased (p less than 0.01) during treatment with TRI/LNG. Fibrinogen plasma values were significantly increased (p less than 0.05) only in women treated with the preparation GSD/30. Fibrinopeptide A (FPA) plasma levels significantly increased (p less than 0.01) during treatment with the pills TRI/LNG and GSD/30, but the levels of FPA were unchanged in the group treated with DOG/20. The overall results of this study confirm that the effects of OCs on haemostasis are dependent on the ethinylestradiol dose. Moreover, they suggest that with reduction of the ethinylestradiol component to 20 micrograms, the effects of OCs on haemostasis seem to be virtually eliminated.     

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.     

An open-label, comparative study of the effects of a dose-reduced oral contraceptive containing 0.02 mg ethinylestradiol/2 mg chlormadinone acetate on hemostatic parameters and lipid and carbohydrate metabolism variables

Objective

The study was conducted to compare the effects of 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), given for 24 days each cycle, with those of 0.02 mg EE/0.15 mg desogestrel (DSG) and 0.03 mg EE/0.15 mg levonorgestrel (LNG), given for 21 days each cycle, on hemostatic, lipid, and carbohydrate metabolism parameters in healthy subjects, over six medication cycles.

Study design

A randomized, multicentre, open-label, Phase II trial measured markers of hemostasis, and of lipid and carbohydrate metabolism in 165 subjects randomly assigned to treatment with one of three combined oral contraceptives (COCs).

Results

EE/CMA and EE/DSG had a similar effect on hemostatic parameters, the EE/LNG group showed comparatively smaller increases in the activity of factor VII [8.1% vs. 36.6% (EE/CMA) and 28.2% (EE/DSG)], protein C [5.9% vs. 32.9% (EE/CMA) and 21% (EE/DSG)] and endogenous thrombin potential-based activated protein C resistance [44.1% vs. 93.5% (EE/CMA) and 108.1% (EE/DSG)], and in contrast, free protein S levels decreased in the EE/CMA and EE/DSG groups (−12.7% and −4.3%, respectively) but rose in the EE/LNG group (20.4%). In all treatments, total cholesterol, total triglyceride and apolipoproteins increased. Levels of very low-density lipoprotein cholesterol particularly rose across all groups. Slight increases in high-density lipoprotein (HDL) cholesterol were observed for EE/CMA (14.6%) and EE/DSG (8.5%), with a rise above the upper limit of normal in 30% of the subjects taking EE/CMA. Conversely, for EE/LNG slight decreases in HDL cholesterol were observed (−12.4%) lipoprotein (a) levels decreased in the EE/CMA (−6.6%) and EE/LNG (−16.9%) groups and were unchanged in the EE/DSG group.

Conclusions

The changes observed were typical of those seen across low-dose COCs that differ according to commonly-used progestogens.     

Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone

ObjectivesTo evaluate the effect on endocrine and metabolic parameters of a new combined oral contraceptive (COC) containing estetrol (E4) and drospirenone (DRSP).Study designRandomized, open-label, controlled, 3-arm, parallel study. Healthy subjects received either E4 15 mg/DRSP 3 mg (E4/DRSP) (n = 38), or ethinylestradiol (EE) 30 µg/levonorgestrel (LNG) 150 µg (n = 29), or EE 20 µg/DRSP 3 mg (n = 31) for 6 treatment cycles. Median percentage change from baseline to cycle 3 and to cycle 6 were evaluated for endocrine parameters, liver proteins, lipid profile, and carbohydrate metabolism.ResultsAt cycle 6, E4/DRSP treatment had less effect on gonadotropins (follicle stimulating hormone [FSH] +30.5%, luteinizing hormone [LH] ?7.5%) compared to EE/LNG (FSH ?84.0%, LH ?92.0%) and EE/DRSP (FSH ?64.0%, LH ?90.0%). With E4/DRSP increases in total cortisol (+26.0%) and cortisol binding globulin ([CBG] (+40.0%) were less compared to EE/LNG (cortisol +109.0%, CBG +152.0%) and EE/DRSP (cortisol +107.0%, CBG +140.0%). Liver proteins, except CRP, increased, but the effect was less pronounced with E4/DRSP for angiotensinogen (+75.0%) compared to EE/LNG (+170.0%) and EE/DRSP (+206.5%) and for sex hormone binding globulin ([SHBG] +55.0%), compared to EE/LNG (+74.0%) and EE/DRSP (+251.0%). E4/DRSP had minimal impact on lipid parameters; the largest effect was observed for triglycerides (+24.0%), which was less compared to EE/LNG (+28.0%) and EE/DRSP (+65.5%). E4/DRSP had no effect on carbohydrate metabolism.ConclusionsE4/DRSP treatment has limited effects on endocrine and metabolic parameters. The effects on gonadotropins, cortisol, CBG, angiotensinogen, SHBG and triglycerides were less pronounced compared to EE-containing products.Implications statementCombining E4 15 mg with DRSP 3 mg resulted in a COC with a different metabolic profile in comparison to EE-containing products. The clinical relevance of these findings needs to be further assessed, using clinical endpoints to establish the safety profile of this new COC.     

Double-blind, randomized study comparing the effects of two monophasic oral contraceptives containing ethinylestradiol (20 microg or 30 microg) and levonorgestrel (100 microg or 150 microg) on lipoprotein metabolism

The effects of two monophasic oral contraceptives containing ethinylestradiol 20 microg in combination with levonorgestrel 100 microg (EE20/LNG100) or 30 microg and 150 microg (EE30/LNG150), respectively, on lipoprotein metabolism was investigated in a double-blind, randomized study of 12 treatment cycles in healthy female volunteers. Total triglycerides (+32% to +46%, p < 0.05 in comparison to baseline) increased significantly. Triglycerides were highest after six cycles of treatment, decreasing thereafter. Total cholesterol (+1% to +7%), apolipoprotein (apo) B (+21% to +29%) and low-density lipoprotein (LDL) cholesterol (+7% to +17%) increased slightly. High-density lipoprotein (HDL) cholesterol decreased slightly (-11% and -5%), HDL triglycerides increased (+16% and +26%). Apo AI did not change during the study, suggesting that the molar concentration of HDL particles did not change. Apo E (-23% to -14%) decreased, and there was a transitory decrease of lipoprotein (a). Essentially, there was no difference regarding the changes in lipoprotein metabolism between the two treatment groups. The effects of the two combinations of ethinylestradiol and levonorgestrel on triglyceride-rich lipoproteins appear less pronounced than those produced by preparations containing third-generation progestins. It is not likely that the changes in lipoprotein metabolism brought about by the two preparations will alter the risk of future cardiovascular disease in a clinically relevant fashion.     

The effects of seven monophasic oral contraceptive regimens on hemostatic variables: conclusions from a large randomized multicenter study

We investigated the effects of ethinylestradiol dose (50, 30 and 20 μg) and progestogen type [desogestrel (DSG), gestodene (GSD), levonorgestrel (LNG) and norgestimate (NGM)] in oral contraceptives on 24 hemostatic variables. In a multicenter, randomized, comparative study, 707 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested. Significantly greater increases in prothrombin fragment 1+2 and factor VII (activity and antigen), were found in the DSG, NGM and GSD groups compared to the LNG group. Similarly, significantly lower levels of protein S (free and total) and increased APC-sr (endogenous thrombin potential based) were found in the same groups compared with the LNG group. In addition, the estradiol dose (50 vs. 30 μg) significantly influenced these parameters. All changes were within the normal range and have not been associated with an increased risk of venous thromboembolic event (VTE). However, raised levels of these variables are associated with prothrombotic states such as pregnancy. The significance of the haemostatic changes found in this study in relation to VTE risk remains to be determined, but results of this study probably cannot explain the differences in risk of VTE between OCs containing different progestogens.     

Effect of a new oral contraceptive with estradiol valerate/dienogest on carbohydrate metabolism

Background

Insulin resistance may be induced by both the estrogen and progestin component in hormonal contraception. When estrogen dose is reduced from 50 to 20 mcg, the extent of hyperinsulinemia decreases. Recently, the oral combination contraceptive (COC) containing estradiol valerate (E2V) in combination with dienogest (DNG) was developed in a new estrogen step-down, progesterone step-up dosing strategy (Qlaira, Bayer Healthcare Pharmaceuticals). This study was conducted to evaluate of the effect of a 3-month treatment with E2V/DNG on carbohydrate metabolism in women with polycystic ovarian syndrome (PCOS) and insulin resistance.

Study Design

Study consisted of subjects attending the gynecological clinic of Siena or Pisa, with PCOS and insulin resistance, and without contraindications for the use of COCs. PCOS females (n= 20) aged 18 to 33 years were treated with a contraceptive formulation containing E2V/DNG for 3 months. Before treatment and during the third month of therapy, body mass index (BMI) measurement and an oral glucose tolerance test (OGTT) were performed.

Results

Median values of insulin after treatment were lower than median values before treatment. In particular, the median value of insulin at T₀ was reduced by 54.6% (p<.001), and the mean difference between time 0 and 30 min was significantly reduced [42.96 (9.99) mU/mL vs 38.00 (15.10) mU/mL; p<.05]. Homeostasis model assessment of insulin resistance levels were significantly decreased following treatment. OGTT after treatment revealed median fasting glucose levels to be stable (p=.895) at T₀. At T₃₀, T₆₀, T₁₂₀ and T₁₈₀ min, glucose median values were moderately reduced in comparison to median values before treatment. No significant difference was observed between median BMI values before [26 (4.8) kg/m²] and after treatment [26 (3.7) kg/m²].

Conclusions

Median insulin levels at T₀ and the mean difference between time 0 and 30 of insulin following OGTT were significantly reduced than values before treatment with E2V/DNG for 3 months. Median BMI and glucose levels were not significantly modified. Natural estradiol and nonandrogenic progestogen in the Qlaira formulation could be recommended as an oral contraceptive in women with PCOS who are insulin resistant or who are overweight.     

A double-blind comparative study of the effects of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 30 microg ethinyl estradiol and 75 microg gestodene on hemostatic variables, lipids, and carbohydrate metabolism.

In this double-blind study we compared the influence of two oral contraceptives, a 23-day regimen with 20 microg ethinyl estradiol and 75 microg gestodene (23-day 20/75) and a 21-day regimen with 30 microg ethinyl estradiol and 75 microg gestodene (21-day 30/75), on hemostatic variables, lipids, and carbohydrate metabolism. The volunteers received the preparations daily for six 28-day cycles. Hemostatic variables and lipids were measured at baseline and after six treatment cycles. Carbohydrate metabolism was assessed by determination of the area under the curve (AUC) of carbohydrate parameters after oral glucose tolerance tests performed at baseline and after three treatment cycles. Data from 33 volunteers in each group were obtained. No significant differences between the effects of both treatments on the hemostatic system were detected. Neither the overall change of all hemostatic variables from baseline to treatment Cycle 6 [defined as primary target variable in the study] nor the change of any of the individual hemostatic parameters differed significantly between the treatment groups. Likewise, no significant nor clinically relevant differences in the effects of both treatments on the volunteers' lipid profiles were detected. The data on carbohydrate variables suggested a slightly more favorable influence of the 23-day 20/75 regimen. The increase of the glucose AUCs after three cycles tended to be stronger with the 21-day 30/75 regimen than with the 23-day 20/75 regimen. In addition, the AUCs for insulin and C-peptide were slightly reduced after three cycles with the 23-day 20/75 regimen but slightly increased with the 21-day 30/75 regimen. Both study treatments were safe and well tolerated by the volunteers as shown by the nature and frequency of adverse events, the routine laboratory examinations, and the physical and gynecological examinations. Both preparations provided adequate contraceptive reliability. The only pregnancy during treatment was attributable to intake errors. In conclusion, the prolongation of the treatment phase of an oral contraceptives with 20 microg ethinyl estradiol does not evoke more pronounced metabolic effects than a conventional 21-day regimen with 30 microg ethinyl estradiol.     

Effects of oral contraceptive steroids on enzymes of carbohydrate metabolism in extracts of human endometrium

Both the combined steroid contraceptive pill and the individual components influenced the activities of several enzymes of carbohydrate metabolism in extracts of human endometrium. Lactate dehydrogenase, for instance, was strongly inhibited by the combined pill and by individual steroid components of the pills. The effects of the steroids on the activities of the various enzymes were more pronounced in secretory-phase endometrium.The results suggest that oral contraceptive steroids may have a direct effect on carbohydrate metabolism in human endometrium.     

Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen.

The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.     

Prospective, open-label, noncomparative study to assess cycle control, safety and acceptability of a new oral contraceptive containing gestodene 60 microg and ethinylestradiol 15 microg (Minesse)

OBJECTIVE: A prospective, open-label, noncomparative, multicenter study was carried out in 163 women aged 18-39 (mean 25+/-5 years), who used an ultra-low-dose oral contraceptive pill (OCP) containing gestodene (GTD) 60 mug/ethinylestradiol (EE) 15 mug for 6 months. The objective of the study was to evaluate the acceptability, safety, bleeding patterns and premenstrual symptomatology in these women. METHODS: Patients used the OCP from Days 1-24, followed by a 4-day pill-free interval from Days 25-28 of the menstrual cycle. Physical and gynecological examinations were carried out at baseline and after 3 and 6 months, at which time blood pressure, weight, hemoglobin, hematocrit, SGOT, SGPT and urinalysis were also assessed. The Moos Menstrual Distress Questionnaire (MDQ) was completed on three consecutive days (Days 25-27 of the cycle) at baseline and at the end of the third and sixth cycles. Patients kept a menstrual diary throughout the study. RESULTS: A total of 146 women completed the study. Ten women discontinued because of adverse events and one undesired pregnancy occurred during treatment. No adverse metabolic effects were observed. The adverse event most frequently reported was breakthrough bleeding, which diminished, however, as the time of OC use increased. Cycle length and duration of bleeding decreased significantly with OC use (p<.01 and p<.05, respectively, after 6 months). Intensity of menstrual bleeding tended to decrease with OC use, but this difference was not statistically significant. Systolic and diastolic blood pressure were significantly lower after 6 months of OC use compared to baseline (p<.02). No alterations were recorded in body weight or laboratory evaluations. Statistically significant changes were found both in the total MDQ score and in several of the factors evaluated, and patients showed a statistically significant improvement in well-being with respect to premenstrual complaints and symptoms. CONCLUSION: This OC regimen is safe, well-accepted and well-tolerated, affects menstrual patterns beneficially by reducing both the intensity and duration of bleeding, provides good cycle control and improves premenstrual symptomatology.     

Effects of an oral contraceptive containing estetrol and drospirenone on ovarian function

ObjectiveTo evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function.Study designSingle-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of ovulation after treatment cessation, and safety throughout the study.ResultsNone of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated.ConclusionsE4 15 mg/DRSP 3 mg results in adequate ovulation inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP.Implications statementTreatment with E4 15 mg/DRSP 3 mg showed complete ovulation inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP.     

Vitamin metabolism and the effects of multivitamin supplementation in oral contraceptive users

The effect of combined oral contraceptives containing 158 micrograms of levonorgestrel and 38 micrograms of ethinyl estradiol on vitamin B-1, B-2, B-6, B-12, folates, vitamin A, carotenoids, vitamin E and tryptophan load test was studied in a group of 34 healthy non-lactating women. This was compared to an identical study conducted in another group of 19 subjects who used IUCDs for contraception, and also in two other groups of subjects who were given an additional multivitamin preparation on a daily basis (33 subjects) and on the days when OC was not taken (29 subjects). Assessments were made prior to, and during the third week of the 4th, 7th and the 13th cycles of OC treatment. Urinary xanthurenic acid excretion (XA), plasma vitamin A and the folate content of the sera and red blood cells were significantly increased by OC treatment, although this excessive XA excretion was adequately corrected with 18 mg of daily vitamin B-6 supplementation. The metabolism of the rest of the vitamins was not significantly altered by OC usage. This suggests that a routine use of multivitamin supplement may not be necessary.     

Long-term use of an injectable contraceptive: effect of depot-norethisterone oenanthate on carbohydrate metabolism

In order to determine the metabolic effects of long-term use of the injectable contraceptive norethisterone oenanthate, plasma glucose and serum insulin concentrations were studied in two groups of women who had used the method continuously for at least five years. Group 1 comprised 24 subjects, from whom only fasting blood samples were taken. Despite similar plasma glucose concentrations to those of the controls, the subjects had significantly increased serum insulin concentrations (164.5 (39.9) v 120.3 (34.3) pmol/l, p less than 0.01). In addition the insulin:glucose ratios were also significantly increased (34.3 (8.5) v 24.6 (6.7), p less than 0.01), consistent with decreased insulin sensitivity. Group 2 comprised 13 of the original 24 subjects who also had an oral glucose tolerance test. Basal plasma glucose concentrations were similar in the subjects and their controls, whilst the significantly increased insulin:glucose ratios (35.0 (7.7) v 28.7 (5.6), p less than 0.05) were consistent with the results of the larger group. Following oral glucose challenge, plasma glucose concentrations, serum insulin concentrations and insulin:glucose ratios were similar in the subjects and their controls throughout the test. Thus, long-term use of norethisterone oenanthate injections is associated with a decrease in peripheral insulin sensitivity. However, these changes are not associated with any evidence of oral glucose intolerance.