Gestodene Group Research Articles

A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels

ObjectiveTo assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DesignProspective, double-blind, double-dummy, placebo-controlled study. SettingOutpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. Patient(s)One hundred fifty-two healthy hysterectomized postmenopausal women. Intervention(s)Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17β-E2, 50 μg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 μg (n = 33), followed by four cycles of placebo in each group. Main outcome measure(s)Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. Result(s)Mean (±SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 ± 2.5 μmol/L vs. 8.2 ± 2.0 μmol/L; mean change, −7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 ± 1.6 μmol/L vs. 8.6 ± 2.0 μmol/L; mean change, −4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. Conclusion(s)Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

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.

Genetic polymorphisms modify the response of factor VII to oral contraceptive use: an example of gene–environment interaction

Elevated plasma levels of factor VII and fibrinogen are risk factors for cardiovascular disease, especially arterial thrombosis. Oral contraceptive use increases factor VII and fibrinogen plasma levels. It has been described that DNA polymorphisms are associated with the plasma levels of hemostatic variables and their regulation. The R/Q353 polymorphism in the factor VII gene and the −455G/A polymorphism in the fibrinogen β-gene are associated with plasma levels of factor VII and fibrinogen, respectively. We analysed data of a randomised study ( n=95) in which two types of oral contraceptives were compared with regard to their effect on factor VII and fibrinogen, in which we also determined R/Q353 and −455G/A polymorphisms. Women were allocated randomly to either receiving a monophasic oral contraceptive containing 75 μg of gestodene and 20 μg of ethinyl estradiol, or 150 μg of desogestrel and 20 μg of ethinyl estradiol. Blood was taken before treatment and after 3 and 6 months of oral contraceptive use. Factor VII and fibrinogen increased significantly after 3 and 6 months of oral contraceptive use; the increase in factor VII was higher in the desogestrel group than in the gestodene group at 3 and 6 months. For fibrinogen, there were no intergroup differences at 3 and 6 months. At baseline, an association between genotype and plasma factor VII and fibrinogen levels was observed. In multivariate analysis, the R/Q353 polymorphism and the type of oral contraceptive were determinants of the effect on the change in factor VII, with the highest increase in women carrying the Q allele and using the desogestrel-containing oral contraceptive, and the lowest increase in women with the RR genotype who use the gestodene-containing oral contraceptive. For fibrinogen, no interaction among type of oral contraceptive, −455G/A polymorphism, and change in plasma levels was observed. We conclude that an individual's genetic variation may contribute to the response of plasma factor VII to oral contraceptive use.

Latin American experience with two low–dose oral contraceptives containing 30 μg ethinylestradiol/75 μg gestodene and 20 μg ethinylestradiol/150 μg desogestrel

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 μg ethinylestradiol and 150 μg desogestrel with a preparation containing 30 μg ethinylestradiol combined with 75 μg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilian group (95% confidence limit, ± 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, ± 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study

This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 μg of ethinyl estradiol combined with either 75 μg of gestodene (EE/GSD) or 150 μg of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.

A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 μg ethinylestradiol and either 150 μg desogestrel or 75 μg gestodene

Objective To compare the cycle control and tolerability of two oral contraceptives containing 20 μg ethinylestradiol and either 150 μg desogestrel or 75 μg gestodene.Methods A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles.Results No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0–2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly.Conclusion Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.

A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 μg ethinylestradiol/75 μg gestodene and 30 μg ethinylestradiol/75 μg gestodene, with respect to efficacy, cycle control, and tolerance

The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 μg ethinylestradiol (EE2) and 75 μg gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 μg ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 μg EE2 oral contraceptive. For the 20 μg EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 μg EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 μg EE2) and 11.8% (30 μg EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 μg EE2) and 7.2% (30 μg EE2) of all cycles, and the break-through bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 μg EE2 + 75 μg GSD group, two in the 30 μg EE2 + 75 μg GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 μg EE2 + 75 μg GSD, and 7.2% for 30 μg EE2 + 75 μg GSD) and was in the lower range known for other oral contraceptives. Both preparations were well accepted by the volunteers. The data obtained demonstrate clinically acceptable cycle control, good tolerance, and a high standard of contraceptive reliability for both drugs. Prescription of the 20 μg EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible. In case of persistent cycle control problems, a switch to the 30 μg EE2 drug should be considered.

The effect of monophasic and triphasic oral contraceptives containing gestodene and desogestrel on body weight and composition

This study compared the effects on body weight and body composition of contraceptive preparations containing monophasic gestodene, triphasic gestodene and monophasic desogestrel. The randomized study was open-label and consisted of three parallel groups of 150 women over 13 cycles. This interim analysis involved a total of 227 women aged 18-34 years over six cycles. The study parameters determined were body weight, waist-to-hip girth ratio, skinfold thickness measurements and bioelec-trical impedance determinations. Body weight was constant throughout the study in all treatment groups and mean changes from baseline were statistically insignificant between treatment groups. Apart from a small but significant decrease of 0.012 (95% CI 0.001-0.024) in waist-to-hip girth ratio in the monophasic gestodene group and a slight increase of 2.0 mm (95% CI 0.9-3.2) in right triceps skinfold thickness in the triphasic gestodene group, only minor changes from baseline were recorded. From these interim data, there was no evidence that the use of any of the low-dose preparations was associated with significant clinical changes in body composition parameters.

A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 μg ethinylestradiol/75 μg gestodene and 20 μg ethinylestradiol/150 μg desogestrel, with respect to efficacy, cycle control and tolerance

The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 μg ethinylestradiol and 75 μg gestodene, with a reference preparation containing the same dose of estrogen combined with 150 μg desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p = 0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparations are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

Clinical comparison of monophasic oral contraceptive preparations of gestodene/ ethinyl estradiol and desogestrel/ethinyl estradiol

The efficacy, cycle control, subjective complaints, and safety of monophasic preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV clinical study in Latin America. Of a total of 176 women in each group, 163 in the gestodene group and 160 in the desogestrel group completed 6 cycles, providing data for 1,015 and 1,006 cycles, respectively. Subject compliance was excellent; pills were missed during only 6.9% of the cycles in each group. No woman became pregnant during the study. Gestodene group exhibited significantly better cycle control as evidenced by the lower incidence of breakthrough bleeding and spotting. Spotting in some cycles was reported by 11.9% of women taking the gestodene-combination compared with 21 % of women taking the desogestrel-combination. Based on number of women, 86.4% of the gestodene group reported all cycles were normal (no BTB) compared with 76.7% of the desogestrel group. Also, the women in the gestodene group reported a significantly lower incidence of nuisance side effects during treatment cycles. No amenorrhea was observed for either group. There were no clinically significant differences between groups with respect to body weight, blood pressure, or laboratory evaluations. Seven women withdrew from the gestodene group and 8 women withdrew from the desogestrel group because of adverse reactions. The results of this study indicate that, although both OCs provided effective contraception, in comparison to the desogestrel-combination, the gestodene-containing OC is associated with better cycle control, less bleeding, and fewer subjective complaints.

Metabolic changes during treatment with two different progestogens

Two triphasic oral contraceptives containing the same amount of ethinyl estradiol in combination with gestodene or levonorgestrel were compared with respect to contraceptive effect, cycle control, and effects on lipid metabolism and coagulation. Serum concentrations of gestodene, levonorgestrel, ovarian and pituitary hormones, and sex hormone-binding globulin were measured. Thirty-three healthy women were randomized into two groups receiving either of the preparations. Before treatment and in the third and sixth cycles, blood sample were drawn in the morning while subjects were still in bed to obtain basal conditions. The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects. Sex hormone-binding globulin was elevated twofold in the levonorgestrel group and threefold in the gestodene group. The gestodene concentration in serum varied more than the levonorgestrel concentration, but with correction for variations in sex hormone-binding globulin binding, less variability in gestodene and levonorgestrel concentrations were seen. High-density Iipoprotein2 cholesterol decreased in the levonorgestrel group but was unchanged in the gestodene group, whereas apolipoprotein A, increased in the gestodene group but not in the levonorgestrel group. Antithrombin III decreased in the gestodene group but was unchanged in levonorgestrel-treated women. Factor VII increased in both groups but more in the gestodene group. We conclude that gestodene has a positive influence on lipid metabolism, probably because of its lower androgenicity, and a slightly negative influence on coagultion. The latter, however, probably has no clinical relevance. (AM J OasTET GVNECOL 1990;163:374-7.) During the past 25 years, oral contraceptives (OCs) have been improved continuously with respect to de­ creasing the dose of total steroid content and the in­ troduction of new progestogens in an attempt to min­ imize adverse effects and provide contraception safety. Several epidemiologic studies l

Metabolic changes during treatment with two different progestogens

Two triphasic oral contraceptives containing the same amount of ethinyl estradiol in combination with gestodene or levonorgestrel were compared with respect to contraceptive effect, cycle control, and effects on lipid metabolism and coagulation. Serum concentrations of gestodene, levonorgestrel, ovarian and pituitary hormones, and sex hormone-binding globulin were measured. Thirty-three healthy women were randomized into two groups receiving either of the preparations. Before treatment and in the third and sixth cycles, blood sample were drawn in the morning while subjects were still in bed to obtain basal conditions. The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects. Sex hormone-binding globulin was elevated twofold in the levonorgestrel group and threefold in the gestodene group. The gestodene concentration in serum varied more than the levonorgestrel concentration, but with correction for variations in sex hormone-binding globulin binding, less variability in gestodene and levonorgestrel concentrations were seen. High-density lipoprotein, cholesterol decreased in the levonorgestrel group but was unchanged in the gestodene group, whereas apolipoprotein A, increased in the gestodene group but not in the levonorgestrel group. Antithrombin III decreased in the gestodene group but was unchanged in levonorgestrel-treated women. Factor VII increased in both groups but more in the gestodene group. We conclude that gestodene has a positive influence on lipid metabolism, probably because of its lower androgenicity, and a slightly negative influence on coagultion. The latter, however, probably has no clinical relevance. (Am J Obstet Gynecol 1990;163:374-377.)

Clinical and hormonal effects of two contraceptives: Correlation to serum concentrations of levonorgestrel and gestodene

Two triphasic oral contraceptives containing gestodene (GES) (a new progestogen) and levonorgestrel (LNG) were compared with respect to contraceptive effect, cycle control, acceptability and side effects. The serum concentrations of ingested hormones were measured together with ovarian, pituitary, and some adrenal hormones, as well as sex hormone binding globulin (SHBG).The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects.SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group. The GES concentration in serum varied more than the LNG concentration, but with correction for variations in SHBG binding, less variability in actual GES and LNG concentrations was seen. Serum levels of FSH, LH, estradiol and progesterone were all depressed with both preparations. The depression was more marked in the GES group, despite lower progestogen ingestion and similar serum concentrations. Equal decreases were found in testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) with both preparations.

Lipid metabolism and coagulation of two contraceptives: Correlation to serum concentrations of levonorgestrel and gestodene

The effects of two triphasic oral contraceptives containing the same amount of ethinylestradiol (EE) in combination with levonorgestrel (LNG) or gestodene (GES), respectively, on lipid metabolism and coagulation were studied. Serum concentrations of GES and LNG were determined at the same time. Thirty-three healthy women were randomized into two groups receiving either of the preparations. Before treatment and in the 3rd and the 6th cycle, blood samples were drawn in the morning while subjects were still in bed to obtain basal conditions. HDL 2-cholesterol decreased in the LNG group but was unchanged in the GES group, whereas apolipoprotein Al increased in the GES but not in the LNG group. Antithrombin III decreased in the GES group but was unchanged in the LNG- treated women. Factor VII increased in both groups, but more in the GES group. It is concluded that GES has a positive influence on lipid metabolism, and has a slightly negative influence on coagulation but the latter is more likely to be without clinical relevance. The positive influence of GES compared to LNG on lipids is probably due to its lower androgenicity and not to differences in bioavailability.

Effects Of Two Triphasic Oral Contraceptives Containing Ethinylestradiol Plus Levonorgestrel Or Gestodene On Blood Coagulation And Fibrinolysis

The hemostatic effects of a new triphasic oral contraceptive combination containing ethinylestradiol and the new progestogen gestodene were compared with those of a triphasic combination of ethinylestradiol and levonorgestrel. A total of 19 women who did not use any kind of hormonal contraception 3 months prior to the study were recorded. The following parameters were measured: whole blood clotting time (WBCT), whole blood clot lysis time, fibrinogen, antithrombin III, factors V, VII and VIII. Blood samples were taken before treatment and in cycles 1, 3 and 6. A significant shortening of WBCT was observed in cycle 3 and 6 in both groups and also in cycle 1 in the gestodene group. This may indicate an increased sensitivity for activation of platelets, since the assay appears to be quite sensitive to this process. In the other parameters tested there were no significant changes except for a slight increase in plasma fibrinogen in cycle 1 in the gestodene group.