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At least 19 recordsLinked to original sources
PubMed1988

Alterations in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 75 micrograms gestodene.

The serum concentrations of gestodene have been measured radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with an oral contraceptive containing 30 micrograms ethinylestradiol and 75 micrograms gestodene during the first 4 hours and 24 hours after intake. During the 1st cycle the maximal gestodene levels increased from 2.1 to 6.2 ng/ml on Day 1 to values between 7.5 and 22.0 ng/ml on Day 21. During the 3rd and 6th treatment cycle the levels were still higher with maxima between 10.1 and 26.3 ng/ml, while during the 12th cycle the gestodene concentrations were slightly lower. The serum levels of SHBG rose significantly during intake of the pill up to values between 210 and 240 nmol/l on Day 21 of each cycle, and were reduced to a certain degree during the pill-free interval. The SHBG concentrations correlated closely with the area under the gestodene concentration-versus-time curves (AUC) indicating a pronounced influence of serum protein binding upon the pharmacokinetics of gestodene. The gestodene levels of the individual women remained relatively constant during the 12 treatment cycles, although great interindividual differences were found. It is concluded that the relatively high serum concentrations of gestodene are not only based on the binding to SHBG, but probably also on an impeded metabolism of gestodene.

Adolescent↗
PubMed1996

Investigation of the influence of two low-dose monophasic oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, on lipid metabolism in an open randomized trial.

An open comparison at a single center was performed in volunteers (n = 58) randomly allocated to two treatment groups, one receiving tablets containing 20 micrograms ethinylestradiol (EE) + 75 micrograms gestodene, and the other 30 micrograms EE + 75 micrograms gestodene. The study consisted of three treatment-free pre-cycles, followed by thirteen 28-day treatment cycles. Analysis of results revealed that there were no statistically significant differences between the two groups with regard to the plasma levels of HDL-cholesterol and its subfractions, LDL-cholesterol and apolipoproteins. There was, however, a trend toward a more favorable effect on HDL-cholesterol in the 20 micrograms EE group, where levels increased by 3% compared with the 30 micrograms EE group, where levels decreased by 9%. There was a statistically significant difference between the adjusted mean values of total triglycerides in the two groups in favor of the 20 micrograms EE group (+21%), compared with the 30 micrograms EE group (+64%) (p = 0.029). Two serious adverse events were reported (lymphadenopathy and vertigo), but neither were considered to be causally related to either study medication. The formulation containing 75 micrograms gestodene and 20 micrograms EE was shown to be a reliable and well tolerated oral contraceptive, with a favorable lipid profile.

Adolescent↗
PubMed1997

A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms 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 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms 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 micrograms 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 micrograms EE2) and 11.8% (30 micrograms 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 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms 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 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms 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 micrograms 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 micrograms EE2 drug should be considered.

Adult↗
PubMed1992

Pharmacokinetics of gestodene in 12 women who received a single oral dose of 0.075 mg gestodene and, after a wash-out phase, the same dose during one treatment cycle.

The pharmacokinetics of gestodene (GEST) was determined in 12 healthy women (age 22 to 34 years), following single dose administration of 0.075 mg GEST. The same preparation was also administered during one treatment cycle after a wash-out phase of 1 week. After single dose administration, maximum concentrations of GEST in the serum were 4.9 +/- 2.5 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.2 +/- 0.2 h and 14.9 +/- 6.7 h, respectively. The apparent clearance was calculated to be 0.8 +/- 0.4 ml x min-1 x kg-1. The free fraction of GEST was 1.3 +/- 0.3% and the fractions bound to SHBG and albumin were 64.3 +/- 10.7% and 34.4 +/- 10.4%, respectively. The results showed that there was a gradual decrease in serum trough levels of GEST during the cycle, due to a concomitant and equally high decrease in SHBG concentrations in the serum of about 26%. At the end of one treatment cycle, the free fraction of GEST increased to 1.8 +/- 0.5%, the SHBG-bound fraction decreased to 57.0 +/- 10.2% and the albumin-bound fraction increased to 41.3 +/- 9.9%. Total serum clearance increased during the same time period from a mean value of 0.8 to about 1.2 ml x min-1 x kg-1. The clearance of unbound GEST, however, remained unchanged. An examination of the free GEST concentrations revealed the same time course of GEST trough levels during the cycle as the simulated curve. This was derived from the pharmacokinetic parameters which were obtained after single dose administration. Thus, the present study showed that the pharmacokinetics of GEST can be fully explained on the basis of single dose pharmacokinetics and the changes in serum protein binding which were caused by a reduction of SHBG levels in the serum during chronic treatment with GEST. There was no evidence of GEST inhibiting its own metabolism.

Administration, Oral↗
PubMed1993

Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.

The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively, which corresponds to an about 30% increase as compared to single dose administration, where an AUC(0-4h) value of 216.1 pg x ml-1 x h was found. Total and free testosterone concentrations decreased during treatment cycles one and three by about 36% and 60%, respectively, compared with the corresponding values measured prior to treatment. The fraction of unbound testosterone thus decreased from 0.5% to 0.3% during treatment.

Adolescent↗
PubMed1989

Gestodene: a novel synthetic progestin--characterization of binding to receptor and serum proteins.

Gestodene, 17 alpha-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one, is a new orally active progestational agent, which is available for clinical use in oral contraceptives. The aim of the present study is to make a broad characterization of gestodene at the receptor level and to discuss the results in comparison to those of established progestogens. Kinetic studies of 3H-gestodene uptake show a rapid increase in the amount of specific binding during the first three hours. After saturation, the amount of specifically bound 3H-gestodene remained almost constant up to 24 hours at 4 degrees C. The dissociation of 3H-gestodene from the cytoplasmic myometrial progestone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a biphasic or two-component first order dissociation curve. As anticipated, sucrose gradient centrifugation analysis of the 3H-gestodene-labeled cytosol of human myometrial tissue showed that the gestodene binding components sedimented in the 4S and 8S region. A 200-fold molar excess of nonradioactive gestodene reduced only the 8S binding of 3H-gestodene. 4S binding of 3H-gestodene was not reduced, which indicate the existence of a second high capacity binding component. In biological test systems, such as the Clauberg test or Kaufmann test, gestodene has proved to be a very effective progestogen. Among nortestosterone derivatives it is one of the most potent and resembles progesterone biologically in its progestogenic effects. This biologically identical gestagenic activity of gestodene and progesterone is reflected by a very similar behavior in vitro in terms of binding to progesterone receptors of human uterus cytosol. Furthermore, competitive studies indicated that gestodene like other synthetic progestagens also displays some affinity for androgen and glucocorticoid receptors but no measurable affinity for the estrogen receptor. Remarkable is the high binding affinity of gestodene to the binding sites of the mineralocorticoid receptor of rat kidney with a RBA value of 350% compared to aldosterone.

Animals↗
PubMed1994

Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene.

A cross-over study of two oral contraceptive formulations, containing 30 micrograms ethinylestradiol in combination with 150 micrograms desogestrel (Marvelon) or 75 micrograms gestodene (Femovan), has been performed to compare the serum distribution and pharmacokinetics of gestodene and the active metabolite of desogestrel, namely 3-ketodesogestrel. Serum concentrations of both sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) were also measured and were increased more than 3-fold and 2-fold, respectively, on day 21 of the treatment cycle, with no statistically significant difference between treatment groups. In addition, 35 days after ingestion of either oral contraceptive had ceased, the serum SHBG and CBG concentrations were similar to the pretreatment values. During treatment cycles, increased serum SHBG levels were associated with a redistribution of 3-ketodesogestrel and gestodene such that the non-protein-bound (NPB) and albumin-bound fractions were reduced in concert with an increase in the relative proportions bound to SHBG. The proportion of gestodene bound to SHBG was consistently higher than that observed for 3-ketodesogestrel, and this undoubtedly reflects the higher affinity of SHBG for gestodene (Kd = 1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel (Kd = 4.7 nM at 37 degrees C). It also probably accounts, in part, for the much higher total serum levels of gestodene (8.58 nmol/L) when compared to 3-ketodesogestrel (2.37 nmol/L) during the treatment cycles. Consequently, the absolute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are significantly higher than those measured for 3-ketodesogestrel. It is concluded that ethinylestradiol-induced increases in serum SHBG levels during treatment with Marvelon or Femovan, influenced the distribution and total amount of 3-ketodesogestrel and gestodene in serum, respectively, and that this, combined with the higher affinity of SHBG for gestodene, results in a greater amount of bioavailable gestodene compared to 3-ketodesogestrel, despite the smaller dose of gestodene administered.

Adult↗
PubMed1987

Pharmacological and endocrine profiles of gestodene.

Efforts to minimize oral contraceptive side effects have focused on the use of new dosage schemes and the synthesis of new steroids that can be used in safer, low-dose formulations. To determine whether the new progestogen gestodene offers an advantage in this regard, we studied its pharmacological and endocrine profiles. Gestodene was found to exhibit relative binding affinity and biological activity profiles similar to or better than those of progestogens in current use. Modulation by gestodene of luteinizing hormone-releasing hormone (LH-RH)-stimulated gonadotropin release in vitro and in vivo in a rat model system indicated that gestodene is some three times as biologically active as levonorgestrel. The borderline dose for inhibition of ovulation by gestodene was estimated in a total of 23 women with normal cycles. Levels of LH-RH, follicle-stimulating hormone, 17 beta-estradiol, and progesterone were estimated during the ingestion of various doses of gestodene. A dose of 30 micrograms of gestodene caused inhibition of ovulation in 11 out of 12 subjects, and eight out of 11 showed follicular maturation. When 40 micrograms of gestodene was taken, six out of seven women did not ovulate, and one out of seven had a cycle with luteal insufficiency. These data indicate that 40 micrograms of gestodene is the borderline dose for inhibition of ovulation. A combination of 75 micrograms gestodene with 30 micrograms ethinyl estradiol was found to inhibit ovulation in ten subjects, and no follicular maturation was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays.

Gestodene is a novel progestin used in oral contraceptives with an increased separation of progestogenic versus androgenic activity and a distinct antimineralocorticoid activity. This specific pharmacological profile of gestodene is defined by its pattern of binding affinities to a variety of steroid hormone receptors. In the present study the affinity of gestodene to the progesterone receptor (PR), the androgen receptor (AR), the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR) and the estrogen receptor (ER) was re-evaluated by steroid binding assays and compared to those obtained for 3-keto-desogestrel and progesterone. The two synthetic progestins displayed identical high affinity to rabbit PR and similar marked binding to rat AR and GR, while progesterone showed high affinity to PR but only low binding to AR and GR. Furthermore, 3-keto-desogestrel exhibited almost no binding to MR, whereas gestodene, similar to progesterone, showed marked affinity to this receptor. In addition to receptor binding studies, transactivation assays were carried out to investigate the effects of gestodene on AR-, GR- and MR-mediated induction of transcription. In contrast to progesterone, which showed antiandrogenic activity, gestodene and 3-keto-desogestrel both exhibited androgenic activity. Furthermore, all three progestins exhibited weak GR-mediated antagonistic activity. In contrast to progesterone, which showed almost no glucocorticoid activity, gestodene and 3-keto-desogestrel showed weak glucocorticoid action. In addition, gestodene inhibited the aldosterone-induced reporter gene transcription, similar to progesterone, whereas unlike progesterone, gestodene did not induce reporter gene transcription. 3-Keto-desogestrel showed neither antimineralocorticoid nor mineralocorticoid action.

Animals↗
PubMed1993

Pharmacokinetics and protein binding of 3-ketodesogestrel and gestodene in the serum of women during 6 cycles of treatment with two low dose oral contraceptives.

The serum concentrations of 3-ketodesogestrel (KDG) and gestodene have been measured in 30 and 31 women respectively who took low dose oral contraceptives containing 30 micrograms ethinylestradiol together with either 150 micrograms desogestrel or 75 micrograms gestodene for 6 months. On days 1, 10 and 21 of the first third and sixth treatment cycles blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4 and 24 h. KDG and gestodene levels were measured by radioimmunoassays and were evaluated for Cmax (peak serum concentration), tmax (time to Cmax), and AUC (area under the curve) to 4 and 24 h. The overall total gestodene concentrations were higher and the accumulation of the steroid throughout a cycle greater than that of KDG. For example, the AUC0-4 of gestodene increased in cycle 1 by a factor of 2.8 (day 10 vs. day 1) and 3.6 (day 21 vs. day 1) compared to 2.3 and 2.6 for KDG. The higher concentration of gestodene reflects a lower volume of distribution than KDG, and is consistent with gestodene binding to sex hormone binding globulin (SHBG) with a higher affinity than KDG. Concentrations of KDG and gestodene were higher on day 1 of cycles 3 and 6 than on day 1 of cycle 1. The serum concentrations of KDG and gestodene during multiple dosing cannot be predicted on the basis of single dose pharmacokinetics.

Adolescent↗
PubMed1995

Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations.

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1993

Inhibition of ovulation by a triphasic gestodene-containing oral contraceptive.

The minimal effective dose of gestodene for inhibition of ovulation was studied in 30 female volunteers. Daily doses of 10 micrograms to 50 micrograms gestodene were given orally for 21 days. A control cycle prior to treatment and a treatment cycle were monitored for LH, FSH, estradiol, progesterone and cervical score. At a daily dose of 40 micrograms of gestodene, 6/7 volunteers exhibited inhibition of ovulation and 1/7 had a cycle with luteal insufficiency. Ovulation was inhibited in all volunteers on 50 micrograms gestodene, suggesting that the minimum dose required to inhibit ovulation was 40 micrograms gestodene. Cervical score was blunted even at 10 micrograms gestodene. Similarly, 20 volunteers were treated with coated tablets containing ethinylestradiol/gestodene at 30/50 micrograms for 6 days, 40/70 micrograms for 5 days and 30/100 micrograms for 10 days. This triphasic gestodene-containing preparation inhibited ovulation in all 20 females. In one cycle in which follicle development was observed only 43 pg estradiol/ml was secreted. Data from this investigation suggest that this triphasic gestodene-containing OC has a high contraceptive efficacy.

Adult↗
PubMed1989

Development and application of a radioimmunoassay of the new progestagen gestodene.

A radioimmunoassay for the determination of gestodene (17-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one) in human plasma is described with regard to procedure, specificity, accuracy and reproducibility. Antiserum was raised against gestodene-3-O-(carboxymethyl)oxime-BSA in rabbits and [9,11-3H]-gestodene tracer was used with a specific radioactivity of 2.16 TBq/mmol. The final antiserum dilution was 1: 200,000. RIA was performed according to routine methods using diethylether plasma extracts and the charcoal separation technique. Cross-reactivity of antiserum with cortisol, 17 beta-estradiol, progesterone, testosterone and ethinylestradiol was less than 0.03%; levonorgestrel exhibited a 5% cross-reactivity. No cross-reactivity with metabolites of gestodene or ethinylestradiol was found. Accuracy and precision of the assay were tested using human plasma samples spiked with 1, 5 and 10 ng/ml gestodene. Accuracy was within 94 to 104% of the nominal values. Within-assay and between-assay coefficients of variation were in the range of 4.7-6.5% and 10.3-13.1%, resp. This RIA was used to follow plasma gestodene levels after single oral administration of 75 micrograms of gestodene combined with 30 micrograms ethinylestradiol as tablet and coated tablet in a cross-over design in 6 female test subjects. Plasma gestodene levels were equivalent after both treatments.

Analysis of Variance↗
PubMed1991

The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel.

Single doses of ethynylestradiol (30 micrograms) were given alone and in combination with either gestodene (75 micrograms) or desogestrel (150 micrograms) to 10 healthy female volunteers. The doses of steroids were given both orally and by i.v. infusion over 5-7 minutes. Blood samples were taken at regular intervals over 24 hours. The area under the plasma concentration versus time curve (AUC) for oral EE2 alone was 867 +/- 338 pg/ml x h, for oral EE2 in the presence of gestodene it was 795 +/- 206 pg/ml x h and for oral EE2 in the presence of desogestrel it was 614 +/- 132 pg/ml x h. With either gestodene or desogestrel present, the AUC of EE2 was not significantly different from that found when EE2 was given alone. In addition, there was no significant difference between EE2 + gestodene and EE2 + desogestrel. Comparing the relative oral and iv doses, the bioavailability of EE2 (alone) was 59.0 +/- 13% (n = 6), for EE2 plus gestodene it was 62.1 +/- 10% and for EE2 in the presence of desogestrel it was 62.1 +/- 4.4%. The clearance of EE2 (alone) was 19.9 +/- 5.5 l/h and in the presence of gestodene it was 19.4 +/- 9.6 l/h. The clearance of EE2 in the presence of desogestrel appeared slightly greater at 27.7 +/- 8.9 l/h but none of these clearance values were significantly different from each other. The urinary excretion of 6-beta-hydroxy cortisol was similar after all 6 doses of EE2. These data strongly suggest that following single dose administration, neither gestodene nor desogestrel have any inhibitory effect on the metabolism of EE2 or alter its kinetics to any clinically significant extent.

Administration, Oral↗
PubMed1987

Blood coagulation with a combination pill containing gestodene and ethinyl estradiol.

The coagulation effects of oral contraceptives are determined by the interaction of the estrogen and the progestogen components. Serial studies on the coagulation system were carried out in 120 randomly allocated healthy women to compare the effects of (1) triphasic gestodene/ethinyl estradiol and triphasic levonorgestrel/ethinyl estradiol and (2) monophasic gestodene/ethinyl estradiol and monophasic desogestrel/ethinyl estradiol. The triphasic study showed significant increases in factor VII, factor X, fibrinogen, plasminogen, and fibrinolytic activity. No significant differences were noted between levonorgestrel and gestodene except for factor VII, which was higher with gestodene. Antithrombin III and anti-Xa were unchanged, and platelet aggregation was slightly accelerated with gestodene. The monophasic study is still in progress: Significant increases of factor VII, factor X, plasminogen, and fibrinolytic activity and no changes in antithrombin III, anti-Xa, and platelet aggregation have been found with both monophasic gestodene and desogestrel. The results of the triphasic study indicate that the effect of gestodene on the blood coagulation system is similar to that of levonorgestrel and that both formulations increase fibrinolytic activity. The increased coagulation activity would appear to be counteracted by enhanced fibrinolysis, so protecting the dynamic balance between coagulation and fibrinolysis. Further data are required in the monophasic gestodene and desogestrel study before any conclusions can be drawn.

Adolescent↗
PubMed1995

Metabolic profile of six oral contraceptives containing norgestimate, gestodene, and desogestrel.

The alterations in lipid metabolism that occur with the use of oral contraceptives (OCs) have aroused considerable concern that OCs might increase the risk of premature atherosclerosis. However, most studies examining the role of OCs in atherogenesis were performed using earlier-generation preparations employing larger doses of sex hormones than present formulation. Therefore, we undertook a comparative and standardized determination of the effects on lipid metabolism of six modern, low-dose OCs. This open, randomized, comparative study included patients recruited at 21 study centers throughout Europe. Four hundred sixty-six women, aged 18-38 years, participated. They were randomly assigned to the following OC formulations:(1) norgestimate 250 micrograms + ethinyl estradiol (EE) 35 micrograms (Cilest); (2) norgestimate 180/215/250 micrograms + EE 35 micrograms (Tricilest); (3) desogestrel 150 micrograms + EE 20 micrograms = (Marvelon); (4) desogestrel 150 micrograms + EE 30 micrograms (Mercilon); (5) gestodene 75 micrograms + EE 30 micrograms (Femovan); and (6) gestodene 50/70/100 micrograms + EE 30/40/30 micrograms (Trifemovan). There were three parallel studies with six parallel patient groups. Fasting blood samples were drawn at baseline (between days 24 and 28) and on days 18-22 of cycle 6, and cycle 12. Sample were analyzed for total cholesterol,high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein (apo)A1, and apoB at one central laboratory. Two hundred eighty-two women completed all 12 cycles and were included in the final evaluation. As expected, triglyceride and total cholesterol concentrations increased in all study groups but to lesser levels with the formulations containing gestodene. All OCs, except the monophasic gestodene preparation, slightly but significantly increased HDL. The HDL2 subfraction did ot change significantly except in the group using the monophasic gestodene preparation; in this group, the HDL2 subfraction slightly but significantly decreased. The LDL concentration increased slightly with the monophasic and triphasic norgestimate preparations and with desogestrel + 20 micrograms EE. The LDL/HDL ratio did not change significantly except with the use of the triphasic norgestimate preparation, in which case it decreased slightly. ApoA1 and apoB levels increased only slightly with all formulations. Importantly, while all of the OCs tested altered lipid levels to some extent, after 12 cycles there were no statistically significant differences in lipid effects among OC preparations. Modern, combined OCs that contain norgestimate, desogestrel, or gestodene all have some impact on lipid levels. However, it would appear likely that they do not contribute to atherogenesis in healthy women.

Adolescent↗
PubMed1990

Pharmacokinetics of gestodene and ethinyl estradiol after oral administration of a monophasic contraceptive.

The pharmacokinetic and protein-binding properties of gestodene and ethinyl estradiol have been investigated after single and multiple dosing in several studies in 83 healthy, young women. After oral administration, gestodene is completely absorbed and bioavailable and exhibits dose-linear pharmacokinetics. During long-term pill use, serum levels of gestodene were four to five times higher than after single administration, showing a periodic increase from day 1 to day 10 during each cycle. Ultrafiltration studies revealed that 75.3% of total serum gestodene is bound to sex hormone-binding globulin, 24.1% is bound to albumin, and only 0.6% is not protein bound. Thus gestodene levels during steady state are explained by an increase in sex hormone binding-globulin as a result of concomitant administered ethinyl estradiol and a specific binding of gestodene to this protein. Serum levels of ethinyl estradiol during single and multiple administration were identical and were not different from those observed with another preparation containing 30 micrograms of ethinyl estradiol.

Absorption↗
PubMed1995

A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms 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 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms 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 preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

Adolescent↗