gestodene and Arteriosclerosis

To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17beta-oestradiol (E(2)) 50 micro g (tE(2) group, n = 33), or oral E(2) 1 mg (oE(2) group, n = 37), or oral E(2) 1 mg combined with gestodene 25 micro g (oE(2) + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE(2) group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P <0.001). In cycle 17, significantly lower values were observed in the oE(2) group compared to cycle 13 and to the placebo group (-49%, P <0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E(2) significantly increased CRP levels. This change was larger than the increase found during oral E(2) + G. Transdermal E(2) did not affect CRP levels.

Topics: Administration, Cutaneous; Administration, Oral; Arteriosclerosis; Biomarkers; C-Reactive Protein; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Female; Humans; Middle Aged; Norpregnenes; Placebos; Postmenopause

In a prospective open-label multicenter trial, safety, tolerance, cycle control and changes in lipid metabolism before and during intake of a low-dose hormonal contraceptive (gestodene 75 mcg + ethinylestradiol 30 mcg) have been investigated under normal conditions of a general or gynecology practice (232 testing physicians, 1321 women). The atherogenic index remained almost unchanged over six cycles observed (3.3 before drug intake vs. 3.28 after drug intake, cycle 6). HDL cholesterol levels increased significantly in the period between prestudy and cycle 6 (+4.4%, p < 0.0001). A very good cycle control was demonstrated, and reliable contraception was achieved, combined with excellent general tolerance. The preparation conclusively suits very well for oral hormonal contraception.

Topics: Adult; Arteriosclerosis; Blood Pressure; Body Weight; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Humans; Lipids; Norpregnenes; Progesterone Congeners; Prospective Studies

To evaluate the lipid and lipoprotein changes induced by a triphasic oral contraceptive (OC) containing ethinyl estradiol and gestodene, 25 healthy women from the Baltimore metropolitan area were enrolled in an open-label, noncomparative study. Serum lipids were measured prior to starting the OCs and again during the 3rd, 6th and 12th treatment cycles. Mean lipid concentrations in each treatment cycle were compared to baseline levels using the t test for paired samples. Small but statistically significant (P < or = .05) increases in the mean concentrations of total cholesterol, total triglycerides, total high density lipoprotein (HDL) cholesterol, HDL3 cholesterol, apolipoprotein A1 and apolipoprotein B were noted. Although the increases were statistically significant, the mean lipid concentrations were still within the normal range. The mean HDL2 and low density lipoprotein cholesterol concentrations were unchanged, as was the mean total cholesterol/HDL ratio. Healthy women taking a triphasic OC containing ethinyl estradiol and gestodene have minimal changes in lipids and should not be at increased risk of atherosclerosis due to OC-induced lipid alterations.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Humans; Longitudinal Studies; Norpregnenes; Risk Factors; Triglycerides

In a randomized comparative study, changes in lipoprotein metabolism during the use of two low-dose oral contraceptives with similar doses of ethinyl estradiol but with different progestogenically active compounds were evaluated for their effective estrogen/androgen balance. Sixty-eight healthy women who did not take hormonally active drugs or were pregnant the previous 3 months took either 75 micrograms of gestodene + 30 micrograms of ethinyl estradiol or 150 micrograms of desogestrel + 30 micrograms ethinyl estradiol during 12 cycles. During the first three cycles serum levels of the following parameters increased: triglycerides, cholesterol in high-density lipoprotein, and apolipoproteins A1, A2, and B. Additional increase was observed in apolipoprotein B only after three and six cycles. The induced changes were not significantly different in the two groups, and the levels generally remained within normal limits. The changes seen with both pills reflect a mild estrogenic dominance. On the basis of current knowledge, moderately altered lipoprotein metabolism is not expected to impose an extra risk of atherosclerosis.

Topics: Adult; Arteriosclerosis; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Ethinyl Estradiol; Female; Humans; Lipoproteins; Norpregnenes; Progesterone Congeners; Random Allocation; Reference Values; Risk Factors

Three oral contraceptive preparations were studied in 60 healthy women. This randomized, comparative, baseline controlled study was designed to investigate the effects of the preparations on plasma lipids and lipoproteins. The following formulations were studied: a monophasic preparation containing ethinylestradiol and desogestrel (M-DSG) and two triphasic formulations containing ethinylestradiol and gestodene or levonorgestrel respectively (T-GSD and T-LNG). These preparations were studied for six treatment cycles. Total cholesterol and apoprotein B did not change in any group. Low density lipoprotein (LDL) cholesterol was significantly decreased in the groups of women treated with M-DSG and T-GSD respectively. No changes were observed in the T-LNG group. With M-DSG, significant increases were observed in high-density lipoprotein (HDL) cholesterol and HDL3 cholesterol, whilst HDL2 cholesterol did not change. With both T-GSD and T-LNG, no changes were observed in HDL cholesterol, whilst a significant increase in HDL3 cholesterol together with a trend to decrease in HDL2 cholesterol were observed. Apolipoprotein AI increased with the following ranking M-DSG greater than T-GSD greater than T-LNG. The LDL/HDL cholesterol ratio significantly decreased with both M-DSG and T-GSD. In the T-LNG group there was no change in this ratio. Triglycerides increased to the same extent in all treatment groups. As far as concerns the risk of arterial diseases, these three oral contraceptive formulations mostly induced negligible and/or partly favorable changes in plasma lipids and lipoproteins; however, the lipoprotein pattern during M-DSG treatment resulted better than during T-GSD, and the latter turned out to be better than during T-LNG.. 3 oral contraceptive (OC) preparations were studied in 60 healthy women. This randomized, comparative, baseline controlled study was designed to investigate the effects of the preparations on plasma lipids and lipoproteins. The following formulations were studied: a monophasic preparation containing ethinyl estradiol and desogestrel (M-DSG) and 2 triphasic formulations containing ethinyl estradiol and gestodene or levonorgestrel respectively (T-GSD and T-LNG). These preparations were studied for 6 treatment cycles. Total cholesterol and apoprotein B did not change in any group. Low density lipoprotein (LDL) cholesterol was significantly decreased in the groups of women treated with M-DSG and T-GSD respectively. No changes were observed in the T-LNG group. With M-DSG, significant increases were observed in the high density lipoprotein (HDL) and HDL3 cholesterols, while HDL2 cholesterol did not change. With both T-GSD and T-LNG, no changes were observed in HDL3 cholesterol together with a trend to decrease in HDL2 cholesterol were observed. Apolipoprotein AI increased with the following ranking M-DSG T-GSD T-LNG. The LDL/HDL cholesterol ratio significantly decreased with both M-DSG and T-GSD. In the T-LNG group there was no change in this ratio. Triglycerides increased to the same extent in all treatment groups. As far as the risk of arterial diseases, these 3 OC formulations mostly induced negligible and/or partly favorable changes in plasma lipids and lipoproteins; however, the lipoprotein pattern during M-DSG treatment was better than during T-GSD, and the latter was better than during T-LNG.

Topics: Adolescent; Adult; Arteriosclerosis; Clinical Trials as Topic; Contraceptives, Oral; Contraceptives, Oral, Combined; Contraceptives, Oral, Sequential; Desogestrel; Dose-Response Relationship, Drug; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Lipids; Norgestrel; Norpregnenes; Prospective Studies; Random Allocation

Progestins in combination with estrogen are believed to have different effects on the cardiovascular system. The aim of this study was to investigate the influence of different oral contraceptive formulations on the development of experimental atherosclerosis and vascular reactivity.. A total of 160 sexually mature rabbits were ovariectomized and randomly assigned to equally large groups: (i) a cholesterol-rich diet (320 mg/day), either given alone (placebo), or together with (ii) ethinyl estradiol (EE 70 micro g/day, oral), (iii) desogestrel (DSG 525 micro g/day, oral), (iv) gestodene (GSD 262.5 micro g/day, oral), (v) levonorgestrel (LNG 525 micro g/day, oral), (vi) EE + DSG, (vii) EE + LNG, or (viii) EE + GSD. After 31 weeks of treatment, aortic accumulation of cholesterol and vascular vasoreactivity (in vitro) were determined.. Progestins alone did not reduce the accumulation of cholesterol. EE alone or in combination with a progestin reduced the accumulation of cholesterol relative to placebo (P < 0.0001). Isolated vessels from EE-treated animals relaxed significantly more to physiological concentrations of acetylcholine than did placebo (P < 0.001), whereas vessels treated with EE plus a progestin showed an intermediate response.. The progestins investigated can be combined with EE without attenuating the anti-atherogenic effect of EE.

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol; Contraceptives, Oral, Synthetic; Desogestrel; Drug Therapy, Combination; Estrogens; Ethinyl Estradiol; Female; Levonorgestrel; Norpregnenes; Progestins; Rabbits

The effect of sex steroids on lipid metabolism depends on the type and dose of the compounds, the route of administration, and the duration of treatment. Therefore the composition of an oral contraceptive determines the resultant effect on lipids and lipoproteins. During 12 months of treatment, the effects of two oral contraceptives containing 30 micrograms of ethinyl estradiol and 150 micrograms of desogestrel (EE/DG) or 75 micrograms of gestodene (EE/GSD) on 19 serum parameters of lipid metabolism were followed in 11 women each. There was no change in total cholesterol and phospholipids. Total triglyceride levels were significantly elevated only by EE/GSD. After 3 and 6 months of intake of both preparations, a transitory increase in the triglyceride content of very low-density lipoprotein and low-density lipoprotein and a decrease in low-density lipoprotein-phospholipids was observed. After 12 months, very low-density lipoprotein cholesterol, very low-density lipoprotein phospholipids, and apolipoprotein B were significantly elevated, whereas very low-density lipoprotein triglycerides and all components of low-density lipoprotein were unchanged. Most of the components of high-density lipoprotein (HDL) were increased as a result of a rise in HDL3 and apolipoprotein A2, whereas HDL2 and apolipoprotein A1 were not altered. There was no significant difference between the effects of the two preparations, although those of EE/GSD were mostly more pronounced. The increase in high-density lipoprotein, very low-density lipoprotein, and total triglycerides reflects a slight preponderance of the effect of the estrogen component. Because low-density lipoprotein cholesterol and total cholesterol were not changed, treatment with both formulations is in all probability not associated with an elevated risk of atherosclerosis.

Topics: Adolescent; Adult; Arteriosclerosis; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Dose-Response Relationship, Drug; Ethinyl Estradiol; Female; Humans; Lipids; Norpregnenes; Progesterone Congeners; Reference Values; Risk Factors; Time Factors