RESUMEN
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.
Asunto(s)
Anticonceptivos Orales Combinados/farmacología , Anticonceptivos Hormonales Orales/farmacología , Lípidos/sangre , Adolescente , Adulto , Arteriosclerosis/epidemiología , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Hormonales Orales/administración & dosificación , Desogestrel , Relación Dosis-Respuesta a Droga , Etinilestradiol/farmacología , Femenino , Humanos , Norpregnenos/farmacología , Congéneres de la Progesterona/farmacología , Valores de Referencia , Factores de Riesgo , Factores de TiempoRESUMEN
The effect of two oral contraceptives containing 30 micrograms ethinylestradiol + 75 micrograms gestodene (EE/GSD) or 30 micrograms ethinylestradiol + 150 micrograms desogestrel (EE/DG) upon serum lipids and lipoproteins were measured in 11 women each on days 1, 10, and 21 of the first, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle. There was no change in total cholesterol (CH) and phospholipids (PL), while total triglycerides (TG) were significantly elevated only during treatment with EE/GSD. After 3 and 6 months of intake of both oral contraceptives, a transitory increase in the TG content of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), and a decrease in LDL-PL was observed. After 12 months, VLDL-CH, VLDL-PL, and apolipoprotein B were significantly elevated, while VLDL-TG and all components of LDL were unchanged. Most of the components of high-density lipoprotein (HDL) were increased due to a rise in HDL3 and apolipoprotein A-II, while HDL2 and apolipoprotein A-I 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 time-dependent change in the effects of the oral contraceptives on various parameters of lipid metabolism demonstrates that the relevance of results of short-time studies may be questionable. There was also a significant alteration in some parameters between day 1 and 10 of the treatment cycles and a tendency to return to the pretreatment levels during the pill-free week, e.g., in total TG and in the PL component of VLDL, LDL and HDL. The increase in HDL, VLDL, and total TG reflects a slight preponderance of the effect of ethinylestradiol on lipid metabolism. The unchanged total CH and LDL-CH and the elevated HDL levels indicate that the risk of the development of atherosclerosis is in all probability not increased during treatment with both preparations.
Asunto(s)
Anticonceptivos Orales Combinados/farmacología , Anticonceptivos Sintéticos Orales/farmacología , Metabolismo de los Lípidos , Adolescente , Adulto , Colesterol/sangre , Desogestrel , Etinilestradiol/farmacología , Femenino , Humanos , Norpregnenos/farmacología , Fosfolípidos/sangre , Triglicéridos/sangreRESUMEN
The effect of two oral contraceptives containing 30 micrograms ethinylestradiol + 75 micrograms gestodene or 30 micrograms ethinylestradiol + 150 micrograms desogestrel upon various hormonal parameters were measured in 11 women each on days 1, 10, and 21 of the first, second, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle. There was no significant difference in the clinical effects or in the influence on the serum hormone parameters between both formulations. A significant decrease in the serum concentrations of luteinizing hormone and follicle stimulating hormone was observed during each cycle which was dependent on the duration of intake. Contrary to this, prolactin was not significantly altered, but 6 out of the 22 women showed episodically elevated prolactin levels. Serum estradiol and progesterone were profoundly suppressed, except one woman who ovulated during the twelfth cycle probably due to a therapy with metamizol, trimethoprim and sulfamethoxazole. The concentrations of dehydroepiandrosterone-sulphate were significantly and time-dependently reduced by 20 to 25% during each treatment cycle. There was also a significant decrease in the serum levels of testosterone by 20 to 30% and of free testosterone by 40 to 60%, while sex hormone-binding globulin increased by 250 to 300%. It could be observed that during the pill-free interval of 7 days the pituitary and ovarian function recovered, while the sex hormone-binding globulin levels remained elevated by 100%.
Asunto(s)
Anticonceptivos Orales Combinados/farmacología , Etinilestradiol/farmacología , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Norpregnenos/farmacología , Prolactina/sangre , Adolescente , Adulto , Desogestrel , Femenino , Humanos , Factores de TiempoRESUMEN
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.
Asunto(s)
Etinilestradiol/farmacología , Norpregnenos/sangre , Globulina de Unión a Hormona Sexual/análisis , Adolescente , Adulto , Femenino , Humanos , Norpregnenos/farmacocinética , Factores de TiempoRESUMEN
The serum concentrations of 3-keto-desogestrel (KDG) have been determined radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel during the first 4 hours and 24 hours after intake. On the first day of each cycle the KDG levels were low, but increased thereafter until Day 21. Highest serum concentrations were measured on Day 21 of the 3rd and 6th cycle with peak levels between 1.5 and 6.2 ng/ml. Contrary to this, the KDG levels were significantly reduced during the 12th treatment cycle. The serum concentrations of SHBG rose significantly between Day 1 and Day 21 of each cycle reaching values which were 3-fold of those at the beginning of treatment. During the pill-free intervals, SHBG levels decreased but remained elevated as compared to controls. There was a significant correlation between the SHBG levels and the area under the KDG-concentration-versus-time curves (AUC) indicating a pronounced influence of the serum steroid-binding protein upon the pharmacokinetics of KDG. There were great interindividual differences in the KDG levels. The serum levels of the individual woman remain, however, in a relatively constant range throughout the treatment period of 12 months, possibly due to genetic factors.
Asunto(s)
Etinilestradiol/farmacocinética , Norpregnenos/sangre , Norpregnenos/farmacocinética , Globulina de Unión a Hormona Sexual/análisis , Adulto , Desogestrel , Femenino , Humanos , Ciclo Menstrual/efectos de los fármacos , Factores de TiempoRESUMEN
In a randomised study on 20 healthy female subjects we compared the effect of two low-dosage antiovulants containing gestodene or desogestrel on ovarial and adrenal function and on fatty metabolism. Both antiovulants produced a moderate inhibition of gonadotropin secretion and a marked suppression of serum levels of oestradiol, testosterone and free testosterone; there was a strong increase in sex hormone-binding globulin, and an increase in cortisol--probably due to the increase on corticosteroid-binding globulin--and a continuous drop in dehydroepiandrosterone S. In all cases there was no significant difference between the effect of both preparations. Whereas there was no change in total and LDL cholesterol, total phospholipids and VLDL triglycerides, there was a significant increase in the concentrations of apolipoprotein B, total triglycerides, the cholesterol and phospholipid properties of VLDL as well as of all components of HDL. The LDL triglycerides were also elevated, whereas the LDL phospholipids dropped. On the whole the changes in lipid metabolism, which indicate a certain predominance of the oestrogen effect, were low. However, it became that the duration of intake exercises considerable influence.