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At least 19 recordsLinked to original sources
PubMed1984

Changes in relative fatty acid composition of serum lecithin and cholesterol ester after treatment with two gonane progestins administered alone and in combination with ethinyl estradiol.

Twenty women, oophorectomized as part of treatment for cervical carcinoma of the cervix participated in the study. Ten of them were given desogestrel (DG) 150 micrograms/day for 3 weeks followed by DG + 30 micrograms ethinyl estradiol (EE) for 6 weeks, and finally EE alone for 3 weeks. The other 10 women were given 150 micrograms levonorgestrel (NORG) and EE in a similar way. Before treatment and after each period of treatment the relative fatty acid composition of serum lecithin and serum cholesterol ester were assessed by gas-liquid chromatography. In both groups ethinyl estradiol, when administered alone, increased arachidonic acid in serum lecithin. This increase was not observed on the DG + EE or the NORG + EE combination indicating that both progestins counteracted this estrogenic effect.

Adult↗
PubMed1988

Changes in lipoprotein composition in women receiving two low-dose oral contraceptives containing ethinylestradiol and gonane progestins.

In a prospective double-blind study of the effects of two low-dose oral contraceptives (OCs) on lipid and lipoprotein metabolism, two groups of eighteen young healthy women selected at random were submitted to a six months' use of either monophasic ethinylestradiol (EE) + desogestrel (DG) or triphasic EE + levonorgestrel (LNG). Total cholesterol (C), triglycerides (TG), phospholipids (PL), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) together with apoproteins A-I, A-II, B and lecithin cholesterol acyltransferase activity (LCAT) were determined in serial plasma samples collected before, at three and six months during, and one month after OC use. Cholesterol and apoproteins (A-I, A-II, B) composition of lipoproteins (HDL-2, HDL-3, LDL) isolated by ultracentrifugation were additionally determined. On Mono-EE + DG, plasma TG (+39.3%, +45.6%), PL (+21.9%, +16.8%) and apo A-I (+35.5%, +23.3%) levels were significantly increased at 3 and 6 months of use; plasma HDL-C (+24%) and Apo A-II (+21.4%) were transiently increased at 3 months. Lipid and apoprotein composition of HDL-2, HDL-3 and LDL were unchanged. On Tri-EE + LNG, a slight but not significant decrease in HDL-C was observed throughout the study while other plasma lipids and apoproteins were unchanged. Ultracentrifugation revealed a lower content of C (-44.2%) and apo A-I (-44.6%) in HDL-2. LCAT activity expressed as molar esterification rate (MER) rose in a more sustained way during EE + DG use than during EE + LNG treatment. Covariance analysis shows a further significant difference between results of both treated groups for the Apo AI/Apo B ratio that was increased by Mono-EE + DG.

Adult↗
PubMed1985

The effects of two gonane progestins alone and in combination with ethinyl estradiol on serum lipoproteins.

Twenty women, oophorectomized as part of the treatment for cervical carcinoma in an early stage but otherwise healthy, participated in the study. Ten of them were given desogestrel (DG) 150 micrograms/day for 3 wk followed by DG + 30 micrograms ethinyl estradiol (EE) for 6 wk, and finally EE alone for 3 wk. The other ten women were given 150 micrograms levonorgestrel (NORG) and EE in a similar way. Before treatment and after each period, total and free cholesterol (TC, FC) triglycerides (TG) and phospholipids (PL) were assayed in serum and in the ultracentrifugally isolated lipoprotein fractions very low, low and high density lipoproteins (VLDL, LDL and HDL). The results indicate that both progestins induced the same 'androgenic' pattern when given alone, i.e. a decrease in serum- and HDL-TC and a decrease in VLDL-lipids. In combination with EE, however, DG seems to counteract the effects of EE to a lesser extent than NORG, as judged particularly from the effects on TG and PL in serum and VLDL.

Adult↗
PubMed1979

Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism.

Oral glucose-tolerance tests were performed and fasting serum cholesterol and triglyceride levels measured in 1628 Caucasian women taking combined oestrogen/progestagen oral contraceptives (o.c.) and 577 women not taking O.C. The former were divided into six groups according to the composition of the O.C Glucose tolerance deteriorated in all O.C. groups containing oestrane progestagens (nortestosterone-derived) or the gonane, norgestrel, but was unaltered by O.C. containing a pregnane progestagen (derived from progesterone). The greatest deterioration was with O.C. containing 75 microgram or more oestrogen, and this was associated with impairment of the early insulin response to glucose. In O.C. containing a pregnane progestagen insulin secretion was unaffected. In the remaining O.C. groups insulin secretion was increased; this was most pronounced with the O.C. containing a gonane progestagen. Serum-cholesterol was elevated only with O.C. containing 75 microgram or more oestrogen and an oestrane progestagen and tended to be lower in O.C. containing a gonane progestagen. O.C.-induced hypertriglyceridaemia was oestrogen-dose-related, and this effect was potentiated by the pregnane progestagen. The gonane progestagen antagonised oestrogen-induced hypertriglyceridaemia.

Adult↗
PubMed1990

Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level.

Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.

Blood Glucose↗
PubMed1990

Pharmacokinetics of oestrogens and progestogens.

There are large inter- and intra-individual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral ingestion of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the first liver passage. Oestradiol and oestrone are interconvertible, dependent on the local concentrations in liver and target organs, and oestrone sulphate serves as a large reservoir. The oestrone/oestradiol ratio has no physiological significance, as oestrone is only a weak oestrogen. Oestrone is both a precursor and a metabolite of oestradiol. Oestriol is extensively conjugated after oral administration. Therefore, the oestriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg oestriol resulting in similar systemic effectiveness. Conjugated oestrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinylestradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes, should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group.

Estrogens↗
PubMed1997

Comparison of dentinal crack incidence and of post removal time resulting from post removal by ultrasonic or mechanical force.

The purpose of this study was to compare the frequency of canal and intradentin cracks after intraradicular post removal using ultrasonic instrumentation or the Gonan post removal system. Sixty cadaver teeth were divided into 4 groups of 15 teeth each: group 1, ultrasonic removal; group 2, Gonan post removal system; group 3, cemented posts not removed; and group 4, no posts. Groups 1 and 2 were contralateral matched pairs. Para Posts were placed in groups 1, 2, and 3 to 7 mm apical to the cementoenamel junction and luted with ZnPO4 cement. The time required for post removal in groups 1 and 2 was recorded. The teeth were extracted, sectioned, and examined. Canal and intradentin cracks were mapped, and their frequency was recorded at each level. There were statistically more cracks present in the ultrasonic group than the no post group. There were no other differences that reached statistical significance. It took significantly longer for post removal using the ultrasonic tip versus the Gonan system.

Cadaver↗
PubMed2002

Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus.

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.

Adult↗
PubMed1990

Clinical aspects of the relationship between oral contraceptives, abnormalities in carbohydrate metabolism, and the development of cardiovascular disease.

Although large epidemiologic studies indicated no difference in the frequency of diabetes mellitus in nonusers and everusers of high-dose combination oral contraceptives, other studies had shown an increased risk of impaired glucose tolerance in current users, which is estimated to be roughly twice as frequent as that in nonusers. Women at risk of developing impaired glucose tolerance while receiving high-dose oral contraceptives either had previous gestational diabetes mellitus or were older, obese, or had a positive family history of diabetes mellitus. The tendency to decreased glucose tolerance seems essentially related to the dosage and chemical structure of the progestogen used in oral contraceptives, namely, estrane and particularly gonane progestins. However, increased frequency of impaired glucose tolerance and potentially diabetes mellitus are obviously not linked to the use of the more potent gonane progestins. The use of low-dose oral contraceptives, particularly with reduced progestogen content (such as in the triphasic formulations and last-generation monophasic preparations), is accompanied by a low risk of impaired glucose tolerance, even in previous gestational diabetes mellitus. The mechanism of decreased glucose tolerance in oral contraceptive users is unknown but seems related partially to increased peripheral resistance that is potentially caused by a postreceptor defect in insulin action. Changes in insulin production or metabolic clearance rate are not excluded by recent, sophisticated investigations of carbohydrate metabolism in oral contraceptive users. Impaired glucose tolerance and diabetes mellitus, chronic hyperglycemia, and hyperinsulinemia are believed to increase atherogenic risk either by their direct action or their effects on lipid metabolism. Newer epidemiologic studies now indicate that the incidence of cardiovascular disease in low-dose, low-risk, current oral contraceptive users has been substantially decreased. The use of low-dose oral contraceptives with reduced dosages of better adapted progestogens seems effective in decreasing alterations in carbohydrate metabolism and may thereby contribute to decrease further atherogenic risk in oral contraceptive users.

Carbohydrate Metabolism↗
PubMedDate not supplied

Synthesis of 12-mono- and di-substituted 8-aza-11-oxasteroids.

The synthesis of unsaturated derivatives of 8-aza-11-oxa-17-oxo-gonane and D-homo-gonane carrying one or two functional substituents at C-12 is reported. The key step for the construction of the heterosteroid skeleton was the cyclocondensation reaction of aldol adducts 1, derived from 1,3-cycloalkanediones and diethyl 2-oxo-malonate, with tosyl chloride and isoquinoline.

Azasteroids↗
PubMed2001

[New gestagens--advantages and disadvantages].

Due to their high oral bioavailability synthetic progestagens are used for therapy, hormone replacement therapy and contraception There are different types of progestogens. There are progesterone derivatives, nortestosterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes), spirolactone derivatives and norpregnance derivatives which differ in their efficacy and hormonal profile. All progestagens show antiestrogenic activities, inhibit the estrogen-induced proliferation of the endometrium and, hence, decrease the risk of endometrial hyperplasia. With the exception of Dienogest, the derivatives of 19-nortestosterone are characterized by a 17-alpha-ethynyl group and show slight androgenic properties which may antagonise some estrogen-dependent alterations of hepatic serum parameters. Tibolone which is a derivative of norethynodel also belongs to this group. Among the nortestosterone derivatives, there are the so-called "Prodrugs". Prodrugs are rapidly transformed after intake to the active progestagens. Progesterone derivatives partly exert moderate androgenic or antiandrogenic effects, while the spirolactone derivative Drospirenone shows antimineralocorticoid and antiandrogenic activities. The progesterone derivatives as well as Gestodene and Desogestrel have certain glucocorticoid activities which, at the doses used, are not clinically relevant, but possibly may influence vascular function. The effects of 19-norpregnane derivatives are comparable with those of progesterone derivatives. According to their different hormonal profiles and activities, the various available progestogens allow the choice of preparations which are best suitable for the individual woman for contraception or hormone replacement therapy.

Biological Availability↗
PubMed2004

Clinical profile of contraceptive progestins.

The term progestogen has been widely utilized to indicate the general class of agents that includes both progesterone and its synthetic analogs, whereas the term progestin refers only to synthetic progestational steroids. The development of progestins has been influenced in a major way by the search for orally active hormonal contraceptives, since it is likely that hormonal contraceptives will continue to utilize a progestin, the only possible alternative being represented by the utilization of antiprogestins. Synthetic progestogens in clinical use today belong to three main chemical families: progesterone derivatives (progesterone, retro-progesterone, 19-norprogesterone and 17alpha-hydroxyprogesterone); gonane and 19-nortestosterone derivatives (norethisterone, levonorgestrel, desogestrel, gestodene, norgestimate); a spironolactone derivative. Biological potency of progestogens varies depending on the end-point measured, usually ovulation inhibition and endometrial transformation; with both these tests, the most active compounds are all gonane derivatives, with a potency over a 100 times that of the natural hormone. When administered in adequate doses, a progestin inhibits fertility by inhibiting ovulation. This action is mainly exerted at the hypothalamic level where, physiologically, progesterone decreases the number of LH pulses. When progestogens are delivered directly to the uterine cavity, their action seems to be purely local. It has been amply proven that--even when administered in doses that do not constantly inhibit ovulation--a progestin can still remain effective as a contraceptive by acting at the level of the cervical mucus and, at least in part, of the endometrium. Progestogens utilized today differ largely in their pharmacokinetics. In general, after intake, these compounds are rapidly absorbed and distributed so that peak serum concentrations are reached between 1 and 4 h. Third-generation progestins (desogestrel, gestodene, norgestimate) have common characteristics: a higher affinity for progesterone receptors than their predecessors, a lower affinity for androgen receptors, a higher selectivity of action, a higher central inhibitory activity, a higher potency at the level of the endometrium, and an overall metabolic neutrality, in terms of effects on lipid and carbohydrate metabolism. In general, progestins can induce two types of adverse effects: changes in lipid metabolism and bleeding irregularities. Whereas the newer compounds seem to have overcome the first of these adverse effects, the second remains untouched: to this day, proper cycle control can only be achieved with combined hormonal contraceptives.

Contraceptive Agents↗