Effect of ethynodiol diacetate and mestranol on serum folic acid and vitamin B12 levels and on tryptophan metabolism in baboons.
The effect of an oral contraceptive agent on serum folate and vitamin B12 levels and on some aspects of tryptophan metabolism in the baboon has been investigated. Folate levels were not affected by this treatment. Vitamin B12 levels were lowered during oral contraceptive treatment (P smaller than 0.1) and increased during a 30-day period of pyridoxine supplementation (P smaller than 0.01). Trends indicating deterioration of glucose tolerance and abnormal tryptophan metabolism were also observed. Definite conclusions concerning the effect of oral contraceptive agents on nutritive parameters could not be made. This is in keeping with the vast volume of literature published on the effects of oral contraceptive agents in humans and other species. It is concluded that perhaps, due to the biologically variable responses to oral contraceptive agents by individuals of any species, studies of serum levels of vitamins and other superficial biochemical parameters. Further, we conclude that the baboon could be a useful model for the study of endocrine influences on nutritive parameters, first because endocrine parameters resemble those of humans and second, because experimental protocols can be rigidly adhered to. (+info)
Effect of oral contraceptive agents on vitamin nutrition status.
Effects of low estrogen combination type oral contraceptives on some of the biochemical parameters used for assessing vitamin nutritional status were investigated in a group of women who had used the pill for 6 to 12 months. Another group of women was examined initially and then at one or more points of time within the first 6 months of treatment. Following changes were observed in women treated with oral contraceptives: 1) increased excretion of kynurenic acid and xanthurenic acid following tryptophan load; 2) increased EGOT activity and also an increase in vitro stimulation of EGOT with added PALP; 3) increased plasma vitamin A levels; 4) fall in erythrocyte folate levels; 5) fall in erythrocyte transketolase activity with no change in vitro stimulation with TPP; and 6) fall in erythrocyte riboflavin concentration associated with a decrease in erythrocyte glutathione reductase activity and increase in vitro stimulation with FAD. Most of these changes were observed during the first few cycles of oral contraceptive treatment. (+info)
The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.
BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles. (+info)
Contraceptive steroid effects on lipids and lipoproteins in cynomolgus monkeys.
Seventy-three adult female cynomolgus monkeys fed an atherogenic diet were studied to determine the effect of two different combination contraceptive steroid preparations containing equivalent amounts of estrogen but different progestin components on plasma lipids and lipoproteins. Our hypothesis was that any high density lipoprotein (HDL) lowering effect of the contraceptive steroid preparations was proportional to the rise in total serum cholesterol caused by the progestins. For 2 years, one group (Ovral [Wyeth Laboratories], n = 23) received 75 micrograms norgestrel and 7.5 micrograms ethinyl estradiol daily, while another (Demulen [Searle & Co.], n = 25) received 150 micrograms ethynodiol diacetate and 7.5 micrograms ethinyl estradiol daily. The control group (n = 24) received no treatment. On average, the two oral contraceptive groups had higher total serum cholesterol and triglyceride concentrations but lower HDL cholesterol concentrations and smaller low density lipoproteins (LDL) compared with the control group. There was an inverse relationship between total serum cholesterol and HDL cholesterol for all three groups, but at any given total serum cholesterol concentration between 350 and 500 mg/dl, the Ovral group had HDL cholesterol concentrations that averaged 37% and 14% lower than the control and Demulen groups, respectively. The decrease in HDL concentrations with oral contraceptive treatment was associated with a sharp decrease in (HDL2b)gge protein (82% for Ovral and 59% for Demulen) and a corresponding increase in (HDL3b,c)gge protein as determined by gradient gel electrophoresis. Of 23 animals in the Ovral group, six had HDL subfractions greater than 10 nm diameter (HDL2b)gge compared with 22 of 24 animals in the control group. Although LDL size, on average, was smaller and plasma triglycerides were greater with oral contraceptive treatment compared with controls, there was no apparent relationship between LDL size and plasma triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Effects of an angiotensin II antagonist; [sarcosine 1, isoleucine 8] angiotensin II, on blood pressure, plasma renin activity and plasma aldosterone concentration in hypertensive and normotensive subjects taking oral contraceptives.
To examine the involvement of renin-angiotensin-aldosterone system in the etiology of oral contraceptive induced hypertension, normal women (Group I), normotensive (Group II) and hypertensive (Group III) women taking Ovulen (R) were infused with a competitive angiotensin II (AII) antagonist, [1-sarcosine, 8-isoleucine] angiotensin II. The angiotensin II antagonist was infused at a rate of 600 ng/kg/min for 30 min 1.5 hrs after intravenous injection of 40 mg of furosemide. Blood pressure was monitored and pre-infusion and post-infusion plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Pre-infusion PRA and PAC showed no significant differences among these three groups. In response to the AII antagonist infusion blood pressure rose in Groups I and II, but blood pressure responses in Group III were variable. Four out of the total 6 subjects had pressor responses and only one subject had a significant blood pressure reduction. In both Groups I and II, PRA decreased and PAC rose after infusion of the antagonist. In Group III, PRA decreased to a lesser degree and PAC showed no consistent change. These data suggest that the renin-angiotensin-aldosterone system in hypertensive women or oral contraceptives is different from that of the normotensive users. However, the pathophysiology of oral contraceptive induced hypertension is not homogenous and angiotensinogenic hypertension is uncommon. (+info)
Liver hamartomas in patients on oral contraceptives.
Three cases are reported of tumour-like lesions of the liver in women who had been on oral contraceptives for long periods. These malformations have a prominent vascular component and may present with haemoperitoneum and shock. The possibility of an association between liver hamartomas and oral contraceptive therapy has to be considered. (+info)
Relation between headaches from oral contraceptives and development of endometrial arterioles.
The incidence of headaches during the first year on oral cotraceptives corrleates closely with the incidence of well-developed arterioles in endometrial biopsy specimens. This relationship appears to depend on the ratio between progestogenic and oestrogenic components of the pill as well as the particular steroids. Therefore endometrial biopsies are useful for assessing the vascular response to an oral contraceptive and also provide a short cut to clinical evaluation of new formulations. (+info)
Synthetic progestagen-oestrogen preparations and endometrial morphology.
19-nor steroids in high and medium dosage in continuous or cyclic combined regimens with oestrogen produce an endometrium characterized by hyperinvoluted glands, a prominent predecidual reaction, suppressed arterioles, and dilated venules. When daily dosage is decreased to 2.0 mg. or less, the endometrium is composed of hyperinvoluted glands in an inert stroma; predecidual reactions are weak and infrequent; venules are rarely dilated, but spiral arterioles are suppressed.17-alpha-Acetoxyprogesterone derivatives in high and medium dosage given in a cyclic combined regimen with oestrogen produce similar but less intense effects to the 19-nor steroids. When given in cyclic sequential regimen, they produce an early secretory endometrium closely resembling normal patterns, chronologically retarded by about five days; in some instances a regressing, undatable secretory pattern is found, but predecidual response is minimal, and dilated venules are not seen.19-nor steroids in medium dosage given for 20 days without added oestrogen produce a late secretory endometrium with unpredictable variation from patient to patient and even from site to site within the same endometrium. Inhibition of the development of spiral arterioles is a common denominator in all progestagenoestrogen regimens. Modification of this element within the target tissue may be decisive for the morphogenesis of later vascular and stromal changes. Using synthetic progestagen-oestrogen regimens, endometrial gland secretion appears only after progestagen, whether given ab initio concomitantly with oestrogen or begun after a phase of oestrogen priming. Secretory vacuoles become evident about four to five days after progestagen is administered. The role of progestagen in secretion is interpreted as an indirect effect whereas its role in the development of decidual-like changes is construed as direct. (+info)