Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy.

To evaluate which women using oral contraceptive agents might be at risk, biochemical indices known to be affected by the estrogens and progestogens were studied in women who take oral contraceptive agents, in women who do not use oral contraceptive agents, in women in third trimester of pregnancy and 6 weeks after parturition, and in men with normal and high blood lipid levels. The most consistent changes due to oral contraceptive agents were in serum levels of copper, triglycerides, and vitamin A and in the urinary excretion of xanthurenic acid and niacin derivatives before and after a tryptophan load test. There was only a slight suggestion, with no statistical significance, that serum vitamin C levels decreased when the serum levels of ceruloplasmin were high. The highest blood pressures and serum triglycerides and vitamin A levels were obtained in those women who ingested the highest level of estrogens. Pregnant women had the lowest levels of serum vitamin A. The oral contraceptive agents users had the lowest average levels of carotenoids corresponding to the highest average levels of vitamin A in the serum. Thus, estrogens not only increase the rate of change of tryptophan to niacin but may also increase the rate of conversion of carotene to vitamin A. Relative reactivity to oral contraceptive agents and possible risk to a patient might be evaluated by a profile of blood pressure and serum triglycerides, copper, and vitamin A.

PIP: To determine if methods can be developed which will show those patients for whom oral contraceptive agents (OCAs) constitute a hazard, data on blood lipids, serum levels of Vitamis-A, E, and C and copper are reported. Results of the tryptophan load test are also given. This tes t is related to the levels of pyridoxine in the tissues. The program was designed to show the relationship of any changes to each other, and to get a better understanding of their significance. Results are compared from subjects taking OCAs, from those not taking OCAs, from women in the last trimester of pregnancy, from women after parturition, and from males. All blood and urine samples were taken at 21 days after the beginning of subjects' menstrual periods, except for those who were pregnant and males. There were 49 women taking a variety of OCAs. 32 not taking OCAs served as controls. Included were 22 pregnant women in the last trimesters of their pregnancies. Of these, 11 were tested again 6 weeks postpartum. 9 men with high blood lipids and 12 men with normal lipid levels were also tested. Diastolic blood pressures averaged higher in the group taking OCAs (p less than .01), except for the males who were older or who wer known to have high lipids. Serum cholesterol levels in OCA users were unaltered. Serum phospholipids showed some increase in OCA users (p less than .05). Triglycerides show ed the greatest increase in OCA users (p less than .001), especially in those taking the most estrogen. The pregnant women had high serum levels of cholesterol, triglycerides, phospholipids, and total lipids. All of these levels were found to be less at 6 weeks postpartum. Serum copper levels were increased in all OCA users to above 1.5 mcg/ml but in only 2 of the nonusers to this level. Serum Vitamin-A was increased in the OCA user group (p less than .001). The pregnant women had relatively low levels of Vitamin-A. This increased by 6 weeks after parturition to the level of OCA users. An 8-hour urine collection after a 2-g tryptophan load showed at 6 times increased excretion of xanthurenic acid in those using OCAs as compared with nonusers. An increased ability of pregnant women to convert tryptophan to nictionic acid was shown. It is not known to what degree the biological changes caused by OCAs are undesirable. However, it is assumed that women showing the greatest changes are at greater risk. Analyses which may serve as incicators of potential risk include serum triglycerides, copper, and Vitamin-A levels. Carbohydrate intolerance and triglyceride elevation have been associated. Blood pressure measurements should be included in any profile.

Some effects of medroxyprogesterone acetate on intermediary metabolism in rat liver.

PIP: This study examines the effects of MPA (medroxyprogesterone acetate) on some of the hepatic enzymes of carbohydrate and lipid metabolism in the rat, and compares these with the effects of cortisol and saline. Levels of reduced nicotinamide adenine dinucleotide phosphate (NADPH) were also measured. Intact mature female Wistar rats with average initial weight of 200 gms were injected with MPA (mO mg/kg IM) once a week for 4 weeks and were sacrificed 3 to 5 days after the last injection. Hydrocortisone (Solu-Cortef [R]) 40 mg/kg IM were given to cortisol-treated animals twice daily for 7 days. The animals were sacrificed 2-4 hours after the last dose was given. Normal saline (0.2 mg. IM) was injected in control animals twice a day. The method of Jellinek, Amako, and Willman was used to analyze NADPH. Liver samples were assayed for various enzymatic activities such as phophofructokinase (PFK); pyruvate kinase (PK), glycerol-3-phosphate dehydrogenase (G3PD), "malic" enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PD). The methods of Colowick and Kaplan were used in enzymatic analyses. Lipogenic stimulation by MPA is indicated by increased levels of G3PD and ME, both of which are implicated in lipogenesis, as well as by NADPH. PFK, PK, and G6PD were all unaffected by the MPA regimen, suggesting that elevation of ME and NADPH activities may reflect increased amino acid conservation. The enzymatic pattern of MPA treatment shows lipogenesis and protein conservation, while that of cortisol regimen shows significantly lower levels of ME, G3PD, and PRK.^ieng

Effects of progesterone on some enzymes of fat and carbohydrate metabolism in rat liver.

The known effect of progesterone on carbohydrate metabolism prompted a study of some of the hepatic "lipogenic" and "gluconeogenic" enzymes in rats treated with progesterone. Several enzymes providing lipid precursors (phosphofructokinase, malic enzyme, glucose-6-phosphate dehydrogenase, and citrate cleavage enzyme) showed increased specific activity. These changes may represent insulin effects. Specific activity of phosphoenolpyruvate carboxykinase, usually associated with control of gluconeogenesis, was also increased. The latter is compatible with increased capability for glycogenesis, which is recognized as a progesterone effect.

PIP: The effects of progesterone on some of the hepatic enzymes associated with lipogenesis and gluconeogenesis in rats is presented. Progesterone was given, 1.25 mg, twice daily, for 14 days followed by 2.5 mg twice daily for 7 days. Animals were killed after 21 days of treatment. Enzymes studied included phosphofructokinase (PFK) malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), citrate cleavage enzyme (CCE), glycerol-3-phosphatee dehydrogenase (g-3-PD), fatty acid synthetase (FAS), pyruvate carboxylase (PC), phosphenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDPase), and lactate dehydrogenase (LDH). PFK, ME, G-6-PD, and CCE were elevated significantly after progesterone administration, while FAS and G-3-PD were unchanged. These changes may represent insulin effects. Progesterone treatment also results in increased PEPCK. This enzyme is associated with control of gluconeogenesis. PEPCK is considered to be a key rat-limiting enzyme in the "dicarboxylic acid shuttle." This finding may indicate an increased capability for glycogen formation.