The urinary excretion of 4-pyridoxic acid (PIC), the principle end-product of vitamin B₆ metabolism found in human urine, was measured in two populations in whom altered vitamin B₆ metabolism has been reported: in women who use oral contraceptives and in mental retardates with and without Down's syndrome. In the first study 4 women who had been taking an oral contraceptive for 2 to 12 months served as experimental subjects; two women who did not use an oral contraceptive pill served as control subjects. They were placed on a constant diet that met the requirements for all essential nutrients. The study lasted for 11 days. During this period five 24-hr urine specimens were collected from each subject and were analyzed for 4-pyridoxic acid as well as for total creatinine. The urinary excretion of PIC by the subjects using an oral contraceptive was similar to that by the control group in this study and that by normal women subjects reported in the literature. The results of this study suggest that the alteration in vitamin B₆ metabolism observed in women using steroid contraceptives is not reflected by any change in urinary excretion of PIC. In general all subjects excreted more PIC during the latter part of the study than the initial stage, probably reflecting an adjustment to the higher intake of the vitamin supplied by the diet. Also, there was an inverse relationship between the urinary excretion of PIC and the body weight of the participants. In another study the excretion of PIC before and after pyridoxine (PIN) loading was studied in 12 patients with Down's syndrome and 12 mentally retarded controls without Down's syndrome. Three mongoloids and three non-mongoloids of the same sex and matched for age and weight were studied at a time for 6 days. They received a constant diet that was adequate in all essential nutrients for man. PIC was determined in urines collected on days 1, 5, and 6, 50 mg of pyridoxine being orally administered on day 5. Data show that the basal urinary excretion of PIC is similar in the mongoloid and control subjects. The total increase in PIC excretion by patients with Down's syndrome during the two days following the ingestion of the test dose of pyridoxine averaged 22.03 mg, while the excretion by the controls averaged 19.34 mg. The larger excretion of PIC by Down's syndrome patients compared with controls following pyridoxine loading was significant (P < 0.05). An explanation for this greater excretion by mongoloids is proposed. / Graduation date: 1973

Graduation date: 1974

Norethynodrel, a common progestin in oral contraceptives, produces in female rats several significant physiological, cytological and biochemical changes at dose levels of 1 mg and 20 mg per kg: 1) a relative increase in liver mass 2) modification of appearance and extent of the endoplasmic reticulum 3) augmentation of the protein content of the liver 4) increase of the level of cytochrome P- 450 in the liver as determined by : a) difference spectroscopy b) increases in biotransformation of aniline and aminopyrine in vitro and c) reduction of sleeping times of rats dosed with phenobarbital The significance of these findings becomes evident when it is realized that norethynodrel affects and is affected by the same enzyme system which oxidizes medicaments in general in the body: induction of cytochrome P-450 by administration of norethynodrel may interfere with the action of other drugs . Ethinyl estradiol alone showed none of the inductive effects. At high dose levels (20 mg per kg) both norethynodrel and ethinyl estradiol caused a marked inhibition of growth of the animals, producing a net loss of body mass over the 30- day experimental period. Electron micrographic evidence implies that there is also a lowering of glycogen content and a chemical change in the lipids of adrenocortical and liver cells accompanying the use of these agents.

Oral contraceptive (OC) users frequently have lower vitamin B₆ status than non-oral contraceptive (NOC) users. However, normal dietary intake, a possible factor, has not been adequately studied. Therefore, 26 OC users and 25 NOC users, of college age, were compared with respect to dietary intake of vitamin B₆ and blood vitamin B₆ levels. OC users had been taking "the pill" for at least five months and NOC users had not taken any estrogen-progestin hormones for at least five months. A 72-hour continuous dietary intake record, kept by each subject, was used to calculate intakes of vitamin B₆ and nine other nutrients. Subjects consumed self-selected diets and none had used vitamin B₆ supplements within two weeks of this study. Intakes of all nutrients studied were comparable between the two groups. The mean intakes exceeded the recommended dietary allowance (RDA) for all nutrients except iron, calories and vitamin B₆. The mean intake of vitamin B₆ (1.4 [plus or minus] 0.5 mg/day for OC and 1.6 [plus or minus] 0.5 mg/day for NOC) did not differ significantly between the two groups. The RDA for this age group is 2.0 mg/day of vitamin B₆. The mean protein intakes were not significantly different for OC versus NOC users (72.6 [plus or minus] 19.4 g/day for OC and 66.9 [plus or minus] 13.6 g/day for NOC). The ratio of vitamin B₆ to protein was calculated for each subject. Mean ratios were 0.020 [plus or minus] 0.004 for OC and 0.025 [plus or minus] 0.01 for NOC users. This difference was significant at p<0.05. The mean ratio for both groups exceeded 0.019, which is considered to be adequate. Fasting blood samples were collected during the luteal phase (NOC) or after seven days of the pill cycle for 0C users. These samples were analyzed for whole blood and plasma (by Lind, 1980) vitamin B₆, using a microbiological assay (S.uvarum). These values were used to calculate vitamin B₆ levels in the red blood cell (RBC). A significant difference (p [less than or equal to] 0.05) was found between the mean level of RBC vitamin B₆ in the 0C users versus the NOC (12.4 [plus or minus] 5.4 ng/ml for 0C and 16.8 [plus or minus] 8.5 ng/ml for NOC). Plasma vitamin B₆ concentrations were also significantly different between the two groups. The mean ratio of plasma vitamin B₆ to RBC vitamin B₆ was not statistically different between 0C and NOC users. A questionnaire was used to compare the subject groups with respect to exercise, alcohol intake, general health, general vitamin B₆ intake and other indices. With the exception of alcohol intake, the mean scores for both groups, from this questionnaire, were similar. 0C users had a significantly higher intake of alcohol than NOC users, as measured by the questionnaire. However, the actual alcohol intake from the dietary record did not differ statistically between the two groups. The lack of a significant difference in vitamin B₆ intake, coupled with significantly different blood vitamin B₆ levels for 0C versus NOC users, tends to indicate that the 0C may be altering vitamin B₆ metabolism. Estrogens may cause a redistribution of vitamin B₆ in various body pools, with the vitamin leaving the blood and entering other tissues. Blood levels are generally used to determine vitamin status. By this assessment, 0C users have a lower vitamin B₆ status than controls. It is recommended that 0C users be encouraged to consume at least 2.0 mg/day of vitamin B₆ in their normal diets. / Graduation date: 1981

The effect of oral contraceptives on the urinary excretion of several methionine metabolites was determined in women before and after they had received a 3-g dose of L-methionine. Nine women between the ages of 20-29 years served as subjects: five had been using a combination-type oral contraceptive for six months or more (experimental group), and four had not been using these drugs (control group). Cystathionine excretion by both groups before and after the methionine loading was in the range reported for normal female subjects who were not deficient in vitamin B₆ (Krishnaswamy, 1972; Shin and Linkswiler, 1974). Changes in urinary methionine metabolites that were apparently produced by oral contraceptive drugs are: (1) homocysteine was detected in the basal urine of three of the oral contraceptive users. After methionine loading, it was found in the urine of four of these subjects, two of whom excreted measurable quantities. In contrast, three of the control subjects excreted traces of homocysteine only after methionine loading. (2) The mean excretion of taurine by oral contraceptive users was only one-tenth of that excreted by the control subjects. The activity of erythrocyte glutamic oxaloacetic transaminase (EGOT) before and after in vitro stimulation with added pyridoxal phosphate was similar in both groups. Basal activity of erythrocyte glutamic pyruvic transaminase (EGPT) was lower in oral contraceptive users, although the mean values for both groups were within the normal range reported by Miller et al. (1975) and Woodring and Storvick (1970). The percent in vitro stimulation after addition of pyridoxal phosphate was somewhat higher in oral contraceptive users, but the difference was not statistically significant. Thirteen free acidic and neutral amino acids (including metabolites of the methionine pathway) were measured in the urine specimens. The sum of the urinary excretion of these 13 amino acids was significantly lower (p < 0.01) for oral contraceptive users than for control subjects. However, total α-amino nitrogen excretion, measured in the same urine specimens, was similar for both groups. / Graduation date: 1976

The effect of oral contraceptives on urinary and plasma vitamin B₆ as well as erythrocyte transaminase activities was investigated in women. Five women who were taking oral contraceptives and four who were not using these drugs served as subjects. They were apparently healthy and free from any known metabolic disorder. The subjects, who consumed normal diets, recorded their dietary intake for three days. Twenty-four hour urine specimens were collected on two consecutive days by the subjects. On the morning of the second day blood for the various biochemical measurements was drawn from fasting subjects. Following the blood drawing the women were given an oral dose of 3 g of L-methionine. Results of the methionine load test are reported elsewhere. The subjects consumed diets that supplied at least two-thirds or more of their National Academy of Science-National Research Council (1974) Recommended Dietary Allowances (RDA) for most nutrients except iron and vitamin B₆. The mean dietary intake of vitamin B₆ was 1.57 mg per day for the untreated women and 1.52 for the oral contraceptive users. On both days the mean levels of free and total vitamin B₆ in urine were less in the oral contraceptive users than that in the untreated controls, but the differences were not statistically significant. There appeared to be some relationship between dietary intake of vitamin B₆ and urinary excretion of the vitamin. The methionine loading dose did not affect the excretion of vitamin B₆ The mean plasma level of vitamin B₆ was lower for the oral contraceptive users than for the untreated controls although the difference is not statistically significant. There was, however, a large variation in values among the subjects taking oral contraceptives. Two of them had extremely low plasma vitamin B₆ levels. Vitamin B₆ in the plasma did not appear to be related to dietary intake or urinary excretion of the vitamin. Erythrocyte glutamic oxaloacetic transaminase (EGOT) and erythrocyte glutamic pyruvic transaminase (EGPT) activities with and without in vitro stimulation with pyridoxal phosphate (PALPO) were also measured. There were no significant differences between the two groups in EGOT and EGPT activities with and without in vitro stimulation. According to the activity indexes (PALPO stimulated activity/activity without added PALPO) for EGOT and EGPT (Sauberlich et al., 1972), all subjects had adequate vitamin B₆ nutritional status. Activity indexes for EGOT and EGPT did not appear to be related to urinary or plasma levels of vitamin B₆ Urinary and plasma vitamin B₆ levels and erythrocyte trans- aminase activities were not related to the length of time the women had been taking oral contraceptives or the estrogen content of their oral contraceptive agent. / Graduation date: 1976

No description available.

No description available.

PhD, Faculty of Health Sciences, University of the Witwatersrand / Many studies have shown a negative effect of depot-medroxyprogesterone acetate (DMPA) hormonal contraception on bone mineral density (BMD) in women. There is limited information on the effect of norethisterone enanthate (NET-EN) on BMD and the effect of combined oral contraceptives (COCs) on BMD is inconclusive, however emerging evidence is showing that low-dose COCs maybe detrimental to BMD in young women. The aim of this research was to evaluate, in a 5-year follow-up study, the possible effect of DMPA, NET-EN and COCs on BMD among young (15-19 years) and older (40-49 years) South African women. Method: This prospective study was conducted at the Commercial City Family Planning clinic in Durban, South Africa between 2000 and 2007. In the adolescent group women with no history of hormonal contraception who were initiating use of DMPA (n=115), NET-EN (n=115) or COCs (n=116) and 144 nonuser controls were recruited. In the older group, one hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users of at least one year were compared to 161 nonuser controls. BMD was measured at the distal radius and midshaft of the ulna using dual x-ray absorptiometry. In the crosssectional component of the study conducted at the end of the longitudinal phase, BMD was measured at the hip, spine and femoral neck in a sub-group of 96 of the younger women. Results: In the longitudinal study of adolescents, BMD increased in all four groups during follow-up (p<.001). There was evidence for lower BMD increases per annum in NET-EN (p=.050) and COC (p=.010) users compared to nonusers but no difference between DMPA and nonusers (p=.76). In 14 NET-EN discontinuers, an overall reduction of 0.61% per year BMD was followed, upon cessation, by an increase of 0.69% per year (p=.066). The cross-sectional sub-study found that young women in the injectables-only user group had lower BMDs compared to the non-user group after adjusting for BMI at the spine (p=0.042), hip (p=0.025), and femoral neck (p=0.023). The mixed COC/injectable user group BMD values were lower than controls; however, they were not significant at any of the three sites. In the older women, there was no significant difference in radius BMD between the contraceptive user groups and the non-user controls (p=.26) with and without adjustment for age at baseline, or after two and a half years of follow-up (p=0.52). Conclusion: This study suggests that BMD increases in adolescents may be less in NETEN and COC users; however, recovery of BMD in NET-EN users was found in the small sample of adolescents followed post-discontinuation. The cross-sectional sub-study showed similar findings in long-term injectable users, but not when women had mixed injectable and COC use. There was no evidence that long-term use of DMPA, NET-EN and COCs affected BMD in the older women.

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