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

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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.

MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand / Background: The knowledge of contraceptive use is high among men and women in South Africa. However, contraceptive prevalence rate is moderate and unplanned pregnancies are common. Understanding the determinants of contraceptive use and unplanned pregnancy will inform future interventions that aim to maintain consistent contraceptive use and reduce unplanned pregnancies. Aim: The study aims to describe factors associated with contraceptive use and unplanned pregnancy in the South African population. Methods: A secondary data analysis was carried out on data collected in a cross–sectional survey conducted in Potchefstroom, South Africa between August 2007 and March 2008.Results: Contraceptive prevalence was 69.5% and unplanned pregnancy was 59.7%. The risk factors for contraceptive use included woman’s employment status at the last pregnancy, woman’s partner employment status at the last pregnancy and number of miscarriages a woman had experienced. The risk factors for unplanned pregnancy included race, woman’s age , education level and employment status at last pregnancy, number of miscarriages, contraceptive use and partner’s employment status at last pregnancy. Conclusion: If the prevalence of unplanned pregnancies is to be reduced, policies and programmes need to address economic factors which were associated with both contraceptive use and unplanned pregnancy. Further study needs to be carried out as to the reasons behind why a woman with a previous history of a miscarriage is less likely to have an unplanned pregnancy yet she is less likely to be on contraception.

Background Contraceptive prevalence in sub-Saharan Africa is low compared to other regions of the world. Despite this, some countries within the sub-Saharan African region, such as Malawi, have been identified as champions of contraceptive use within the region but still face many reproductive health challenges, such as a high total fertility rate of 5.7 births per woman (Malawi Demographic and Health Survey (MDHS), 2011). The purpose of the study is to examine the prevalence of the use of modern contraception given different dimensions of family structure and what significant relevance this may have in creating contextually appropriate family planning interventions. A literature search of studies on family structure in Africa shows little evidence of such a study in Malawi. Methodology The study was cross-sectional and made use of the 2010 Malawi Demographic and Health Survey (MDHS). It focused on women of reproductive ages (15-49 years). A total of 12, 490 women made the sample of the study. In order to address the objectives, descriptive statistics and chi-square tests were conducted to assess the levels and patterns of modern contraceptive use in Malawi. Lastly, binary logistic regression was carried out in order to test the association between different dimensions of family structure and modern contraceptive use. Results The study established that the prevalence of modern contraceptive use in women of reproductive age (15-49) in Malawi was estimated at 48%. The study showed that family structure did have an influence on modern contraceptive use. Specifically the likelihood of modern contraceptive use was higher among women with larger family sizes. The association between sex composition of children and modern contraceptives was also significant. Findings further showed that women in female-headed households were less likely to use modern contraceptives compared to women in male-headed households. Conclusion Family structure was found to have an influence on modern contraceptive use in Malawi. The study findings have implications towards achieving the reproductive goals of the Malawi Growth and Development Strategy (2011-2016) and the Malawi Health Sector Strategy Plan of (2011-2016) or future policies which have important reproductive health goals for women.

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