WHO undertook a study to examine the effects of combination type oral contraceptives containing 30 or 50 ƒÊg ethinyl estradiol and 150 ƒÊg d-norgestrel on undernourished women from India and Thailand. As compared with a middle-income population of women in each of these centers, women recruited for the study were undernourished. To discriminate hormone effects from other time-related changes, the baseline data on the cross-section of the study population were analyzed for effects of duration of lactation, anthropometry, and season. Both oral pills brought about a similar small but significant deterioration in

Two types of intravaginal rings (IVR) containing 50-128 mg of levonorgestrel (LNOG) and 28-60 mg of estradiol were inserted in 18 apparently normal subjects belonging to the low socioeconomic group on day 5 of the cycle. A total of 120 cycles were studied with cyclic insertion and withdrawal. Data on menstrual cycle changes were noted. For bioavailability study, blood samples were collected twice weekly for a period of one month in the first cycle in 8 women. All the plasma samples were analysed for LNOG and progestrone by RIA. Cycle control was excellent in IVR users. Expulsion of the ring was noted in 4 instances. The plasma LNOG levels were found to reach a peak level ranging from 2.7-7.5 ng/ml within 4 days after the IVR insertion. In between day 9 to 24, the plasma levels appeared to be almost steady, and once the ring was removed, the levels dropped off rapidly. The mean plasma LNOG calculated during the steady-state period of the cycle ranged from 1.6-5.1 ng/ml. These mean LNOG levels were found to be inversely correlated with skin-fold at triceps. In all the subjects ovulation was found to be inhibited, as reflected by plasma progesterone values. The range of release rates calculated from plasma steady-state values was 51-119 micrograms/day. The average release rates over the entire period of observation based on area under curve were 102-200 micrograms/day. On the other hand, the release rates obtained from the residual drug in the ring after a period of use ranged from 184-259 micrograms/day.

The effects of combined oral contraceptives containing 30 or 50 micrograms ethinyl oestradiol and 150 micrograms levonorgestrel or a 3-monthly injectable preparation depo-medroxyprogesterone acetate (DMPA) on the vitamin status of low-income group women from two urban centres in India (Bombay and Hyderabad) and one rural centre in Thailand (Chiang Mai) were examined in a follow-up study over a period of 1 year. The magnitude of malnutrition in the study population vis-à-vis a middle-income reference group was assessed by comparing the baseline data on the two groups. Effects of time-related variables such as lactation and season were also examined by a cross-sectional analysis of the baseline data on the study population. In all three centres the majority of the study population suffered from biochemical riboflavin and/or pyridoxine deficiency even before initiating contraception. Lactation appeared to have an effect on the vitamin status, which varied among the different populations. Seasonal effects were seen, but showed inconsistent trends in the three centres. Both the oral contraceptive pills and DMPA tended to increase serum vitamin A and blood folate. The thiamin, riboflavin and pyridoxine status of the women who were already deficient did not deteriorate further with the use of hormonal contraception, as judged by enzyme saturation tests. Some deterioration in the riboflavin status of the normal women of Hyderabad was seen with the use of oral pills. Women who were biochemically deficient prior to the use of oral contraceptives tended to show some improvement in B-vitamin status, over the 1-year period of hormonal contraception.

WHO undertook a study to examine the effects of combination type oral contraceptives containing 30 or 50μg ethinyl estradiol and 150μg d-norgestrel on undernourished women from India and Thailand. As compared with a middle-income population of women in each of these centers, women recruited for the study were undernourished. To discriminate hormone effects from other time-related changes, the baseline data on the cross-section of the study population were analyzed for effects of duration of lactation, anthropometry, and season. Both oral pills brought about a similar small but significant deterioration in glucose tolerance. The change tended to be progressive in some women, but the overall trend was not significant. Effects on other parameters were absent or inconsistent. Maternal nutritional status (as assessed by body weight) and lactational status did not modify the metabolic effects of the oral contraceptives.

Effect of continuous and intermittent vitamin supplements on vitamin status, serum proteins and llpids were examined in Indian women of low-income group, receiving a low-dose oral contraceptive over a period of 3–6 months. To find out non-specific time related changes, vitamin supplemented and unsupplemented control groups of non-OC users were also examined.

Women using an estrogen-progestogen combination contraceptive exhibited an increased frequency of sister-chromatid exchange (SCE), supporting our previous observation. These elevated SCE frequencies tended to decline 3 months after the discontinuation of the pill. Women using a progestogen injectable contraceptive, on the other hand, had unaltered SCE rates. The analysis, in vitro; of mitomycin-C-induced SCE frequencies in women using either the combination or the progestogen injectable contraceptives showed significantly higher rates of induced SCE.

Plasma dopamine beta-hydroxylase (DBH) activity was estimated in non-pregnant women, normotensive pregnant women during the third trimester and women with pregnancy-induced hypertension (PIH). Non-pregnant women from a high income group had significantly higher DBH activity than their low income counterparts. DBH activity was significantly elevated in women with PIH when compared with non-pregnant and normal pregnant women from a low income group, but was lower than the level in well-nourished, non-pregnant normotensive women.

A low dose combination pill containing levonorgestrel 150 µg and ethynylestradiol 50 µg was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The π t1/2 was lower in Group A women and the α-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (β t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.

The effect of the time of introduction of supplements on the duration of lactation, lactational amenorrhea, and interpregnancy interval is investigated in 428 women belonging to an urban low income group in Hyderabad, India. The mean duration for which the infants were solely breastfed was 8.9 months; the durations of lactation, lactational amenorrhea, and interpregnancy interval were 21.4, 11.5, and 24.3 months respectively. Early introduction of supplements (before 6 months) was associated with shorter duration of lactation, lactational amenorrhea, and interpregnancy interval. Undue delay in the introduction of supplements (beyond 18 months) did not result in indefinite postponement of the return of menstruation.

A study was undertaken to investigate the effects of oral contraceptives (OCs) on body weight and food intake among low income undernourished women in India. The cross-sectional component of the study compared women seeking contraceptive care (control group) and OC users. Data on height weight arm circumference skin-fold thickness and hemoglobin levels were collected. From 34 women attending the general outpatient department and 29 OC users a 24-hour dietary recall survey was conducted. The longitudinal component monitored the body weight of 132 OC users prior to beginning use and after 3 6 9 and 12 months. Data from the cross-sectional study indicated that the mean body weights of the control group and the OC users did not differ significantly. The longitudinal study results showed tendencies to gain or lose weight in different women but no significant difference in the mean body weight with OC use in different durations. The diet survey revealed inadequate intake among both groups of women. However the OC users consumed more meat and vegetables which may account for the significant difference in iron intake. The data did not show a pattern of weight gain that is associated with OC use in developed countries. Financial constraints of the study group may inhibit increased food intake or possibly the anabolic effects of the ingested steroids may be offset by the adverse environmental conditions and consequent infective morbidity. Other studies have reported higher hemoglobin levels in OC users and contraceptive seekers than in the general outpatient population which may be due to more awareness of health services and better utilization among contraceptors and women seeking contraception. Undernourished women who use OCs do not seem to undergo the benefits nor the deleterious changes in nutritonal status.

In 3461 low-income, urban pregnant Indian women, nearly 50% were anemic at the time of delivery. Perinatal mortality rates progressively increased with a decline in maternal hemoglobin values to below 11 g/dl. Mean infant birth weight also fell significantly with maternal hemoglobin values below 8 g/dl, although low birth weight was due in part to an increased number of premature deliveries and to intrauterine growth retardation. Maternal risk factors known to be associated with low birth weight were more prevalent in anemic women. It was concluded that coexisting obstetrical problems (toxemia, twins, antenatal hemorrhage, high susceptibility to infection, underweight, etc.), rather than maternal anemia per se, contributed to the poor pregnancy outcomes seen in anemic women. In women with hemoglobin below 8 g/dl, anemia was part of an overall undernutrition

Clinical trials were undertaken with an injectable low dose progestational contraceptive, norethisterone enanthate 20 mg monthly (Net-en — 20). Data from the study indicate that Net-en — 20 is an effective contraceptivs with lower incidence of menstrual cycle disturbances than the currently used injectable progestogens. There was a prompt return of fertility after the withdrawal of the drug. Net-en — 20 did not have any adverse effect on maternal nutritional status as assessed by anthropometric indices of nutritional scatus, and clinical sign of nutritional deficiencies or on lactational performance as assessed by mothers' impression on milk output and mean duration of lactation.

This study assesses the possible impact of uterine perforations and cervical perforations on the wider use of IUDs. Clinical data in cases of cervical and uterine perforations with Cu T 200 reported from various Indian centres participating in these trials were collected and analyzed. 4357 women (82,384 women months of use) were investigated over a 54 month period. Of these, 5 cases of cervical and 5 cases of uterine perforations were discovered. Results indicate that cervical perforations occurred several months to years after insertion. These perforations were asymptomatic and were recognized during routine examination. Removal was easy and the cervical tissues healed readily. All of the uterine perforations occurred in women who delivered 8-10 weeks prior to insertion. All the women were lactating and were amenorrheic. In 4 cases the uterus was small, hyperinvoluted, and freely mobile during insertion. All the perforations may have occurred at the time of insertion. At the time of removal the Cu T was surrounded by dense inflammatory adhesions. It is recommended that: 1) the addition of a terminal rounded bead to the lower end of the vertical limb of Cu T might reduce or prevent perforations, 2) it might be preferable to postpone insertion of an IUD in lactating women until the uterus regains its normal size and menstruation returns, and 3) Cu IUDs should be removed as early as possible following diagnosis of perforation. Health consequences of untreated perforations with Cu IUDs are greater than with inert devices like Lippes Loop.

Metabolic effects of a long-acting low dose injectable contraceptive, norethisterone enanthate 20-mg, monthly injections (Neten-20), was tested in 13 women belonging to the low income groups over a period of 1 year. No change was observed in hemoglobin, hematocrit, glucose tolerance, plasma lipids, iron, calcium, or serum glutamate-oxaloacetate transaminase after treatment. Marginal rise in albumin and fall in some globulin fractions was observed. The slight fall seen in serum alkaline phosphatase could be attributed to a change in lactation status. Vitamin A, pyridoxine and riboflavin status were not altered. A peculiar aberration in the tryptophan-niacin pathway as indicated by rise in kynurenic acid excretion after tryptophan load was observed. This could be corrected by multivitamin therapy. These data suggest that the use of Neten-20 for one year does not lead to adverse metabolic effects analogous to those seen with combination type oral contraceptives.

Plasma norethindrone (NET) and progesterone were estimated by radioimmunoassay in seven Indian women after intramuscular administration of 20 mg NET enanthate. One subject had intermenstrual bleeding throughout the cycle. Out of the six subjects considered for analysis, three subjects showed ovulation suppression, two had delayed ovulation and the remaining one exhibited normal ovulatory pattern. Post-peak average plasma NET values ranged from 1.0 to 2.1 ng/ml. These values showed a significant positive correlation with the anthropometric indices such as body weight and mid-arm-circumference. The subjects with lower anthropometry showed exponential decline of plasma NET. A possible role for nutritional status of an individual in drug disposition is indicated from this study.