Shrikant S. Betrabet

ICMR task force study on hormonal contraception: Transfer of levonorgestrel (LNG) administered through different drug delivery systems from the maternal circulation into the newborn infant's circulation via breast milk

The transfer of levonorgestrel (LNG) from the maternal plasma via breast milk to the infant was studied in 38 fully lactating and breast-feeding women at 4-6 weeks postpartum, for a duration of 28 days. These volunteers were provided with LNG contraceptive treatment delivered through three, different routes of drug delivery system: (i) intrauterine devices impregnated with LNG (LNG-IUD); (ii) subdermal implant (Norplant (R)-2); and (iii) minipills (LNG 30 micrograms daily). On the first day after either the LNG-IUD (n = 14 women) or Norplant (R)-2 (n = 14 women) insertion, the maternal blood and breast milk samples were collected at 2, 4 and 8 hourly intervals. This was followed by daily collection of these samples as well as infants blood from days 2 to 4 and thereafter on days 7, 14 and 28. For infants blood samples from LNG minipill users (n = 10 women), only a single 4-hour sample was collected on the first day and no samples were collected on days 3 and 4. The rest of the schedule for collection of maternal blood and breast milk as well as infants blood samples were the same in minipill users as for the other two treatment groups. The study revealed a lower LNG percentage transfer from maternal sera to breast milk--11.8 +/- 2, 7 +/- 2 and 8 +/- 1 and relatively higher percentage LNG transfer from breast milk to infants sera--75 +/- 17, 68 +/- 20 and 32 +/- 3, in LNG-IUD, Norplant (R)-2 and minipill users, respectively. Therefore, LNG contraceptive steroid is transferred into the infants circulation, the biological significance of which remains to be established.

ICMR task force study on hormonal contraception: Biological activity of ethinyl estradiol present in the breast milk

A study was conducted to compare the biological activity of the estrogenic component of the endogenous steroids in breast milk samples collected during various phases of lactation with those milk samples collected from women who were on estrogen therapy. The estrogenic biological activity in the milk sample was assessed by the immature mouse uterine weight gain assay. Milk samples collected during postpartum period from six different study groups, viz., control colostrum of 1-3 days and 4-6 days, transitional milk (10-20 days) and mature milk (1-3 months) were compared with colostrum and mature milk of women treated with Lynoral (ethinyl estradiol 0.1 mg) three times a day for three days. Estrogenic activity was observed only in animals injected with milk extracts of colostrum samples from both control and Lynoral-treated women; however, they were not significantly different from each other. Therefore it is not the exogenous estrogens, but the endogenous estrogen present in large quantities in the colostrum that is responsible for the biological activity.

Indian Council of Medical Research ICMR Task Force Study on hormonal contraceptives

Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infants circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.Abstract Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infants circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 ug daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences ( P > 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group ( n =10) when compared with oral minipill of Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.

A sensitive ELISA for 6β-hydroxycortisol in urine using enzyme penicillinase (β-lactamase)

Abstract A sensitive and specific, enzyme labelled immunosorbent assay (ELISA) for 6β-hydroxycortisol in diluted urine using penicillinase was developed. 6β-Hydroxycortisol-21-hemisuccinate was conjugated with enzyme penicillinase. Antibody immobilized on a polyvinylchloride ELISA plate (Dynatech) was used for separation of bound from free ligand. The sensitivity of the assay was between 2.0–3.0 pg per well and recovery of 6β-hydroxycortisol from urine ranged between 85.0–108.0%. The assay is simple, rapid and precise.

A nomogram of the neonatal peak of urinary follicle stimulating hormone, luteinizing hormone and testosterone in normal male infants

Daily urinary follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels were estimated in a group of 10 normal one month old male infants. Four-hourly urine samples were collected from each infant over a three months period i.e., from one month to four months of infants age. The hormonal levels were expressed as mIU of FSH, LH and ng of T per mg creatinine. The normal hormonal pattern thus obtained could be used to compare patterns obtained from pathological cases or when monitoring the effects of drugs on infants.