Alfred Moo-Young

Subdermal norethindrone pellets — A method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.

COPPER LEVELS IN MATERNAL AND FETAL TISSUES OF RABBITS BEARING INTRAUTERINE COPPER WIRES

A study was undertaken to determine if copper wire, placed within the uterine lumen after implantation and kept in situ throughout pregnancy, results in an excessive accumulation of the metal in maternal and/or fetal tissues; and if so, what effect if any, such an accumulation may have on both mother and offspring. Copper wires were inserted into the uterine cavities, near the utero-tubal junction, of rabbits on Day 7 of pregnancy and were allowed to remain in situ until Day 28, at which time the animals were sacrificed. Tissues from mother and offspring were subjected to routine histological examinations and their copper content was determined. A parallel series of sham-operated animals served as the control. Copper was released from the intrauterine copper wires at an average daily rate of 38.81 plus or minus 7.26 mcg. Histological examination of maternal adrenal, brain, heart, kidney, liver, lung, ovary, spleen, and uterus revealed no anatomical abnormalities. There was no increase in copper in any of the tissues except the uteri and placentae of animals bearing intrauterine copper wires. There were no anatomical abnormalities in either fetal brain, heart, kidney, liver, or lung. There was an increase in the amount of copper found in the liver of fetuses obtained from animals bearing intrauterine copper wires. As there were no histological differences between livers of the control and experimental groups, and no evidence of teratological effects due to copper, it is assumed that this small but significant increase in fetal liver copper is insufficient to produce any toxic effects on the offspring.