Effects of Various Drugs on the Uterotropic Response to Mestranol and Norethynodrel in the Rat

Abstract

Mestranol and norethynodrel are synthetic steroids commonly used in oral contraceptive drug formulations. The efficacy of such preparations may be affected by other drugs which influence the hormonal activity of these agents.The present study utilizes the induction phase response of the rat uterus to a single dose of hormone as a method of evaluating possible interactions between mestranol, norethynodrel, and various other drugs.MateriaZs and Methods. Immature female rats (19 days old) were obtained from the Holtzman Colony, Madison, Wisconsin. The rats were caged individually and receivedPurina laboratory chow and water ad Zibiturn. Animal quarters were kept at a constant temperature (24') and on a controlled constant lighting schedule (12 hr dark, 12 hr light).Drugs were dissolved in saline with the exception of phenylbutazone and diphenylhydantoin, which were suspended in carboxymethylcellulose medium. Dru.gs were administered intraperitoneally twice daily for 3 days at the following doses: phenobarbital, 3 7 mgJkg; SKF 525A (Proadifen) 40 mg/kg; tolbutamide, 125 mg/kg ; chlorpromazine, 5 mg/kg; imipramine, 8 mg/kg: paraaminosalicylic acid, 3 mg/kg ; diphenylhydantoin, 12 5 mg/kg ; phenylbutazone, 60 mg/kg ; scopolamine hydrobromide, 0.5 mg/kg. The total volume per dose was 0.2 ml .Mestranol and norethynodrel were dissolved in corn oil and administered in a volume of 0.2 ml by oral intubation 18 hr following the last pretreatment dose.

Interactions between oral Yvonne contraceptives and other drugs: a review

“…5 reported similar results in their investigations on the effect of a number of drugs, including phenobarbitone, on the uterotropic response to mestranol and norethynodrel. Pre-treatment of immature female rats with 37 mg./kg.…”

Nitric oxide synthase inhibition and the uterotrophic response to oestrogen in immature rats

“…Oestradiol was dissolved in corn oil and all other drugs were dissolved in sterile 0.9% (w/v) saline. The test drugs used did not have any effect on uterine Bioassay of oestrogen The technique described by Calhoun et al (1971) to measure oestrogen was used. Groups of 6-10 immature female rats were administered oestradiol in a single s.c. dose of 2.5, 5 or 10 µg per rat to study the uterine oedema response after 6 h or in repeated doses of 3 µg per rat per day for three consecutive days to study the uterine growth response after 72 h. At the end of the 6 h or 72 h period, the animals were killed by an excess of ether and the wet and dry uterine masses were obtained and expressed in mg per 40 g body mass.…”