Long term toxicological studies on the progestin STS 557.

The toxicity of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) was studied by its oral administration of 0.1, 1.0 or 10.0 mg/kg/day to Wistar rats for six months, and of 0.01, 0.1 or 1.0 mg/kg/day to beagle dogs for six months, respectively. Levonorgestrel at a dose of 1.0 mg/kg/day was used as the standard in the dog study. With respect to the progestational activity of the compound the main target organs were the hypophysis, the reproductive organs and the adrenals. Mammary hyperplasia was observed in dogs treated with STS 557 or levonorgestrel at the dose of 1.0 mg/kg/day, but in no case mammary nodules could be detected. At the dose of 1.0 mg/kg/day STS 557 and levonorgestrel were found to increase the plasma insulin response to i.v. glucose in bitches, but neither the mean blood glucose levels nor the glucose utilization were affected. Moreover, during administration of both steroids to dogs temporary changes in serum concentrations of triglycerides and total cholesterol were noted. The results obtained in rats and dogs from functional and morphological investigations did not reveal any toxic side effects of STS 557 on the liver, the kidneys, the bone marrow or on blood coagulation. The effects on the reproductive organs observed following STS 557 especially in dogs are related to both the hormonal effects of the compound and the specific response of the dog to potent progestagens.

[Measurement of serum activity in short and long-term application of various hormonal contraceptives]. / Serumaktivitätsmessungen bei Kurz- und Langzeitapplikation verschiedener hormonaler Kontrazeptiva.

The influence of several oral contraceptives on various serum enzymes was tested during a short-term and a prolonged (24 therapeutic cycles) application period. A total of 8,790 examinations was performed in 211 females, each patient being examined up to 8 times during the cycles 0, 1, 3, 6, 12, 18, 24 and the first cycle following termination of oral contraception. Since sufficiently sensitive steroid-dependent makers are lacking, it cannot be dispensed with determining the serum enzymes gamma-GT, GPT, GOT, and LAP altogether, in order to detect early damage of the liver.

PIP: The influence of several oral contraceptives (OCs) on various serum enzymes was tested during a short-term and a prolonged (24 therapeutic cycles) application period. A total of 8790 examinations were performed in 211 females, each patient being examined up to 8 times during the cycles 0, 1, 3, 6, 12, 18, 24, and the 1st cycle following termination of OCs. Since sufficiently sensitive steroid-dependent markers are lacking, it cannot be dispensed with determining the serum enzymes gamma-GT, GPT, GOT, and LAP altogether, in order to detect early damage to the liver. (author's modified)

[Behavior of various serum enzymes following ligation of the superior mesenteric artery in the rat (preliminary report)]. / Das Verhalten einiger Serumenzyme nach Unterbindung der Arteria mesenterica superior bei der Ratte.

In rats, shortly after ligation of superior mesenteric artery serum enzyme activities are found significantly altered. Those changes concern aspartate aminotransferase (GOT), alanine aminotransferase (GPT), lipase, alpha amylase, and isocitrate dehydrogenase as well as glutamate dehydrogenase. The causes are discussed. The authors emphasize that the assessment of serum enzymes possibly gives some help in diagnosing acute intestinal ischemias in early stages.