Long term toxicological studies on the progestin STS 557

Area of Science:

• Endocrinology and Toxicology
• Pharmacology of Steroid Compounds

Background:

• 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) is a synthetic steroid compound.
• Understanding the toxicological profile and hormonal effects of novel steroid compounds is crucial for their potential therapeutic applications.

Purpose of the Study:

• To evaluate the subchronic toxicity of STS 557 following oral administration in Wistar rats and beagle dogs.
• To identify target organs and assess potential adverse effects related to the progestational activity of STS 557.

Main Methods:

• Oral administration of STS 557 to Wistar rats (0.1-10.0 mg/kg/day) and beagle dogs (0.01-1.0 mg/kg/day) for six months.
• Levonorgestrel (1.0 mg/kg/day) used as a reference standard in the dog study.
• Functional and morphological investigations were conducted, including assessment of hormonal effects, plasma insulin response, and serum lipid profiles.

Main Results:

• Mammary hyperplasia observed in dogs treated with STS 557 or levonorgestrel at 1.0 mg/kg/day; no mammary nodules detected.
• STS 557 and levonorgestrel increased plasma insulin response to glucose in dogs, without affecting blood glucose levels or utilization.
• Temporary changes in serum triglycerides and total cholesterol noted in dogs; no toxic effects on liver, kidneys, bone marrow, or blood coagulation observed in rats or dogs.

Conclusions:

• STS 557 did not exhibit significant toxic side effects in rats and dogs.
• Observed effects on reproductive organs in dogs are attributed to the compound's hormonal activity and the species' response to potent progestagens.
• STS 557 appears to be a safe compound with progestational activity, warranting further investigation.