TOXICOLOGY OF THE SYNTHETIC ESTROGEN DIETHYLSTIL-BESTROL AND1 CERTAIN RELATED COMPOUNDS

¹ From the Department of Pharmacology, Tulane University of Louisiana, New Orleans

A study has been made of the effects of large daily oral doses of synthetic estrogens on body and organ weight, hematopoiesis, and histological structure of various organs in the rat. The estrogens investigated were diethylstilbestrol, diethylstilbestrol dipropionate, diethylstilbestrol monomethyl ether, diethylstilbestrol monomethyl ether acetate, diethylhexestrol, diethylhexestrol monomethyl ether, and estradiol. The dose of diethylstilbestrol varied from 0.001 to 100 mgm./kgm./day and the duration of administration varied from 10 to 86 days. The doses of the other synthetic estrogens lay between 1 to 20 mgm./kgm./day.

The results may be summarized as follows: no animals died during the course of administration of the estrogens. All estrogens studied produced depression of growth. Diethylstilbestrol was shown to produce a slight but definite decrease in the red cells, white cells, and hemoglobin of the circulating blood. It was also found to cause an increase in the weight in the liver, adrenal, pituitary and uterus, a decrease in the weight of the ovary, testis, seminal vesicle, and prostate, and no change in the weight of the kidney.

The histological changes observed were common to all estrogens. All produced characteristic changes in the liver, consisting of hepatic cell vacuolization. The cause of the vacuolization was found not to be a fatty degeneration, but an accumulation of glycogen in the cell. This finding, together with chemical studies of other investigators (14, 11), appears to establish as one of the effects of estrogens, the deposition of glycogen in the liver. The effects of the estrogens on the adrenals, sex organs, pituitary, mammary glands, kidney, spleen, lung, and bladder were also studied. No essential qualitative difference was found among the estrogens as to their action on these organs.