The manifold effects of prolonged administration of sex hormones to female rats

Abstract

Androsterone, transdehydroandrosterone, testosterone propionate and oestradiol dipropionate, alone, or each of the c? hormones in combination with oestradiol dipropionate (in one group also with progesterone) were injected into ovariectomized and normal rats for a period of about 31/2 mos. With oestradiol dipropionate alone, the vagina was restored to normal or supernormal wt., with normal (usually "oestrus") structure, but not even a weekly dose of 0.2 mg. was able to produce normal size and wt. of the uterus, although this dose caused pronounced pathological changes in the structure of this organ. The weak effects of androsterone and transdehydroandrosterone on the uterus were not significantly increased, as compared with expts. of shorter duration, but the vagina and especially the preputial glands were considerably hypertrophied. There was a cooperative effect between oestradiol dipropionate and androsterone or (to a lesser degree) transdehydroandrosterone on the wt. and size of the sex organs, but at the same time the number of rats affected with squamous metaplasia of the uterine epithelium (first step of "precancerous" oestrogenic effect) was increased and this condition became more severe. Testosterone propionate produced pronounced progestational changes in the uterus and less strong ones in the vagina. Testosterone propionate had a co-operative effect with oestradiol dipropionate on the wt. and size of the uterus, but the occurrence and degree of epithelial squamous metaplasia in this organ were about the same as with the [female] hormone alone. If, however, progesterone was added to the combination of [male] and [female] hormones, or a large dose of testosterone propionate was injected with oestradiol, these "precancerous" changes in the uterine epithelium were prevented to a remarkable degree. Male hormones caused decrease in the wt. and size of the adrenals of [female] [female] similar to that previously described in male rats, while the effect of the [female] hormone was characterised by peculiar pathological changes. Enlargement of the adrenals in most cases followed simultaneous injs. of [male] and [female] hormones. The tumour-like hyperplasia of the hypophysis produced by the oestrogens was neutralized to a considerable extent (in 2 rats almost to normal) by [male] hormones. [male] hormones caused hypertrophy (in most cases exceeding normal level) of liver, kidneys, spleen and heart, but the [female] hormone produced either a slight decrease in their actual wts., or (kidneys) no change. Oestradiol dipropionate produced stunted growth and decreased fat deposition, but with the [male] hormones this depressing effect was absent or (with the large dose of testosterone propionate) slight. When injected simultaneously the [male] hormone more or less completely neutralized the effect of the oestrogen on liver, kidneys, heart, spleen, fat deposition and body weight. The effects produced by testosterone propionate on the weight and size of most organs of normal rats were in general similar to those in ovariectomized rats, in most cases differing in degree. A remarkable feature was the "gigantic" uterus distended with oestrus-like secretion. Prolonged adm. of [male] sex hormones produced in general similar results in both sexes.