Regression of Pathologic Changes Induced by the Long-term Administration of Contraceptive Steroids to Rodents

Abstract

The induction of pathologic changes with hormone steroids has been studied in rodents, although comprehensive studies are lacking on the potential reversibility of these lesions. For these purposes, groups of rats were treated with quingestanol acetate and quinestrol, a progestogen-estrogen combination, for 50 weeks and observed for a subsequent 30-week period. Treatment resulted in a significant body weight gain suppression and reduction of food consumption which recovered after withdrawal. Other significant treatment-related effects were hair loss, ataxia due to pituitary enlargement, mammary chain masses with histologic adenocarcinoma, lens opacities, ovarian atrophy with follicular arrest, and uterine atrophic changes with suppurative inflammation throughout 50 weeks. Cessation of treatment did not effect hair loss or lens opacities, while mammary chain masses decreased in size and in incidence; mammary gland tumors showed regressive changes including the disappearance of adenocarcinoma, and the incidence of ataxia diminished together with reduced pituitary weights. Chromophobe cell hyperplasia with decreased eosinophils and acidophils and hemorrhage into the pituitary was observed up to 50 weeks and the tinctorial affinity of basophils and acidophils returned after withdrawal. Ovaries and uteri, which become atrophic and sustained chronic suppurative inflammation in the treatment phase, showed reduction of inflammatory reaction and disappearance of suppuration after withdrawal, and endometrial regeneration occurred with luteal cells seen in the ovaries. These results revealed the regressive characteristics of some of the mammary gland carcinomas as well as steroid-induced endocrine and pathologic lesions other than tegumentary and ocular changes in rats receiving high levels of steroids for prolonged periods of time.

Hormone Replacement Therapy, Reproductive Factors, and Cataract The Blue Mountains Eye Study

“…Interestingly, a recent randomized trial conducted in China found that subjects given a combination of niacin and riboflavin (which helps maintain levels of the antioxidant glutathione) were at increased risk of posterior subcapsular cataract (17). A small study in rats found that a combination of estrogen and progestin led to increased cataract formation (18). Further basic biologic research is needed on the effect of estrogen on the lens.…”

Endocrine Glands

“…50 The pituitary changes were sufficient to displace the brain and raise intracranial pressure with resultant early death in some animals. The daily treatment schedule resulted in average pituitary weights of over 80 mg and the weekly treatment over 120 mg per 100 g body weight (compared with control mean of approximately 5 mg/100 g body weight).…”

“…Despite these variable histological and cytological features, the largest proportion of spontaneous rat pituitary adenomas contains prolactin. 50 Massively enlarged pituitary glands, sufficient to cause severe signs of compression of the central nervous system regressed upon withdrawal of treatment raising the possibility that lesions diagnosed as pituitary adenomas may not all be autonomous neoplastic lesions. Some are totally unreactive to antisera to all the usual pituitary hormones.…”

Protective effects of estrogen in a rat model of age-related cataracts

“…Rats treated with oral contraceptives containing estrogen and progestogen have an increased incidence of cataracts compared with nontreated controls, suggesting that estrogens may actually promote cataract formation (15). However, the effectiveness of estrogen in these treatments is not certain, because the uteri of the treated animals were atrophic (15); progestogen may have produced a predominantly antagonist effect. In another study, long-term treatment with the antiestrogen tamoxifen increased the incidence of cataracts in rats (16).…”