The first two papers in this series (1, 2) described various marked metabolic derangements resulting from paralytic acute anterior poliomyelitis, particularly those involving nitrogen, creatine, calcium and phosphorus metabolism. The third paper (3) related the results of an attempt to minimize these extensive derangements by use of the slowly oscillating bed. The present paper reports results of an effort to modify the disordered metabolism of paralytic poliomyelitis by means of gonadal steroid hormones. These steroids have been shown in various clinical states to be effective in reducing the excretion of nitrogen, calcium and phosphorus and in favoring the positive balance of these elements. Because of these effects, it seemed reasonable to investigate whether or not gonadal steroids would act in a similar manner in a disease following which development of muscle and bone atrophy is prominent.More specifically, the suggestion that gonadal steroids might have value in paralytic poliomyelitis arose from a variety of studies and observations. The protein anabolic effects of androgens have been summarized by Kochakian (4). Papanicolaou and Falk (5) were evidently the first to show that testosterone administration would bring about hypertrophy of the general musculature, indicating that the retained protein was stored in muscle. The effects of androgens on calcium metabolism in post-menopausal and senile osteoporosis have been summarized by Albright and Reifenstein (6, 7). They and others (8-11 ) have 1Aided by a grant from the National Foundation for Infantile Paralysis. 2Present address: National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland. t Died, January 6, 1956. shown the effectiveness of androgens in the osteoporosis of Cushing's syndrome. Presumably androgens act by increasing the amount of protein osteoid matrix, essential for bone formation. Estrogen administration has been shown to be useful in postmenopausal osteoporosis (12, 13), in the osteoporosis of acromegaly (14) and in osteoporosis associated with Paget's disease ( 15 ). Less effective than androgens in enhancing protein deposition, estrogens are thought to act by stimulating osteoblasts to lay down more protein matrix.The effects of both types of gonadal hormones on the skeleton of animals have been extensively studied and summarized by Gardner and Pfeiffer (16). A study particularly related to the present one is that of Armstrong, Knowlton, and Gouze (17) in which disuse atrophy of the skeleton was brought about in mature rats by severing the brachial plexus; estradiol in modest doses was found generally to prevent the atrophy whereas testosterone did not, although only very large doses of the latter steroid were given.
PROCEDUREThe general plan, procedure, clinical care and diets employed in these studies were outlined in the first paper in this series (1). The present report is based on the data of seven patients (D.A., J.C., R.W., F.S., C.R., J.W. and R.V.K.), all of whom were stud...