BACKGROUND OF PROBLEMIn recent years the literature of gerontology has abounded with the pros and cons of therapy involving the major sex steroids. Yet neither unanimity of experimental evidence nor concurrence of clinical opinion has characterized the field. The relatively early involution of the gonads in comparison to the other organs of the endocrine system impresses one as suggesting more than a casual correlation between their reduced functioning and the many other structural and functional changes by means of which senescence is identified. Claims for the effects of various therapeutic regimens have covered the entire spectrum from rather hostile opposition through caution and reserve to almost hysterical optimism. Furthermore, partisanship, rather than impartiality, has often been characteristic of evaluative attempts. Indeed, it would not be wise to sample but a single paper and then try to generalize on the basis of the group of papers from which it was drawn.As Masters stated in a recent article (1), it is up to the advocates of a new type of therapy to demonstrate its merits rather than the responsibility of the skeptics to discredit it. In other words, the correct procedure for appraising any new form of therapy is to assume the validity of the null hypothesis-i.e., that the proposed therapy has no beneficial effects-and then attempt to disprove it. When the therapeutic agent is presumed to have a discrete and specific function to perform, such as lowering of body temperature or destruction of a known bacillus, the justifiability of rejecting the null hypothesis at a given level of confidence is not difficult to demonstrate. However, when the effects of the therapy are believed to be generalized and widespread, affecting simultaneously many organ systems and networks of physiologic functioning, a simple all-or-none acceptance or rejection is seldom feasible. Judgments of the usefulness of steroid therapy are not independent of what is considered acceptable as a criterion of improvement. Changes in the weights of organs, in the number of cell mitoses, in vascularity, in muscle strength, in intelligence and memory, or in reduction of the tendency to hot flashes have all been proposed at one time or other as relevant criteria. Thus experimental attempts to assess the value of a specific form of therapy are confounded by choice of criterion and method of evaluation.With respect to histologic and physiologic changes resulting from hormone therapy, the evidence in the literature is mostly favorable. Positive changes attendant upon different therapeutic regimens have been reported by Masters and associates (2, 3, 4), Kountz (5), McGavack, Weissberg and Pearson (6), * Research Associate.
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