Metabolic Effects in Man of Steroids With Progestational Activity

Abstract

For several years our group has been studying the metabolic properties of progesterone in man.1-4 Having demonstrated some rather surprising effects of the administered hormone, which will be reviewed subsequently, we have been endeavoring to gain some understanding of the mechanisms of its action and the role that progesterone plays in regulating the economy of the body during the reproductive years in women. This has involved the exploration of metabolic interactions of progesterone with other internal secretions and a study of the relationship of chemical structure to physiological action. It is in large measure from the latter point of view that we have studied the effects of other steroids that possess progestational activity.It should be emphasized at the outset that this is a preliminary report. Studies on some of the substances must be repeated in other subjects and under different conditions. Compounds have been studied more or less as they became available. The steroids tested have not always been those that could provide the most definitive leads on the structural characteristics responsible for each of the metabolic effects of progesterone.It would probably surprise no one if a synthetic progestational compound failed to simulate all of the actions of progesterone. If, however, a drug is proposed as a substitute for progesterone because of exceptional potency or ease of administration, it would seem highly desirable that it mimic the full constellation of progesterone's effects, which include its influence on the endometrium, myometrium, the hypophysis, the breasts, body temperature, and the metabolism of protein, sodium, chloride, potassium, and water. On the other hand, the potential therapeutic value of a new agent might depend upon the accentuation of some properties of progesterone and the suppression of others or perhaps even some effect not manifested by progesterone. Accordingly, we also examined the metabolic characteristics of some progestational steroids in the hope of contributing to their evaluation as therapeutic agents.I n 1944 Abels and Dobriner5 published a single experiment that indicated that progesterone was moderately catabolic when given to a man in a dosage of 100 mg./day. For a long time this brief and rather obscure report was and The Upjohn Company, Kalamazoo, Mich. 588We also have a clinical interest in progestational steroids, however.

Kidney and Adrenocortical Hormones

“…From unpublished observations and studies in the literature [19,24,44,51,52,56,57,80,93], it is reasonable to propose a systemic relationship between these steroids. It is probable that the Na+-retaining activity of a given adrenal steroid can be 'antagonized' by another adrenal steroid or its analogue with greater glucocorticoid properties, i.e., Na+retention due to Aldo or DOCA is antagonized by CpF or cortisone while that of the latter two steroids is antagonized by prednisone which in turn can be antagonized by 6-methylprednisolone.…”

Effect of Medroxyprogesterone Acetate and <i>d</i>-Norgestrel on Plasma Renin Activity, Antidiuretic Hormone, and Urinary Aldosterone in Postmenopausal Women

“…The 17-OH derivatives, for example, are without natri uretic potency and do not stimulate the renin-aldosterone system, while norethisterone slightly increases natriuresis and urinary aldosterone with out an increase in PRA or angiotensin II [8,13]. Aldosterone excretion was transiently increased by chlormadinone acetate, but norethindrone had no significant effect [3], There have been no previous publications concerning the relationship between ADH and the progestational compounds.…”

Effect of Long‐term Salbutamol Treatment on Renin‐aldosterone System in Twin Pregnancy

“…The depot-formed oxyprogesterone, administered during the study and thought to have a gestagenic significance in pregnancy, did not possess any discernible effect on aldosterone excretion according to the results of this study. This is quite conceivable, because 17a-OH-progesterone, like certain other synthetic progestagens, is devoid of natriuretic effect as shown by earlier studies (9,11).…”

“…1OO-t 12 (9) 104k 16 ( 5 ) 14 97-tl6 (7) 111123 (6) 21 116-t 5 (4) 109-tl1 (4) dU-K (mmol/day) Group A Group B 6 9 i 5 (9) 90+18 (4) 82k7 (9) 108+20 ( 5 ) 8526 (7) 99-t 16 (6) 89-t7 (4) 98k 10 (4) dU-Na/dU-K Group A Group B 1.9-tO.4 (9) 1.320.3 (4) 1.3k0.2 (9) 1.020.1 ( 5 ) 1.3-tO.2 (7) 1.310.4 (6) 1.3-tO.1 (4) l.O-tO.l (4)…”