The menstrual cycle of the primates VIII—The œstrin-withdrawal theory of menstruation

Abstract

In spite of ample evidence that œstrin is not the sole endocrine factor directly concerned in the changes which take place in the uterus, the hypothesis that normal menstruation is essentially a katabolic process following a temporary cessation of œstrin activity, still finds acceptance ( e. g ., De Jongh and Laqueur, 1931; Allen, 1932). This hypothesis, formulated originally by Allen (1927), is primarily based upon three sets of well-established observations on monkeys. These are: ( a ) uterine bleeding follows soon after bilateral, sometimes after unilateral, ovariectomy;( b ) uterine bleeding may be precipitated by injury to large or cystic ovarian follicles; and ( c ) uterine bleeding almost always begins a few days after the cessation of injection of œstrin into both normal and castrate monkeys. Corresponding observations have also been reported for man. Thus, the first is a clinical fact which had been recognized long before monkeys were used experimentally in studies of the reproductive processes. The same applies to the second; for example, as long ago as 1890 Cohnstein reported that menstruation is precipitated by manual pressure of the ovaries. The third finding has also been recently shown to be true for man; thus Kaufmann (1934) found that uterine bleeding occurs in women after the administration of 1,000,000 international units of œstrin. In spite of its apparently solid foundation, the œstrin-withdrawal theory of menstruation nevertheless falls short as an adequate statement because of its failure to account for certain essential facts. These deficiencies are discussed in the conclusion to this paper. Regarded purely as a working hypothesis, however, the theory immediately suggests that menstruation would be completely inhibited or delayed by the administration of œstrin previous to the expected onset of uterine bleeding. This deduction has not been systematically tested. The following are the only observations bearing on the question that I have been able to find, ( a ) Kurzrok (1932) has reported that too prolonged injections of œstrin may completely stop menstruation in young patients with oligomenorrhœa; ( b ) Hartman (1934) has described an experiment in which a monkey was given 995 rat units of œstrin over a period of 8 days, beginning on the 18th day of a cycle. Menstruation began during the course of injections, at approximately the time that it would have occurred if œstrin had not been given, and demarcated a cycle of 24 days. Unfortunately, conclusions cannot be drawn from either of these observations, although what both Kurzrok and Hartman did is essentially what should be done if the œstrin-withdrawl hypothesis of menstruation is to be critically tested. The experiments described in this paper, carried out in 1933 and 1934, aimed at providing such a test. Attempts were made, by injecting keto-hydroxy-œstrin (œstrone), to influence the rhythm of successive cycles of two regularly menstruating monkeys.