THE EFFECTS OF CHORIONIC GONADOTROPIN AND PROLACTIN ON THE MAINTENANCE OF CORPUS LUTEUM FUNCTION*†

Publisher Website
Google Scholar
Abstract
IN RECENT years increased importance has been attached to corpus luteum dysfunctions as causes of habitual abortion, sterility and menorrhagia (1). The reported investigations to correct corpus luteum disturbances in humans in a direct physiologic manner with luteinizing or luteotropic gonadotropins have been indeterminate and led to the present study. After Aschheim and Zondek had reported in 1927 that human chorionic gonadotropin induced follicular maturation and corpus luteum formation in rats and mice (2), the hormone was used extensively in the human as a luteinizing agent, most commonly in instances of functional uterine bleeding. The initial enthusiasm (3) waned gradually as further reports (4) of the responses in humans and monkeys following such therapy provided little evidence to support the therapeutic value of chorionic gonadotropin in ovarian dysfunctions. Since then, references to such therapy in the literature have, in the main, been limited to reviews and editorials which have questioned the value of chorionic gonadotropic therapy in women (5, 6). As recently as 1949 one reviewer considered any therapeutic responses to the drug to be due to the psychic effect of the injections and suggested, as had others (7–9), that failure of response might be due to an inadequacy of the usual clinical dosages of 500 and 1,000 I.U. Hamblen and Ross (8) have postulated that the effective pharmacologic dose in the human is probably in excess of 8,000 units daily. Hisaw (10) reported a limited prolongation of corpus luteum function in the monkey with the use of large daily doses (1,000 I.U.) of chorionic gonadotropin. Since large dosages of the commercial products were bulky and had caused severe reactions in the human (9, 11, 12), similar investigations in women were not possible until Brown and Bradbury's (11) recent use of a special chorionic gonadotropin preparation.1 This product prolonged the life span of corpora lutea, as evidenced by menstrual histories, endometrial tissue studies, urine pregnanediol assays, and the finding of corpora lutea at laparotomy. In 2 cases, the daily administration of 20,000 I.U. of the hormone, the largest amount used, produced menstrual delays of twelve and nineteen days so long as the injections were continued, and in 1 patient, 5,000 I.U., the minimal effective amount, deferred menses for six days. A fourth patient received 10,000 I.U. of the hormone and noted a menstrual delay of ten days. Doses of 2,500 I.U. were ineffectual. The action was considered to be luteotropic, since it was limited to the maintenance of the corpus luteum. Since then de Watteville (12) similarly has used 20,000 I.U. of chorionic gonadotropin with analogous corpus luteum effects in 3 patients, but reported severe general and local toxic reactions in all cases. The luteotropic doses advised by Brown and Bradbury (11) have not been used generally, a) because their special preparation is not generally available, and b) because of the relatively high cost of such dosages and toxic reactions to them, when available commercial products are used.