[Gestagen-estrogen combinations in gynecology. On the history, dosage and use of a hormone principle].

The first experimental and clinical investigations with gestagen-oestrogen combinations were undertaken in the late 'forties and the early' fifties of this century. In the course of further research and development, the dosage and mixture ratio of this hormonal principle were adjusted, according to the physiological status of the corpus luteum phase and its imitation by means of administration of hormonal doses. Considering the relatively large individual variations, an average daily production of 0.05 mg oestradiol/oestrone and 25 mg progesterone can be assumed, the mixture ratio being 1:50. Further indicators for the dosage were obtained by studying the biological valency of the semi-synthetic substances on the basis of the following parameters: transformation dose, menstruation delay test, anti-oestrogenic effectiveness and ovulation inhibition dose. Finally, dosage was also determined by the relevant indications; in this respect, depending on the intended use, preparations with the emphasis either on the oestrogen component or the gestagen component were deliberately produced. Up to the end of the 'fifties', parenteral gestagen-oestrogen combinations were the only preparations available for gynaecological hormonal therapy. Oral medication was predominant from 1957 onwards. The high ranking achieved by the combination preparations was due to their properties with respect to regulating menstrual haemorrhage and inhibiting proliferation and ovulation, as well as to their antiandrogenic properties. As far as methods of application were concerned, cyclical administration was most frequently employed (including phase variants), therapeutic amenorrhoea being second, whereas high-dosage application in the sense of hormonal pseudopregnancy was less often used. The gestagen-oestrogen combinations have become the most important hormonal principle in gynaecology as therapeutic agents and hormonal contraceptives.