EFFECT OF DYDROGESTERONE ON HUMAN ENDOMETRIUM AND OVARIAN ACTIVITY

ABSTRACT Some of the pharmacological properties of dydrogesterone (9β,10α-pregna-4,6-diene-3,20-dione) were studied in the human female. When dydrogesterone was administered by mouth in daily doses of 10 mg for 10 to 14 days to amenorrhoeic women primed with ethinyloestradiol progestational transformation of the endometrium was found in 30 out of 32 artificial cycles. When administration of ethinyloestradiol was not continued until the end of the artificial cycle, break-through bleeding occurred in 30 out of 35 occasions, whereas it took place in only 9 out of 30 cycles, when ethinyloestradiol was given throughout the cycle. Dydrogesterone was administered in 77 cycles to women with incapacitating dysmenorrhoea from the 5th to the 25th day. When the daily dose was 10 mg, the subsequent period was not incapacitating on 20 out of 31 occasions whereas with daily doses of 15 or 20 mg the corresponding results were 40 out of 46. Forty-eight out of 60 cycles labelled »not incapacitating« were completely painless. No side-effects whatsover were observed. Studies of basal temperature records in amenorrhoeic and dysmenorrhoeic women indicate that dydrogesterone has no thermogenic activity. When the compound was given to normally menstruating women in daily doses of 10 to 40 mg from the beginning of the cycle, it did not interfere with the characteristic biphasic temperature pattern, with the urinary excretion of oestrogen and pregnanediol or with the formation of a corpus luteum as proved at laparotomy. Even following the administration of as much as 400 mg per day a corpus luteum was found. It is concluded therefore, that dydrogesterone does not inhibit ovulation. In a previous paper the effect of alterations in the stereochemical configuration of steroid hormones at C-9 and C-10 on their pharmacological properties was reported (Reerink et al. 1960). Among various derivatives of 9β,10α-progesterone (retro-progesterone) tested, one, 9β,10α-pregna-4,6-diene-3,20-dione (hereafter referred to as »dydrogesterone«), see Fig. 1, was found to be a potent progestational agent when administered orally to rabbits (Schöler 1960) and to amenorrhoeic women (Tillinger & Diczfalusy 1960). The purpose of the present communication is to report on some of the pharmacological properties of this compound in the human female.