PITUITARY AND OVARIAN FUNCTION IN WOMEN ON CONTINUOUS LOW DOSE PROGESTOGENS; EFFECT OF CHLORMADINONE ACETATE AND NORETHISTERONE

Abstract

ABSTRACT Chlormadinone acetate (6-chloro-17α-hydroxypregna-4,6-diene-3,20-dion-17-acetate; hereafter CAP = chloro-acetoxy-progesterone) was administered continuously in daily oral doses of 0.5 mg to three normally menstruating women and the urinary excretion of luteinizing hormone (LH), oestrone (OE1), 17β-oestradiol (OE2), oestriol (OE3) and pregnanediol (5β-pregnane-3α,20α-diol; hereafter P-diol) was studied. Forty-eight hour specimens were analyzed during a pretreatment cycle, the first and fourth CAP cycles and the first posttreatment cycle. Considerable individual variations were found in all parameters studied. In addition, significant differences were observed in the response of the same subjects to the first and to the fourth course of CAP. A well defined midcycle LH-peak was found in all pretreatment cycles. The administration of CAP abolished the midcycle LH peak in 5 of the 6 treatment courses studied; the »ovulatory« LH peak re-appeared in all subjects during the first posttreatment cycle. The oestrogen and P-diol excretion patterns were often inconsistent with the LH pattern; on several occasions a distinct »ovulatory« oestrogen or P-diol pattern was found in the absence of any midcycle LH peak. Such a P-diol pattern was accompanied by an elevated basal body temperature. A similar study was conducted in two normally menstruating women, before and during the continuous administration of a low dose (0.1 mg/d) of oestrogen-free norethisterone (17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one; hereafter NET), followed by a course of a high dose (2.5 mg/d) of NET. The inhibitory effect of NET on LH excretion was less marked than that of CAP. The oestrogen excretion remained rather high. In only one of the two subjects did the administration of 0.1 mg of NET abolish the »ovulatory« P-diol pattern. Elevated P-diol values were not found during the administration of 2.5 mg of NET. The correlation between »ovulatory« LH- and P-diol patterns was rather poor. The data indicate that the continuous administration of low doses of CAP interferes only slightly with oestrogen excretion, but has a marked effect on the midcycle LH-peak. It is concluded that the assertion of ovulation inhibition on the basis of urinary LH- and steroid excretion studies may be associated with major uncertainties. Also, it seems that for a better understanding of the mechanism of contraceptive action of low level progestogens more information is required on the minimal amounts of urinary LH and P-diol, which are still compatible with a normal ovulation and corpus luteum function.