Pituitary and ovarian function in women on continuous low dose progestogens; effect of chlormadinone acetate and norethisterone.

To determine the effect of chlormadinone acetate and norethisterone on pituitary and ovarian function in women a study was performed on 5 normally menstruating healthy women of the following ages: K.M.: 31 A.S.: 21 G.O.: 34 G.T.: 23 and M.W.: 28. All were nulliparous with exception of M.W. who had 2 previous pregnancies. To determine the effect of chlormadinone acetate (CAP) 48 hour urine specimens were collected from subjects K.M. A.S. and G.O. continuously during a pretreatment (control) cycle followed by the first CAP cycle. Uninterrupted daily administration of CAP (.5 mg) continued during 3 more cycles but urine was only collected during the first pretreatment cycle. Basal body temperature was recorded daily. G.T. and M.W.s program consisted of the analysis of a pretreatment cycle a cycle with a low dose (.1 mg per day) of norethisterone (NET) followed by a course with a high dose (2.5 mg per day). No posttreatment was analyzed and the basal temperature was not recorded. M.W. estrogen assays could only be conducted during the high dose of NET. In all parameters studied; luteinizing hormone (LH) estrone (E) 17 beta-estradiol (E2) estriol (E3) and pregnanediol considerable variation was found. Significant differences were observed in the response of the same subjects to the first and fourth course of CAP. A well defined midcycle LH-peak was found in all pretreatment cycles while CAP abolished the midcycle LH peak in 5 of the 6 treatment courses. The ovulatory LH peak reappeared in all subjects during the first posttreatment cycle. The estrogen and pregnanediol excretions were often inconsistent with the LH pattern. On several occasions a distinct ovulatory or pregnanediol pattern with an elevated basal body temperature was found in the absence of any midcycle LH peak. In the NET patients estrogen excretion remained high and in 1 subject (.1 mg NET) had abolished the ovulatory pregnanediol pattern. 2.5 mg of NET did not elevate pregnanediol values with a correlation bet ween LH and pregnanediol patterns being rather poor. These data indicate that continuous administration of low dose CAP interferes only slightly with estrogen excretion but has a marked effect on the midcycle LH peak. Assertation of ovulation inhibition on the basis of urinary LH and steroid excretion studies has many uncertainties. Information on minimal amounts of urinary LH and pregnanediol which are compatible with normal ovulation and corpus luteum function is required for a better understanding of contraceptive action with a low level of progestagen. (AUTHORS MODIFIED)