CHLORMADINONE, A POTENT SYNTHETIC ORAL PROGESTIN: EVALUATION OF 1002 CYCLES.

A clinical evaluation of chlormadinone acetate a synthetic steroid preparation with marked and selective progestational effect on the endom etrium is presented. Like progesterone it demonstrates no estrogenic activity; in fact it is a potent antiestrogen and requires either endogenous or exogenous estrogenic priming of the endoemtrium to produce secretory effect. It does not show androgenic properties that might predispose either the patient or her female female to masculinization. 279 patients were followed for 1002 menstrual cycles. 143 received various dosages either alone or in combination with mestranol for either primary or secondary sterility lasting from 1 to 10 years; 90% had sterility of 2 years or more. These women were treated for 451 cycles. Withdrawal bleeding occurred within 7 days of cessation of therapy in 79.5% of cycles; in all but 5 of the remaining cases bleeding occurred within 14 days. The oral contraceptive group consisted of 130 women who took 80 mcg mestranol daily from Cycle Day 5 to 19 followed by 2 mg chlo rmadinone and 80 mcg mestranol taken from Day 20 to 24. 15 patients rec eived a hemogram a clotting profile routine urinanalysis and a battery of liver thyroid and adrenal function tests as well as endomet rial biopsy at 3-6 month intervals. In 98.7% of all cycles withdrawal bleeding occurred within 7 days; in 4 cycles there was pregnancy and in 2 patients failed to follow the regimen properly. 8 patients experienced prolonged menstrual flows and 1 markedly diminished flows. No adverse effects were found in any of the laboratory examinations. 6 patients were selected for special study while on chlormadinone therapy. In 3 with secondary amenorrhea investigators found secretory endometrium; in 3 with normal menstrual cycles regressive glandular changes with pseudodecidualization was found. Undesirable side effects included breakthrough bleeding some nausea (although less with chlormadinone alone than when combined with estrogen) mastalgia and dysmenorrhea. No cases of thrombophlebitis or pulmonary embolism were observed. Doses of 2-4 mg proved adequate to stimulate normal secretory endometrium with predictable withdrawal bleeding.