COMPARATIVE CLINICAL EVALUATION OF ESTROGENIC PREPARATIONS BY THE MENOPAUSAL AND AMENORRHEAL INDICES*†

Abstract

The comparative efficacy of steroidal and nonsteroidal estrogens was studied in the man by means of the menopausal and amenorrheal indices. The menopausal index represents a numerical conversion factor of the severity of the 11 most common menopausal symptoms. 18 different prepns. were used in comparative formulation of the menopausal index, including most of the oral estrogenic prepns. available, vitamin E, phenobarbital, and placebo tablets. Based upon changes induced in the menopausal index and the dose employed, the following order of effectiveness was observed with the various preparations: ethinyl estradiol (Estinyl), conjugated estrogens-equine (Premarin) and ethinyl estradiol plus free estradiol (Amboral) were the most effective. Vit. E was no more effective than a placebo. Phenobarbital was more active than a placebo in controlling the menopausal symptoms. Various crystalline estrone sulfate compounds, including a piperazine derivative (sulestrex), were not as effective as equivalent doses of conjugated estrogens-equine. Stilbestrol, dienestrol, hexestrol and TACE, together with estradiol Unguents (Progynon buccal tablets) and tablets (Progynon tablets) and equine estrogenic factors, were intermediate in activity between the first 3 groups of drugs and phenobarbital. Evaluation by the amenorrheal index confirmed the order of activity assayed by the menopausal index. The amenorrheal index represents the numerical conversion of the degree of withdrawal bleeding occurring after the patient has received therapy for 3 weeks with the estrogen to be tested, followed by a single intramuscular injn. of 100 mg. of progesterone. The factor is obtained by dividing the duration of bleeding in days by the time required for onset of bleeding in days after the admn. of progesterone, and multiplying by the extent of bleeding. Ethinyl estradiol, alone and in combination with free estradiol, and conjugated estrogens-equine were the most effective estrogens when administered in twice the daily dose used in obtaining the menopausal index. The use of these 2 indices has resulted in reproducible hormone assay procedures for the comparative evaluation of estrogens in the human.