Biological Effects of Various Doses of Conjugated Equine Estrogens in Postmenopausal Women*

To determine which dosage of estrogen might provide physiological replacement and also avoid possible harmful side effects, 21 postmenopausal women were studied before and after the oral administration of conjugated equine estrogens. The dosages studied were 0.15, 0.30, 0.625, and 1.25 mg/day, with each being given for 6 weeks. Fifteen premenopausal women were also studied, and their values were presumed to reflect normal physiological function. Variable responses of the different biochemical and biological markers of the action of estrogen were observed. Both LH and FSH levels showed stepwise decreases with increasing amounts of estrogen, but even 1.25 mg/day did not suppress these hormones to the range found in premenopausal women, suggesting a subphysiological response. The lower dosages of conjugated estrogen had minimal effects on vaginal cytology, with only the 1.25-mg dose changing the maturation index to values similar to those found in premenopausal subjects. The 0.3-mg dose of conjugated estrogen was the lowest amount that resulted in a significant reduction (P < 0.05) of the urinary calcium to creatinine ratio (an index of bone resorption). Liver protein synthesis was the most sensitive parameter to the action of estrogen. Hepatic resoponses were variable depending on which protein was assessed. These data indicate that the oral administration of conjugated equine estrogens results in inconsistent effects. All doses exerted subphysiological, physiological, and pharmacological responses at the different sites of action.