Metabolic, hormonal, and vascular changes after synthetic oestrogen therapy in oophorectomized women

Mestranol, the three-methyl ether form of ethinyloestradiol and one of the two oestrogens used in oral contraceptive steroids, was administered in a dose of 0.02 mg daily for 120 days to 25 oophorectomized women.Urinary oestriol and pregnanediol excretions were unaffected by the mestranol treatment but there was a shift of the maturation index of the vaginal smear to the right, indicating a correction of the pretreatment oestrogen deficiency. No significant change in the blood pressure or electrocardiograph recordings occurred during this relatively short period of administration. A significant rise in the serum protein-bound iodine, which might be regarded as an undesirable effect of mestranol on a long-term basis, occurred. Hepatic function as measured by bromsulphthalein was not impaired by the treatment. Mestranol had no effect on the total body water or on the total exchangeable potassium of the women. Its two most serious adverse effects were impairment of glucose tolerance and a high incidence (16%) of venous thrombo-embolic disease.The gravity of the adverse effects far outweighs any beneficial ones and precludes the use of mestranol alone for long-term hormone replacement therapy in postmenopausal women.