Potency and hepato-cellular effects of oestrogens after oral, percutaneous, and subcutaneous administration

Abstract

During the last five years much attention has been focused upon the hazards of oestrogens on the endometrium and other potentially adverse effects have been less comprehensively investigated. Although oestrogen therapy has been associated with hypertension (Crane et al., 1971) and with cardiovascular and gall-bladder disease (Gow and MacGillivray, 1971; Boston Collaborative Drug Surveillance Program, 1972; Rosenberg et al., 1976; Stein et al., 1976), the validity of certain of the reports remains disputed as other data indicate a reduction in risk of death from cardiovascular disease with long-term oestrogen exposure (Ross et al., 1981). Adverse changes in fibrinolytic/coagulation mechanisms have been observed during oestrogen therapy (Åstedt, 1971; Coope et al.,1975), but it is not clear if these side effects are caused by all oestrogens, or if they are dose-dependent. Meaningful, comparative data on the biological effects and relative potencies of different oestrogens are incomplete and this is partially due to a lack of pertinent studies and also to a failure to appreciate that different end-organs and physiological systems exhibit quite dissimilar sensitivities to exogenous oestrogens. For example, Geola et al., (1980) have reported that in post-menopausal women conjugated equine oestrogens 1.25 mg/day exhibited supra-physiological effects on the hepatic synthesis of renin substrate, physiological actions on the vaginal epithelium, and sub-physiological activity in terms of suppression of gonadotrophin levels.