Selective oestrogen receptor modulators (SERMs) are the new designer oestrogens, constructed to exert tissue-specific oestrogen effects. With the US Food and Drug Administration approval in December, 1997, of the first SERM, raloxifene, a new age of preventive health for women is upon us. But perhaps these drugs are not as new as they are purported to be.
There is some evidence that digoxin may share intriguing similarities to SERMs. Cardiac glycosides share a structural homology with steroid hormones (figure
) which has prompted investigations of possible functional similarities. In 1979, The Lancet
published an epidemiological review by the US National Cancer Institute which showed that women with breast cancer who took digoxin had smaller, less aggressive tumours and were less likely to develop metastatic disease than those not on digoxin.1
The investigators concluded that digoxin “interferes with the oestrogen receptors in some way”. This finding is supported by the well-recognised oestrogen-like side-effect of digoxin—gynecomastia in men.
Structural homology between oestrogen receptor-active compounds and a cardiac glycoside
The effects of cardiac glycosides on the rat uterus has been reported. Digitoxin, like oestradiol, significantly increased uterine weight in rats, whereas digoxin did not.2
Conversely, more recent studies suggest that oestrogens may modulate the autonomic nervous system;3
an effect touted as one of digoxin's possible mechanisms of action. In fact, digoxin's potential salubrious actions have been poorly defined—maybe they are oestrogenic in nature? We are unaware of any published reports of the effect of cardiac glycosides on lipid profiles and perhaps future studies will address digoxin's effects on bone metabolism.
As with most advances in medicine, new therapeutics prompt examination of older agents. Our old friend digoxin may be more in vogue than we thought. Could this agent have tissue-specific oestrogen effects, like the new designer oestrogens?