overcomes the hypocorticosteroid effect, which explains the good tolerance of RU 486 when it is administered briefly, as in abortion or emergency contraception.
There are several potential uses of RU 486 or antiglucocorticosteroid analogues. The long-term use of RU 486—for instance, to treat tumors—may be improved if a compound blocking steroid biosynthesis is given simultaneously. In breast cancer this could be an antiaromatase because production of estrogens increases when adrenal androgen hypersecretion occurs with RU 486 treatment.
An antiglucocorticosteroid with a short half-life should be useful for the kinetic studies of the hypothalamus-pituitary-adrenal axis, in particular to classify different types of depression (Ammar et al., 1986; Kling et al., 1989; Krishnan et al., 1992). In several instances, an acute increase of glucocorticosteroids, for instance, during the stress of aggressive conditions, might be antagonized by RU 486, which could therefore protect against immune depression. Conversely, RU 486 might be detrimental in the pharmacological manipulation of septic shock (Broukaert et al., 1992).
It is not impossible that RU 486 or another antiglucocorticosteroid deprived of antiprogesterone effect might be useful in the treatment of certain cases of psychosis or arterial hypertension, since these two pathological features are remarkably cured when present in Cushing's syndrome treated with RU 486 administration [here RU 486 has been a lifesaving drug (see review in Chrousos et al., 1989)]. However, this will concern only a small number of patients. Whether some chronic conditions involving hypercortisolism, such as certain forms of obesity, can benefit from RU 486 is still debatable (Okada et al., 1992). The use of RU 486 (or analogues) has been suggested in premenstrual syndrome, postmenopausal flushes, Alzheimer's disease, and AIDS, but there is currently no firm scientific background to justify trials.
More generally, any long-term treatment with an antiprogestin or an antiglucocorticosteroid should be carefully followed up. Chronic antiprogesterone activity may create an unopposed estrogenic state, counteract the osteogenic effect of P, or interfere with the activity of P in the central nervous system. Signs of adrenal insufficiency may also develop.
It is probably the local use of RU 486, or its derivatives with antiglucocorticosteroid activity, that will develop rapidly. Trials are on the way for treating glaucoma, and for accelerating or amplifying the slow healing of wounds and burns, particularly in stressed or aging patients (who have increased or normal cortisol and low adrenal androgen levels).
Much work remains to be done (Hodgen, 1991). I single out four approaches that I believe to be most important.