Anti-oestrogens: their clinical physiology and use in reproductive medicine

The anti-oestrogens are important both as therapeutic agents in reproductive medicine and as tools to investigate the physiology of the oestrogen receptor and hormonal control mechanisms. Clomiphene occupies the oestradiol receptor and, although initially stimulatory, has a net antagonistic effect as oestrogen receptors are not replenished. The major fertility-enhancing effect is to cause an increase in LH and FSH output by increasing the frequency of pulsatile output of these hormones. Many effects due to an anti-oestrogenic effect have been postulated; some, such as an adverse effect on cervical mucus, have been proven. The clinical use of the anti-oestrogens is outlined in Table 1. In well chosen patients a rewarding pregnancy rate is obtained with minimal intervention and few important side-effects. The challenge for the reproductive biologist is successfully to manage the patient who is clomiphene-resistant, either because of failure to ovulate or failure to conceive once ovulation is induced.