Some patients (20%-28%) do not respond to clomiphene citrate in spite of high dose as the anti-oestrogenic effect is dose-dependent; a daily dose of clomiphene citrategreater than 150mg is not recommended.16
Most of the phytooestrogens-based preparations freely available on the market are proposed as legal and non-toxic anti-oestrogenic compounds (to counterbalance the side effects of anabolic steroids, mainly based on methoxyflafones (Usui, 2006)), as fat lowering products or sexual enhancing compounds based mainly on plant extracts from Commiphora Mukul (Guggulsterone), Eurycoma Longifolia (methoxyflavone), Vitex Agnus Castus and Astragalus Root (isoflavones).
Special emphasis has been placed on the mechanism of action of the aromatase inhibitor compared to that of clomiphene citrate, since the aromatase inhibitor lacks an anti-oestrogenic effect on the endometrium and cervical mucus.
Where concentrations of endogenous oestrogens are relatively high, as in premenopausal women, they can exclude the more potent oestrogen from binding to the receptor and, therefore, the overall effect is anti-oestrogenic. The presence of two types of oestrogen receptors, the classic ER[alpha] and the more recently discovered ER[beta], is of special relevance to the mechanism of action of phytoestrogens.
A recent Oxford University study found smokers take, on average, around two months longer to conceive because ciggies produce anti-oestrogenic chemicals which can affect egg quality and even suppress ovulation.
The centre, which is based at the Welsh School of Pharmacy at Cardiff University, is trying to identify the complex mechanisms that the cancer cells use to become resistant to these anti-oestrogenic drugs.