Clinical evidence supporting the rationale for constant oestrogen, intermittent progestogen hormone replacement therapy.

Hormone replacement therapy (HRT) effectively relieves vasomotor and other symptoms associated with menopause, yet is underutilised by the majority of menopausal women. Current HRT regimens combine continuous oestrogen with continuous or sequential progestogen in order to achieve the beneficial effects of oestrogen while avoiding the potential for increased risk of endometrial cancer. Uterine bleeding and other adverse progestogenic effects are major reasons for patient noncompliance and early discontinuation of combination HRT, which can ultimately limit the achievement of long-term oestrogenic benefits. A novel constant 17beta-oestradiol, intermittent norgestimate regimen has been developed based on theoretical hormone receptor dynamics in an attempt to minimise the hormonal doses needed, thereby potentially reducing the occurrence of adverse effects associated with higher oestrogen and progestogen doses. Clinical trial data with this novel low-dose HRT regimen demonstrate effective relief of vasomotor symptoms in postmenopausal women, acceptable bleeding rates, no endometrial hyperplasia, beneficial effects on lipids, and excellent tolerability. This regimen has the potential to increase long-term use resulting in important clinical benefits.