Comparison of megestrol acetate and clomiphene citrate as supplemental medication in postmenopausal oestrogen replacement therapy.

In a prospective clinical trial lasting one year, 35 postmenopausal women with severe climacteric symptoms were cyclically treated with conjugated oestrogens (1.25 mg daily). This oestrogen replacement therapy was randomly supplemented with 10 mg of megestrol acetate daily (18 women) or 50 mg of clomiphene citrate (17 women) for 10 days four times a year. Both treatment regimens significantly alleviated climacteric symptoms. At the end of the oestrogen-megestrol acetate treatment no endometrial proliferation or hyperplasia was seen, while at the end of the oestrogen-clomiphene citrate treatment the endometrium was proliferative or hyperplastic in two women and atrophic in the other 15. Regular uterine bleeding occurred in each woman after megestrol acetate but never after clomiphene citrate administration. Break-through bleeding during the oestrogen treatment periods appeared in the megestrol and clomiphene groups in five and eight women, respectively. There were no clinically adverse hormonal or metabolic changes during megestrol acetate or clomiphene citrate treatment periods. Our results provide further evidence that in addition to progestins postmenopausal oestrogen replacement therapy can safely be supplemented with antioestrogen and thereby avoid the bleeding which occurs regularly after progestin withdrawal.