HRT: some unresolved clinical issues in breast cancer, endometrial cancer and premature ovarian insufficiency.

Many important issues regarding HRT and the management of postmenopausal women are unresolved and require ongoing consideration and some explanation. HRT is only one of many factors affecting the risk of breast cancer and the risk of breast cancer is not increased in past users of HRT. There is seemingly a paradox in the effect of body weight and HRT on breast cancer risk. It is unclear whether the benefit of giving progestin with estrogen to prevent endometrial cancer in HRT outweighs the increased risk of breast cancer. Sequential HRT may not fully prevent endometrial cancer, and continuous combined regimes are to be preferred. The prevention of the consequences of premature ovarian insuffiency, both immediate and long term, has been neglected, and a strong case can be made for estrogen replacement therapy in all women with premature ovarian insuffiency, particularly following bilateral oophorectomy.