In men and premenopausal women the major sites of steroid hormone synthesis are the gonads. Castration decreases circulating testosterone in males by over 95% and oestrogens in premenopausal women by 60% (relative to follicular phase levels).These endocrine effects produce benefits in about 80% of men with metastatic prostate cancer and in 30-40% of unselected premenopausal women with advanced breast cancer. Oophorectomy is rarely beneficial in postmenopausal women because the postmenopausal ovary produces little oestrogen.
These response rates represent the gold standard against which to compare other forms of endocrine therapy. Hypophysectomy and adrenalectomy have been used in postmenopausal women with breast cancer. Whilst these may produce benefit in about one-third of cases, the procedures do have significant morbidity and lack specificity, removing other classes of hormones in addition to sex steroids. The irreversible nature of surgical ablation of endocrine organs, when all patients cannot be guaranteed benefits, has provided the impetus to develop alternative drug-based therapies that are specific, reversible, and self-limiting. Thus if therapy proves ineffective, drug withdrawal allows hormone levels to return to normal with amelioration of side-effects.
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