The present study shows the effects of two different steroid replacement therapies, with conjugated estrogens or with a new synthetic steroid derivative, ORG OD14, on plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels in postmenopausal subjects. Blood samples were collected before treatment and after 1, 2 and 4 months of treatment; a third group of patients was treated with placebo. After 2 months of treatment both groups of patients who underwent steroid supplementation showed circulating levels of beta-EP and beta-LPH higher than basal levels. ORG OD14 treatment increased beta-EP and beta-LPH levels more than conjugated estrogens at the 2nd month of therapy. No further change was found after 4 months. The two drugs were effective in reducing hot flushes and improving physical and psychological symptoms. These data indicate that sex steroids are able to increase beta-EP and beta-LPH secretion in postmenopausal women, with a concomitant relief of climacteric symptoms.