This may possibly be due to inadequate tissue exposure of the uterus to raloxifene in these estrogen-rich individuals.In premenopausal women, raloxifene increases levels of follicle-stimulating hormone (FSH) and estradiol. Conversely, in postmenopausal women, raloxifene has been found to reduce levels of the gonadotropins, luteinizing hormone (LH) and FSH, while not affecting levels of estradiol. Raloxifene also decreases prolactin levels in postmenopausal women. In men, raloxifene has been found to disinhibit the hypothalamic–pituitary–gonadal axis (HPG axis) and thereby increase total testosterone levels. Due to the simultaneous increase in sex hormone-binding globulin (SHBG) levels however, free testosterone levels often remain unchanged in men during therapy with raloxifene.Raloxifene has estrogenic effects on liver protein synthesis. It increases SHBG levels in both pre- and postmenopausal women as well as in men. The medication decreases levels of total and low-density lipoprotein (LDL) cholesterol, C-reactive protein, apolipoprotein B, and homocysteine. Conversely, it has little effect on levels of triglycerides and high-density lipoprotein (HDL). Raloxifene has been shown to inhibit the oxidation of LDL cholesterol in vitro. The medication has been found to decrease insulin-like growth factor 1 (IGF-1) levels in pre- and postmenopausal women as well as in men. It has also been found to increase insulin-like growth factor binding protein 3 (IGFBP-3) levels in pre- and postmenopausal women. Due to activation of estrogen receptors in the liver, raloxifene has procoagulatory effects, such as decreasing levels of fibrinogen and influencing levels of other coagulation factors.
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"Raloxifene". Drug Information Portal. U.S. National Library of Medicine. "Raloxifene hydrochloride". Drug Information Portal. U.S. National Library of Medicine.