This effect was similar regardless of Gail score, whereas the effects were markedly stronger for women with higher baseline estradiol

levels [206]. SERMs and menopausal symptoms In breast cancer patients, it has been well documented that tamoxifen increases both severity and frequency of hot flushes. The situation is likely less VS-4718 manufacturer severe when using raloxifene. Some RCTs did not buy GDC-0994 report an increased frequency or severity of vasomotor symptoms in women discontinuing oestrogen–progestin as compared with placebo [207, 208]. Nevertheless, other studies reported an increase in hot flushes when using raloxifene [209], which led to the suggestion of a gradual conversion to raloxifene from low-dose oestrogen, with BX-795 cell line a progression from 60 mg every alternate day to 60 mg/day. It has been showed in short duration studies that it is possible to avoid SERMs associated hot flushes and menopausal symptoms, using

a combination of a SEM (bazedoxifene) and estrogens (conjugated estrogens) [210]. Some non-skeletal side effects are favourable (breast cancer protection); others on the other hand are unfavourable (stroke risk, thromboembolism and endometrial cancer). The presence and the magnitude of these side effects vary between SERMs concluding that women with breast cancer treated with tamoxifen have an 82% increased risk of ischemic stroke and a 29% increased risk of any stroke, although the absolute risk remains small. Strontium ranelate Strontium ranelate is a first-line treatment for the management of postmenopausal osteoporosis. Its dual mode of action simultaneously reduces bone resorption and increases bone formation [211]. Strontium Gemcitabine concentration ranelate has a limited number of non-skeletal effects, for which most of

the evidence comes from post hoc analyses of these two trials. Strontium and cartilage Osteoarthritis involves the degeneration of joint cartilage and the adjacent bone, which leads to joint pain and stiffness. There is some preclinical evidence for an effect of strontium ranelate on cartilage degradation. Strontium ranelate has been demonstrated to stimulate the production of proteoglycans in isolated human chondrocytes, leading to cartilage formation without affecting cartilage resorption [212]. There is also evidence for an impact on biomarkers of cartilage degradation. Treatment with strontium ranelate was associated with significantly lower levels of urinary excretion of a marker of cartilage degradation (CTX-II) (p < 0.0001) [213, 214]. The potential for a clinical effect of strontium ranelate in osteoarthritis indicated that 3 years’ treatment with strontium ranelate was associated with a 42% lower overall osteoarthritis score (p = 0.0005 versus placebo) and a 33% reduction in disc space narrowing score (p = 0.03 versus placebo). These changes were concomitant to a 34% increase in the number of patients free of back pain (p = 0.03 versus placebo) [215].