Objective: Ospemifene, a novel selective estrogen receptor modulator (SERM), shows promise for bone preservation in postmenopausal women. This study examined the effects of ospemifene on different vascular surrogate markers.
Design: A double-blinded study was conducted in 160 healthy, postmenopausal women who used, in a randomized order, ospemifene (at daily doses of 30, 60, or 90 mg) or placebo for 3 months.
Results: Although ospemifene caused falls from basal levels in total cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and a rise in high-density lipoprotein cholesterol, the only statistically significant difference between ospemifene and placebo was an increase of triglyceride levels (11.3%) in the 90-mg group. Ospemifene caused no significant effect on endothelial markers or homocysteine. Of the markers reflecting coagulation and fibrinolysis, plasma fibrinogen was significantly reduced in the 60- and 90-mg groups of ospemifene (8.7% and 8.5%, respectively) when compared with the placebo group. No changes were seen in generation of thrombin or degradation of crosslinked fibrin D-dimer. The uterine or carotid arteries and 24-h ambulatory blood pressure were not affected by ospemifene. Ospemifene caused no changes in basal insulin or in a 2-h glucose tolerance test, suggesting unaltered insulin sensitivity.
Conclusions: Neutral effects of short-term use of ospemifene on vascular surrogate markers imply no effect for ospemifene on the risk for cardiovascular disorders in healthy, postmenopausal women.
Osteoporosis and osteoporotic bone fractures are among the most significant disorders in the older female population. 1,2 Early detection of increased bone loss and effective prophylactic measures against fractures thus present a great challenge for healthcare systems in the Western world. Of the therapeutic options, hormone replacement therapy (HRT) reduces the risk for nonvertebral fractures by 27%, with a possible attenuation of this benefit when HRT is begun after age 60. 3 However, HRT is associated with a number of side effects, including increased risk for breast cancer, 4 and some authors question the final impact of HRT in prevention of fractures. 5 HRT has not been approved by the US Food and Drug Administration (FDA) for treatment of osteoporosis, whereas bisphosphonates, calcitonin, and raloxifene, a selective estrogen receptor modulator (SERM), have this approval. Indeed, raloxifene reduces the risk for vertebral fracture 6 but does not eliminate hot flushes and may even aggravate them. 7
Ospemifene, a novel SERM, 8 has demonstrated a strong bone-sparing effect in ovariectomized rats. 9 Therefore, we designed a placebo-controlled, randomized trial to study the clinical efficacy and safety of ospemifene in healthy, postmenopausal women. 10 Ospemifene, given at daily doses of 30, 60, or 90 mg for 3 months, was well tolerated, did not worsen hot flushes, and caused no harmful effects on genital tract; in contrast, it had an estrogenic effect on vaginal epithelium. 10 Ospemifene may, therefore, show promise as a potential drug for prevention and treatment of osteoporosis in postmenopausal women. Because postmenopausal women are also characterized with an increased risk for cardiovascular disorders (CVD) that may develop, at least in part, from estrogen deficiency-induced changes in lipids, 11,12 in endothelial function, 13 and in coagulation and fibrinolysis, 14–17 we also studied the effect of ospemifene on different cardiovascular surrogate endpoints.
From the 1Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland; 2Hormos Medical Corporation, Turku, Finland; 3Wihuri Research Center, Helsinki, Finland; and 4Oulu Deaconess Institute, Oulu, Finland.
Received May 21, 2002; revised and accepted February 5, 2003.
The study was supported by a research grant from Hormos Medical Corporation.
Address correspondence to: Olavi Ylikorkala, MD, Helsinki University Central Hospital, Department of Obstetrics and Gynecology, PO Box 140, 00029 HUS, Finland. E-mail: firstname.lastname@example.org.