Estradiol was used as a positive control and raloxifene was used because it is in the same drug class as ospemifene. Multiple doses of oral ospemifene were tested. 10 mg/kg/day of Ospemifene was found to cause a greater increase in vaginal weight and vaginal epithelial height than 10 mg/kg/day of raloxifene. Vaginal weight had a 1.46x increase after a two-week treatment of 10 mg/kg/day of ospemifene. The number of progesterone receptors was increased in the vaginal stroma and epithelium, which indicates that ospemifene has "estrogenic activity. "Two 12-week phase 3 clinical trials were performed for ospemifene. One evaluated the effects of Ospemifene on vaginal tissue thickness, composition and vaginal pH. The other evaluated the effects of Ospemifene on vaginal tissue and on symptoms of dyspareunia. Between the two trials, 4 signs and symptoms were measured. These included three tissue-related signs, two of which represented histological changes in the vaginal tissue (change in percent parabasal cells and change in percent superficial cells) and the third was "change in vaginal pH". Dyspareunia was evaluated in one of the trials. It was defined as "change in most bothersome symptom" of discomfort during sexual activity and further limited to symptoms of either vaginal dryness or vaginal pain." Ospemifene produced more changes in vaginal tissue and greater reduction in dyspareunia symptoms than placebo. A dose-response also was observed in the trial; ospemifene 60 mg had greater efficacy than ospemifene 30 mg. Safety was also evaluated in these phase 3 trials.
These include, but are not limited to, thromboembolism, allergic reactions, fatigue, and headache, and others could occur. There are other additional adverse effects. Ospemifene is a selective estrogen receptor modulator. As such, many of the effects produced by estrogens are produced by ospemifene. The boxed warning of the medication indicates ospemifene may thicken the endometrium, which could lead to unusual bleeding and endometrial cancer. For women taking estrogens, concurrently taking a type of drug called a progestin has been shown to decrease the occurrence of endometrial hyperplasia. In theory, progestins may be expected to attenuate ospemifenes effects on endometrial thickening. However clinical trials confirming this have not been conducted. Like estrogens, ospemifene also may increase the risk for cardiovascular events, including "stroke, coronary heart disease, venous thromboembolism," and others. The risk of thrombotic and hemorrhagic strokes is given as 0.72 and 1.45 per 1,000 women, while that of deep vein thrombosis is estimated to be 1.45 per 1,000 women. The risks of these adverse events in women taking ospemifene are lower than those in women taking estrogen alone in the form of oral conjugated estrogens. Studies have not documented the relative risk compared with women taking estrogen/progestin therapy. Pharmacology
Pharmacodynamics
Ospemifene is "an estrogen agonist/antagonist that makes vaginal tissue thicker and less fragile resulting in a reduction in the amount of pain women experience with sexual intercourse." This medication should be used for the shortest amount of time possible due to associated adverse effects.