Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy

Three hundred and one healthy women between 45 and 65 yr of age and at leas t I yr postmenopausal were randomly assigned to 12-month double-blind thera py with levormeloxifene [1.25 (n = 51), 5, 10, or 20 mg/day], low dose cont inuous combined hormone replacement therapy [HRT; 1 mg 17 beta -estradiol a nd 0.5 mg norethisterone acetate/ day], or placebo (all n = 50). All of the women were also given a daily supplement of calcium (500 mg). Serum CrossL aps decreased by about 50% in the levormeloxifene groups, with no dose-resp onse effect. The group receiving HRT decreased more (>60%), and the placebo group (500 mg calcium alone) decreased by about 10%. The pattern was simil ar for bone alkaline phosphatase, except that the decreases were smaller, a bout 30% for the levormeloxifene groups and 50% for the HRT group. Serum os teocalcin also showed highly significant decreases, of the same magnitude i n the levormeloxifene and HRT groups. Spinal bone mineral density (BMD) dec reased by less than 1% in the placebo group and increased by about 2% in th e levormeloxifene groups and by almost 5% in the HRT group (P < 0.001 for t he difference between levormeloxifene and HRT vs. placebo). BMD of the tota l hip and total body changed in the same direction, although differences be tween groups were not as pronounced as those for BMD spine. Total cholester ol decreased by about 13-20% during levormeloxifene therapy, whereas daily doses of 1 mg estradiol and 0.5 mg norethisterone acetate produced a decrea se of only about 8%. Levormeloxifene decreased low density lipoprotein chol esterol by about 22-30% compared with about 12% in the low dose HRT group. High density lipoprotein cholesterol was unchanged in all groups. Endometri al thickness increased both clinically and statistically significantly in t he levormeloxifene groups independently of the dose; the difference from th e placebo and HRT groups was significant (P < 0.001). There was no signific ant difference between the HRT and placebo groups. Other adverse events of interest include hot flushes, which did not occur more frequently in the le vormeloxifene than the placebo groups, but occurred significantly less freq uently in the HRT group (P < 0.05). Breast tenderness was much more common in the HRT group (<0.001) than in all other groups. In conclusion, the stud y shows that levormeloxifene, a new selective estrogen receptor modulator, has positive effects on BMD and bone turnover and apparently strong estroge nic effects on the serum concentrations of different cholesterol subfractio ns. Levormeloxifene at the doses tested had an estrogen-like effect on endo metrium and no effect on hot flushes. The study was unable to differentiate between the effects of the different doses of levormeloxifene.