Raloxifene is not associated with biologically relevant changes in hot flushes in postmenopausal women for whom therapy is appropriate - 25/08/11

Doi : 10.1016/j.ajog.2003.10.701

Santiago Palacios, MD, PhD, Maria Lucia F. Farias, MD, PhD, Horst Luebbert, MD, PhD, Gustavo Gomez, MD, Juan A Yabur, MD, Deborah C Quail, BSc, Carmen Turbi, MD, Marcia J Kayath, MD, Maria J Almeida, PharmD, Elisabeth Mönnig, PhD, Thomas Nickelsen, MD, PhD ^⁎
Instituto Palacios, Madrid, Spain, HUCFF-Universidade Federal do Rio de Janeiro, Brazil, Universitätsklinikum Benjamin Franklin, Freie Univerität Berlin, Berlin, Germany, Centro Medico Imbananco–Universidad del Valle, Cali, Colombia, Hospital De Clinicas Caracas, Caracas, Venezuela, Eli Lilly and Company, Indianapolis, Ind USA

Reprint requests: Thomas Nickelsen, MD, Lilly Deutschland GmbH, Saalburgstrasse 153, D-61350 Bad Homburg, Germany.

Abstract

Objectives

Raloxifene is approved for the treatment and prevention of postmenopausal osteoporosis. Previous studies have described a raloxifene-associated increase in hot flushes, reported as adverse events. This study was undertaken to provide a detailed evaluation of the potential of raloxifene to induce or exacerbate hot flushes in postmenopausal women.

Study design

In this double-blind, placebo-controlled, parallel group multicenter study, 487 postmenopausal women were randomized to receive 8 months of treatment with either raloxifene (RLX) at the recommended dose of 60 mg/day, or by slow-dose escalation for the first 2 months, followed by the standard dose for the rest of the study (SDE), or placebo (PL). The frequency, duration, intensity, severity, and impact of hot flushes were measured.

Results

With 3-5 hot flushes per week, the mean number at baseline was low. During treatment, it increased by <1 hot flush/week in both active treatment groups and decreased by <1 hot flush/week with PL. The high proportion (60%) of asymptomatic patients at baseline had increased further by the end of treatment in all groups. The proportion of women whose pre-existing hot flushes abated during treatment was significantly greater with SDE (P=.005) and PL (P=.050), but not with RLX, when compared with the proportion with treatment-emergent flushes. There were no statistically significant between-group differences in the distribution of the number of hot flushes after 2 months of treatment. At end point, there were no significant differences between SDE and either RLX or PL, but the difference between RLX and PL was statistically significant (P=.035). There were no significant between-group differences in the hot flush impact scores, in treatment satisfaction, and in the proportion of patients requesting symptomatic treatment to alleviate hot flushes.

Conclusion

In a postmenopausal population meeting the criteria for the prescription of RLX, the overall effect of the drug on hot flushes is low. Previous studies using adverse event reports have overestimated the importance of hot flushes in postmenopausal women during treatment with RLX. Slow-dose escalation seems to decrease the number of symptomatic patients further and may be a useful strategy in women reporting flushes when starting RLX.

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Keywords : Raloxifene, Hot flushes, Postmenopausal women, Osteoporosis, Selective estrogen receptor modulators