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Luteinizing hormone–releasing hormone receptor antagonist may reduce postmenopausal flushing

van Gastel, Petri MD1; van der Zanden, Moniek MD2; Telting, Darryl PhD3; Filius, Margreet PhD4; Bancsi, Laszlo MD, PhD2; de Boer, Hans MD, PhD1

Menopause: The Journal of The North American Menopause Society: February 2012 - Volume 19 - Issue 2 - p 178–185
doi: 10.1097/gme.0b013e31822542ca
Original Articles
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Objective Hormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone–releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP flushing.

Methods We conducted an open-label treatment with cetrorelix 250 μg twice a day on 10 women with a baseline daily flush score of 15 or higher for a period of 4 to 6 weeks. The response to treatment was evaluated through monitoring serum gonadotropin levels, flush scores, and quality of life.

Results At baseline, the mean (SEM) daily flush score was 36.1 ± 1.8 (mean ± SEM range, 29-44). All women demonstrated a decrease in serum luteinizing hormone and follicle-stimulating hormone during treatment, but the premenopausal levels of both gonadotropins were reached in only two women. The mean daily flush score decreased by 42.0% ± 7.7% (P < 0.001). This was caused by a decrease in flush frequency of 26.2% ± 6.0% (P < 0.01) and by a decrease in flush severity of 21.2% ± 7.7% (P < 0.05).

Conclusions In an open-label setting, luteinizing hormone–releasing hormone receptor blockade reduced PMP flushing by at least 25% in 8 of 10 women with severe flushing. A placebo-controlled study will be needed to demonstrate the true benefit of this approach. The present data suggest that the treatment period must be longer than 6 weeks to capture the maximal effect.

The results of this pilot study in 10 women with severe postmenopausal flushing indicate that LHRH receptor blocking holds promise as a new treatment option for postmenopausal flushing. A placebo-controlled study will be performed to validate this concept.

From the 1Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands; 2Department of Obstetrics and Gynecology, Rijnstate Hospital, Arnhem, The Netherlands; 3Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands; and 4Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands.

Received March 24, 2011; revised and accepted May 19, 2011.

Funding/support: This investigator-initiated study was partially supported by a limited grant from Serono BV, The Netherlands. Serono had no influence on the design and the analysis of the study and did not contribute to the writing of the manuscript.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Petri van Gastel, MD, Department of Internal Medicine, Rijnstate Hospital, PO Box 9555, 6800 TA Arnhem, The Netherlands. E-mail: pvangastel@rijnstate.nl

©2012The North American Menopause Society