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Factor V Leiden mutation accelerates the onset of natural menopause

van Asselt, Kristel M. MD1,2,3; Kok, Helen S. MD1,2,3; Peeters, Petra H. M. MD, PhD1; Roest, Mark PhD1,4; Pearson, Peter L. PhD2; te Velde, Egbert R. MD, PhD3; Grobbee, Diederick E. MD, PhD1; van der Schouw, Yvonne T. PhD1

doi: 10.1097/01.GME.0000056040.51813.1A

Objective Smoking is consistently associated with a younger age for menopause. Although this may be because of the direct toxic effects of tobacco smoke on follicles, we hypothesize that there may also be a relationship between smoking and a vascular origin of early menopausal onset. Several lifestyle factors have been investigated, but never factors of the clotting cascade. The objective of this study, then, was to determine the effect of factor V Leiden mutation and smoking with respect to age at menopause.

Design Data were used from a subset of 373 postmenopausal participants of a Dutch population-based cohort, born between 1911 and 1925. All women had experienced natural menopause, without use of hormone replacement therapy.

Results Female carriers of the factor V Leiden mutation (n = 14) reported the onset of menopause at an earlier age than noncarriers (n = 359; difference, 3.1 years; 95% CI: 0.3, 5.9). Smoker carriers (n = 5) were 4.3 years younger at menopause than smoker noncarriers (n = 92; 95% CI: 0.9,7.6). In nonsmokers, this relationship was less strong.

Conclusions We found that the factor V Leiden mutation was related, but not statistically significant, to an earlier age at menopause; smoking possibly enhances this effect. The mutation can be one of the genetic determinants of menopausal age operating through a vascular mechanism.

From the 1Julius Center for Health Sciences and Primary Care, the 2Department of Biomedical Genetics, the 3Department of Reproductive Medicine, and the 4Research Laboratory of the Department of Clinical Chemistry, University Medical Center, Utrecht, The Netherlands.

Received October 3, 2002; revised and accepted December 23, 2002.

Financial support was provided by N. V. Organon, The Netherlands, the University Medical Center Utrecht and the Netherlands Heart Foundation.

Address correspondence to: K. M. van Asselt, University Medical Center Utrecht, Location Academic Hospital Utrecht, Heidelberglaan 100, Hp Str. 6.119, 3684 CX Utrecht, The Netherlands. E-mail:

©2003The North American Menopause Society