Estrogen receptor polymorphism predicts the onset of natural and surgical menopause

Angelique Weel, André Uitterlinden, ICD (Iris) Westendorp, H (Hens) Burger, SCE Schuit, Bert Hofman, Theo J.M. Helmerhorst, Hans van Leeuwen, Huib Pols*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.

Original languageEnglish
Pages (from-to)3146-3150
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
Publication statusPublished - Sept 1999

Bibliographical note

Copyright © 1999 by The Endocrine Society

This work was supported by the Netherlands Organization of Scientific Research (Grant 950 –10-618)

Research programs

  • EMC 02-01-38-02-00
  • EMC MM-03-52-02-A
  • EMC NIHES-01-64-02


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