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Renal stones, timing hypothesis, and eu-estrogenemia

Turner, Ralph J. MD, FACOG, NCMP1; Kerber, Irwin J. MD, FACOG, FACS, NCMP2

Menopause: The Journal of The North American Menopause Society: January 2012 - Volume 19 - Issue 1 - p 104–108
doi: 10.1097/gme.0b013e318221be9b
Brief Report

Objective The aim of this study was to apply the theory of the timing hypothesis to the data presented on the incidence of renal stones in the Women’s Health Initiative and the theory of eu-estrogenemia.

Methods The study is a review of the literature on the theory of renal stone formation and postmenopausal women, including data from the Nurses’ Health Study and the Women’s Health Initiative.

Results The analysis of the hazard ratios and CIs of renal stones in the Women’s Health Initiative shows that specific subgroups are affected. The CIs of the hazard ratios did not overlap 1.0 in the 60- to 64-year-old age group and in women whose time since menopause at study entry was 6 to 10 years. The CIs of all other age groups and years from menopause overlapped 1.0. Hormone therapy use by women described as “current users” at time of entry into the study in the treatment had a hazard ratio of 0.99.

Conclusions The timing hypothesis of Clarkson (Menopause 14:373-384; 2007) seems to explain the hazard ratio and CI of renal stones in the Women’s Health Initiative. A closer analysis of the subgroups of women who had a higher incidence of renal stones suggests that the timing hypothesis may explain the results from the Women’s Health Initiative versus previous studies such as the Nurses’ Health Study. The CIs of the hazard ratios of the subgroups that did not overlap 1.0 included women 6 to 10 years beyond menopause, those who were aged from 60 to 64 years, and “never users” of hormone therapy. The hazard ratio for renal stones among “current users” in the Women’s Health Initiative was 0.99. This analysis suggests that the timing hypothesis may affect estrogen receptor-α–mediated processes in the kidney. Furthermore, Clarkson’s work may support the vascular etiology of renal stones.

Re-evaluation of the data from the renal stone subset of the Women’s Health Initiative provides evidence of Clarkson’s Timing Hypothesis.

From the 1University of Texas Health Science Center at Tyler, Tyler; and2University of Texas Southwestern Medical School, Dallas, TX.

Received February 2, 2011; revised and accepted April 27, 2011.

Funding/support: None reported.

Financial disclosure/conflicts of interest: Drs. Turner and Kerber are on the Speakers’ Bureau for Prolia (denosumab) for Amgen.

No reprints are available.

Address correspondence to: Ralph J. Turner, MD, FACOG, NCMP, University of Texas Health Science Center, 11937 US Hwy 271, Tyler, TX 75708. E-mail:

©2012The North American Menopause Society