Renal stones, timing hypothesis, and eu-estrogenemia

Abstract

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.

A theory of eu-estrogenemia: a unifying concept

“…We proposed the geripause effect on kidney stone formation around small atherosclerotic niduses in the renal pelvis, that is, estrogen administration in women 6 to 10 years postmenopausal or aged 60 to 64 were at increased risk of kidney stone formation. 18 The serendipitous discovery of the timing hypothesis appearing in the WHI database for renal stones corroborated the Theory. An expanded review of the WHI health records for other disease processes that reflect the timing hypothesis manifested in other organ systems may give other insights into ER function.…”

“… Hazard ratios of renal stones with 95% confidence intervals by time since menopause at study entry. Reprinted from Turner and Kerber 18 with permission of the publisher. Copyright © 2011, North American Menopause Society.…”

“…Figure 1 shows the changing estrogenic milieus throughout a woman's life. 16 - 18 She is pre-estrogenic before menarche and eu-estrogenemic after menarche. She becomes hyperestrogenemic during pregnancy, with dramatic changes in estrogen concentration and function.…”

Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation

“…During the past two decades, several studies have attempted to address this hypothesis, especially in calcium oxalate (CaOx) stone, which is the most common type of kidney stones found globally . However, the data obtained from different studies were inconclusive and cellular mechanisms underlying such protective effects of estrogen remained unclear …”

“…[9] However, the data obtained from different studies were inconclusive and cellular mechanisms underlying such protective effects of estrogen remained unclear. [10][11][12] We hypothesized that estrogen might induce renal cell response (e.g., by alterations of protein expression) that affected CaOx kidney stone formation. The present study thus aimed to address such hypothesis by investigating the effects of estradiol (which is the most prevalent and potent form of estrogen in females at the reproductive age [13] ) on cellular proteome of renal tubular cells.…”