Study reveals a dose-response relationship between cumulative estrogen dose and renal function loss.


Oral estrogen therapy in post-menopausal women is associated with loss of renal function, according to Canadian researchers.

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Sofia B. Ahmed, MD, of the University of Calgary in Alberta, and her colleagues studied 1,459 women on hormone therapy (HT) and 4,386 HT non-users. The women had at least two serum creatinine measurements during the two-year study period. A total of 1,083 women (mean age, 75 years) were taking estrogen only, 40 women (mean age, 74 years) were taking progestin only, and 336 women (mean age, 73 years) were taking both hormones. The HT non-users had a mean age of 77.5 years.


After adjusting for various potential confounders, HT was associated an additional decline in mean estimated glomerular filtration rate (eGFR) of 1.24 mL/min per 1.73 m2 compared with HT non-users, the investigators reported in Kidney International (2008;74:370-376).


Estrogen-only use was associated with an additional decline of 1.21 mL/min per 1.73 m2 in mean eGFR over the study period; the researchers observed no association between progestin-only or the use of both hormones and eGFR decline. Estrogen-only users had a 17% increased risk of rapid loss of renal function compared with HT nonusers. Oral, but not transvaginal, estrogen was associated with significant additional decline in eGFR. Users of progestin only or a combination of estrogen and progestin had no increased risk of rapid loss of renal function.


In addition, the study revealed a dose-response relationship between cumulative estrogen dose and renal function loss. The investigaors noted that eGFR was predicted to decrease by about 3 mL/min per 1.73 m2 more in women taking 0.625 mg of conjugated estrogen on a daily basis for two years compared with HT non-users.


Study findings suggest that surveillance of renal function in postmenopausal women on HT may be prudent, the researchers wrote.


The study is among the first to look at the relationship between HT use and renal function decline in a large community-based elderly population. Citing study strengths, the researchers observed that it is the first to look at the impact of cumulative estrogen dose and route of administration on kidney function.


They also noted that the size of the cohort and its community-based setting increase the generalizability of the findings. In their discussion of study limitations, the investigators pointed out that they could not control for clinical factors such as BP, proteinuria, obesity, smoking and use of over-the-counter medications and herbal preparations, “raising the possibility of residual confounding.”