Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method

Abstract

Objective: Oestrogens could be protective against the development of Alzheimer's disease (AD) but reports on oestrogen levels in AD have been conflicting. Design and methods: A meta-analysis using robust regression was carried out to assess whether the sensitivity of the assays of past studies had affected the reported level of total oestradiol. We had also measured total oestradiol in women with AD ðn ¼ 66Þ and controls ðn ¼ 62Þ not using hormone replacement therapy. We used two assays for total oestradiol to assess the difference between sensitive (radioimmunoassay with a specific rabbit antibody: 3 pmol/l) and relatively insensitive (immunoassay: 37 pmol/l) assays. Results: Meta-analysis using robust regression indicated that insensitive assays gave higher levels of total oestradiol when many samples fall below the level of sensitivity of the method. Earlier reports of low levels of total oestradiol in AD might be explained by this phenomenon, since total oestradiol levels (using the sensitive assay) in our controls were one third of those reported in the earlier studies. Using the sensitive assay we found that women with AD had significantly ðP , 0:01Þ higher levels ð26^13 pmol=lÞ of total oestradiol than controls ð21^13 pmol=lÞ: Using the insensitive assay, there was no significant difference in the levels of total oestradiol. Conclusions: The sensitivity of the assay determines the reported value of the oestradiol levels. Studies using a sensitive assay do not report significantly lower levels of total oestradiol in women with AD. This weighs against the hypothesis that low levels of total oestradiol are a risk factor for AD.

Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry

“…The measurement of serum E 2 forms an integral part of the assessment of female reproductive function, including studies of infertility, oligoamenorrhea, menopause, and hormone therapy, and is widely used in the monitoring of ovulation induction (16) as well as in assisted reproduction (17). Serum E 2 concentrations are also indicated in the study of cardiovascular disorders and Alzheimer's disease (18).…”

Lifelong Endocrine Fluctuations and Related Cognitive Disorders

“…Finally, Hogersvorst et al pointed out that the sensitivity of the assay could determine the reported value of the estradiol levels [179]. They carried out a meta-analysis to assess whether the sensitivity of the assays of past studies had affected the reported level of total estradiol, and also measured total estradiol in 66 women with AD and 62 controls.…”

Evidence for the Role of Luteinizing Hormone in Alzheimer Disease

“…For example, only two of nine recent observational studies comparing estrogen levels in women with AD with controls reported lower estrogen levels in AD [8,9], with two studies reporting increased estrogen levels in AD [10,11] and five reporting no significant differences between AD and controls [12][13][14][15][16]. The variability in the results of these studies is thought to be caused in part by the sensitivity of the assay used, as studies that used less *Address correspondence to these authors at the Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA; Tel: 216-368-3670; Fax: 216-368-8964; E-mail: mark.smith@case.edu sensitive assays reported higher total estrogen levels [11] resulting in an overemphasis of the impact of low estrogen levels on the study.…”