Associations of pituitary-ovarian hormones and white matter hyperintensities in recently menopausal women using hormone therapy

Abstract

Objective: Little is known about how menopausal hormone treatment (HT) may influence the development of white matter hyperintensities (WMHs) in the brain. This study evaluated the associations of changes in levels of pituitary-ovarian hormones during HT and changes in WMH.

Methods: Women (n = 78 adherent to treatment) enrolled in the Kronos Early Estrogen Prevention Study underwent brain magnetic resonance imaging, and blood collection before and after 48 months of randomization to 0.45 mg/d oral conjugated equine estrogen (oCEE) daily, 50 μg/d transdermal 17β estradiol (tE2), or placebo pills and patches. Women in the active treatment groups also received oral 200 mg/d micronized progesterone the first 12 days of the month. Estradiol (E2), estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum by high sensitivity liquid chromatography/mass spectrometry at baseline and following 48 months of HT. Longitudinal change in WMH volume was determined from fluid-attenuated inversion recovery magnetic resonance imaging using a semiautomated image segmentation algorithm.

Results: Serum levels of FSH, LH, E1, or E2 did not associate with WMH volume at baseline. After 48 months of treatment, smaller increases in WMH associated with decreases in FSH from baseline in the tE2 group and increases in E1 in both tE2 and oCEE groups. Changes in LH did not associate with changes in WMH in any group.

Conclusions: Circulating levels of pituitary-ovarian hormones associate with changes in WMH volume in recently menopausal women using HT. Whether these relationships would be influenced by different doses of tE2 or oCEE remains to be determined. : Video Summary:http://links.lww.com/MENO/A590.

Trial registration: ClinicalTrials.gov NCT00154180.

Conflict of interest statement

Financial disclosures/conflicts of interest: Kejal Kantarci serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc.; receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from NIH and Alzheimer’s Drug Discovery Foundation. Other authors have nothing to disclosure.

Figures

FIG. 1

Boxplots of total change in WMH volume and total changes in hormones levels from baseline to month 48. The horizontal lines of the box from bottom to top show the 25th, 50th, and 75th percentiles of the data. The height of the box, 75th to 25th percentile, is the interquartile range (IQR). Whiskers extend 1.5*IQR from the box. Points farther out are considered outliers and drawn individually. E1, estrone; E2, estradiol, FSH, follicle-stimulating hormone; oCEE, oral conjugated equine estrogen; tE2, transdermal estradiol; WMH, white matter hyperintensity.

FIG. 2

Scatterplots between total change in WMH volume and total changes in hormones levels by treatment group. The line represents the predicted linear relationship between the change in hormone and change in WMH. Each point represents a participant. E1, estrone; E2, estradiol, FSH, follicle-stimulating hormone; oCEE, oral conjugated equine estrogen; tE2, transdermal estradiol; WMH, white matter hyperintensity