Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy

Abstract

Objective: Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS).

Methods: KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17β estradiol (t-E2, 50μg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences.

Results: During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments.

Conclusions: Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol. Clinical Trial Registration for KEEPS: NCT00154180.

Keywords: 17β estradiol; Appetite; Conjugated equine estrogen; Hypocretin; KEEPS; Leptin; Sleep.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Copyright © 2017. Published by Elsevier B.V.

Figures

Fig. 1

Trend analysis of Orexin-A across treatment groups from Baseline (t = 0) to 84 months using a two slope mixed model. Each individual line represents plasma OXA levels (ng/mL) from each study participant over time by treatment groups. Treatment exposure was from Baseline to 48 months with assessment following discontinuation of treatment at 84 months.