Longitudinal Relationships between Reproductive Hormones and Cognitive Decline in Older Men: The Concord Health and Ageing in Men Project

J Clin Endocrinol Metab. 2015 Jun;100(6):2223-30. doi: 10.1210/jc.2015-1016. Epub 2015 Apr 13.


Context: The longitudinal relationship between declining levels of reproductive hormones and cognitive function remains unclear in older men.

Objectives: The objective of this study was to examine the temporal relationship between changes in major reproductive hormone levels and cognitive decline over time.

Design, setting, and participants: Men age 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) were assessed at baseline (2005-2007; n = 1705), 2-year followup (2007-2009; n = 1367), and 5-year followup (2010-2013; n = 958).

Main outcomes and measures: At all assessments, T, dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH by immunoassay. Dementia was diagnosed at baseline by clinical assessment and review by a specialist panel. Cognitive function was measured at all three assessments by the Mini Mental State Examination.

Results: None of the baseline reproductive hormones predicted cognitive decline in men without dementia over 5 years. However, the change in serum hormones over time was associated with cognitive decline. In univariate analysis, change in all the studied hormones, except for E2, was significantly associated with cognitive decline. However, in multivariate-adjusted models accounting for potential confounders, only change in serum T (β = 0.067), DHT (β = 0.394), calculated free T (β = 0.005), and E1 (β = 0.009) remained significantly associated (P < .05) with cognitive decline. Men who had dementia at baseline had significantly greater decline in serum T levels, but not in other studied hormones, over the 5 years.

Conclusions: Our findings show that decline in androgen status is associated with cognitive decline in older men, but the causality of this association requires further elucidation.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / psychology*
  • Cognition / physiology
  • Cognition Disorders / blood*
  • Cognitive Dysfunction / blood
  • Dementia / blood
  • Dihydrotestosterone / blood
  • Estradiol / blood
  • Estrone / blood
  • Gonadal Steroid Hormones / blood*
  • Humans
  • Longitudinal Studies
  • Male
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood


  • Gonadal Steroid Hormones
  • Sex Hormone-Binding Globulin
  • Dihydrotestosterone
  • Estrone
  • Testosterone
  • Estradiol