Novel therapeutic strategies for Alzheimer's disease based on the forgotten reproductive hormones

Cell Mol Life Sci. 2005 Feb;62(3):313-9. doi: 10.1007/s00018-004-4386-y.

Abstract

The relationship between hormones and Alzheimer's disease (AD) has been intensely researched. While the majority of this work has focused on the sex steroids, estrogens, and more recently androgens, a serendipitous patient encounter led one of us (R.L.B.) to question whether other hormones of the hypothalamic-pituitary-gonadal axis might play a role in the pathogenesis of AD. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum gonadotropin concentrations. Indeed, there is growing evidence that the gonadotropin luteinizing hormone, which regulates serum estrogen and testosterone concentrations, is an important causative factor in the development of AD. This review provides information supporting the 'gonadotropin hypothesis'. We put forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of AD and discusses potential therapeutic anti-gonadotropin compounds.

Publication types

  • Review

MeSH terms

  • Aging
  • Alzheimer Disease / blood
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Gonadotropin-Releasing Hormone / physiology
  • Gonadotropins / physiology*
  • Humans
  • Luteinizing Hormone / blood
  • Male
  • N-Methylaspartate / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Gonadotropins
  • Gonadotropin-Releasing Hormone
  • N-Methylaspartate
  • Luteinizing Hormone