Hormonal treatment, mild cognitive impairment and Alzheimer's disease.
A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.
Ryan
Joanne
J
Inserm, U888, Montpellier, F-34093 France.
Scali
Jaqueline
J
Carriere
Isabelle
I
Ritchie
Karen
K
Ancelin
Marie-Laure
ML
D000279:Administration, Cutaneous; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008569:Memory Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011372:Progestins / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011960:Receptors, Estrogen / Q000235:genetics; D012107:Research Design / Q000592:standards / Q000639:trends; D012720:Severity of Illness Index; D016896:Treatment Outcome
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D018696:Neuroprotective Agents; D011372:Progestins; D011960:Receptors, Estrogen; D004958:Estradiol