Neurological dysfunction of menopause can arise from low estrogen. Women risk Alzheimers ApoE4 age

cognitive & neurological health

What are the impacts of menopause on a woman's brain?

A preponderance of mid-life hormonal changes drastically impact the dynamic mantle of a woman's neurological integrity.  This occurs regardless of a woman's race, ethnicity or nationality.  Female brain  function is impacted by dose-dependent, estrogen-modulated membrane signaling, and this fact has yet to be incorporated into women's healthcare.   Extensive estrogen receptor mapping work in translational neurobiology has provided a working model of estrogen-dependent neurophysiological functions in women.   Estrogen's influence on specific brain regions and a few of their respective corresponding functions include: 


  • pre-frontal cortex (executive functions, learning); 
  • amygdala (emotional interpretation, motivation); 
  • hippocampus (short-term memory); 
  • hypothalamus (circadian rhythm, sleep, temperature regulation, appetite control); 
  • thalamus (sensory input interpretation);  
  • raphe nucleus (mood, serotonergic system), 
  • posterior cingulate  (default mode network);  
  • adrenergic system (attention, arousal & anxiety). 


These areas also govern entire brain networks and modulate centralized functions that profoundly impact a woman's body and mind.  If a woman experiences symptoms in any of these areas, it is entirely plausible that the cause may be rooted in hormonal changes.   Estrogen also activates at least 504 genes, protects brain volume, and exerts neurological modulation of mitochondrial and synaptic functions in the brain.  Alzheimer's disease is a condition of degenerating neural synapses and subsequent brain volume atrophy.  Progesterone, on the other hand, antagonizes genomic upregulation of estrogen-sensitivity.  Therefore, neuroprotective prescribing strategies of estrogen and progesterone must be considered on an individual basis when considering menopausal  hormone replacement.    


Dr. Parker's approach to whole-woman healthcare embraces a systems-biology approach and critical appraisal of medical literature to curate contemporary clinical advancements for personalized menopausal hormone therapy. 


Compared with men, women are predominantly impacted by Alzheimer's disease with 66% more cases in the United States alone.   Importantly, there are risks associated with not addressing the decline of estrogen in women undergoing menopause.  These risks are multi-factorial, including underlying genetic mutations such as the ApoE gene and the MCM8 gene. Apo E 4/4 alleles have been linked with increased atrophy of the hippocampus  in postmenopausal for women not undergoing hormone replacement therapy, and it has been shown that estrogen replacement, when given at the right time and dose, can prevent hippocampal atrophy (Hu et al, 2006).    As a woman undergoes estrogen deficiency,  women with at-risk allele expression of either of these genes  have greater development of the pathophysiological processes associated with Alzheimer's disease (Nebel et al 2018, Waring et al 2018, Zandi et al, 2002, Paganini et al 1996).  Based upon a woman's unique phenotypic risks, cognitive changes and deficits arising in perimenopause may be best served when addressed with hormone replacement prior to moving into full blown estrogen decline of menopause.   


Select References: 

Hu L, Yue Y, Zuo PP, Jin ZY, Feng F, You H, Li ML, Ge QS. Evaluation of neuroprotective effects of long-term low dose hormone replacement therapy on postmenopausal women brain hippocampus using magnetic resonance scanner. Chin Med
Sci J. 2006 Dec;21(4):214-8.


Mosconi L, Berti V, Guyara-Quinn C, McHugh P, Petrongolo G, Osorio RS. Perimenopause and emergence of an Alzheimer’s bioenergetic phenotype in brain and periphery. PLoS One. 2017;12:e0185926.


Nebel RA, Aggarwal NT, Barnes LL, Gallagher A, Goldstein JM, Kantarci K. Understanding the impact of sex and gender in Alzheimer’s disease: A call to action. Alzheimers Dement. 2018;14:1171–1183.


Paganini-Hill A., Henderson V.W. Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med. 1996;156:2213–2217. 


Waring S, Rocca W, Peterson R, O’Brien P, Tangalos E, Kokmen E. Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology. 1999;52:965–970.


 Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002;288:2123–2129. 

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