Interactions between melatonin and estrogen may regulate cerebrovascular function in women: Clinical implications for the effective use of HRT during menopause and aging

Christopher G. Harrod, Bernard R. Bendok, H. Hunt Batjer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A number of clinical trials associated with the Women's Health Initiative (WHI) have assessed the potential benefits of hormone replacement therapy (HRT) for protection against the development of cardiovascular disease and memory loss in menopausal women. The results of the WHI Memory Study suggest that HRT increases the risk of stroke and dementia in menopausal women. This finding has called into question the results of hundreds of basic science studies that have suggested that estrogen could protect brain cells from damage and improve cognition. A number of researchers have argued that inappropriate formulation, improper dosing, a limited study population, and poor timing of administration likely contributed to the reported findings from the clinical trial. Regarding appropriate formulation, it has been suggested that interactions between estrogen and other hormones should be considered for further investigation. A review of the literature has led us to conclude that a thorough investigation into such hormonal interactions is warranted. We hypothesize that the increased risk of cerebrovascular disease observed in menopausal women may, in part, be due to changes in the circulating levels of melatonin and estrogen and their modulatory affects on many relevant endothelial cell biological activities, such as regulation of vascular tone, adhesion to leukocytes, and angiogenesis, among others. Our hypothesis is supported by numerous studies demonstrating the reciprocal inhibitory effects of melatonin and estrogen on vascular tone, neuroprotection, and receptor expression. We believe that a thorough analysis of the distribution, localization, expression, quantification, and characterization of hormonal receptor subtypes, as well as changes in structural morphology in diseased and normal, healthy cerebrovascular tissue, will substantially aid in our understanding of the effects of HRT on the cerebrovascular circulation. The application of new molecular biological techniques such as tissue microarray analysis, gene and protein arrays, and multi-photon confocal microscopy may be of tremendous benefit in this regard.

Original languageEnglish (US)
Pages (from-to)725-735
Number of pages11
JournalMedical Hypotheses
Volume64
Issue number4
DOIs
StatePublished - 2005

Fingerprint

Hormone Replacement Therapy
Melatonin
Menopause
Estrogens
Women's Health
Blood Vessels
Cerebrovascular Circulation
Clinical Trials
Tissue Array Analysis
Cerebrovascular Disorders
Protein Array Analysis
Memory Disorders
Photons
Confocal Microscopy
Cognition
Dementia
Leukocytes
Cardiovascular Diseases
Endothelial Cells
Stroke

ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)
  • Drug Discovery

Cite this

Interactions between melatonin and estrogen may regulate cerebrovascular function in women : Clinical implications for the effective use of HRT during menopause and aging. / Harrod, Christopher G.; Bendok, Bernard R.; Batjer, H. Hunt.

In: Medical Hypotheses, Vol. 64, No. 4, 2005, p. 725-735.

Research output: Contribution to journalArticle

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