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Does genetic testing for ER? gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

ABSTRACT: It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cognition proved to be contradictory. It seems that the essence of the problem is more complicated than only estrogen deficiency. It is suggested that estrogen receptor ? (ER?) polymorphism may be responsible for the differences in the effect of estrogens on cognitive processes. The article presents current knowledge concerning the effect of estrogens on the central nervous system, especially the role of ER? polymorphism, with respect to foreseeing benefits from the use of exogenous estrogens for cognitive functions. At the present stage of research, ER? appears to be poorly specific; nevertheless, it may be an important instrument for the classification of peri- and post-menopausal patients in the group where therapy with the use of estrogens may bring about benefits in terms of prevention and treatment of cognitive disorders. It also seems necessary to conduct prophylactic, screening examination of cognitive functions in post-menopausal women, in order to identify those at risk of the development of dementia.

SUBMITTER: Gujski M

PROVIDER: S-EPMC5575213 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

Gujski Mariusz M Pinkas Jarosław J Wierzbińska-Stępniak Anna A Owoc Alfred A Bojar Iwona I

Archives of medical science : AMS 20160922 5

It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cogniti ...[more]

PMID: 28883865

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Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

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Does genetic testing for ER? gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

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Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

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