Endogenous Hormones and Cognitive Decline in Women: Unveiling the Complex Interplay
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Cognitive Impairment
3.2. Dementia
4. Discussion
4.1. Limitations
4.2. Future Directions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
AI | artificial intelligence |
CI | confidence interval |
DHEA | dehydroepiandrosterone |
DHEAS | dehydroepiandrosterone sulfate |
E2 | estradiol |
FT | free testosterone |
HR | hazard ratio |
HRT | hormone replacement therapy |
MMSE | Mini-Mental Status Examination |
MRI | magnetic resonance imaging |
SHBG | sex hormone globulin binding |
TT | total testosterone |
WHO | World Health Organization |
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PICOS | Inclusion | Exclusion |
---|---|---|
Population: | Adults 30 and older, including women | Age less than 30, men only in the study population |
Intervention: | Evaluation of endogenous reproductive hormone levels, such as estradiol and its metabolites, estriol, progesterone and its metabolites, testosterone, sex hormone globulin building but not limited to them, and cognitive assessment using neurophysiological tests | |
Comparators: | Participant groups based on the hormone level detected | |
Outcomes: | Cognitive assessment score, risk of dementia, and Alzheimer’s disease | |
Study design: | Prospective cohort studies, retrospective cohort studies, cross-sectional studies, and randomized clinical trials | Case reports, expert opinions, letters to editors, conference reports, protocols, editorials, and commentaries |
Other | English language, publication since 1990 | Publication before 1990 |
Authors | Year | Population | Hormone Tested | Cognitive Function Measured | Results |
---|---|---|---|---|---|
Yaffe et al. [29] | 1998 | 532 women aged 65 years or older | Estrone and E2 (serum) | Global measures of cognition (3 tests) | Initial cognitive performance did not correlate with E2 and estrone levels, as well as cognitive decline and E2 levels assessed in 5 years. However, women with elevated estrone levels had worse cognitive performance in 2 tests. |
Barrett-Connor et al. [30] | 1999 | 393 women aged 55 to 89 | Bioavailable testosterone, total and bioavailable E2, and estrone (serum) | Global measures of cognition, mental control, verbal memory, mathematical skills, memory score, visuomotor tracking, and attention (12 standard tests of cognitive function) | Women with better cognitive performance demonstrated notably elevated mean total testosterone (TT) levels (p = 0.009). Conversely, higher estrogen levels did not exhibit a statistically significant correlation with improved cognitive function test outcomes. |
Drake et al. [31] | 2000 | 39 women (age range: 65 to 90, mean 78.8) | Total E2, bioavailable E2, estrone, progesterone, testosterone, and androstenedione (serum) | Global measures of cognition, verbal fluency, semantic memory, semantic score, non-verbal skills such as visual memory and non-verbal attention, spatial perception, and executive functioning (17 tests) | Increased E2 concentrations corresponded with enhanced performance on delayed verbal memory and retrieval efficiency tests, while reduced levels were linked to improved immediate and delayed visual memory tests. Elevated testosterone levels demonstrated a positive correlation with verbal fluency. Conversely, cognitive performance exhibited no significant correlation with the levels of progesterone and androstenedione. |
Yaffe et al. [32] | 2000 | 425 women, 65+ years old | Free E2, bioavailable E2, free testosterone | Global measures of cognition (1 test) | Women exhibiting elevated levels of non-protein-bound and bioavailable E2 in their serum were found to have a reduced likelihood of experiencing cognitive impairment, as opposed to those with lower concentrations. This discovery provides evidence in favor of the theory that increased levels of endogenous E2 play a role in preventing cognitive decline. |
Wolf et al. [33] | 2002 | 38 women (median age: 68) | E2 and testosterone (blood) | Stroop, verbal memory, mental rotation, spatial memory, and verbal fluency (5 tests) | Elevated E2 and testosterone concentrations demonstrated a connection with improved verbal memory performance. Specifically, E2 was linked to reduced susceptibility to interference. |
Yonker et al. [34] | 2003 | 36 participants, 18 women and 18 men, aged 35–85 | E2, free testosterone, and DHEA-S (blood) | Episodic memory, verbal memory, face recognition, semantic memory, spatial visualization, and problem-solving | A significant correlation between E2 levels and face recognition performance in women (p < 0.02), but not in men, with a similar trend observed for episodic memory composite score, free recall, verbal recognition, and semantic memory. |
Hogervorst et al. [35] | 2004 | 145 participants (66 women) aged 61–91 | TT and total E2 (serum) | Global measures of cognition, verbal memory, and visuospatial memory functions (8 tests) | A correlation was observed between the levels of TE2 in serum and verbal list recall in women, although no such correlation was found with other verbal memory tests. Conversely, serum TT levels were found to have a negative association with verbal recall. |
Thrillers et al. [36] | 2006 | 1276 women and 1107 men aged 35–90 | Free testosterone (FT) | Visuospatial, verbal fluency, semantic, and episodic memory tasks | In the case of women, FT showed a negative correlation with verbal fluency, semantic memory, and episodic memory, with only verbal fluency demonstrating statistical significance at standard alpha levels. These findings provide evidence for the assertion that FT has gender-specific effects on cognitive functioning. |
Herlitz et al. [37] | 2007 | Premenopausal: 45 (n = 129), perimenopausal: 50 (n = 58), postmenopausal: 55 (n = 55) | Estrogen (serum) | Episodic memory tasks, verbal fluency tasks, visuospatial tasks, face recognition tasks, semantic memory tasks (15 tests) | No significant distinction in cognitive activity among premenopausal, perimenopausal, and postmenopausal women in association with serum estrogen levels. |
Yaffe et. al. [38] | 2007 | 792 participants (45% are women) aged 70–79 | Bioavailable E2 and free testosterone (serum) | Global measures of cognition, verbal memory, and selective memory (3 tests) | Women exhibiting lower serum E2 concentrations at the initial assessment were markedly inclined to manifest significant cognitive deterioration over a period of 2 years, reflecting impairments both in executive cognitive functioning and verbal memory. Men followed a similar trend. |
Hogervorst et al. [39] | 2010 | 521 participants (51% female) aged 64–94 | Testosterone, sex hormone globulin building (SHBG) (serum) | Global measures of cognition (2 tests) | In older individuals without health issues, higher levels of testosterone were linked to improved MMSE scores at the beginning of the study. Further investigation revealed that in men, lower testosterone levels were identified as a potential risk factor for significant cognitive decline after a 2-year period. |
Ryan et al. [40] | 2011 | 147 women aged 56–64 (recent natural menopause, median age: 53) | SHBG, estrone, free E2, and free testosterone (serum) | Executive functioning (visual scanning, working memory, attention, and response alternation) (5 tests) | Regression analysis revealed that out of 20 initial correlations, 2 displayed significance at p < 0.05. Specifically, estrone levels exhibited a positive association with executive functioning performance (p = 0.02), while the ratio of free testosterone to free E2 demonstrated a positive relationship with psychomotor speed (p = 0.04). Subsequently, no hormone was identified as predictive of the change in cognitive function over a two-year period. |
Henderson et al. [41] | 2013 | 643 healthy postmenopausal women. Two groups: early: median age 55.4 and late 65.4 | E2, estrone, progesterone, and testosterone (serum) | Verbal episodic memory, executive functioning, and global cognition (17 tests) | Hormone concentrations did not show a correlation with verbal memory, executive functions, global cognition, or mood. However, among women in the early-stage group, higher progesterone levels were linked to improved memory and global cognition. |
Koyama et al. [42] | 2016 | 3044 women, aged 30–55 at the beginning of the study | Estrone, estrone sulfate, E2, androstenedione, testosterone, DHEA, and DHEA-S (plasma) | General measures of cognition, working memory, semantic memory, and verbal memory (6 tests) | No association was observed between hormone levels and neuropsychological test performance. Additionally, the correlation between elevated plasma estrone levels and higher scores for both overall cognition (p = 0.1) and verbal memory was found to be insignificant. |
Authors | Year | Population | Hormone Tested | Results |
---|---|---|---|---|
Manly et al. [51] | 2000 | 50 women, 93 controls (mean age: 75.4) | E2 and estrone (serum) | Individuals diagnosed with AD had decreased E2 (p = 0.005) concentrations compared to those in the control group. Similarly, patients also demonstrated lower estrone levels; however, this contrast did not fully meet the significance criteria (p = 0.06). Women with AD were four to six times more likely to have levels below 20 pg/mL. |
Geerlings et al. [52] | 2003 | 508 women (mean age: 72.1), 438 men (mean age: 69.8) | E2 (serum) | Patients with elevated total E2 levels demonstrated an elevated risk of developing dementia. Furthermore, the age-adjusted hazard ratio of AD and vascular dementia were associated with heightened total E2 levels. |
Schupf et al. [53] | 2006 | 119 (age range: 42–59) | Total E2, estrone, follicle-stimulating hormone (FSH), DHEAS, and SHBG (serum) | Women with initially low levels of bioavailable E2 demonstrated a fourfold increased likelihood of developing and an earlier onset of AD, with an average difference of 3 years compared to individuals with high levels of bioavailable E2, following appropriate adjustments. |
Ravaglia et al. [54] | 2007 | 433 women (mean age: 74), 376 men (mean age: 73) | Total E2 and free testosterone (serum) | There was no observed relationship between free testosterone and dementia in women, nor between E2 or free testosterone in men. Elevated E2, however, stands as an autonomous predictor for dementia and AD in older women. |
Muller et al. [55] | 2010 | 731 individuals (men and women), 65+ years old, mean age 77.4 years | SHBG (serum) | Elevated levels of SHBG were linked to a higher likelihood of AD and dementia in both males and females. These findings remained consistent regardless of vascular risk factors and levels of bioactive hormones. |
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Targonskaya, A.; Wieczorek, K.; Maslowski, K. Endogenous Hormones and Cognitive Decline in Women: Unveiling the Complex Interplay. Women 2024, 4, 116-129. https://doi.org/10.3390/women4020009
Targonskaya A, Wieczorek K, Maslowski K. Endogenous Hormones and Cognitive Decline in Women: Unveiling the Complex Interplay. Women. 2024; 4(2):116-129. https://doi.org/10.3390/women4020009
Chicago/Turabian StyleTargonskaya, Anna, Karolina Wieczorek, and Katherine Maslowski. 2024. "Endogenous Hormones and Cognitive Decline in Women: Unveiling the Complex Interplay" Women 4, no. 2: 116-129. https://doi.org/10.3390/women4020009