Has a High Dose of Vitamin D3 Impacted Health Conditions in Older Adults?-A Systematic Review and Meta-Analysis Focusing on Dose 100,000 IU.

BACKGROUND: Older adults are prone to vitamin D3 (VD3) deficiency, which may impair their health. A high dose of VD3 (HDVD3 = 100,000 IU) could improve their 25-hydroxyvitamin D3 [25(OH)D] level and health outcomes. However, evidence for such a beneficial effect of HDVD3 in older adults coming from clinical trials is mixed. OBJECTIVE: To review the literature on the efficacy of a single dose of 100,000 IU of VD3 in older people. METHODS: We searched PubMed/Medline, Science Direct, and NIH's clinical trials registry for clinical studies on the effect of a single high dose of VD3 on various health outcomes in older people. We also performed a meta-analysis using the standardized mean difference to assess the effect of VD3 on its blood level. Due to expected high heterogeneity, its amount (i.e., tau2) was estimated using the DerSimonian-Laird estimator. To estimate tau2, the Q-test for heterogeneity and the I2 statistic were calculated. RESULTS: Search results identify 13 studies that reported diverse health outcomes, such as lung and cardiovascular function, skin cancer progression, intensive care unit mortality, immune system response, and bone density. The meta-analysis showed a significant increase in 25(OH)D blood levels after treatment in 10 studies, with an average standardized mean difference of 2.60 ng/mL (95% CI: 2.07 to 3.13). Their results suggested that a single high dose of VD3 may benefit intensive care unit patients and skin cancer patients in remission. However, evidence for other beneficial health effects of HDVD3 was mixed due to high heterogeneity among studies. CONCLUSIONS: A single high dose of VD3 may positively affect some health outcomes in older people, possibly due to its pleiotropic and immunomodulatory effects. However, the evidence needs to be more extensive and consistent, and more rigorous studies are required to confirm the benefits and safety of VD3 high doses in older patients.

Antenatal Classes in the Context of Prenatal Anxiety and Depression during the COVID-19 Pandemic.

Perinatal maternal anxiety and depression negatively affect intrauterine fetal development, birth outcome, breastfeeding initiation, duration, and milk composition. Antenatal classes potentially reduce the anxiety of pregnant women and may thus contribute to healthy infant development. The study investigates the relationship between participation in online or in-person antenatal classes and levels of anxiety and depression in Polish women during the COVID-19 pandemic. The study group included 1774 adult, non-smoking pregnant women. We compared the state anxiety (STAI-State) and depression levels (EPDS) in women who (i) attended antenatal classes in-person, (ii) attended online classes, and (iii) did not attend any of them. The statistical analyses included a GLM model and trend analysis, while controlling for maternal trait anxiety, age, pregnancy complications, trimester of pregnancy, previous pregnancies, and COVID-19 infections. We observed statistically significant differences in the level of anxiety (and depression). Women who did attend antenatal classes in person had the lowest levels of anxiety and depression. Considering the importance of maternal mental well-being on fetal development, birth outcome, and breastfeeding, in-person participation in antenatal classes should be recommended to pregnant women.

Digit ratio (2D:4D) does not correlate with daily 17ß-estradiol and progesterone concentrations in healthy women of reproductive age.

OBJECTIVES: Second-to-fourth digit ratio (2D:4D) is proposed as a proxy for the prenatal balance of sex hormones, is related to hormone-dependent characteristics in adult life, and is a possible predictor of disease later in life. Here, we studied the relationship between 2D:4D and ovarian steroid hormones (17ß-estradiol and progesterone) among women of reproductive age. METHODS: From 186 healthy premenopausal women, aged 24-37 years, we collected saliva samples daily during the entire menstrual cycle. Data on reproductive and lifestyle characteristics were collected via questionnaires, and anthropometric measurements were performed. RESULTS: No statistically significant relationships were detected between adult women's sex hormone concentrations (17ß-estradiol and progesterone) during the menstrual cycle and 2D:4D, in either left or right hand, when controlling for size at birth, body mass index, and physical activity. CONCLUSIONS: This study shows, for the first time in a large sample of women of reproductive age, that 2D:4D is not a predictor of adult women's sex hormone concentration. The lack of relationship may be because 2D:4D might be genetically determined and is not related to maternal nutritional environment during fetal development. These results support the hypothesis that, in contrast to the nutritional quality of the fetal environment, the fetal hormonal environment (reflected by 2D:4D) does not determine reproductive physiology in later life.

Trait anxiety moderates the association between estradiol and dominance in women.

The aim of the study was to investigate the relationship between self-assessed social dominance trait and levels of free basal sex steroids: estradiol and testosterone, in reproductive age women. Polish urban women aged 24-35 (N = 72) filled in Trait Dominance-Submissiveness Scale (TDS) and State and Trait Anxiety Inventory (STAI). They also gave a single blood sample during the follicular phase of the following menstrual cycle. The blood sample was analyzed for concentration of free testosterone (T), estradiol (E2) and cortisol (C). We found that self-assessed social dominance was negatively associated with free E2 and E2 to T ratio. This general relationship was moderated by Trait Anxiety. Higher social dominance was associated with lower E2 and lower E2 to T ratio in moderate and highly anxious women. No such relationship was found in low anxious women. Results of this study evidence important contribution of estradiol and question the independent role of testosterone in shaping dominance in women. They might also suggest important biological and psychological cost of maintaining high social dominance in reproductive age women.

Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

Relationships between biomarkers of inflammation, ovarian steroids, and age at menarche in a rural Polish sample.

OBJECTIVES: To test the hypothesis that life history trade-offs between maintenance and reproductive effort would be evident through inverse associations between levels of a biomarker of inflammation [C-reactive protein (CRP)], and ovarian hormones. Associations between CRP and age at menarche were also explored. METHODS: Urinary CRP, salivary progesterone, and estradiol were measured over one menstrual cycle from rural Polish women (n = 25), representing a natural fertility sample. Age of menarche was assessed through interview recall methods. We used minimum second-order Akaike Information Criteria as a means of multiple regression model selection, and repeated measures ANOVA to test cycle-dependent hypotheses. RESULTS: Comparisons of individuals in high and low CRP tertiles revealed that those with high CRP had significantly lower progesterone (luteal P = 0.03, mid luteal P = 0.007) but not estradiol (follicular P = 0.21, luteal P = 0.15) concentrations through the menstrual cycle. However, when the age at menarche was included in the analysis, both age at menarche and urinary CRP were negatively associated with estradiol (R(2) = 0.44, P = 0.0007). Age at menarche and estradiol were the strongest negative predictors of CRP (R(2) = 0.52, P = 0.0001). CONCLUSIONS: Inflammation itself may suppress ovarian function, or indicate immune challenges that lead to ovarian suppression. The timing of menarche may also influence adult inflammatory sensitivity and ovarian hormone concentrations. This lends support to existing models of trade-offs between maintenance and reproduction in women.

CYP17 genotypes differ in salivary 17-beta estradiol levels: a study based on hormonal profiles from entire menstrual cycles.

Variation in the levels of sex-steroid hormones results from differences in developmental conditions, adult lifestyle, and genetic polymorphism. Genes involved in sex-steroid biosynthesis have been implicated to influence levels of hormones in premenopausal women, but the results were inconclusive. We tested variation among women in levels of salivary estradiol (E(2)) corresponding to CYP17 genotypes. CYP17 encodes cytochrome P450c17alpha, which mediates two enzymes important in E(2) synthesis. In contrast to the earlier studies that relied on one or a few samples for assessing the E(2) levels of an individual woman, our study is based on daily collected saliva samples for one entire menstrual cycle. Sixty Polish women, ages 24 to 36 years, with regular menstrual cycles and no reported fertility problems participated in the study. Women with A2/A2 genotype had 54% higher mean E(2) levels than women with A1/A1 genotype (P = 0.0001) and 37% higher than women with A1/A2 genotype (P = 0.0008). Heterozygous A1/A2 women had 13 % higher E(2) levels than homozygous A1/A1 women (but this difference was significant only in a nonparametric test). Levels of E(2) during the day with highest E(2) (day -1) were 72% higher in A2/A2 compared with A1/A1 (P = 0.01) and 52 % higher compared with A1/A2 (P = 0.03). Our results suggest that CYP17 genotype may serve as a biomarker of endocrine function in women of reproductive age. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2131-5).

Habitual physical activity and estradiol levels in women of reproductive age.

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

High ponderal index at birth predicts high estradiol levels in adult women.

Inter-individual variation in levels of sex hormones results from differences in genetic, developmental, and environmental factors. We tested a hypothesis that programming of the fetal neuroendocrine axis may predispose some women to produce higher levels of steroid hormones during their menstrual cycles as adults. One hundred forty-five regularly menstruating 24- to 36- year-old women collected daily saliva samples for one menstrual cycle. Data on women's birth weights and birth lengths were obtained from medical records. A positive relationship was observed between ponderal index at birth (an indicator of nutritional status, calculated as birth weight/(birth length)(3)) and levels of estradiol (E2) in menstrual cycles, after controlling for potential confounding factors. Mean E2 was 16.4 pmol/l in the low ponderal index tertile, 17.3 pmol/l in the moderate ponderal index tertile, and 19.6 pmol/l in the high ponderal index tertile (the high ponderal index group had significantly higher E2 than both low and moderate ponderal index groups, P=0.0001). This study shows a positive association between ponderal index recorded for women at birth and levels of E2 measured during their menstrual cycles as adults. This suggests that conditions during fetal life influence adult production of reproductive hormones and may contribute to inter-individual variation in reproductive function. In addition, because large size at birth is one of the factors linked with an increased risk of breast cancer, our findings provide a physiological link for the observed positive relationship between indicators of energetic conditions during fetal growth and breast cancer in women.

Body mass, depressive symptoms and menopausal status: an examination of the "Jolly Fat" hypothesis.

PURPOSE: Estrogens are linked with depression due to their ability to alter the function of the serotonin neural systems. We hypothesize that postmenopausal women should have a higher degree of depressive symptoms than premenopausal women. Further, because estrogen levels in postmenopausal women positively correlate with body fat, we hypothesize that there is an inverse relationship between body fat and depressive symptoms among postmenopausal women. METHODS: We enrolled 1156 Polish urban women aged 45 to 64 in a cross-sectional study. Depressive symptoms were assessed by the Center for Epidemiologic Studies-Depression Scale (CES-D) scale. Menopausal status and education level was assessed by a standardized questionnaire. MAIN FINDINGS: Postmenopausal women had higher mean CES-D scores of depressive symptoms than premenopausal women (14.4 versus 13.2 respectively, p = .018). Both among pre- and postmenopausal women, those with higher education had lower scores of depressive symptoms. In addition, in postmenopausal women with lower education an inverse relationship was observed between body mass index (BMI) and depressive symptoms: a higher BMI was associated with a lower score of depressive symptoms (p = .009). Such a relationship was not present among premenopausal women or women who were postmenopausal but better educated. CONCLUSIONS: This study indicates that menopausal status is related to differences in the degree of occurrence of depressive symptoms. Our results support the "Jolly Fat" hypothesis for postmenopausal women with lower education, namely, a higher BMI is associated with lower score of depressive symptoms.

Large breasts and narrow waists indicate high reproductive potential in women.

Physical characteristics, such as breast size and waist-to-hip ratio (WHR), function as important features used by human males to assess female attractiveness. Males supposedly pay attention to these features because they serve as cues to fecundity and health. Here, we document that women with higher breast-to-underbreast ratio (large breasts) and women with relatively low WHR (narrow waists) have higher fecundity as assessed by precise measurements of daily levels of 17-beta-oestradiol (E2) and progesterone. Furthermore, women who are characterized by both narrow waists and large breasts have 26% higher mean E2 and 37% higher mean mid-cycle E2 levels than women from three groups with other combinations of body-shape variables, i.e. low WHR with small breasts and high WHR with either large or small breasts. Such gains in hormone levels among the preferred mates may lead to a substantial rise in the probability of conception, thus providing a significant fitness benefit.