Menopausal Hormone Therapy, Age, and Chronic Diseases: Perspectives on Statistical Trends

Bolton, Judy L.

doi:10.1021/acs.chemrestox.6b00272

Cited by 20 publications

(22 citation statements)

References 98 publications

(221 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, in the youngest group (50–54 years) the greatest decrease in mortality was observed in the 2005–2009 period, which could be related to the decline of the prescription of the HRT 14 , 15 and the increasing use of bisphosphonates 16 . On the contrary, in the period 2009–2015 a slow decrease in th mortality rate was observed.…”

Section: Discussionmentioning

confidence: 96%

“…Regarding pharmacological interventions, for many years the prevention of postmenopausal bone loss was marked by the use of hormone replacement therapy (HRT) 12 until in 2001, when Women’s Health Initiative study finding the association between HT and several cancers was published 14 , 15 . The widespread use in the prescription of bisphosphonates in developed countries began in 2002.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A join point regression analysis of trends in mortality due to osteoporosis in Spain

Dragomirescu

Llorca

Gómez‐Acebo

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Osteoporosis is a major health problem in terms of fracture probability and disability. The aim of this ecological study is to identify the temporal trends in osteoporosis mortality in Spain from 1999 to 2015. Data on the Spanish population and number of deaths due to osteoporosis were obtained from the Spanish National Institute for Statistics. Age-adjusted mortality rates were estimated. Join point regression was used to identify the years when changes in mortality s and annual percentage change in mortality rates took place. Women presented a greater mortality rate decrease (p < 0.001), though this mortality difference by sex was reduced by half at the end of the period. The higher the age, the faster the mortality rate declined in women, while no clear pattern could be identified in men. In women, significant changes in trends were identified in three age groups (50–54, 60–64 and 80–84 years old). A sustained decrease in osteoporosis-associated mortality was found in women aged 75–79 and ≥85 years and men aged 60–64. In conclusion, mortality caused by osteoporosis in Spain is decreasing faster in the older age ranges especially in women.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

A join point regression analysis of trends in mortality due to osteoporosis in Spain

Dragomirescu

Llorca

Gómez‐Acebo

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“… 2 , 6 , 7 As traditional hormone therapy (HT) is associated with an increased risk of breast cancer, many women use BDSs, which are perceived as safer alternatives for the relief of menopausal symptoms. 2 , 8 − 10 However, efficacy claims are not only disallowed for BDSs but also remain questionable for botanicals used in this field. In particular, the effect of estrogenic BDSs on estrogen metabolism is unknown.…”

Section: Introductionmentioning

confidence: 99%

Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism

Dunlap

Howell

Mukand

et al. 2017

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women’s health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism. The methoxy estrogen metabolites (2-MeOE1, 4-MeOE1) were measured by LC-MS/MS, and CYP1A1 and CYP1B1 gene expression was analyzed by qPCR. Nonmalignant ER-negative breast epithelial cells (MCF-10A) and ER-positive breast cancer cells (MCF-7) were derived from normal breast epithelial tissue and ER+ breast cancer tissue. Red clover extract (RCE, 10 μg/mL) and isoflavones had no effect on estrogen metabolism in MCF-10A cells. However, in MCF-7 cells, RCE treatments downregulated CYP1A1 expression and enhanced genotoxic metabolism (4-MeOE1/CYP1B1 > 2-MeOE1/CYP1A1). Experiments with the isoflavones showed that the AhR agonists (BA, FN) preferentially induced CYP1B1 expression as well as 4-MeOE1. In contrast, the ER agonists (GN, DZ) downregulated CYP1A1 expression likely through an epigenetic mechanism. Finally, the ER antagonist ICI 182,780 potentiated isoflavone-induced XRE-luciferase reporter activity and reversed GN and DZ induced downregulation of CYP1A1 expression. Overall, these studies show that red clover and its isoflavones have differential effects on estrogen metabolism in “normal” vs breast cancer cells. In breast cancer cells, the AhR agonists stimulate genotoxic metabolism, and the ER agonists downregulate the detoxification pathway. These data may suggest that especially breast cancer patients should avoid red clover and isoflavone based BDSs when making choices for menopausal symptom relief.

show abstract

“…A meta-analysis study investigating the new-onset of T2DM in post-menopausal women following estrogen replacement therapy revealed a 30% lower relative risk [RR 0.7 (CI [0.6–0.9])] of diabetes compared with placebo (Salpeter et al, 2006). However, the use of estrogen to prevent chronic diseases is still challenging and controversial (Bolton, 2016).…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women

Ereqat

Cauchi

Eweidat

et al. 2019

PeerJ

View full text Add to dashboard Cite

Background Type 2 diabetes mellitus (T2DM) is a multifactorial disease where both genetic and environmental factors contribute to its pathogenesis. The PvuII and XbaI polymorphisms of the estrogen receptor 1 (ESR1) gene have been variably associated with T2DM in several populations. This association has not been studied in the Palestinian population. Therefore, the aim of this study was to investigate the association between the PvuII and XbaI variants in the ESR1 and T2DM and its related metabolic traits among Palestinian women. Methods This case–control study included 102 T2DM and 112 controls in which PvuII and XbaI variants of the ESR1 gene were genotyped using amplicon based next generation sequencing (NGS). Results Allele frequencies of both PvuII and XbaI variants were not significantly different between patients and control subjects (P > 0.05). In logestic regression analysis adjusted for age and BMI, the ESR1 PvuII variant was associated with risk of T2DM in three genotypic models (P < 0.025) but the strongest association was observed under over-dominant model (TT+CC vs. TC) (OR = 2.32, CI [1.18–4.55] adjusted P = 0.013). A similar but non-significant trend was also observed for the ESR1 XbaI variant under the over-dominant model (AA+GG vs. AG) (OR = 2.03, CI [1.05–3.95]; adjusted P = 0.035). The frequencies of the four haplotypes (TA, CG, CA, TG) were not significantly different in the T2DM patients compared with control group (P > 0.025). Among diabetic group, an inverse trend with risk of cardio vascular diseases was shown in carriers of CG haplotype compared to those with TA haplotype (OR = 0.28, CI [0.09–0.90]; adjusted P = 0.035). Further, stratified analyses based on ESR1 PvuII and XbaI genotypes revealed no evidence for association with lipid levels (TC, TG, HDL, LDL). Conclusions This is the first Palestinian study to conclude that ESR1 PuvII and XbaI variants may contribute to diabetes susceptibility in Palestinian women. Identification of genetic risk markers can be used in defining high risk subjects and in prevention trials.

show abstract

Menopausal Hormone Therapy, Age, and Chronic Diseases: Perspectives on Statistical Trends

Cited by 20 publications

References 98 publications

A join point regression analysis of trends in mortality due to osteoporosis in Spain

A join point regression analysis of trends in mortality due to osteoporosis in Spain

Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women

Contact Info

Product

Resources

About