scholarly journals Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 573 ◽  
Author(s):  
Marta D’Alonzo ◽  
Valentina Elisabetta Bounous ◽  
Michela Villa ◽  
Nicoletta Biglia
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Current Evidence ◽  
Conjugated Equine Estrogen ◽  
Colon Cancer Risk ◽  
Increased Risk ◽  
Intact Uterus ◽  
Progestin Therapy

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women’s Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT’s effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65–0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07–10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56–0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42–0.87). Data about ovarian and cervical cancer are still controversial.

scholarly journals Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Enrique Soto-Pedre ◽  
Moneeza K. Siddiqui ◽  
Cyrielle Maroteau ◽  
Adem Y. Dawed ◽  
Alex S. Doney ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Hormone Replacement Therapy ◽  
Thyroid Hormone ◽  
Candidate Gene ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Thyroid Hormone Replacement ◽  
Increased Risk ◽  
Thyroid Hormone Replacement Therapy

AimsAtrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.Methods and ResultsA retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e–02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e–04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).ConclusionHomozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.

Menopause, cognition and dementia – A review

2019 ◽  
Vol 25 (4) ◽  
pp. 200-206 ◽  
Author(s):  
S Pertesi ◽  
G Coughlan ◽  
V Puthusseryppady ◽  
E Morris ◽  
M Hornberger
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Current Evidence ◽  
Negative Effects ◽  
Cognitive Changes ◽  
Positive Effects ◽  
Dementia Risk ◽  
Increased Risk

There is increasing evidence that menopausal changes can have an impact on women’s cognition and potentially, the future development of dementia. In particular, the role of reduced levels of estrogen in postmenopausal changes has been linked to an increased risk of developing dementia in observational studies. Not surprisingly, this has led to several clinical trials investigating whether postmenopausal hormone replacement therapy can potentially delay/avoid cognitive changes and subsequently, the onset of dementia. However, the evidence of these trials has been mixed, with some showing positive effects while others show no or even negative effects. In the current review, we investigate this controversy further by reviewing the existing studies and trials in cognition and dementia. Based on the current evidence, we conclude that previous approaches may have used a mixture of women with different genetic risk factors for dementia which might explain these contradicting findings. Therefore, it is recommended that future interventional studies take a more personalised approach towards hormone replacement therapy use in postmenopausal women, by taking into account the women’s genetic status for dementia risk.

Influence of Hormone Replacement Therapy on Tamoxifen-Induced Vasomotor Symptoms

2006 ◽  
Vol 24 (24) ◽  
pp. 3991-3996 ◽  
Author(s):  
Ivana Sestak ◽  
Roseann Kealy ◽  
Robert Edwards ◽  
John Forbes ◽  
Jack Cuzick
Keyword(s):  
Breast Cancer ◽  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Vasomotor Symptoms ◽  
Hot Flushes ◽  
Limited Effectiveness ◽  
Increased Risk ◽  
Cancer Intervention

Purpose Tamoxifen is an effective drug, but its role in prevention is limited by its adverse effect profile. Non–life-threatening adverse effects, such as vasomotor symptoms, have an important influence in its use for prevention. Vasomotor symptoms were evaluated according to follow-up time, severity, and use of hormone replacement therapy (HRT) in a retrospective analysis. Patients and Methods In the International Breast Cancer Intervention Study-I study, 7,154 women at increased risk of breast cancer were randomly assigned to either tamoxifen 20 mg/d or placebo for 5 years. Women gave detailed information on any vasomotor symptoms at each 6-month follow-up visit. Results Hot flushes were reported more often in the tamoxifen group than in the placebo group (70.6% v 57.1%, respectively; odds ratio, 1.80; 95% CI, 1.63 to 1.99). Severe hot flushes were more strongly related to tamoxifen. In the tamoxifen arm, more women taking HRT at entry experienced hot flushes in the first 6 months than those who did not take HRT (60.8% v 49.2%, respectively; P = .09). In contrast, women on placebo taking HRT at entry experienced fewer hot flushes than women who stopped HRT (22.9% v 34.3%, respectively; P = .03). Furthermore, for women who first began HRT in the first 6 months of the trial compared with women who did not begin HRT, HRT seemed to be much more effective in controlling hot flushes in months 6 to 12 in the placebo arm (47.9% v 20.4%, respectively) than in the tamoxifen arm (51.4% v 39.0%, respectively). Conclusion HRT use at entry or during the trial was not effective in alleviating hot flushes for women in the tamoxifen arm. Our retrospective study suggests that estrogen-based HRT has limited effectiveness among women receiving tamoxifen.

Risks and Benefits of Hormone Replacement Therapy

Cephalalgia ◽  
2000 ◽  
Vol 20 (3) ◽  
pp. 164-169 ◽  
Author(s):  
B de Lignières ◽  
E A MacGregor
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Mortality And Morbidity ◽  
Oestrogen Deficiency ◽  
Disease Mortality ◽  
Increased Risk ◽  
Deficiency Diseases ◽  
Symptomatic Side ◽  
Natural Progesterone

Menopause, the permanent cessation of menstruation, is due to ovarian failure, which may lead to oestrogen deficiency diseases, particularly osteoporosis, cardiovascular disease and cerebrovascular disease. Mortality and morbidity caused by these conditions can be modified by using hormone replacement therapy, but the benefits of this therapy must be weighed against the increased risk of breast cancer and the symptomatic side-effects the treatment may cause. The combination of transdermal oestrogen and natural progesterone offers the most favourable risk-to-benefit profile.

scholarly journals Determinants of first prescription of hormone replacement therapy. A follow-up study among 1689 women aged 45–60 years

Maturitas ◽  
1994 ◽  
Vol 20 (2-3) ◽  
pp. 81-89 ◽  
Author(s):  
F.P.M.J. Groeneveld ◽  
F.P. Bareman ◽  
R. Barentsen ◽  
H.J. Dokter ◽  
A.C. Drogendijk ◽  
...  
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Follow Up Study

Meta-Analysis

2005 ◽  
Vol 44 (01) ◽  
pp. 127-135 ◽  
Author(s):  
D. Böhning
Keyword(s):  
Breast Cancer ◽  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Mixed Model ◽  
Unobserved Heterogeneity ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Large Trial ◽  
Increased Risk ◽  
The One

Summary Objectives: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. Methods: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. Results: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. [1] concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. Conclusions: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. [1]. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

scholarly journals Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study

2019 ◽  
Vol 123 (5) ◽  
pp. 574-582 ◽  
Author(s):  
L. C. Stasinopoulos ◽  
A. Zhou ◽  
E. Hyppönen
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Cancer Mortality ◽  
Hormone Replacement ◽  
Sensitivity Analyses ◽  
Milk Consumption ◽  
Inverse Association ◽  
Uk Biobank ◽  
Supplement Use ◽  
Increased Risk

AbstractExcessive Ca intakes have been proposed to associate with vascular calcification and a higher risk of prostate cancer. We investigated the associations of supplemental and dietary Ca intake with mortality using data from 497 828 UK Biobank participants. The average follow-up was 4·2 years and 14 255 participants died, 8297 from cancer, 2959 from CVD and 572 from respiratory disease. The use of Ca supplements and milk consumption were associated with differences in mortality in younger (≤65 years) but not in older participants (>65 years, Pinteraction ≤ 0·04 for all comparisons). Among participants <65 years, there was an inverse association between Ca supplementation (OR 0·91, 95 % CI 0·83, 0·99) and milk consumption (OR 0·93, 95 % CI 0·86, 1·00) with respect to all-cause mortality. In the same age group, milk drinkers had lower odds of cancer mortality (OR 0·89, 95 % CI 0·80, 0·98) but Ca supplement use was associated with increased odds of respiratory mortality (OR 1·69, 95 % CI 1·16, 2·74). All associations in participants aged ≥65 years were null after full adjustment. In sensitivity analyses stratified by hormone replacement therapy, Ca supplement use was associated with decreased odds of cancer mortality in users but increased risk in other women (OR 0·81, 95 % CI 0·69, 0·94 v. OR 1·17, 95 % CI 1·01, 1·35, respectively). To conclude, we saw little evidence for harm with dietary or supplemental Ca. Further studies are required to confirm the proposed interaction with hormone replacement therapy and to exclude reverse causation as a determinant in the association between Ca supplements and increased risk of respiratory diseases.

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