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Hormone therapy and clinical and surrogate cardiovascular endpoints in women with chronic kidney disease: a systematic review and meta-analysis.
Ramesh, S, Mann, MC, Holroyd-Leduc, JM, Wilton, SB, James, MT, Seely, EW, Ahmed, SB
Menopause (New York, N.Y.). 2016;(9):1028-37
Abstract
OBJECTIVE Women with chronic kidney disease (CKD) experience kidney dysfunction-mediated premature menopause. The role of postmenopausal hormone therapy (HT) in this population is unclear. We sought to summarize current knowledge regarding use of postmenopausal HT and cardiovascular (CV) outcomes, and established surrogate measures of CV risk in women with CKD. METHODS This is a systematic review and meta-analysis of adult women with CKD. We searched electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) (inception to 2014 December), relevant conference proceedings, tables of contents of journals, and review articles. Randomized controlled trials and observational studies examining postmenopausal HT compared with either placebo or untreated control groups were included. The intervention of interest was postmenopausal HT, and the outcome measures were all-cause and CV mortality, nonfatal CV event (myocardial infarction, stroke), and surrogate measures of CV risk (serum lipids, blood pressure). RESULTS Of 12,482 references retrieved, four randomized controlled trials and two cohort studies (N = 1,666 participants) were identified. No studies reported on CV outcomes or mortality. Compared with placebo, postmenopausal HT was associated with decreased low-density lipoprotein cholesterol (-13.2 mg/dL [95% CI, -23.32 to -3.00 mg/dL]), and increased high-density lipoprotein (8.73 mg/dL [95% CI, 4.72-12.73 mg/dL]) and total cholesterol (7.96 mg/dL [95% CI, 0.07-15.84 mg/dL]). No associations were observed between postmenopausal HT triglyceride levels and blood pressure. CONCLUSIONS Studies examining the effect of postmenopausal HT on CV outcomes in women with CKD are lacking. Further prospective study of the role of postmenopausal HT in this high-risk group is required.
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CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.
Garcia-Albeniz, X, Rudolph, A, Hutter, C, White, E, Lin, Y, Rosse, SA, Figueiredo, JC, Harrison, TA, Jiao, S, Brenner, H, et al
British journal of cancer. 2016;(2):221-9
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Abstract
BACKGROUND Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. METHODS We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test. RESULTS The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10(-9)). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10(-5) (alpha threshold=3.1 × 10(-4)). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively. CONCLUSIONS Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.
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Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.
Asi, N, Mohammed, K, Haydour, Q, Gionfriddo, MR, Vargas, OL, Prokop, LJ, Faubion, SS, Murad, MH
Systematic reviews. 2016;(1):121
Abstract
BACKGROUND Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model. RESULTS We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81. CONCLUSIONS Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
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Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.
Pizot, C, Boniol, M, Mullie, P, Koechlin, A, Boniol, M, Boyle, P, Autier, P
European journal of cancer (Oxford, England : 1990). 2016;:138-54
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BACKGROUND Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. METHODS After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). RESULTS The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. CONCLUSION Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out.
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[Role of hormone-replacement therapy for prevention of coronary artery disease in women].
Gohlke-Bärwolf, C, von Schacky, C
Zeitschrift fur Kardiologie. 2005;:III/74-8
Abstract
The postmenopausal increase in the incidence of coronary artery disease implied a protective effect of estrogens. Nonrandomized, clinical and experimental studies have supported this notion. In the first randomized study (HERS 1998) no protective effect on prognosis of postmenopausal women with coronary artery disease was demonstrated. Also, in healthy postmenopausal women no beneficial effect of a hormone-replacement therapy on coronary events was shown (WHI-Study 2002, 2004). Therefore, hormone-replacement therapy is not recommended for prophylaxis of cardiovascular disease in healthy women or in women with documented coronary artery disease (Recommendation class I, evidence-level A). The continuation or the start of a hormone- replacement therapy is only justified for therapy of severe menopausal symptoms. Women should be informed that changes in lifestyle including not smoking, a heart healthy diet, and regular exercise are the most important measures to prevent cardiovascular diseases.