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Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review.
Burgos, N, Cintron, D, Latortue-Albino, P, Serrano, V, Rodriguez Gutierrez, R, Faubion, S, Spencer-Bonilla, G, Erwin, PJ, Murad, MH
Endocrine. 2017;(3):413-425
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Abstract
PURPOSE Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. METHODS A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. RESULTS The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent. CONCLUSIONS Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.
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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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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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Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus.
Xu, Y, Lin, J, Wang, S, Xiong, J, Zhu, Q
The Kaohsiung journal of medical sciences. 2014;(7):350-61
Abstract
Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT) on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone) on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95% confidence interval (CI), 0.55-0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51-0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, -1.41 mM/L; 95% CI, -2.49 to -0.33 mM/L) and HbA1c (mean difference, -0.73%; 95% CI, from -1.28 to -0.18%) compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, -0.34 mM/L; 95% CI, from -0.53 to -0.15 mM/L) and low-density lipoprotein (mean difference, -0.43 mM/L; 95% CI, from -0.71 to -0.14 mM/L) but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from -0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.
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Treatments for suppression of lactation.
Oladapo, OT, Fawole, B
The Cochrane database of systematic reviews. 2012;(9):CD005937
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BACKGROUND Various pharmacologic and non-pharmacologic interventions have been used to suppress lactation after childbirth and relieve associated symptoms. Despite the large volume of literature on the subject, there is currently no universal guideline on the most appropriate approach for suppressing lactation in postpartum women. OBJECTIVES To evaluate the effectiveness and safety of interventions used for suppression of lactation in postpartum women (who have not breastfed or expressed breastmilk) to determine which approach has the greatest comparative benefits with least risk. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2012). SELECTION CRITERIA Randomised trials evaluating the effectiveness of treatments used for suppression of postpartum lactation. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. MAIN RESULTS We included 62 trials (6428 women). Twenty-two trials did not contribute data to the meta-analyses. The trials were generally small and of limited quality. Three trials (107 women) indicated that bromocriptine significantly reduced the proportion of women lactating compared with no treatment at or within seven days postpartum (three trials, 107 women; risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.54). Seven trials involving oestrogen preparations (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol) suggested that they significantly reduced the proportion of lactating women compared with no treatment at or within seven days postpartum (RR 0.40, 95% CI 0.29 to 0.56). We found no trials comparing non-pharmacologic methods with no treatment. Trials comparing bromocriptine with other pharmacologic agents such as methergoline, prostaglandins, pyridoxine, carbegoline, diethylstilbestrol and cyclofenil suggested similarity in their effectiveness. Side effects were poorly reported in the trials and no case of thromboembolism was recorded in the four trials that reported it as an outcome. AUTHORS' CONCLUSIONS There is weak evidence that some pharmacologic treatments (most of which are currently unavailable to the public) are better than no treatment for suppressing lactation symptoms in the first postpartum week. No evidence currently exists to indicate whether non-pharmacologic approaches are more effective than no treatment. Presently, there is insufficient evidence to address the side effects of methods employed for suppressing lactation. When women desire treatment, bromocriptine may be considered where it is registered for lactation suppression in those without predisposition to its major side effects of public concerns. Many trials did not contribute data that could be included in analyses. Large randomised trials are needed to compare the effectiveness of pharmacologic (especially bromocriptine) and non-pharmacologic methods with no treatment. Such trials should consider the acceptability of the intervention and lactation symptoms of concern to women and be large enough to detect clinically important differences in major side effects between comparison groups.