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Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.

ABSTRACT: The aim of this study was to assess risks and benefits of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal Chinese women.A retrospective cohort study was undertaken using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women aged 50 to 79 years were classified as exposed to CEE 0.625 mg/day with MPA 5.0 mg/day (estrogen [E] + progestin [P], n = 4,712) or CEE 0.625 mg/day only (E-only, n = 1,208) and were age-matched to unexposed women (n = 10,125). Follow-up was complete in 96% of the participants. The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. The global index summarized risks of primary outcomes, stroke, pulmonary embolism, colon and endometrial cancers, hip fractures, and death. Time-to-event analyses were performed.Median durations of exposure in the E + P and E-only groups were 6.9 and 9 months, respectively. Median follow-up was 110 months. Hazard ratios (95% CI) for E + P exposure were as follows: myocardial infarction, 0.78 (0.51-1.19); CHD death, 1.21 (0.53-2.70); breast cancer, 1.48 (1.20-1.83); global index, 0.79 (0.72-0.87). Hazard ratios for E-only exposure were as follows: myocardial infarction, 0.76 (0.35-1.68); CHD death, 0.57 (0.11-2.80); breast cancer, 1.44 (0.99-2.10); global index, 1.09 (0.92-1.28). Per 10,000 person-years, there were 12 excess breast cancer cases with E + P exposure; there were 39 fewer global index events with E + P exposure. Adjusting for age, statin and aspirin use, hypercholesterolemia, diabetes, and hypertension did not significantly change estimates.In postmenopausal Chinese women, CEE with or without MPA was not associated with increased rates of CHD, but CEE with MPA may be associated with a higher breast cancer rate. E + P exposure conferred lower global index event rates.

SUBMITTER: Su IH

PROVIDER: S-EPMC3387327 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.

Su Irene H IH Chen Yu-Chun YC Hwang Wei-Ting WT Liu Ziyue Z Su Tung-Ping TP Chen Tzeng-Ji TJ Barnhart Kurt T KT Yang Yu-Xiao YX

Menopause (New York, N.Y.) 20120801 8

<h4>Objective</h4>The aim of this study was to assess risks and benefits of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal Chinese women.<h4>Methods</h4>A retrospective cohort study was undertaken using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women aged 50 to 79 years were classified as exposed to CEE 0.625 mg/day with MPA 5.0 mg/day (estrogen [E] + progestin [P], n = 4,712) or CEE 0 ...[more]

PMID: 22453198

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Project description:BackgroundCardiovascular disease (CVD) remains the leading cause of death among postmenopausal women but standard primary prevention strategies in women are not as effective as in men. By comparison, the Early versus Late Intervention Trial with Estradiol (ELITE) study demonstrated that hormone therapy (HT) was associated with significant reduction in atherosclerosis progression in women who were within six years of menopause compared to those who were 10 or more years from menopause. These findings are consistent with other studies showing significant reductions in all-cause mortality and CVD with HT, particularly when initiated in women younger than 60 years of age or within 10 years since menopause. To explore the biological mechanisms underlying the age-related atheroprotective effects of HT, we investigated changes in methylation of blood cells of postmenopausal women who participated in ELITE.ResultsWe first validated the epigenetic data generated from blood leukocytes of ELITE participants by replicating previously known associations between smoking and methylation levels at previously identified CpG sites, such as cg05575921 at the AHRR locus. An epigenome-wide association study (EWAS) evaluating changes in methylation through interactions with time-since-menopause and HT revealed two significantly associated CpG sites on chromosomes 12 (cg19552895; p = 1.1 × 10-9) and 19 (cg18515510; p = 2.4 × 10-8). Specifically, HT resulted in modest, but significant, increases in methylation levels at both CpGs but only in women who were 10 or more years since menopause and randomized to HT. Changes in carotid artery intima-media thickness (CIMT) from baseline to 36 months after HT were not significantly correlated with changes in methylation levels at either cg19552895 or cg18515510. Evaluation of other previously identified CpG sites at which methylation levels in either blood or vascular tissue were associated with atherosclerosis also did not reveal any differences in methylation as a function of HT and time-since-menopause or with changes in CIMT.ConclusionsWe identified specific methylation differences in blood in response to HT among women who were 10 or more years since menopause. The functional consequence of these change with respect to atherosclerosis progression and protective effects of HT remains to be determined and will require additional studies.

Project description:Genitourinary syndrome of menopause (GSM) is a chronic and progressive condition with a series of vulvovaginal, sexual, and lower urinary tract discomforts, mainly due to hypoestrogenism. Menopausal hormone therapy (MHT) has generally been considered as the most effective treatment for GSM. In addition, vaginal microbiota is of particular significance to gynecological and reproductive illnesses and potentially has some intimate connections with GSM. Consequently, we sought to evaluate how MHT impacts the composition and structure of vaginal microbiota while alleviating GSM in Chinese menopausal women aged 45-65 years, which has not been investigated previously. 16S rRNA gene sequencing was performed to analyze microbial diversity and composition using vaginal swabs obtained from 100 menopausal women, classified as MHT women who have been taking tibolone regularly (n = 50) and non-treated women who never received any treatment (n = 50). Vaginal Health Index Score (VHIS) and GSM symptoms inquiry were also performed. We found that the vaginal microbial diversity decreased and that the abundance of Lactobacillus increased to be the dominant proportion significantly in the MHT group, in considerable contrast to vaginal microbiota of the non-treated group, which significantly comprised several anaerobic bacteria, namely, Gardnerella, Prevotella, Escherichia-Shigella, Streptococcus, Atopobium, Aerococcus, Anaerotruncus, and Anaerococcus. In this study, women without any MHT had significantly more severe GSM symptoms than those receiving tibolone, especially with regard to vulvovaginal dryness and burning, as well as decreased libido (P < 0.01). However, there was no significant difference in the severity of urological symptoms between the groups (P > 0.05). Furthermore, Lactobacillus was demonstrated to be associated with VHIS positively (r = 0.626, P < 0.001) and with GSM negatively (r = -0.347, P < 0.001). We also identified Chlamydia (r = 0.277, P < 0.01) and Streptococcus (r = 0.270, P < 0.01) as having a prominent association with more serious GSM symptoms. Our study provided an elucidation that MHT could notably alleviate GSM and conspicuously reshape the composition of the vaginal microbiota, which is of extreme importance to clinical practice for the management of GSM.

Project description:ImportanceCarpal tunnel syndrome (CTS) is a common and debilitating condition that commonly affects postmenopausal women.ObjectiveTo determine the effect of menopausal hormone therapy (HT) in healthy postmenopausal women on CTS risk.DesignWe conducted a secondary analysis of the Women's Health Initiative's (WHI) HT trials linked to Medicare claims data. Separate intention-to-treat analyses were performed for the two trials; the conjugated equine estrogens alone (CEE alone) and the trial of CEE plus medroxyprogesterone acetate (MPA) trial. (ClinicalTrials.gov, NCT number): NCT00000611.SettingTwo randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers.ParticipantsThe sample size included in the analysis was 16,053 community-dwelling women aged ≥65 years at study entry or those who later aged into Medicare eligibility, and who were enrolled in Medicare (including Part A and/or Part B coverage).InterventionWomen with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203).Main outcome(s)The primary outcome was incident CTS and the secondary outcome was therapeutic CTS procedure occurring during the intervention phases of the trials.ResultsA total of 16,053 women were randomized in both trials. During mean follow up of 4.5 ± 2.8 years in the CEE trial (n = 6,833), there were 203 incident CTS cases in the intervention and 262 incident CTS cases in the placebo group (HR, 0.78; 95% CI, 0.65-0.94; P = 0.009). The CEE+MPA trial (n = 9,220) followed participants for a mean of 3.7 ± 2.3 years. There were 173 incident CTS cases in the intervention compared to 203 cases in the placebo group (HR, 0.80, 95% CI, 0.65-0.97; P = 0.027).ConclusionsThese findings suggest a protective effect of menopausal HT on the incidence of CTS among postmenopausal women. A potential therapeutic role for other forms of estrogen therapy in the management of CTS warrants future research.

Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

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Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.

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Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.

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