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The timing hypothesis: Do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?

ABSTRACT: The Women's Health Initiative (WHI), a landmark randomized trial of menopausal hormone therapy (HT) for prevention of chronic disease in postmenopausal women aged 50-79, established that such therapy neither prevents coronary heart disease (CHD) nor yields a favorable balance of benefits and risks in such women as a whole. However, a nuanced look at the data from this trial, considered alongside other evidence, suggests that timing of HT initiation affects the relation between such therapy and coronary risk, as well as its overall benefit-risk balance. Estrogen may have a beneficial effect on the heart if started in early menopause, when a woman's arteries are likely to be relatively healthy, but a harmful effect if started in late menopause, when those arteries are more likely to show signs of atherosclerotic disease. However, even if HT-associated relative risks are constant across age or time since menopause onset, the low absolute risk of CHD in younger or recently menopausal women translates into low attributable risks in this group. Thus, HT initiation for relief of moderate to severe vasomotor symptoms in early menopausal patients who have a favorable coronary profile remains a viable option.

SUBMITTER: Bassuk SS

PROVIDER: S-EPMC4834454 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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The timing hypothesis: Do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?

Bassuk Shari S SS Manson JoAnn E JE

Metabolism: clinical and experimental 20160112 5

The Women's Health Initiative (WHI), a landmark randomized trial of menopausal hormone therapy (HT) for prevention of chronic disease in postmenopausal women aged 50-79, established that such therapy neither prevents coronary heart disease (CHD) nor yields a favorable balance of benefits and risks in such women as a whole. However, a nuanced look at the data from this trial, considered alongside other evidence, suggests that timing of HT initiation affects the relation between such therapy and c ...[more]

PMID: 27085786

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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:Study questionWhat is the association between menopausal hormone therapy (MHT) and cause-specific mortality?Summary answerSelf-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.What is known alreadyEvidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.Study design, size, durationCohort study (the UK Biobank), 178 379 women, recruited in 2006-2010.Participants/materials, setting, methodsPostmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.Main results and the role of chanceAmong the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).Limitations, reasons for cautionSelf-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.Wider implications of the findingsThe current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.Study funding/competing interest(s)This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.Trial registration numberN/A.

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The timing hypothesis: Do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?

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The timing hypothesis: Do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?

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