Bilateral Oophorectomy and Accelerated Aging: Cause or Effect?

Rocca, Walter A.; Rocca, Liliana Gazzuola; Smith, Carin Y.; Grossardt, Brandon R.; Faubion, Stephanie S.; Shuster, Lynne T.; Kirkland, James L.; Stewart, Elizabeth A.; Miller, Virginia M.

doi:10.1093/gerona/glx026

Cited by 71 publications

(72 citation statements)

References 20 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Associated estrogen deficiency symptoms may also affect quality of life. These adverse outcomes have also been reported in young women with secondary POI due to bilateral oophorectomy [7], with outcome reports including overall acceleration of the aging process [8]. Although guidelines recommend continuous use of hormone therapy (HT) until the average age of menopause [2 9], studies show a mean duration of about one year [10].…”

Section: Introductionmentioning

confidence: 99%

Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review

et al. 2017

View full text Add to dashboard Cite

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 8 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 3 out of 8 studies showing HT associated increase benefits. Only 1 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. Registration PROSPERO CRD 4201603616

show abstract

Section: Introductionmentioning

confidence: 99%

Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Both ICD-9 (through Sept 2015) and ICD-10 (after Oct 2015) codes were pooled together by the REP under seven cardiovascular and metabolic conditions proposed by the U.S. Department of Health and Human Services in 2010 as indicators of vascular health 20 : hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke. The specific codes pooled together are tabulated in the supplemental material.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to using each individual component of vascular health separately, we also computed a composite score (referred here as CMC) which represents the summation of the presence or absence of each of these conditions. To reduce the false positive rates, we required that individuals received two codes for any given condition separated by more than 30 days within the 5-year capture period as done previously by REP investigators 19, 20 .…”

Section: Methodsmentioning

confidence: 99%

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

Vemuri

Lesnick

Przybelski

et al. 2017

Annals of Neurology

144

117

View full text Add to dashboard Cite

OBJECTIVE To investigate the associations between age, vascular health, and Alzheimer’s disease (AD) imaging biomarkers in an elderly sample. METHODS We identified 430 individuals along the cognitive continuum aged>60 years with amyloid-PET, Tau-PET, and MRI scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had FDG-PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from healthcare records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac-arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from PiB-PET, entorhinal cortex tau uptake (ERC-tau) from Tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC=0 (CMC−) vs. CMC>0 (CMC+) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEM), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and APOE effects. RESULTS CMC+ participants had significantly greater neurodegeneration than CMC− participants but did not differ by amyloid or ERC-tau. The SEM models showed that i) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and ii) vascular health specifically the presence of hyperlipidemia had a significant direct impact on ERC-tau. INTERPRETATION Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health.

show abstract

“…However, it remains difficult in a non-experimental setting to test definitively whether accelerated aging leads to symptoms that prompt bilateral oophorectomy or whether bilateral oophorectomy prompts hormonal changes leading to acceleration of aging processes (cause-effect uncertainty). In 2017, we addressed the cause-effect uncertainty with new analyses of the MOA-2 study restricted to women who did not have any of 18 chronic conditions at baseline (34). The MOA-2 cohorts were restricted to 420 premenopausal women who underwent bilateral oophorectomy before age 46 yr for a benign indication from 1988 to 2007 in Olmsted County, MN and age-matched referent women (Ϯ1 yr) who had not undergone bilateral oophorectomy.…”

Section: Cause and Effect Controversymentioning

confidence: 99%