Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women

Wassertheil‐Smoller, Sylvia; Hendrix, Susan L.; Limacher, Marian C.; Heiss, Gerardo; Kooperberg, Charles; Baird, Alison E.; Kotchen, Theodore A.; Curb, J. David; Black, Henry R.; Rossouw, Jacques E.; Aragaki, Aaron K.; Safford, Monika; Stein, Evan A.; Laowattana, Somchai; Mysiw, W. Jerry

doi:10.1001/jama.289.20.2673

Cited by 1,037 publications

(259 citation statements)

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“…This has long been considered to be due to the abrupt fall of endogenous estrogen production. However, studies from the Women's Health Initiative (WHI) evaluating the role of hormone replacement therapy (HRT) could not provide consistent evidence of a beneficial effect of HRT on primary and secondary cardio-and cerebro-vascular protection (1,2). The timing of HRT initiation has been hypothesized as a factor modulating estrogens' actions on the vasculature.…”

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

Παππά

Alevizaki

2012

European Journal of Endocrinology

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Objective: Cardio-and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio-and cerebro-vascular disease in the postmenopausal period. Design and methods: We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. Results: The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Conclusions: Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio-and cerebro-vascular disease remains an interesting field of future research.

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Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

Παππά

Alevizaki

2012

European Journal of Endocrinology

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“…These findings relate to earlier WHI reports that women assigned to CEE 1 MPA, compared with placebo, had a 41% increase in stroke over 5.2 years, 15 and CEE with and without MPA was associated with an increased risk of clinical stroke. 16,17 In addition, WHIMS-MRI2 women with the lowest 3MSE scores at WHI enrollment who were treated with active HT had the largest decrements in hippocampal (p 5 0.02) and total brain volumes (p 5 0.05) between the 2 MRI measures. These findings are interesting, not only because they corroborate the prior WHIMS-MRI report, 2 but they also show that despite the relatively younger and healthier WHIMS-MRI2 cohort, a subset of women who were most vulnerable cognitively had the smallest hippocampal and total brain volumes on longitudinal MRI.…”

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confidence: 98%

Change in brain and lesion volumes after CEE therapies

et al. 2014

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Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2.Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixedeffect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures.Results: Total brain volume decreased an average of 3.22 cm 3 /y in the active arm and 3.07 cm 3 /y in the placebo arm (p 5 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm 3 /y (p 5 0.88).Conclusions: Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings. Numerous cross-sectional and observational studies on humans and animal models have examined whether postmenopausal hormone therapy (HT) affects brain structure, with inconsistent results. 1 This relationship was examined in the context of the MRI substudy of a large randomized placebo-controlled clinical trial: the Women's Health Initiative Memory Study (WHIMS)-MRI. Women aged 65 to 79 years treated for an average of 4.0 years with conjugated equine estrogen (CEE) with medroxyprogesterone acetate (MPA) or 5.6 years with CEE alone, compared with placebo, had smaller frontal lobe and hippocampal volumes on posttrial brain MRI.2 Because these findings were based on a single cross-sectional brain scan, it is unknown when the increased rate of atrophy occurred and whether it continued to increase, thereby signaling growing concerns about risks of cognitive impairment.

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“…heart disease due to arteriovenous thromboembolism 10) , cerebrovascular disease 11) , and exacerbation of liver dysfunction 12) . In the field of reproductive medicine, the technology for cryopreservation of ovarian tissue with the aim of preserving fertility has made rapid strides since the beginning of the 21st century, and there have been many reported cases of young cancer patients becoming pregnant and giving birth following treatment with anticancer drugs 13)14) .…”

Section: Discussionmentioning

confidence: 99%

Anti-aging Effect on Skin of Autologous Transplantation of Tissue Fragments from Thawed Cryopreserved Ovaries

Imanishi

Igarashi

Yamaguchi³

et al. 2017

J St. Marianna Univ

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Transplanting the ovaries of young mice into menopausal mice has been shown to extend their lifespan, suggesting that the reproductive organs may play an important role in combating aging. Preventing skin aging is an extremely important matter with respect to maintaining quality of life, but little basic research has been carried out on this issue. The effects of treatment with cryopreserved ovarian tissue, tissue hormone therapy (THT), and hormone replacement therapy on inhibiting skin aging in experimental animals were investigated. The effects on skin elasticity and body weight changes in 6-week-old mice resulting from the transplantation of cryopreserved ovarian tissue were evaluated, as were the effects on skin of estrogen administration after bilateral oophorectomy or transplantation. Estrogen was secreted by mouse ovaries that had been frozen, thawed, and transplanted, and the estrus cycle was restored, but this was insufficient to have any effect on skin elasticity. After oophorectomy, the body weight of the mice increased, and their skin elasticity decreased. Estrogen administration after these changes had occurred neither restored skin elasticity nor suppressed body weight gain. However, when estrogen was continuously administered from immediately after oophorectomy, skin elasticity decreased transiently and then improved. If techniques for THT using cryopreserved ovaries to maintain the blood estrogen concentration above a specific level can be established, this might help to prevent or improve the deterioration of skin appearance in young women who require oophorectomy due to gynecological disease and also in childhood, adolescent, and young adult cancer patients.

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Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women

Cited by 1,037 publications

References 55 publications

MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

Change in brain and lesion volumes after CEE therapies

Anti-aging Effect on Skin of Autologous Transplantation of Tissue Fragments from Thawed Cryopreserved Ovaries

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