Postmenopausal women

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Ultrasound-based estimates of cortical bone thickness and porosity are associated with non-traumatic fractures in postmenopausal women: A pilot study

Ultrasound-based estimates of cortical bone thickness and porosity are associated with non-traumatic fractures in postmenopausal women: A pilot study

Abstract Recent ultrasound axial transmission techniques exploit the multimode waveguide re- sponse of long bones to yield estimates of cortical bone structure characteristics. This pi- lot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission (BDAT) device to discriminate between fractured and non-fractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) es- timates were obtained for 201 postmenopausal women, among whom 109 were non-fractured (62.6±7.8 years), 92 with one or more non-traumatic fractures (68.8±9.2 years), 17 with hip fractures (66.1±10.3 years), 32 with vertebral fractures (72.4±7.9 years), and 17 with wrist fractures (67.8±9.6 years). The areal bone mineral density (aBMD) was obtained using dual-energy X-ray absorptiometry (DXA) at the femur and spine. Femoral aBMD correlated weakly but significantly with Ct.Th (R=0.23, p < 0.001) and Ct.Po (R=-0.15, p < 0.05). Femoral aBMD and both ultrasound parameters were significantly different between the sub- group of all non-traumatic fractures combined and the control group (p < 0.05). The main findings were (i) that Ct.Po was discriminant for all non-traumatic fractures combined (odds ratio OR=1.39; area under the receiver operating characteristic curve AUC=0.71), for ver- tebral (OR=1.96; AUC=0.84) and wrist fractures (OR=1.80; AUC=0.71), while Ct.Th was discriminant for hip fractures only (OR=2.01; AUC=0.72); (ii) the demonstration of a sig- nificant association between increased Ct.Po and vertebral and wrist fractures when these
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Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study

Study subjects Ambulatory postmenopausal women were recruited at 75 centers in 11 European countries and in Australia. Women were eligible in the study: 1) if they had a femoral neck bone mineral density (BMD) 0.600 g/cm 2 or less (measured with Hologic instruments), corresponding to a T-score less than ⫺2.5 according to the centralized normative data (D. O. Slosman); 2) and were 74 yr or older, or aged between 70 and 74 yr but with one additional fracture risk factor (i.e. history of osteoporotic fracture after menopause, residence in a retirement home, frequent falls, or a maternal history of osteoporotic fractures of the hip, spine, or wrist).
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Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women

Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women

Methods We conducted a multicenter, retrospective study between June 2016 and June 2017 of postmenopausal women with HAE from 13 sites of the National Angioedema Reference Center (CREAK). All postmenopausal patients with type I or II C1-INH-HAE, or nC1-INH-HAE with a F12 mutation, another known mutation or without a F12 mutation (U-HAE) but with a family history, were eligible for inclusion. Diagnosis was performed in a reference center according to the International Recommendations and based on measuring C1-INH concentration and function, C4 level, and genetic testing if the mutation was not known in the family or in the absence of family history [ 1 , 2 ]. Patients with idiopathic non-histaminergic angioedema were excluded. The age of menopause was determined by the referring physician or gynecologist. If this information was missing, menopause was defined as amenorrhea for ≥ 12 months in women over ≥ 51 years of age.
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Estimated numbers of postmenopausal women treated by hormone therapy in France.

Estimated numbers of postmenopausal women treated by hormone therapy in France.

trial conducted in 40 centers in the United States between 1993 and 1998, randomly assigned 16,608 healthy postmenopausal women aged 50–79 years, with an intact uterus, to combined conjugated equine estrogens plus progestogen or placebo. A third group of 10,739 hysterectomized women received estrogens alone. After a mean follow-up of 5.2 years, WHI showed increased estimated rates for coronary heart disease (hazard ratio [HR] 1.29; 95% confidence interval [CI95%]: 1.02–1.63), for invasive breast cancer (HR 1.26; CI95%: 1.00–1.59), for stroke (HR 1.41; CI95%: 1.07–1.85) and for pulmonary embolism (HR 2.13; CI95%: 1.39–3.25). On the contrary, hip fractures were proved to be reduced (HR 0.66; CI95%: 0.45–0.98), as well as colorectal cancer (HR 0.63; CI95%: 0.43–0.92). The risk-benefit profile was judged insufficiently positive to continue the clinical trial and it was stopped in July 2002. The MWS was an observational cohort of women aged 50–64 years, recruited between 1996 and 2001, through the National Health Service Breast Screening Program in United Kingdom. In this study, current use of HT was significantly associated with an increased risk of incident and fatal breast cancer, especially with estrogen–progestogen combinations (HR 2.00; CI95%: 1.88–2.12), whatever the formulations (oral, transdermal and implemented), and the risk increased with treatment duration. Following these results, the French Agency for Accreditation and Evaluation in Healthcare (ANAES) proposed revised clinical practices guidelines in May 2004 for the prescription of HT to postmenopausal women [3], which is now only recommended to healthy women who present climacteric symptoms that adversely affect their quality of life or in a second intention to prevent osteoporosis complications in women with high risk factors [3,6]. HT is recommended to be prescribed at a minimum effective dose and during a short time, which should be reevaluated every year.
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Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial

Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial

Several limitations should be acknowledged in the present study. Special attention was paid to match the CD to GFJ as closely as possible for a range of components, but we cannot fully exclude the possibility that other known or unknown bioactives present in GFJ might also be causally related to the biological outcomes beyond flavanones. A way to strengthen the contribution of flavanones would have been to look at the correlation between the observed effect on PWV and plasma concentrations of flavanones. However, due to our study design, it is irrelevant to seek such a correlation because all flavanone metabolites disappeared from the circulation after an overnight fasting. Given the number of endpoint measures considered in our study, we cannot exclude some inflation of a risk due to multiple comparisons. To address this issue, a specific study focused on PWV is warranted. Despite these limitations, our trial was the first long-term study examining the impact of GFJ con- sumption on vascular function in healthy postmenopausal women. This trial provides evidence of an improvement in arterial stiffness over a long time frame of grapefruit consumption as part of a normal diet. It also highlights a possible role of flavanones in mediating this beneficial effect.
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Effect of Cardiorespiratory Fitness on Vascular Regulation and Oxidative Stress in Postmenopausal Women

Effect of Cardiorespiratory Fitness on Vascular Regulation and Oxidative Stress in Postmenopausal Women

been shown recently that reduced carotid artery compliance of sedentary postmenopausal women was partially restored by infusion of ascorbic acid. 10 Interestingly, it also appears that this compliance is not different between exercise-trained postmenopausal and premenopausal women. 11 Taken to- gether, these data suggest that regular exercise might suppress the reduction of arterial compliance via a decrease in oxida- tive stress. In this context, it has been demonstrated clearly that, in a premenopausal population, regular physical train- ing 12,13 upregulates antioxidant enzymatic systems, which may have implications for attenuating the usual increase in postmenopausal-related oxidative stress. This paradigm is supported by 2 recent studies 14,15 that reported a decrease in plasma thiobarbituric acid reactive substances after 8 and 24 weeks of exercise training in postmenopausal women. How- ever, a recent study reported no significant difference in lipid peroxidation between premenopausal and postmenopausal women randomly matched for body mass index (BMI) and waist circumference. 16 The correlation reported between ox- idative stress and body fat 17 might suggest that the increase in fat mass occurring at menopause 18 may partially explain the elevated levels of oxidative stress markers after menopause. Finally, we demonstrated recently that cardiorespiratory fitness and cerebral blood flow significantly impact cognitive outcomes in older women. 19 In addition, recent findings demonstrating that exercise restored endothelium-dependent dilation via improvement of antioxidant enzyme efficiency and NO bioavailability in old mice. 20 Here, we tested the hypothesis that increases in antioxidant enzyme efficiency and decreased oxidative stress, leading to NO bioavailability, might be a potential mechanism to account for this observed association between fitness and cardiovascular parameters. In the current study, we investigated the impact of fitness status on enzymatic antioxidant efficiency, oxidative stress, and NO production in the same study population of postmenopausal women who had participated in our original study. 19 Second- ary objectives were to determine the strength of the associa- tions among oxidative stress, enzymatic antioxidant and NO production, and arterial blood pressure and cerebrovascular regulation.
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Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women.

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women.

Our results among HRT never users were not statistically different than among HRT users; no significant association between any pattern of OC use and breast cancer risk was observed in postmenopausal women who never used HRT probably due to lack of statistical power. Previous studies [4, 5, 29–32] found an association of early OC use and breast cancer risk among young women. In our study, it was impossible to determine whether there was a greater susceptibility of breast tissue to hormonal exposure at young ages [33]. Due to the long time between OC exposure and inclusion in the study, susceptible women would in fact have already developed breast cancer and consequently were not included in our study population. Stratified on time since last use, significant risk ratios were observed in some strata, but they could be due to chance because of multiple testing following stratification. Finally, there is some potential for misclassification of OC exposure as most of the women included in the analysis had stopped OC use more than ten years before baseline. However, given the prospective design of the study, any misclassification would be non-differential.
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Activated protein C resistance among postmenopausal women using transdermal estrogens: importance of progestogen.

Activated protein C resistance among postmenopausal women using transdermal estrogens: importance of progestogen.

progestogens may oppose the estrogen proliferation effect. Norpregnane derivatives are therefore preferentially prescribed to women with hyperestrogenic symptoms (endometrial susceptibility, benign breast diseases, …) [35-37]. Since endogenous estrogens exposure has been positively related to VTE among postmenopausal women [38], women with stronger estrogenic climate would be more likely to be at high thrombotic risk. As a consequence, we cannot exclude the possibility that APC resistance - which is observed among women using norpregnane derivatives - might also be related to a hypercoagulability state due to the presence of a hyperestrogenic status rather than exclusively to the deleterious effect of these progestogens on haemostasis. Therefore, this bias could in part explain the increased level of blood coagulation activation and APC resistance among users of norpregnane derivatives. Another selection bias could also occur among users of progesterone which is preferentially used by obese women because of its neutral impact on cardiovascular risk factors. However, in our study, women using progesterone had a similar average BMI than control women and means of haemostatic parameters were adjusted for BMI. Finally, a limitation of our study relates to the extrapolation of results. Our data on norpregnanes were restricted to nomegestrol acetate and promegestone and the results cannot be extrapolated to others norpregnane derivatives, including trimegestone.
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Treatment of postmenopausal women with osteoporosis for 5 years with denosumab : two-year results from the FREEDOM trial extension

Treatment of postmenopausal women with osteoporosis for 5 years with denosumab : two-year results from the FREEDOM trial extension

Centro TIEMPO, Buenos Aires, Argentina; 9 Center for Bone Research at the Sahlgrenska Academy, Goteburg, Sweden; 10 Hospital de Clinicas da Universidade Federal do Parana, Curitiba, Brazil; 11 Univ. of Liege, Belgium; 12 Krankenhaus der Barmherzigen Schwestern II. Med. Abteilung, Wien, Austria; 13 Hospital Dr Peset, Valencia, Spain; 14 Hopital Cochin CEMO, Paris, France; 15 San Francisco Coordinating Center, CPMC Res. Inst., San Francisco, United States; 16 Leiden Univ. Medical Center, Leiden, Netherlands Background: The open-label extension of the pivotal, 3-year, phase 3 FREEDOM trial evaluates the long-term efficacy and safety of denosumab (DMAb) for up to 10 years in postmenopausal women with osteoporosis. Objectives: Report results from the first 2 years of the extension, representing up to 5 continuous years of DMAb treatment.
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Hormone therapy and risk of venous thromboembolism among postmenopausal women

Hormone therapy and risk of venous thromboembolism among postmenopausal women

Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper References [1] Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama. 2002 Jul 17;288(3):321-33.

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Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis

Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis

Both raloxifene (RLX) and alendronate (ALN) can treat and prevent new vertebral fractures, increase bone mineral den- sity (BMD), and decrease biochemical markers of bone turn- over in postmenopausal women with osteoporosis. This phase 3, randomized, double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis (femoral neck BMD T-score, less than ⴚ2). Women (aged <75 yr; >2 yr since their last menstrual period) received placebo, RLX 60 mg/d, ALN 10 mg/d, or RLX 60 mg/d and ALN 10 mg/d combined. At baseline, 6 and 12 months, BMD was measured by dual x-ray absorptiometry. The bone turn- over markers serum osteocalcin, bone-specific alkaline phos- phatase, and urinary N- and C-telopeptide corrected for cre- atinine were measured. The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant (P > 0.10) in a two-way ANOVA model. All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups, and between the RLX and RLX ⴙALN groups (P < 0.05). On average, lumbar spine BMD increased by
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Recent Recreational Physical Activity and Breast Cancer Risk in Postmenopausal Women in the E3N Cohort

Recent Recreational Physical Activity and Breast Cancer Risk in Postmenopausal Women in the E3N Cohort

Only a few studies simultaneously considered recent and earlier physical activity, and their results conflict (6– 13). In line with our findings, in the Nurses’ Health Study (13), women who were active close to menopause but not later did not have a lower risk of breast cancer than the least active women (<9 MET-h/week) during both peri- ods, whereas women who were recently active had a risk 10% lower, regardless of whether or not they were active around menopause. However, the two assessments of physical activity might have been separated by a period of up to 20 years. To our knowledge, our study is the first to independently assess the association between breast cancer risk and recreational physical activity both 5 to 9 years earlier and within the previous 4 years, and we found that only recent recreational physical activity was associated with a significantly reduced risk. This suggests that starting recreational physical activity may be fol- lowed relatively rapidly by a reduction in breast cancer risk in postmenopausal women, a reduction that may disappear a few years after the activity stops.
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Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

In this context, we set up two first- in- human randomised controlled trials: the first was a 4- week dietary intervention based on daily consumption of PL- enriched cheeses in postmenopausal women at risk for CVD and the second was a proof- of- principle investigation of acute consumption of PL- enriched cheeses in ileostomy patients. To fit with everyday life diet and ensure prac- tical consistency of such clinical results, we used a common type of dairy product, namely cream cheese, enriched with a milk PL- rich fraction derived from buttermilk. The original strategy here was to formulate cheeses with identical total lipid content with partial substitution of TAG by milk PL to avoid increased energy intake. A unique dose- response design up to 5 g/day was made possible by incorporating a buttermilk concentrate from a PL concentration process specifically designed for the present clinical investigations. 25 The objective of the intervention trial was to determine: 1) whether dietary milk PL consumption (0, 3 or 5 g- PL/day) was able to impact differentially fasting and postprandial lipid metabolism, including intestine- derived chylomicrons and 2) the extent to which these potential milk PL effects were concomitant with changes in gut microbiota and gut- derived metabolites (coprostanol, short- chain fatty acids (SCFA)). The aim of the complementary study in ileostomy patients was to investigate intestinal mechanisms underpinning the impact of milk PL on cholesterol absorption and metabolism using 2 H- cholesterol and 13 C- TAG tracers.
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Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women... ceramide and sphingomyelin species in postmenopausal women.[r]

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Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Methods: We performed a double-blind randomized controlled trial in 58 postmenopausal women with fasting HDL-cholesterol < 1.6 mM. They were subjected to a 4-week dietary intervention with daily consumption of a cream-cheese containing 12 g of milk fat including

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Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.

Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.

w19 G. L. Anderson, M. Limacher, A. R. Assaf, T. Bassford, S. A. Beresford, H. Black, D. Bonds, R. Brunner, R. Brzyski, B. Caan, R. Chlebowski, D. Curb, M. Gass, J. Hays, G. Heiss, S. Hendrix, B. V. Howard, J. Hsia, A. Hubbell, R. Jackson, K. C. Johnson, H. Judd, J. M. Kotchen, L. Kuller, A. Z. LaCroix, D. Lane, R. D. Langer, N. Lasser, C. E. Lewis, J. Manson, K. Margolis, J. Ockene, M. J. O'Sullivan, L. Phillips, R. L. Prentice, C. Ritenbaugh, J. Robbins, J. E. Rossouw, G. Sarto, M. L. Stefanick, L. Van Horn, J. Wactawski-Wende, R. Wallace and S. Wassertheil-Smoller. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Jama 2004;291(14):1701-12. w20 M. R. Vickers, A. H. MacLennan, B. Lawton, D. Ford, J. Martin, S. K. Meredith, B. L. DeStavola, S. Rose, A. Dowell, H. C. Wilkes, J. H. Darbyshire and T. W. Meade. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. Bmj 2007;335(7613):239.
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Strontium ranelate reduces the risk of vertebral fractures in osteoporotic postmenopausal women whatever the baseline vertebral fractures status

Strontium ranelate reduces the risk of vertebral fractures in osteoporotic postmenopausal women whatever the baseline vertebral fractures status

TROPOS was performed (the study designs, centers, BMD and X-ray central reading centers were common to both studies). Among the whole pooled population, vertebral X-rays were performed yearly (semi-quantitative assessment) in 5082 women receiving strontium ranelate 2g/day orally or placebo plus calcium/vitaminD in both groups during 3 years. There was no difference between groups for baseline characteristics of age 74±6.2 years; lumbar BMD T-score –3.0±1.6; femoral neck BMD T-score -3.0 ±0.7 (mean±SD). Among those 5082 women, 2605 had no prevalent vertebral fracture (1320 in strontium ranelate group versus 1285 in placebo), 1110 had one prevalent vertebral fracture (533 versus 577) and 1365 had at least 2 prevalent vertebral fractures (682 versus 683). Whatever the baseline vertebral fracture status, a significant reduction in the incidence of patients experiencing a vertebral fracture was demonstrated in the intent-to-treat population over 3 years with a reduction of the relative risk by: 1) 48% in 2605 women without prevalent vertebral fracture (RR=0.52, 95%CI[0.40;0.67], p<0.001). 87 patients in strontium ranelate group and 161 in placebo had a vertebral fracture during the study, 2) 45% in 1110 women with one only prevalent vertebral fracture (RR=0.55, 95%CI[0.41;0.74], p<0.001), 70 patients in strontium ranelate group and 130 in placebo, 3) 33% in 1365 women with at least 2 prevalent vertebral fractures (RR=0.67, 95%CI[0.55;0.81], p<0.001), 184 patients in strontium ranelate group and 252 in placebo. In conclusion, strontium ranelate 2g/day orally is a new anti-osteoporotic treatment effective in reducing the risk of vertebral fracture in osteoporotic postmenopausal women whatever the prevalent vertebral fracture status.
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The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial

The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial

DISCUSSION In this study, we have demonstrated that tibolone prevented the increase in the occurrence, severity and intensity of hot flushes and sweats associated with tamoxifen treatment following surgical treatment for breast cancer. There was also a trend for tibolone to reduce the impact of hot flushes and sweats on normal daily life. Tibolone has been used effectively for the management of climacteric symptoms in a previous small study involving 15 postmenopausal women with breast cancer who had undergone surgery and radiotherapy. As in the current study, none of the patients suffered a recurrence of breast cancer and eight were still being treated with tibolone one year after the end of the study.
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Plasma estrogen levels, estrogen receptor gene variation, and ischemic arterial disease in postmenopausal women: the three-city prospective cohort study.

Plasma estrogen levels, estrogen receptor gene variation, and ischemic arterial disease in postmenopausal women: the three-city prospective cohort study.

Methods: In the Three-City prospective cohort study among subjects over 65 years, we used a case-cohort design in which plasma levels of 17β-estradiol were measured. After exclusion of postmenopausal women using hormone therapy, a random subcohort of 533 women and 105 incident cases of first IAD events over 4-year of follow-up were analyzed. Five common polymorphisms of ESR1 and ESR2 were genotyped. Hazard ratios (HRs) of IAD for 1-standard deviation increase in estradiol levels by genotypes were estimated from Cox models after adjustment for

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Hormone therapy and hemostasis among postmenopausal women: a review.

Hormone therapy and hemostasis among postmenopausal women: a review.

48, 49 . Nevertheless, the biological mechanism for such APC resistance in postmenopausal women using oral estrogens remains largely not understood. Some studies have found that changes in levels of protein S and Tissue Factor Pathway Inhibitor might have important roles in determining APC resistance in women receiving oral estrogens 15, 61 . Others reported that soluble form of endothelial protein C receptor which has been reported to inhibit APC anticoagulant activity might therefore be a candidate to explain APC resistance
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