The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomised, controlled tamoxifen prevention study

Chang, Jenny C.; Powles, Trevor J.; Ashley, S.; Gregory, R. K.; Tidy, V. A.; Treleaven, J; Singh, Richa

doi:10.1093/oxfordjournals.annonc.a010715

Cited by 108 publications

(42 citation statements)

References 21 publications

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“…Our findings confirm and strengthen the interpretation of prior reports of lower fibrinogen and cholesterol with tamoxifen [2][3][4][5][6]32 and its analogue droloxifene 33 and provide new information concerning C-reactive protein. When the population of women eligible for tamoxifen for the prevention of breast cancer is considered, relevant features of the present study compared with prior studies are as follows: exclusion of women with cancer, 2,32 prohibition of postmenopausal hormone use concurrent with study medication, 4,6 sufficient power, 4,34 and a double-blind control group.…”

Section: Discussionsupporting

confidence: 90%

“…1 Similar to postmenopausal hormone therapy, tamoxifen was predicted to reduce cardiovascular risk on the basis of its lipid-lowering properties. [2][3][4][5][6] Indeed, 3 trials of breast cancer patients have reported 15% to 60% reductions in cardiac death in women treated with tamoxifen. [7][8][9] In the P-1 trial, myocardial infarction rates comparing tamoxifen and placebo did not differ.…”

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confidence: 99%

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Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Cushman¹,

Costantino²,

Tracy³

et al. 2001

Obstetrical and Gynecological Survey

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Abstract-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all PϽ0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Cushman¹,

Costantino²,

Tracy³

et al. 2001

Obstetrical and Gynecological Survey

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“…Since both drugs have similar effects on bone metabolism and turnover, there is a clear AI class effect on bone health in postmenopausal women with hormone-sensitive breast cancer. Tamoxifen has been reported to have some beneficial effects on bone turnover and fracture risk in AI aromatase inhibitor, CI confidence interval, PINP procollagen type I N terminal propeptide, sCTX serum C-terminal telopeptides, uNTX urinary N-terminal telopeptides, ALP alkaline phosphatase postmenopausal women [4,[20][21][22], but the results here show that these positive effects do not carry over once tamoxifen therapy is discontinued. Our study showed an increase in bone turnover that could eventually lead to bone loss.…”

Section: Discussionmentioning

confidence: 61%

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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International audienceALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption

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“…However, in some, but not all, studies, estrogen replacement, 38,45 tamoxifen, 46,47 and raloxifene 33 also reduced antithrombin III levels, potentially a prothrombotic effect. 48 Only limited data are available concerning the effects of estrogen or SERMs on the activation of the coagulation cascade.…”

Section: Effects Of Serms On Hemostasismentioning

confidence: 99%

Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women

Herrington

Pusser

Riley

et al. 2000

ATVB

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Abstract-Selective estrogen receptor modulators, like tamoxifen and related compounds, have mixed estrogen agonistic/ antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with conjugated estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol (PϽ0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) (PϽ0.05). In contrast, estrogen, but not droloxifene, increased high density lipoprotein (18.5%, PϽ0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with estrogen (Pϭ0.004) but produced no estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, PϽ0.05 for both). Droloxifene has estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit. Key words: droloxifene Ⅲ hormone replacement therapy Ⅲ women Ⅲ estrogen Ⅲ cardiovascular disease E strogen replacement therapy favorably influences several domains of vascular health, including lipid metabolism, endothelial function, and aspects of hemostasis. 1 However, estrogen replacement also carries an increased risk of endometrial 2 and possibly breast 3 carcinoma. The recent Heart and Estrogen/Progestin Study trial 4 also raises questions about whether the favorable effects of estrogen on the cardiovascular system may be offset by other, previously unrecognized, adverse cardiovascular effects, resulting in no overall clinical cardiovascular benefit.Selective estrogen receptor modulators (SERMs), like tamoxifen, are compounds with mixed estrogen agonistic/antagonistic effects. Other benzothiophene derivatives, such as raloxifene, and other structurally unrelated compounds, such as soy phytoestrogens and tibolone, have variable degrees of estrogen agonistic and antagonistic effects. 5 Tamoxifen lowers cholesterol, 6 and in trials in women with breast cancer, it was associated with 15% to 63% fewer cardiovascular events. 7 However, tamoxifen also increases the risk for endometrial ...

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The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomised, controlled tamoxifen prevention study

Cited by 108 publications

References 21 publications

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women

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