Influence of treatment with the anti-oestrogen 3-hydroxytamoxifen (droloxifene) on plasma sex hormone levels in postmenopausal patients with breast cancer

Geisler, Jürgen; Haarstad, H.; Gundersen, S.; Raabe, Nils; Kvinnsland, Stener; Lønning, Per Eystein

doi:10.1677/joe.0.1460359

Cited by 21 publications

(8 citation statements)

References 15 publications

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“…Droloxifene, a structural analogue of tamoxifen (3‐hydroxytamoxifen), behaves as an estrogen agonist in terms of its relation to bone as well as its impact on certain components of the lipid and coagulation profiles 12. Its potential for use in advanced breast cancer was suggested by its ability to modulate plasma sex hormone levels in a direction resembling that seen during tamoxifen treatment in postmenopausal women with breast cancer 13. In the phase 2 studies of droloxifene, the prevalence of all prolapse disorders in over 1000 women was 10%, the same in both the treatment and control arms 14.…”

Section: Serm Effects In Reproductive Tissuesmentioning

confidence: 99%

Effect of Selective Estrogen Receptor Modulators on Reproductive Tissues Other Than Endometrium

Hendrix

McNeeley

2001

Annals of the New York Academy of Sciences

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The objective of this paper is to review the published and unpublished knowledge of the effect of selective estrogen receptor modulators on reproductive tissues other than endometrium. Pharmaceutical companies developing or marketing selective estrogen receptor modulators (SERMs) were identified. The investigators at each company responsible for the conduct of investigational trials were contacted and queried about reports of adverse events in any ongoing or completed trials involving SERMs produced by their company. Levormeloxifene and idoxifene trials noted a higher proportion of surgery for pelvic organ prolapse in treated versus untreated women. The development of these pharmaceutical agents was discontinued, primarily for endometrial concerns. However, pelvic organ prolapse was reported to the FDA as an adverse event associated with both drugs. Study weaknesses preclude a definitive association between the agents and pelvic organ prolapse. The treated groups were not necessarily similar for confounding factors such as age, parity, obesity, cigarette smoking, and other risk factors for pelvic organ prolapse. Tamoxifen and raloxifene increase hot flash intensity and frequency. Ovarian cyst formation and uterine fibroid growth have also been reported with some SERMs. The identification and assessment of the impact of current and future SERMs on the pelvic floor and other genital tissues will be important to understanding their potential long‐term application in disease treatment and prevention.

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Section: Serm Effects In Reproductive Tissuesmentioning

confidence: 99%

Effect of Selective Estrogen Receptor Modulators on Reproductive Tissues Other Than Endometrium

Hendrix

McNeeley

2001

Annals of the New York Academy of Sciences

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“…13,14 Preliminary data suggest that it may be useful in advanced breast cancer. 15 The cardiovascular effects of droloxifene in women are unknown. The purpose of the present study was to compare the effects of droloxifene with the effects of conventional estrogen replacement on measures of plasma lipids, coagulation and fibrinolytic factors, and brachial artery flowmediated vasodilation in healthy postmenopausal women.…”

mentioning

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 dose of droloxifene used in that study was 40 mg [41]. Other studies, however, had found droloxifene to express dose-dependent effects on plasma levels of the liver proteins IGF-I, IGFBP-I and SHBG [42][43][44]. In these studies, droloxifene 100 mg daily was found to have an effect on the IGF-system resembling that of tamoxifen 20 or 30 mg daily, while droloxifene 40 mg daily caused smaller changes.…”

Section: Atac-trialmentioning

confidence: 80%

Aromatase inhibitors as adjuvant treatment of breast cancer

Geisler

Lønning

2006

Critical Reviews in Oncology/Hematology

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Influence of treatment with the anti-oestrogen 3-hydroxytamoxifen (droloxifene) on plasma sex hormone levels in postmenopausal patients with breast cancer

Cited by 21 publications

References 15 publications

Effect of Selective Estrogen Receptor Modulators on Reproductive Tissues Other Than Endometrium

Effect of Selective Estrogen Receptor Modulators on Reproductive Tissues Other Than Endometrium

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

Aromatase inhibitors as adjuvant treatment of breast cancer

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