Cardiovascular Side Effects of Diethylstilbestrol, Cyproterone Acetate, Medroxyprogesterone Acetate and Estramustine Phosphate Used for the Treatment of Advanced Prostatic Cancer: Results from European Organization for Research on Treatment of Cancer Trials 30761 and 30762

Voogt, H. J. de; Smith, Philip H.; Pavone‐Macaluso, M.; Pauw, M. De; Suciu, Stefan

doi:10.1016/s0022-5347(17)45620-5

Cited by 171 publications

(71 citation statements)

References 7 publications

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“…Through feedback inhibition of pituitary hormones, estrogen therapy can also be used to maintain anorchid testosterone levels and might thus be an alternative therapy to ADT that alleviates many of the side effects of hypogonadism in men. Oral estrogen therapy, however, has neutral to detrimental effects on cardiovascular and cerebrovascular disease in women (22)(23)(24) and increases the risk of CVD in men (20,21,38). This excess vascular risk may be due to increased hepatic synthesis of procoagulant proteins and thrombotic events.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies have shown that oral estrogen significantly increases the risk of thromboembolic complications, increases triglyceride levels, and raises levels of inflammatory markers in both women and men. These effects may underlie the neutral or detrimental effects on cardiovascular and cerebrovascular disease previously reported from randomized trials of oral estrogen in men and women (21)(22)(23)(24). Parenterally administered estrogens, on the other hand, avoid this first-pass effect on hepatic protein synthesis, and an increased prothrombotic risk has not been reported in men with prostate cancer treated with estrogen using this route of administration (25,26).…”

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confidence: 99%

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Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Purnell

Bland

Garzotto

et al. 2006

Journal of Lipid Research

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Androgen deprivation therapy (ADT) for prostate cancer is now used in earlier disease stages and as adjuvant treatment. Recognizing and reducing the toxicity of this therapy, including worsened lipid levels and cardiovascular disease (CVD) risks, has become an important clinical concern. Oral estrogen therapy induces hypogonadism and mitigates many side effects of ADT, but has a high thrombosis risk. Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral estrogen and may improve CVD risk compared with ADT. This prospective pilot study of 18 men with androgen-independent prostate cancer receiving ADT measured effects of TDE on lipid and inflammatory CVD risk factors before and after 8 weeks of TDE (estradiol 0.6 mg/day). During treatment, estradiol levels rose 17-fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased. HDL 2 cholesterol increased, with no changes in triglyceride or VLDL cholesterol levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association with a decrease in HL activity. Highly sensitive C-reactive protein levels and other inflammatory markers did not worsen. Compared with ADT, short-term TDE therapy of prostate cancer improves lipid levels without deterioration of CVD-associated inflammatory markers and may, on longer-term follow-up, improve CVD and mortality

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Purnell

Bland

Garzotto

et al. 2006

Journal of Lipid Research

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“…Cardiovascular toxicity from oral DES comprised fluid retention, hypertension, and arterial and venous thromboembolism, manifesting as stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism (Byar 1973, de Voogt et al 1986. Orally administered estrogens induce liver synthesis of coagulation factors, renin substrate, and many carrier proteins including SHBG (Geola et al 1980, Schoultz et al 1989.…”

Section: Venous Thromboembolism and Cardiovascular Riskmentioning

confidence: 99%

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Russell

Cheung

Grossmann

2017

Endocrine-Related Cancer

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Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. Conventional endocrine treatment for PCa leads to global sex steroid deprivation. The ensuing severe hypogonadism is associated with well-documented adverse effects. Recently, it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation. Hence there has been interest in revisiting estradiol as a treatment for PCa. Potential roles for estradiol could be in lieu of conventional androgen deprivation therapy or as low-dose add-back treatment while continuing androgen deprivation therapy. These strategies may limit some of the side effects associated with conventional androgen deprivation therapy. However, although available data are reassuring, the potential for cardiovascular risk and pro-carcinogenic effects on PCa via estrogen receptor signalling must be considered.

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“…According to European Association of Urology (EAU) guidelines, GnRH analogues have become the standard of care in ADT (3). They offer a non surgical castration, having lower risk of cardiotoxicity compared to DES (4,5) and having the potential for reversi-bility enabling the use of intermittent androgen deprivation (IAD).…”

Section: Rationalementioning

confidence: 99%

A review of continuous vs intermittent androgen deprivation therapy: Redefining the gold standard in the treatment of advanced prostate cancer. Myths, facts and new data on a perpetual dispute

Kratiras

Konstantinidis²,

Skriapas

2014

Int. braz j urol.

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ARTICLE INFO ______________________________________________________________ ______________________Objectives: To review the literature and present new data of continuous androgen deprivation therapy (ADT) vs intermittent androgen deprivation (IAD) as therapies for prostate cancer in terms of survival and quality of life and clarify practical issues in the use of IAD. Materials and Methods:We conducted a systematic search on Medline and Embase databases using "prostatic neoplasm" and "intermittent androgen deprivation" as search terms. We reviewed meta-analyses, randomised controlled trials, reviews, clinical trials and practise guidelines written in English from 2000 and onwards until 01/04/2013. Ten randomized controlled trials were identified. Seven of them published extensive data and results randomizing 4675 patients to IAD versus CAD. Data from the other three randomized trials were limited. Results: Over the last years studies confirmed that IAD is an effective alternative approach to hormonal deprivation providing simultaneously several potential benefits in terms of quality of life and cost effectiveness. Thus, in patients with non metastatic, advanced prostate cancer IAD could be used as standard treatment, while in metastatic prostate cancer IAD role still remains ambiguous. Conclusions: Nowadays, revaluation of the gold standard of ADT in advanced prostate cancer appears essential. Recent data established that IAD should no longer be considered as investigational, since its effectiveness has been proven, especially in patients suffering from non-metastatic advanced prostate cancer.

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Cardiovascular Side Effects of Diethylstilbestrol, Cyproterone Acetate, Medroxyprogesterone Acetate and Estramustine Phosphate Used for the Treatment of Advanced Prostatic Cancer: Results from European Organization for Research on Treatment of Cancer Trials 30761 and 30762

Cited by 171 publications

References 7 publications

Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

A review of continuous vs intermittent androgen deprivation therapy: Redefining the gold standard in the treatment of advanced prostate cancer. Myths, facts and new data on a perpetual dispute

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