Screening and early hormonal treatment of prostate cancer are accumulating strong evidence and support

Labrie, Fernand

doi:10.1002/(sici)1097-0045(20000515)43:3<215::aid-pros7>3.0.co;2-g

Cited by 31 publications

(10 citation statements)

References 59 publications

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“…In fact, while almost all studies performed so far in localized prostate cancer have used monotherapy (medical or surgical castration) (Bolla et al 1997, Pilepich et al 1997, Granfors et al 1998, Messing et al 1999, Hanks et al 2000, D'Amico et al 2004, there are strong scientific reasons to believe that even much better results can be expected with CAB (Labrie et al 1985, Caubet et al 1997, Bennett et al 1999, Labrie 2000a,b, Prostate Cancer Triallists' Collaborative Group 2000.…”

Section: High Probability Of Cure Of Localized Prostate Cancer By Trementioning

confidence: 99%

Is dehydroepiandrosterone a hormone?

Labrie¹,

Luu‐The²,

Bélanger³

et al. 2005

Journal of Endocrinology

384

242

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Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cellspecific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogensensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

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Section: High Probability Of Cure Of Localized Prostate Cancer By Trementioning

confidence: 99%

Is dehydroepiandrosterone a hormone?

Labrie¹,

Luu‐The²,

Bélanger³

et al. 2005

Journal of Endocrinology

384

242

View full text Add to dashboard Cite

show abstract

“…In fact, although almost all studies performed so far in localized prostate cancer have used monotherapy (medical or surgical castration) (43-46, 48, 82), there are good scientific reasons to believe that much better results can be expected with CAB (32, 33, 70, 73, 83,84). The direct effect of CAB on the volume of prostate cancer is well illustrated in Fig.…”

Section: High Probability Of Cure Of Localized Prostate Cancer By mentioning

confidence: 99%

Gonadotropin-Releasing Hormone Agonists in the Treatment of Prostate Cancer

et al. 2005

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In 1979, the first prostate cancer patient was treated with a GnRH agonist at the Laval University Medical Center in Quebec City, Canada, thus rapidly leading to the worldwide replacement of surgical castration and high doses of estrogens. The discovery of medical castration with GnRH agonists was soon followed by fundamental changes in the endocrine therapy of prostate cancer. Most importantly, the excellent tolerance accompanying the treatment with GnRH agonists has been a key factor that permitted a series of studies demonstrating a major reduction in the death rate from prostate cancer ranging from 31 to 87% at 5 yr of follow-up in patients with localized or locally advanced prostate cancer. In fact, a one third reduction in prostate cancer deaths has been calculated in the metaanalysis of all available studies. The general acceptance of this discovery by patients and physicians is illustrated by world sales above 3.0 billion U.S. dollars in 2003. Although extremely efficient in achieving complete medical castration and well tolerated, with no other side effects than the expected hypoandrogenicity, GnRH agonists should not be administered alone. In fact, shortly after discovery of the castration effects of GnRH agonists, we observed that approximately 50% of androgens remain in the prostate after castration, thus leading to the recognition of the role of adrenal dehydroepiandrosterone as an important source of the androgens synthesized locally in the prostate and in many peripheral target tissues. We therefore developed combined androgen blockade (CAB), whereby the androgens of both testicular and adrenal origins are blocked simultaneously at start of treatment with the combination of a GnRH agonist to block the testis and a pure antiandrogen to block the action of the androgens produced locally. CAB, first used in advanced metastatic disease, has been the first treatment shown to prolong life in prostate cancer. Most interestingly, in 2002, we made the observation that CAB alone given continuously for 6.5 yr or more leads to cure of the disease in at least 90% of cases, thus suggesting that androgen blockade combining a GnRH agonist and a pure antiandrogen could well be the most efficient treatment of localized prostate cancer, and thus offering the possibility of practically eliminating death from prostate cancer.

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“…In fact, while almost all studies performed so far in localized prostate cancer have used monotherapy (medical or surgical castration) [88][89][90][91][92], there are good reasons to believe that even better results can be obtained with combined androgen blockade [2,39,45,48,97,98]. The direct effect of combined androgen blockade on the volume of prostate cancer localized in the prostate is well illustrated in Fig.…”

Section: The High Probability Of a Cure Of Localized Prostate Cancer mentioning

confidence: 99%

“…While its efficacy, especially in localized disease, is well recognized [64,[88][89][90][91][92][93][94][95][96][97][98][99]101,103], androgen blockade is accompanied by hot flushes, loss of libido and sexual potency, as well as bone loss and potentially osteoporosis [104][105][106].…”

Section: The High Probability Of a Cure Of Localized Prostate Cancer mentioning

confidence: 99%