Decreased Serum Level of Dehydroepiandrosterone Sulfate in Postmenopausal Women with Ovarian Cancer

Heinonen, Pentti K.; Koivula, Timo; Pystynen, P

doi:10.1159/000298872

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…Moreover, a series of epidemiological studies suggest an inhibitory effect of DHEA on various types of cancers. These epidemiological data pertain to breast cancer (281), prostate cancer (290), and ovarian cancer (291).…”

Section: Dhea and Other Cancersmentioning

confidence: 99%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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Serum androgens as well as their precursors and metabolites decrease from the age of 30-40 yr in women, thus suggesting that a more physiological hormone replacement therapy at menopause should contain an androgenic compound. It is important to consider, however, that most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin. Much progress in this new area of endocrine physiology called intracrinology has followed the cloning and characterization of most of the enzymes responsible for the transformation of DHEA and DHEA-S into androgens and estrogens in peripheral target tissues, where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation, thus seriously limiting the interpretation of serum levels of active sex steroids. The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured. In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation. In clinical studies, DHEA has been found to increase bone mineral density and to stimulate vaginal maturation without affecting the endometrium, while improving well-being and libido with no significant side effects. The advantage of DHEA over other androgenic compounds is that DHEA, at physiological doses, is converted into androgens and/or estrogens only in the specific intracrine target tissues that possess the appropriate physiological enzymatic machinery, thus limiting the action of the sex steroids to those tissues possessing the tissue-specific profile of expression of the genes responsible for their formation, while leaving the other tissues unaffected and thus minimizing the potential side effects observed with androgens or estrogens administered systemically.

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Section: Dhea and Other Cancersmentioning

confidence: 99%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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“…In humans, low levels of DHEA and DHEAS have been regarded as a concomitance of chronic illness [ 8], malignancy [ 9], heart disease [ 10], osteoporosis [ 11], and human immunodeficiency virus (HIV) infection [ 12]. A fall in serum DHEA was considered as at least partly attributable to loss of TH1 activity in the progression from HIV positive to acquired immunodeficiency syndrome (AIDS) [ 13].…”

Section: Introductionmentioning

confidence: 99%

Attenuation of house dust mite Dermatophagoides farinae‐induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down‐regulation of TH2 response

Yang

Lei

et al. 1999

Clin Experimental Allergy

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“…This profound age-related decline has led to investigation of the possibility that plasma levels of DHEA or DHEA metabolites may be related to the development of age-associated tumorigenesis. Case-controlled studies have shown that low serum DHEA or DHEA-S levels correlate with an increased risk of development of breast cancer in premenopausal women [49,50], ovarian cancer in postmenopausal women [51], bladder cancer [52] and gastric cancer [53]. Some studies have also shown that mean serum DHEA or DHEA-S concentrations in patients with prostate [54] and colon [55] cancer tended to be lower than those in controls.…”

Section: Physiological Roles Of Dhea In Preventing Tumorigenesis In Hmentioning

confidence: 99%

Dehydroepiandrosterone and Its Derivatives: Potentially Novel Anti-Proliferative and Chemopreventive Agents

Matsuzaki¹,

Honda

2006

CPD

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Dehydroepiandrosterone (DHEA) is the most abundant adrenal androgenic steroid in young adult humans. The physiological functions of DHEA in preventing human carcinogenesis are still controversial, but a lot of reports have shown that pharmacological doses of DHEA show chemopreventive and anti-proliferative effects on tumors in rodents. Although a therapeutic dose of DHEA has been reported to promote hepatocarcinogenesis in rats due to peroxisomal proliferation, it remains unclear whether DHEA is a peroxisome proliferator in human liver. The chemopreventive and anti-proliferative effects of DHEA are not explained by a single mechanism, and at least four mechanisms seem to contribute to these effects: 1) depletion of NADPH and ribose-5-phosphate due to the inhibition of glucose-6-phosphate dehydrogenase activity, 2) suppression of cholesterol biosynthetic pathway by inhibition of HMG-CoA reductase, 3) interference with cell proliferation signaling pathways, and 4) suppression of nitric oxide generation through down-regulation of nitric oxide synthase II. In addition to studies of the mechanisms underlying the anti-neoplastic effects, searches for more potent and less androgenic DHEA derivatives are ongoing. A small amount of DHEA is endogenously metabolized to 7-oxygenated DHEA, and this may represent a metabolic pathway to more potent steroid hormones. Androsterone, epiandrosterone and etiocholanolone have been considered to be merely inactive end products of DHEA, but may in fact be physiological effectors in their own right. In addition, DHEA analogs such as 3beta-methyl-5-androsten-17-one, 16alpha-fluoro-5-androsten-17-one and 16alpha-fluoro-5alpha-androstan-17-one have been synthesized and shown to be more effective inhibitors of tumor growth, compared with DHEA itself. However, to design potent and safe DHEA derivatives, identification of the DHEA receptor and clarification of the mechanisms of DHEA action are required.

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Decreased Serum Level of Dehydroepiandrosterone Sulfate in Postmenopausal Women with Ovarian Cancer

Cited by 12 publications

References 10 publications

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Attenuation of house dust mite Dermatophagoides farinae‐induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down‐regulation of TH2 response

Dehydroepiandrosterone and Its Derivatives: Potentially Novel Anti-Proliferative and Chemopreventive Agents

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