Dr. Weeks’ Comment
DHEA is a pre hormone from which we create stress hormones like cortisol and sex hormones like estrogen and testosterone. It helps with energy and stamina and helps optimize hormone functions.
Much research suggest that keeping women at healthy DHEAs levels (not in the high normal range but mid range) and keeping estrogen and testosterone and progesterone levels in health ranges optimizes their outcome when beating breast cancer. See research cited below.
Toxicol Appl Pharmacol. 2017 Oct 15;333:26-34. doi: 10.1016/j.taap.2017.08.002. Epub 2017 Aug 10.
- PMID: 28803991 DOI: 10.1016/j.taap.2017.08.002
Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells;however, the underlying mechanisms have not been elucidated. In this study, the in vitro effect of DHEA on the expression pattern of some EMT-related proteins, such as E-cadherin (epithelial), N-cadherin, vimentin and Snail (mesenchymal) was measured by Western blot and immunofluorescence in MDA-MB-231 breast cancer cells with invasive, metastatic and mesenchymal phenotype. Also, the in vivo effect of DHEA on xenograft tumor growth in nude mice (nu-/nu-) and on expression of the same epithelial and mesenchymal proteins in generated tumors was evaluated. We found that DHEA increased expression of E-cadherin and decreased N-cadherin, vimentin and Snail expression both in MD-MB-231 cells and in the formed tumors, possibly by DHEA-induced reversion of mesenchymal phenotype. These results were correlated with a tumor size reduction in mouse xenografts following DHEA administration either a week earlier or concurrent with breast cancer cells inoculation. In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype.
Eur J Clin Nutr. 1999 Oct;53(10):771-5. doi: 10.1038/sj.ejcn.1600889.
- PMID: 10556982 DOI: 10.1038/sj.ejcn.1600889
Results: DHEA is reported to inhibit the growth of human mammary cancer cells in vitro and also the growth of chemically-induced mammary cancer in rats. However, growth inhibition occurs only in the presence of high oestrogen concentrations, and growth stimulation occurs in both models in the presence of a low-level oestrogen milieu. Epidemiological studies report a positive correlation between higher serum concentrations of DHEA and increased breast cancer risk in the case of postmenopausal but not premenopausal women. Postulated mechanisms include a direct effect on mammary cells by androgenic metabolites of DHEA or an indirect effect by an increase in bioavailable oestrogen levels. The increased serum concentration of free insulin-like growth factor 1 which follows prolonged DHEA intake may also have a role by stimulating oestrogen receptor activity in breast tissue.
Conclusion: Late promotion of breast cancer in postmenopausal women may be stimulated by prolonged intake of DHEA, and the risk may be increased by the endocrine abnormality associated with pre-existing abdominal obesity. Caution is advised in the use of dietary supplements of DHEA particularly by obese postmenopausal women.
Nat Clin Pract Endocrinol Metab. 2007 Aug;3(8):584-93. doi: 10.1038/ncpendmet0559.
- PMID: 17643129 DOI: 10.1038/ncpendmet0559
The first-generation selective estrogen receptor modulator (SERM) tamoxifen has been the mainstream hormone therapy in breast cancer. Tamoxifen benefits all stages of the disease, but its use increases the risk of uterine cancer and thromboembolic events and it can only be administered for 5 years. Aromatase inhibitors are superior to tamoxifen at advanced stages of disease and as adjuvants; however, because they increase fractures, aromatase inhibitors are unlikely to be used to prevent disease. Raloxifene, a second-generation SERM, leads, like tamoxifen, to approximately 50% fewer cases of invasive breast cancer in high risk women, with a lower incidence of thromboembolic events. Several other SERMs are in development to improve tissue specificity, efficacy and tolerance. Raloxifene shows protection against vertebral fractures similar to bisphosphonates; however, no significant effect has been observed on nonvertebral fractures. Many SERMs are in development for prevention and treatment of osteoporosis. As breast cancer metastasizes early and advanced disease cannot be cured, prevention is essential. To avoid the concerns about the use of traditional hormone replacement therapy, dehydroepiandrosterone–a tissue-targeted precursor of sex steroid formation–offers hope of a physiological tissue-targeted hormone replacement that, combined with a SERM, would simultaneously prevent breast and uterine cancer.
Cancer Epidemiol Biomarkers Prev. 1997 Mar;6(3):177-81.
- PMID: 9138660
Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in postmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal women, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 healthy postmenopausal volunteers not taking replacement estrogens when they donated blood and who were diagnosed with breast cancer up to 10 years later (median, 2.9 years). Two randomly selected controls, who also were postmenopausal and not taking estrogens, were matched to each case on exact age, date (+/-1 year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02) gradients of increasing risk of breast cancer were observed for increasing concentrations of DHEA and ADIOL, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in the lowest; their risk ratios were 4.0 [95% confidence interval (CI), 1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEAS concentration was in the highest quartile also exhibited a significantly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this prospective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.
Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118600. doi: 10.1016/j.bbamcr.2019.118600. Epub 2019 Nov 21.
- PMID: 31760088 DOI: 10.1016/j.bbamcr.2019.118600
It is generally assumed that circulating dehydroepiandrosterone sulfate (DHEAS) can be desulfated and further metabolized to estrogen, which is of concern for all patients with estrogen-responsive breast cancer. We addressed this issue by comparing the effects of DHEAS, its desulfated form DHEA, and 17ß-estradiol on human metastatic, estrogen-responsive MCF-7 breast cancer cells. Physiological concentrations of DHEAS promoted phosphorylation of Erk1/2, whereas DHEA and 17ß-estradiol failed to stimulate Erk1/2 phosphorylation, indicating that the sulfated steroid acts as an autonomous hormone. Exposure of MCF-7 cells to 17ß-estradiol stimulated cell proliferation and the expression of pro-metastatic and pro-invasive elements such as claudin-1, matrix metalloproteinase 9 (MMP9), and the CC chemokine ligand 2 (CCL2). In contrast, treatment with DHEAS did not stimulate these responses but prevented all of the actions of 17ß-estradiol, and as a consequence cell migration and invasion were completely inhibited. The results of this study not only challenge the assumption that DHEAS poses a danger as an endogenous source of estrogen, they rather favor the idea that keeping DHEAS levels within a physiological range might be supportive in treating estrogen-responsive breast cancer.
Eur J Pharmacol. 2011 Jun 25;660(2-3):268-74. doi: 10.1016/j.ejphar.2011.03.040. Epub 2011 Apr 9.
- PMID: 21497598 DOI: 10.1016/j.ejphar.2011.03.040
Cancer invasion and metastasis are the leading causes of mortality in patients with breast cancer. Dehydroepiandrosterone (DHEA) has a protective role against cancer, however, the mechanism by which DHEA has this effect remains poorly understood. The present study was aimed at investigating the actions of DHEA on the proliferation, cell cycle, death and migration of breast cancer cell lines. We used MCF-7 cells (estrogen receptors positive) and MDA-MB-231 and Hs578T cells (estrogen receptors negative) for these studies. Cell proliferation was evaluated by crystal violet staining, cell cycle by flow cytometry, and cell death by the carboxyfluorescein FLICA analysis of caspase activation. Migration was evaluated by transwell cell migration and wound assay. We also determined the expression of ECM-1 protein by western blotting and RT-PCR in real time. DHEA inhibited the proliferation of all breast cancer cell lines. This was associated with an arrest in the G1 phase of the cell cycle and death in MCF-7 cells. There was no alteration in any of the cell cycle phases or death in DHEA treated MDA-MB-231 or Hs578T cells. DHEA also suppressed the migration of all breast cancer cell lines, independently of the presence of estrogen receptors and decreased the expression of ECM-1 protein in Hs578T cells. These results suggest that the mechanism of DHEA actions against breast cancer involves the inhibition of cell proliferation and the suppression of migration, indicating that DHEA could be useful in the treatment of breast cancer.
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. 2003 Apr;24(2):152-82. doi: 10.1210/er.2001-0031.
- PMID: 12700178 DOI: 10.1210/er.2001-0031
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.
Steroids. 2012 Apr;77(5):542-51. doi: 10.1016/j.steroids.2012.01.019. Epub 2012 Feb 11.
- PMID: 22342541 DOI: 10.1016/j.steroids.2012.01.019
7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells.
Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA.