Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk

Abstract

Objective: Dietary supplements of the adrernocertical hormone dehydroepiandrosterone (DHEA) are widely taken in the hope of staving off the aging process. Potential dangers have not been fully researched, particularly evidence of a correlation between increased serum concentrations of DHEA and higher breast cancer risk in postmenopausal women. Design: The review examines reports of clinical, epidemiological experimental studies for evidence that DHEA may be a factor in promoting the growth of mammary cancer. Biological mechanisms which might be involved are identi®ed. 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 insulinlike 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.

Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate and Related Steroids: Their Role in Inflammatory, Allergic and Immunological Disorders

“…Thus, mild acne, hirsutism, and oiliness of the skin have been noted in women [157]. There continues to be concern over possible stimulation of hormone-dependent neoplasia, including breast and prostate [158,159]. Apart from these hormonal effects there are some reports of psychiatric manifestations of DHEAS use [160].…”

The Association of Plasma DHEA and DHEA Sulfate with Breast Cancer Risk in Predominantly Premenopausal Women

“…In vitro data suggest that DHEA and DHEAS inhibit breast cell proliferation possibly through epidermal growth factor (26), although they can stimulate proliferation, especially in a low-estrogen environment (1,3,22,24,25). Thus, DHEA and DHEAS may act as estrogen antagonists in a high estrogen environment, but act as weak estrogen agonists in a low-estrogen environment (1,2,27). A second hypothesis posits that women who develop breast cancer have a blunted age-related decline in DHEA and DHEAS levels (1,17,28,29); that is, compared with healthy controls, women who develop breast cancer in early-to midpremenopausal years have similar or lower DHEA or DHEAS , family history of breast cancer (yes, no), age at menarche (<12, 12, 13, z14 years), history of benign breast disease (yes, no), and parity/age at first birth (nulliparous, age at first birth <25 years/1-2 children, age at first birth 25 to 29 years/1-2 children, age at first birth z30 years/1-2 children, age at first birth <25 years/z3 children, age at first birth z25 years/z3 children).…”

Pesticide Residues in Food and Cancer Risk: A Critical Analysis

“…DHEA also inhibited the development of tumors of the rat testis (Rao et al, 1992b) and rat and mouse mammary gland (Schwartz et al, 1981;McCormick et al, 1996). A recent review of clinical, experimental, and epidemiological studies concluded that late promotion of breast cancer in postmenopausal women may be stimulated by prolonged intake of DHEA (Stoll, 1999); however, the evidence for a positive association in postmenopausal women between serum DHEA levels and breast cancer risk is conflicting (Bernstein et al, 1990;Stoll, 1999). Natural Pesticides Natural pesticides, because few have been tested, are markedly underrepresented in our HERP analysis.…”