Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women

Genazzani, Alessandro D.; Stomati, Massimo; Strucchi, Claudia; Puccetti, Simone; Luisi, Stefano; Genazzani, Andrea R.

doi:10.1016/s0015-0282(01)01902-1

Cited by 48 publications

(16 citation statements)

References 24 publications

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“…As pointed out previously, these results should caution against the use of DHEA as a supplement with various 'antiageing' properties (Hankinson et al, 1998). DHEA oral supplementation leads to significant increases in circulating levels of DHEAS, testosterone, androstenedione, oestrone, and oestradiol (Genazzani et al, 2001).…”

Section: Discussionmentioning

confidence: 52%

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study

et al. 2004

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We assessed the association of sex hormone levels with breast cancer risk in a case -control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47 -4.21), P trend ¼ 0.003 for oestradiol; 3.24 (1.87 -5.58), P trend o0.001 for oestrone; 2.37 (1.39 -4.04), P trend ¼ 0.002 for testosterone; 2.07 (1.28 -3.33), P trend o0.001 for androstenedione; 1.74 (1.05 -2.89), P trend o0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31 -0.82), P trend o0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI ¼ 0.92 -1.26 for testosterone; 1.15, 95% CI ¼ 0.95 -1.39 for androstenedione and 1.06, 95% CI ¼ 0.90 -1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production. Nine prospective studies have now reported on the association between endogenous sex hormone levels in postmenopausal women and subsequent breast cancer risk (Moore et al, 1986;Wysowski et al, 1987;Barrett-Connor et al, 1990;Gordon et al, 1990;Garland et al, 1992;Helzlsouer et al, 1994;Toniolo et al, 1995;Berrino et al, 1996;Dorgan et al, 1996;Thomas et al, 1997;Zeleniuch-Jacquotte et al, 1997;Hankinson et al, 1998;Cauley et al, 1999;Kabuto et al, 2000). The Endogenous Hormones and Breast Cancer Collaborative Group (TEHBCCG) conducted a pooled analysis of the original data of these studies and concluded that both oestrogen and androgen hormones were strongly associated with risk (TEHBCCG, 2002). Remaining questions include how long prior to diagnosis the associations between hormone levels and breast cancer are observed and whether androgens play a part independent of their role as substrates for oestrogen production. The New York University (NYU) Women's Health Study was one of the first prospective studies to report a positive association between ...

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Section: Discussionmentioning

confidence: 52%

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study

et al. 2004

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“…In these studies, serum androgens rise to premenopausal levels, with attendant increases in GH and IGF-1 levels [61]. In the present study, the CYP17 A2 allele was associated with lower levels of GH in both pre-and postmenopausal subjects, but this association should be viewed with caution because growth hormone levels are difficult to measure due to diurnal variation and were more often undetectable in A2 allele carriers.…”

Section: Discussionmentioning

confidence: 46%

Association between the T27C polymorphism in the cytochrome P450 c17? (CYP17) gene and risk factors for breast cancer

Hong

Thompson

Jiang

et al. 2004

Breast Cancer Res Treat

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Mammographic density is associated with increased breast cancer risk and is influenced by sex hormones. A T27C polymorphism (alleles A1 and A2, respectively) in the 5' promoter region of CYP17 may be associated with elevated sex hormone levels. In a cross-sectional study of 181 pre- and 173 postmenopausal women, we examined the relationship of this polymorphism with mammographic density and other risk factors for breast cancer. Subjects were recruited across five categories of density. Risk factor and dietary information, anthropometric measures, and blood samples were obtained. Sex hormone, lipid, growth factor levels, and CYP17 genotypes were determined. CYP17 genotype was not associated with mammographic density levels before or after adjusting for risk factors for breast cancer. In premenopausal women, the A2 allele was associated with higher levels of dehydroepiandrosterone sulfate, and in postmenopausal women, with higher levels of total estradiol and lower levels of follicle stimulating hormone. Among premenopausal women, interactions were observed between CYP17 genotype and endogenous insulin levels as well as dietary variables associated with mammographic density. Our findings suggest that the CYP17 A2 allele is associated with hormone levels, and interacts with insulin levels and diet to affect breast density levels and potentially breast cancer risk.

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“…The estrogenic milieu probably underlies the positive modulation of the therapy on the somatotropic axis. DHEA administration in postmenopausal women acts on the GHRH-GH-IGF-1 axis in a manner comparable to estrogenprogestin replacement therapy 43 . In men, exogenous DHEA and/or the steroid metabolites derived from its transformation may influence the spontaneous GH pulsatile release, justifying the significant increase in GH and IGF-1 levels.…”

Section: Discussionmentioning

confidence: 99%

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency

et al. 2004

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Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.

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Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women

Cited by 48 publications

References 24 publications

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study

Association between the T27C polymorphism in the cytochrome P450 c17? (CYP17) gene and risk factors for breast cancer

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency

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