Dehydroepiandrosterone (DHEA)

Delivery of dehydroepiandrosterone to premenopausal women: effects of micronization and nonoral administration.
Casson PR, Straughn AB, Umstot ES, Abraham GE, Carson SA, Buster JE.
Am J Obstet Gynecol. 1996 Feb;174(2):649-53.

 This single-dose study compares three dehydroepiandrosterone delivery methods (oral crystalline steroid, micronized steroid, and vaginal administration) to ascertain whether physiologic levels of circulating dehydroepiandrosterone and dehydroepiandrosterone sulfate can be obtained while increases in testosterone are minimized. Two randomized, double-blind, placebo-controlled single-dose comparisons were made. For oral micronized versus crystalline dehydroepiandrosterone 300 mg doses of micronized or crystalline dehydroepiandrosterone were administered, followed by 6 hours of blood sampling (n=7). Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone levels were measured; areas under the curve and mean peak values were analyzed by Student-Newman-Keuls tests. For oral versus vaginal micronized dehydroepiandrosterone 150 mg oral or vaginal doses of micronized dehydroepiandrosterone were administered, followed by blood sampling over 12 hours (n=5). Data analysis was as described. Oral micronized and unmicronized dehydroepiandrosterone resulted in increases in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. Micronization increased the area-under-the-curve ratios for dehydroepiandrosterone sulfate/dehydroepiandrosterone and dehydroepiandrosterone sulfate/testosterone. Vaginal administration provided equivalent serum dehydroepiandrosterone; however, it failed to increase dehydroepiandrosterone sulfate or testosterone over placebo. Micronization of oral dehydroepiandrosterone diminishes bioconversion to testosterone. Vaginal dehydroepiandrosterone delivers equivalent dehydroepiandrosterone but substantially diminishes dehydroepiandrosterone bioconversion. PMID: 8623801

  Dehydroepiandrosterone supplementation increases baseline follicular phase progesterone levels.
Weissman A, Horowitz E, Ravhon A, Golan A, Levran D.
Gynecol Endocrinol. 2011 Apr 18

 The use of dehydroepiandrosterone (DHEA) supplementation in infertile patients with diminished ovarian reserve (DOR) has become increasingly popular. It has been our observation that serum progesterone levels during the follicular phase are often increased during controlled ovarian stimulation when DHEA is coadministered. Our aim was to compare progesterone levels during the follicular phase before and during DHEA supplementation in women with DOR undergoing in vitro fertilization (IVF). In a case-control study, we compared progesterone levels during the follicular phase in IVF cycles before and during DHEA supplementation in 15 women with DOR who received 75 mg of DHEA daily. Progesterone levels on stimulation day 5 (0.58 ± 0.29 ng/ml vs. 1.54 ± 0.49 ng/ml; p < 0.0001) and on the day of human chorionic gonadotropin administration (0.75 ± 0.31 ng/ml vs. 1.87 ± 0.49 ng/ml; p < 0.0001) were significantly higher during DHEA treatment. The number of retrieved and fertilized oocytes was similar in both the groups. DHEA administration during IVF cycles in women with DOR causes a significant elevation of progesterone levels without an apparent deleterious effect on cycle outcome. PMID: 21500990

  Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men
Kawano H, Yasue H, Kitagawa A, Hirai N, Yoshida T, Soejima H, Miyamoto S, Nakano M,
Ogawa H.
J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5

 The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 ± 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 ± 0.5%; 4 wk, 6.9 ± 0.7%; 8 wk, 7.9 ± 0.6%; 12 wk, 8.4 ± 0.7% (P < 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 ± 0.6%, 4.5 ± 0.5%, 3.9 ± 0.5%, and 4.4 ± 0.6% (P < 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 ± 2.2, 6.4 ± 2.3, 5.5 ± 2.8, and 5.1 ± 2.0 IU/ml (P < 0.01 vs. baseline, by ANOVA); placebo: 9.0 ± 2.1, 10.4 ± 2.2, 9.5 ± 2.2, and 9.6 ± 2.1 IU/ml (P < 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 ± 12.2; 12 wk, 132.0 ± 12.8 mg/dl (P < 0.01, by ANOVA); placebo: 181.0 ± 13.8 and 179.6 ± 12.4 mg/dl (P < 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease. PMID: 12843164

  Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results
Mamas, Leonidas; Mamas, Eudoxia
Curr Opin Obstet Gynecol. 2009 Aug;21(4):306-8.

 To present the possible positive effect of dehydroepiandrosterone administration in assisted reproduction and especially in poor responders, women with diminished ovarian reserve, premature ovarian failure and premature ovarian aging in the course of ovarian stimulation protocols followed either by intrauterine insemination or IVF. Overall, 50-75 mg of dehydroepiandrosterone supplementation for at least 4 months may either result in natural conception or considerably improves intrauterine insemination and IVF outcome and pregnancy rates to women with confirmed diminished ovarian reserve, premature ovarian failure or premature ovarian aging. Positive effect has been reported to oocyte and embryo quality, even to women aged 40-47 years. The number of euploid embryos is increased, and miscarriage rate is decreased. Although more data on the dehydroepiandrosterone effect on assisted reproduction are needed, results obtained over the last few years confirm the improvement of oocyte production and pregnancy rates. No significant side effects are reported, and those include mainly hirstusism and acne.
PMID: 19610174

  DHEA therapy for women: effect on sexual function and wellbeing
Panjari M, Davis SR.
Hum Reprod Update. 2007 May-Jun;13(3):239-48

 DHEA is increasingly available commercially as a supplement aimed at improving libido and wellbeing in postmenopausal women. However there is scant evidence to support the use of DHEA for this purpose, and safety data for DHEA therapy are lacking. Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, providing a large precursor reservoir for the intracellular production of androgens and oestrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young people may have anti-ageing effects and improve wellbeing and sexual function. However this is not supported by the published literature. We have reviewed the physiology of DHEA and DHEAS in women and the published literature pertaining to the use of DHEA therapy for libido and wellbeing in postmenopausal women. The literature was searched using Medline (Ovid) and Pub-Med for original studies. Overall, the interpretation of data from randomised controlled trials conducted in well women is limited by inadequate sample size and short treatment durations with inconsistent results for the outcomes of libido and wellbeing. Studies of DHEA in women with adrenal insufficiency, although indicating potential improvements in mood and libido, are also limited by their short treatment phase durations. In addition safety data for DHEA therapy are lacking. The potential value of DHEA therapy for women still requires exploration in adequately powered well-designed randomised placebo-controlled trials. The studies of DHEA therapy in women with adrenal insufficiency suggest that this group is the most likely to derive health benefits from DHEA supplementation. PMID: 17208951