A notable study sought to determine whether DHEA replacement therapy in older adults reduces indices of arterial stiffness; carotid augmentation index (AI) and carotid–femoral pulse wave velocity (PWV).[14]


A randomized, double-blind trial was conducted to study the effects of supplementing with 50 mg DHEA per day on AI and PWV in women and men aged 65–75 year. Inflammatory cytokines and sex hormones were also measured in fasting serum.


For both men and women, compared to placebo, DHEA supplementation increased total testosterone, free testosterone index, estradiol, and free estradiol index, as outlined in the table (values are means):





Total testosterone (ng/dl)



After 12 months


% change







+ 125 %  







+ 16.4 %

Total estradiol (pg/ml)



After 12 months


% change







+ 62 %






+ 20 %

SHBG (nmol/L)



After 12 months


% change






- 6.4

- 15.1 %





- 1.5        not significant

- 4.3 %    not significant

Free testosterone index



After 12 months


% change







+ 159 %





+ 10.7

+ 24 %

Free estradiol index



After 12 months


% change






+ 9

+ 90 %





+ 5.5

+ 25.3 %


Free testosterone index and free estradiol index is the ratio of total testosterone or estradiol to SHGB.

The free testosterone index was calculated as (total testosterone x 0.0347)/SHBG, with testosterone is expressed in ng/dL and SHBG in nmol/L.

The free estradiol index was calculated as (total estradiol x 0.00367)/SHBG, with estradiol is expressed in pg/mL and SHBG in nmol/L.


AI significantly decreased by 24% in the DHEA groups (no difference between men and women), but not in the placebo groups.

Pulse wave velocity also decreased; however, after adjusting for baseline values, the between-group comparison became non-significant.

The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (TNF-alpha and IL-6) and correlated with increases in serum DHEAS. The reductions in AI also correlated with free testosterone index. There were no differences between men and women, with respect to the DHEA-induced changes in inflammatory markers.

In the supplemented groups, DHEA supplementation also decreased plasma triglycerides (blood fats) by 11.6 % (14 mg/dl), and there were tendencies for reductions in BMI and body weight with DHEA supplementation.

There were no serious adverse events attributable to DHEA replacement in either men or women.

Comment and Conclusion

This study confirms that DHEA supplementation for 1 year is safe. Supplementing with DHEA 50 mg/day for 1 year does not significantly alter lipid profile or adversely affect the endometrium in postmenopausal women.[15] And earlier study showed that supplementing with 50 mg DHEA per day for 2years is safe for both men and women.[16]

This study also confirms the improvement in plasma triglycerides and  inflammatory cytokines (IL-6 and TNFalpha) seen in a previous study, which further demonstrated that DHEA supplementation 50 mg/day for 1 year decreases insulin resistance and  improves glucose tolerance in elderly men and women.[16]An earlier study also showed improvement in insulin sensitivity, and in addition, a 10% reduction in intra-abdominal fat mass (i.e. visceral fat, measured by MRI) in both men and women.[17]

DHEA replacement in elderly men and women improves indices of arterial stiffness (reduces AI and PWV) and enhances arterial elasticity. The 24% decrease in AI that was observed with DHEA supplementation is large in the context of arterial aging. Based on a 0.30 percentage point per year increase in AI during adulthood [8], the DHEA-induced reduction in AI is equivalent in magnitude to a 20-year reversal of arterial aging.

Furthermore, based on a meta-analysis that shows that every ten percentage point increase in AI corresponds with a approximately 36% greater risk for cardiovascular and all-cause mortality during a 4-year follow-up period [18], the reductions in AI that we observed would be expected to correspond with a 17% reduction in mortality risk.[19]Therefore, the improvements observed in this study suggest that DHEA replacement might partly reverse arterial aging and reduce the risk for cardiovascular and the metabolic syndrome.

The hormonal data in this study (see the table) confirms the less known fact the postmenopausal women have lower estradiol levels than men of the same age. It further shows that DHEA has a greater beneficial impact in women on the ratio of free testosterone (index) to free estradiol (index) than in men. In men, it increases free testosterone (index) and free estradiol (index) roughly equally.

The beneficial outcomes of this and related long-term studies substantiates the safety and health promoting effects of DHEA supplementation, and give you another reason to go and get your blood level of DHEA(S) checked. Strive to keep it in the upper end of the normal reference range. If your level is low, regardless of adrenal insufficiency (a disorder of deficient cortisol production), a good starting dose is 50 mg per day. As the studies outlined in this article show, this is a safe and effective long-term dose for both men and women. Check your blood levels of DHEA(S), testosterone, estradiol and SHBG (as well as glucose and insulin) after about 6 months supplementation. Ideally you want to check these before you start supplementing with DHEA as well in order to establish your baseline so you can see the impact of the supplementation.

While most research showing health promoting effects of DHEA have been done in older men and women, the need for DHEA supplementation should be dictated by your blood DHEA(S) level. Thus, even if you are younger, if your level is low, supplementing with DHEA as a primary prevention approach will most likely benefit you in the long run as you get older.



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