3β-hydroxyandrost-5-en-17-one acetate

Endpoint summary

Additional information

• Commonly used doses range from 25 up to 200 mg daily. Clinical trials have demonstrated that incremental increases in serum prasterone levels appear to plateau at an oral dosage of 300 mg/day. These studies demonstrated that doses greater than this have little additional therapeutic value. Topical administration and IV injections have also been used clinically. Topical formulations usually contain 5-10% DHEA. 

Physiological replacement dosages of oral prasterone in healthy people older than 40 years are in the range of 20-50 mg/day in men and 10-30 mg/day in women. These doses are adequate to increase serum DHEA to the levels found in adults 20-30 years of age. A beneficial increase in high-density lipoprotein (HDL) cholesterol has been observed with low doses (25 mg daily). Significant improvement in insulin sensitivity (euglycemic clamp studies) and lipid parameters was reported after one year of treatment with low doses of dehydroepiandrosterone (25 mg daily). Significant increases in HDL cholesterol (12%) and decreases in LDL cholesterol (11%) and triglycerides (20%) were observed at 12 months.

Pharmacologic dosages of 200 mg/day have been effective in patients with systemic lupus erythematosus.It is used daily in women with adrenal failure for 9 months with doses as low as 25 mg. Dosages of 200-500 mg/day have been used in HIV-positive patients with depressed mood and fatigue. Supraphysiological doses of 100 mg/day were shown to increase androstenedione, testosterone and dihydrotestosterone levels 3- to 5-fold in postmenopausal women. Some evidence of improved well-being was seen with 50 mg once daily in men and women 40 to 70 years of age in a small study.

In a meta-analysis of clinical trial studies 25 studies enrolled 1353 elderly men, with a mean follow-up of 36 weeks. DHEA supplementation was associated with a reduction of fat mass. However, the association with fat mass disappeared in a multivariate regression model after adjusting for DHEA-related metabolite increases such as total testosterone and estradiol. In contrast to what was observed for fat mass, no effect of DHEA supplementation in comparison with placebo was observed for various clinical parameters including lipid and glycemic metabolism, bone health, sexual function, and quality of life.

         

• In a 2-year, placebo-controlled, randomized, double-blind study 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA were studied. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. Analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and menin both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects.

Sources:

Sreekumaran K;et al:(2006) DHEA in elderly women and DHEA or testosterone in elderly men, N Engl J Med,355:1647-1659.

Corona, G:et al: (2013) Dehydroepiandrosterone supplementation in elderly men: a metaanalysis study of placebo-controlled trials,J Clin Endocrinol Metab,98:3615-3626.