title: Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies.
abstract: OBJECTIVE
  Because dehydroepiandrosterone may protect against neoplasia, osteoporosis, and cardiac disease, we investigated the bioavailability of oral micronized dehydroepiandrosterone, anticipating its adjunctive use in postmenopausal steroid replacement.
  
  
  METHODS
  Eight postmenopausal women randomly received either a placebo or 150 or 300 mg of oral micronized dehydroepiandrosterone in a lipid matrix. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and estradiol were measured periodically over the 12 hours after each dose. All treatments, all doses, and mean serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone were compared with analysis of variance for repeated measures and Newman-Keuls a posteriori test of statistical significance.
  
  
  RESULTS
  Mean peak steroid concentrations after 150 mg (300 mg) doses were dehydroepiandrosterone 1617 (2639) ng/dl, 7 (11.5)-fold above placebo; dehydroepiandrosterone S 1185 (1688) micrograms/dl, 14 (20)-fold above placebo; and testosterone 183 (311) ng/dl, 4 (7)-fold above placebo. Estradiol concentrations remained less than 20 pg/ml, but androgen concentrations rose by 1 hour and remained elevated through the twelfth hour. Peak androgen concentrations and areas under the curves exhibited proportionality with both doses. A testosterone radioimmunoassay with celite chromatography revealed a 300% overestimation for testosterone in the direct-assay method used in this study. Thus after appropriate readjustment maximum testosterone concentrations were observed consistently within physiologic premenopausal ranges after the 150 mg dose.
  
  
  CONCLUSIONS
  Micronized dehydroepiandrosterone may provide a steroidal postmenopausal replacement that is adjunctive to estrogens and worthy of further investigation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tennessee, Memphis.
authors.forename: J E
authors.initials: JE
authors.lastname: Buster
authors.forename: P R
authors.initials: PR
authors.lastname: Casson
authors.forename: A B
authors.initials: AB
authors.lastname: Straughn
authors.forename: D
authors.initials: D
authors.lastname: Dale
authors.forename: E S
authors.initials: ES
authors.lastname: Umstot
authors.forename: N
authors.initials: N
authors.lastname: Chiamori
authors.forename: G E
authors.initials: GE
authors.lastname: Abraham
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001682:Biological Availability; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D011863:Radioimmunoassay; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate