title: Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.
abstract: OBJECTIVE
  Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA).
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m²), a COC containing 30mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E₂) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo).
  
  
  RESULTS
  During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period -- 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; p<.0001) -- and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E₂.
  
  
  CONCLUSIONS
  An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50 mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG.
  
  
  CONCLUSIONS
  When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely.
authors.affiliation: Pantarhei Bioscience, Zeist, the Netherlands. Electronic address: yz@pantarheibio.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: Department of Gynecology-Obstetrics, University Hospital CHR Citadelle, Site Sainte Rosalie in Liège, Liège, Belgium.
authors.forename: J-M
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: Department of Gynecology-Obstetrics, University Hospital CHR Citadelle, Site Sainte Rosalie in Liège, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Pintiaux
authors.affiliation: Department of Laboratory Medicine, University Hospital CHR Citadelle, Liège, Belgium.
authors.forename: J-M
authors.initials: JM
authors.lastname: Minon
authors.affiliation: Department of Reproductive Medicine & Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Department of Psychology, School of Natural Sciences, University of Stirling, Stirling, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Cobey
authors.affiliation: Pantarhei Bioscience, Zeist, the Netherlands.
authors.forename: H J T
authors.initials: HJ
authors.lastname: Coelingh Bennink
mesh_terms: D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000009:adverse effects; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D000735:Androstenedione / Q000097:blood; D000736:Androstenes / Q000009:adverse effects*; D001530:Belgium; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D012738:Sex Hormone-Binding Globulin / Q000819:agonists* / Q000032:analysis; D012995:Solubility; D013739:Testosterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood* / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D012738:Sex Hormone-Binding Globulin; C534342:drospirenone and ethinyl estradiol combination; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D000735:Androstenedione; D004997:Ethinyl Estradiol; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate
keywords: Androgens; DHEA; Free testosterone; SHBG