title: Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.
abstract: OBJECTIVE
  To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m2) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles.
  
  
  RESULTS
  Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG.
  
  
  CONCLUSIONS
  Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration.
  
  
  CONCLUSIONS
  A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC.
authors.affiliation: Pantarhei Bioscience, Zeist, The Netherlands.
authors.forename: Herjan J T
authors.initials: HJT
authors.lastname: Coelingh Bennink
authors.affiliation: Pantarhei Bioscience, Zeist, The Netherlands. Electronic address: yz@pantarheibio.com.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: Department of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Laan
authors.affiliation: Department of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Hanneke M M
authors.initials: HMM
authors.lastname: Termeer
authors.affiliation: Pantarhei Bioscience, Zeist, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Appels
authors.affiliation: Department of Biostatistics, University Hospital of Liege, Belgium.
authors.forename: Adelin
authors.initials: A
authors.lastname: Albert
authors.affiliation: Department of Reproductive Medicine & Gynecology, University Medical Center Utrecht, The Netherlands.
authors.forename: Bart C J M
authors.initials: BCJM
authors.lastname: Fauser
authors.affiliation: Department of Endocrinology, University Medical Center Utrecht, The Netherlands.
authors.forename: Jos H H
authors.initials: JHH
authors.lastname: Thijssen
authors.affiliation: Department of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Rik H W
authors.initials: RHW
authors.lastname: van Lunsen
mesh_terms: D000328:Adult; D000736:Androstenes / Q000009:adverse effects; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000009:adverse effects*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D004702:Endocrine Glands / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D004970:Estrone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects; D009426:Netherlands; D015203:Reproducibility of Results; D012738:Sex Hormone-Binding Globulin / Q000819:agonists / Q000032:analysis / Q000378:metabolism; D012995:Solubility; D013739:Testosterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D012738:Sex Hormone-Binding Globulin; C534342:drospirenone and ethinyl estradiol combination; C072593:ethinyl estradiol, levonorgestrel drug combination; D004970:Estrone; D013739:Testosterone; D004997:Ethinyl Estradiol; D003687:Dehydroepiandrosterone; D004958:Estradiol; D016912:Levonorgestrel
keywords: Androgens; DHEA; Free testosterone; Oral contraception; SHBG