title: Integrity of the blood-testis barrier in healthy men after suppression of spermatogenesis with testosterone and levonorgestrel.
abstract: OBJECTIVE
  Do exogenous male hormonal contraceptives that suppress intratesticular testosterone and spermatogenesis interfere with the blood-testis barrier integrity in men?
  
  
  CONCLUSIONS
  When spermatogenesis was suppressed by testosterone alone or combined with levonorgestrel (LNG) treatment in men, the structural appearance of Sertoli cell tight junctions remained intact in the human testis.
  
  
  BACKGROUND
  Testosterone promotes the integrity of the blood-testis barrier. Intratesticular androgen deprivation induced by exogenous testosterone plus a progestin to suppress spermatogenesis in a contraceptive regimen may disturb the structural and functional integrity of the blood-testis barrier.
  
  
  METHODS
  Testicular biopsies were obtained from a sub-study of a randomized clinical trial of 36 healthy Chinese men who were treated for 18 weeks and followed for at least a 12-week recovery period.
  
  
  METHODS
  Healthy Chinese male volunteers (27-48 years) were randomized to two treatment groups (n = 18/group) for 18 weeks: (1) testosterone undecanoate (TU) 1000 mg i.m. injection followed by a 500 mg injection every 6 weeks and (2) TU + LNG 250 μg orally daily. Blood samples were obtained from all participants before and during treatment and at the end of the recovery phase. Open testicular biopsies for this study were obtained from four men before treatment and from four men in each of the TU and TU + LNG groups at 2 and 9 weeks of treatment. The presence of antisperm antibodies was checked in the archived serum samples of the subjects at baseline, during treatment and at the end of the recovery period. Stored testicular biopsy samples from cynomolgus monkeys treated with either sub-cutaneous testosterone or placebo for 12 weeks were used for additional protein expression studies.
  Expression of blood-testis barrier associated proteins quantified by immunohistochemistry (claudin 3, claudin 11, junctional adhesion molecule-A, zonula occludens-1) remained unchanged despite a significant decrease in the numbers of pachytene spermatocytes and round spermatids in the seminiferous tubules at 9 weeks in the TU + LNG group. This was confirmed by immunoblots showing a lack of quantitative change in these tight junction proteins in monkeys after testosterone treatment. There were no increases in serum antisperm antibodies in the volunteers during the study.
  
  
  CONCLUSIONS
  The duration of the study was short and the long-term effects of male hormonal contraceptive treatments on the integrity of the blood-testis barrier remain to be determined.
  
  
  CONCLUSIONS
  This study supports the safety of male hormonal contraceptive treatment and does not corroborate the previous findings of disturbed immunological integrity of the blood-testis barrier from animal studies such as androgen receptor knockout mice and exogenous hormonal treatment in rats.
  
  
  BACKGROUND
  The study was supported by grants from the Contraceptive Research and Development Program and the Mellon Foundation (MFG-02-64, MFG-03-67), Endocrine, Metabolism and Nutrition Training Grant (T32 DK007571), the Clinical and Translational Science Institute at Los Angeles Biomedical and Harbor-UCLA Medical Center (UL1RR033176 and UL1TR000124) and the Los Angeles Biomedical Research Institute Summer High School Student Program.
authors.affiliation: Department of Medicine, Division of Endocrinology, Harbor-University of California, Los Angeles, Medical Center and Los Angeles Biomedical Research Institute, 1000 W Carson Street, Torrance, CA 90509, USA.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ilani
authors.forename: Nancy
authors.initials: N
authors.lastname: Armanious
authors.forename: Yan-He
authors.initials: YH
authors.lastname: Lue
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Swerdloff
authors.forename: Sima
authors.initials: S
authors.lastname: Baravarian
authors.forename: Alex
authors.initials: A
authors.lastname: Adler
authors.forename: Christina
authors.initials: C
authors.lastname: Tsang
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Cui
authors.forename: Xing-Hai
authors.initials: XH
authors.lastname: Wang
authors.forename: Zuo-Min
authors.initials: ZM
authors.lastname: Zhou
authors.forename: Jia-Hao
authors.initials: JH
authors.lastname: Sha
authors.forename: Christina
authors.initials: C
authors.lastname: Wang
mesh_terms: D000328:Adult; D001814:Blood-Testis Barrier / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D057167:Claudins / Q000096:biosynthesis; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D057167:Claudins; D003272:Contraceptive Agents, Male; C407243:F11R protein, human; D011956:Receptors, Cell Surface; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D013739:Testosterone; D016912:Levonorgestrel; C010792:testosterone undecanoate