Miglustat has no apparent effect on spermatogenesis in normal men.
BACKGROUND
In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertility, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men.


METHODS
After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays.


RESULTS
Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed.


CONCLUSIONS
In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.
Amory
J K
JK
Department of Medicine, University of Washington, Seattle, WA 98195, USA. jamory@u.washington.edu
Muller
C H
CH
Page
S T
ST
Leifke
E
E
Pagel
E R
ER
Bhandari
A
A
Subramanyam
B
B
Bone
W
W
Radlmaier
A
A
Bremner
W J
WJ
D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D020101:Acrosome Reaction / Q000187:drug effects; D000328:Adult; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012661:Semen / Q000737:chemistry; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D017485:1-Deoxynojirimycin; D013739:Testosterone; C059896:miglustat