Human Reproduction, Vol. 15, No. 7, 1515-1524,
July 2000
© 2000 European Society of Human Reproduction and Embryology
Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary–testicular axis in normal men*
1 Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, 2 School of Biological and Molecular Sciences, Oxford Brookes University, Oxford, 3 Cardiovascular Research Unit, University of Edinburgh and 4 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK
Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 µg, 150 µg or 300 µg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 µg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3x106/ml), and three men achieving azoospermia in the 300 µg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.
Key words: androgen/desogestrel/male contraception/testis/testosterone
5 To whom correspondence should be addressed at: MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh, 37 Chalmers St, Edinburgh EH3 9ET, UK. E-mail: r.a.anderson{at}ed-rbu.mrc.ac.uk
* Presented in part at the 13th European Society of Human Reproduction and Embryology meeting, Edinburgh, June 1997
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B.M. Brady, M. Walton, N. Hollow, A.T. Kicman, D.T. Baird, and R.A. Anderson Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception Hum. Reprod., November 1, 2004; 19(11): 2658 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Meriggiola, A. Costantino, S. Cerpolini, W. J. Bremner, D. Huebler, A. M. Morselli-Labate, B. Kirsch, A. Bertaccini, C. Pelusi, and G. Pelusi Testosterone Undecanoate Maintains Spermatogenic Suppression Induced by Cyproterone Acetate Plus Testosterone Undecanoate in Normal Men J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5818 - 5826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.M. Robertson, T. Stephenson, and R.I. McLachlan Characterization of plasma inhibin forms in fertile and infertile men Hum. Reprod., May 1, 2003; 18(5): 1047 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ramaswamy, G. R. Marshall, C. R. Pohl, R. L. Friedman, and T. M. Plant Inhibitory and Stimulatory Regulation of Testicular Inhibin B Secretion by Luteinizing Hormone and Follicle-Stimulating Hormone, Respectively, in the Rhesus Monkey (Macaca mulatta) Endocrinology, April 1, 2003; 144(4): 1175 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Matthiesson, D. M. Robertson, H. G. Burger, and R. I. McLachlan Response of serum inhibin B and pro-{alpha}C levels to gonadotrophic stimulation in normal men before and after steroidal contraceptive treatment Hum. Reprod., April 1, 2003; 18(4): 734 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.M. Hair, F. C.W. Wu, and G. A. Lincoln An investigation of the effectiveness of testosterone implants in combination with the prolactin inhibitor quinagolide in the suppression of spermatogenesis in men Hum. Reprod., April 1, 2003; 18(4): 749 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. F. E. Garem, A. F. E. Arini, A. H. E. Beheiry, S. A. A. Zeid, and F. H. Comhaire Possible Relationship Between Seminal Plasma Inhibin B and Spermatogenesis in Patients With Azoospermia J Androl, November 1, 2002; 23(6): 825 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.A. Anderson, Z.M. van der Spuy, O.A. Dada, S.K. Tregoning, P.M. Zinn, O.A. Adeniji, T.A. Fakoya, K.B. Smith, and D.T. Baird Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone Hum. Reprod., November 1, 2002; 17(11): 2869 - 2877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. G. Gonzalo, R. S. Swerdloff, A. L. Nelson, B. Clevenger, R. Garcia, N. Berman, and C. Wang Levonorgestrel Implants (Norplant II) for Male Contraception Clinical Trials: Combination with Transdermal and Injectable Testosterone J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3562 - 3572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Anderson, D. Kinniburgh, and D. T. Baird Suppression of Spermatogenesis by Etonogestrel Implants with Depot Testosterone: Potential for Long-Acting Male Contraception J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3640 - 3649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kinniburgh, H. Zhu, L. Cheng, A.T. Kicman, D.T. Baird, and R.A. Anderson Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men Hum. Reprod., June 1, 2002; 17(6): 1490 - 1501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.I. McLachlan, L. O'Donnell, S.J. Meachem, P.G. Stanton, D.M. de Kretser, K. Pratis, and D.M. Robertson Identification of Specific Sites of Hormonal Regulation in Spermatogenesis in Rats, Monkeys, and Man Recent Prog. Horm. Res., January 1, 2002; 57(1): 149 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.M. Behre, S. Kliesch, B. Lemcke, S. von Eckardstein, and E. Nieschlag Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone Hum. Reprod., December 1, 2001; 16(12): 2570 - 2577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. O’Donnell, A. Narula, G. Balourdos, Y.-Q. Gu, N. G. Wreford, D. M. Robertson, W. J. Bremner, and R. I. McLachlan Impairment of Spermatogonial Development and Spermiation after Testosterone-Induced Gonadotropin Suppression in Adult Monkeys (Macaca fascicularis) J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1814 - 1822. [Abstract] [Full Text]
|
|