Langzeit-Suppression von Gonadotropinen und Spermatogenese bei nicht-humanen Primaten durch Testosteronundekanoat und Norethisteronenanthat: Hormonelle und molekulare Wirkung, Effektivität, Reversibilität und Nebenwirkungen
Final Report Abstract
From our findings evaluated so far, we conclude: • TU and NETE co-administration fully suppresses spermatogenesis in the Cynomoigus macaque and all animals in the study independent from their age or sperm counts at the time point when they altered the study responded to the treatment. • NETE CO- or pre-administration blocks testosterone induced prostate growth • All animals that finished the study after 2.5 years of treatment recovered full spermatogenesis and developed normal LH values at study end. However, the period of recovery was remarkably extended and lasts almost 18 months before the sperm concentrations and the testosterone serum values were back to the normal range. • We observed remarkable side effects in the Cynomoigus macaques: Approximately 30% of the animals developed a diabetic phenotype under the treatment. All animals started to lactate and developed signs of gynecomastia. These symptoms might have been caused by the relatively high dosage and the long duration of the administration. However, using this androgen/gestagen combination for hormonal contraception in men should be accompanied by a sufficient monitoring of the users regarding significant alterations of estrogen/prolactin levels and blood sugar values, • The common marmoset is a worthy primate model because of the possibility to address fertility as an endpoint of contraceptive trials directly. However, the administration of TU and NETE as well as of NETE atone revealed that the f ertility of mate marmosets was only slightly affected. Animals fathered offspring in all groups evaluated. • In contrast to macaques resembling the endocrine status of the human very closely, the regulation of the reproductive endocrine axis differs remarkably and does not allow complete suppression of fertility but exhibited only milder effects. • Therefore the marmoset might be a model enabling the analysis of subfertility. For these reasons, the use of these monkeys for studies aiming at the proof of efficiency of hormonal mate contraception in humans must be considered as only limited.
Publications
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TU/NETE hormonal contraception drastically reduces testis size without inducing infertilty in male marmosets 15th European Testis Workshop on Molecular and Cellular Endocrinology of Testis in Naantali, Finland May 2-6, 2008
Luetjens CM, Nieschlag E, Wistuba J, Simoni M
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Does NETE induce, the prostate to shrink? 12th International Summit on Male Hormonal Contraception, Barcelona March 10 2009
Luetjens CM, Nieschlag E, Semjonow A, Simoni M, Wistuba J
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Hormonal male contraception by TU/NETE in cynomolgus macaques: Long term efficacy, reversibility, testicular effects, and side effects in non-human primate models. 12th International Summit on Male hormonal Contraception, Barcelona March 10 2009
Nieschlag E, Luetjens CM, Schlatt S, Simoni M, Wistuba J
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Ko-Administration von Norethisteronenanthat (NETE) vermindert Testosteronundekanoat (TU)-induziertes Prostatawachstum bei kastrierten Javaaffen. 61. Kongress der Deutschen Gesellschaft für Urologie e.V. Dresden 16.-19.09.2009
Wistuba J, Nieschlag E, Semjonow A, Sandhowe R, Zitzmann M, Simoni M, Luetjens CM
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Ko-Administration von Norethisteronenanthat (NETE) vermindert Testosteronundekanoat (TU)-induziertes Prostatawachstum bei kastrierten Javaaffen. Der Urologe 2009 48 Suppl. 1: 50-51
Wistuba J, Nieschlag E, Semjonow A, Sandhowe R, Zitzmann M, Simoni M, Luetjens CM
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Prostate growth under Testosterone undecanoate injections is reduced by co-administration of norethisterone enanthate in castrated cynomoigus monkeys. 9th International Congress of Andrology. Barcelona March 7-10, 2009; Journal of Andrology March/April 2009, 30, 120: P253
Luetjens CM, Nieschlag E, Zitzmann M, Simoni M, Sandhowe-Klaverkamp R, Semjonow A, Wistuba J
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Prostate growth under testosterone undecanoate injections is reduced by co-administration of norethisterone enanthate in castrated cynomolgus monkeys. 9th International Congress of Andrology. Barcelona March 7-10, 2009
Luetjens CM, Nieschlag E, Semjonow A, Sandhowe-Klaverkamp R, Zitzmann M, Simoni M, Wistuba J
