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AAPS PharmSci. Mar 2004; 6(1): 94–99.
Published online Mar 11, 2004. doi:  10.1208/ps060110
PMCID: PMC2750945
Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist
Susan S. D'Souza,1 Francesca Selmin,2 Santos B Murty,3 Wei Qiu,1 BC Thanoo,4 and Patrick P DeLucacorresponding author5
1College of Pharmacy, University of Kentucky, 40536 Lexington, KY
2Istituto di Chimica Farmaceutica e Tossicologica, Universita' degli Studi di Milano, Milano, Italy
3Murty Pharmaceuticals, Lexington, KY
4Oakwood Labs, Oakwood, OH
5Faculty of Pharmaceutial Sciences, University of Kentucky College of Pharmacy, 40536 Lexington, KY
Patrick P DeLuca, Phone: (859) 257-1831, Fax: (859) 323-0242, ppdelul/at/uky.edu.
corresponding authorCorresponding author.
Received January 13, 2004; Accepted February 12, 2004.
The purpose of this study was to assess whether male rats whose testosterone levels were suppressed to castration levels (<0.5 ng/mL) for a 1-year period by the sustained delivery of orntide acetate, a GnRH antagonist, would return to fertility (ie, produce offspring) after serum testosterone returned to control levels. Male rats comprising a treatment group (orntide microspheres, dose=27 mg/kg/y), a vehicle control group, and a control group of proven male breeders were used. For the treatment and vehicle control groups, serum orntide and testosterone levels were monitored at periodic intervals for 14 months from the initiation of treatment. After serum testosterone levels returned to vehicle control levels and orntide serum levels were no longer discernible for the treated group, each of the animals was housed with 2 drug-naive, female, proven breeders. All the breeder females produced offspring with the exception of 1 female housed with a male rat from the treatment group and the 2 females housed with a single male rat from the vehicle control group. The mean size and weight of the litters from each group were not statistically different. Further, fertility of the offspring from each group was assessed. The male and female offspring studied were all shown to be fertile. The results suggest that lack of fertility due to testosterone suppression in male rats is reversible after cessation of treatment with the GnRH analog, orntide.
Keywords: orntide acetate, PLA microspheres, return to fertility, chemical castration, GnRH antagonist
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