Short term administration of cyproterone acetate for contraception: Effects on testosterone secretion and semen characteristics in rams (Ovis aries) and bucks (Capra hircus)

Viviana N Flores-Gil,Julián Santiago-Moreno,Rosario Velázquez,Antonio López-Sebastián,Adolfo Toledano-Díaz

doi:10.5424/sjar/2020184-16871

Abstract

Aim of study: To examine the influence of administering cyproterone acetate (CPA), at the beginning of the mating season, on the testosterone concentration and morphometric and functional characteristics of ram and buck semen.Area of study: Madrid, SpainMaterial and methods: Five rams and five bucks were intramuscularly administered 200 mg of CPA in 2 mL of olive oil twice per week - from July 1st to 31st in the rams, and from August 1st to 31st in the bucks. Five control animals of each species were administered 2 mL of olive oil. Blood samples and ejaculates analysed from the start of treatment until eight weeks after the last day of treatment.Main results: GLM-ANOVA showed the interaction species × CPA treatment to have effect (p<0.05) on sperm motility, progressive motility and acrosome integrity; and greater effect (p<0.01) on curvilinear velocity (VCL), straight-line velocity (VSL), viability, and morphological abnormalities. In both the rams and bucks, plasma testosterone levels fell from the first week from the start of CPA administration until three weeks after the end of treatment. In rams, the total sperm count, sperm motility, progressive motility, viability, morphological abnormalities, VCL and VSL were all negatively affected by the treatment (p<0.001); acrosome integrity was also affected (p<0.05). In bucks, sperm motility, progressive motility, VCL, VSL and morphological abnormalities were negatively affected (p<0.05).Research highlights: Treatment with CPA affected testosterone secretion, semen characteristics and sperm morphometry in both the rams and bucks, and thus it might be used as short term contraceptive protocol in small ruminants.

Highlights

Cyproterone acetate (CPA) [6-chloro-17α-hydroxy-1,2α-methylene-Δ 4,6-diene-3,20-dione-acetate] is the only pharmaco-hormonal compound with anti-androgenic, anti-gonadotropic and progestational properties (Neumann & Berswordt-Wallrabe, 1966; Steinbeck et al, 1971). In males it behaves as an anti-androgenic steroid, acting (i) as a competitive antagonist of androgen receptors, thereby inhibiting testosterone and 5-α-dihydrotestosterone synthesis (Semet et al, 2017), (ii) as an anti-gonadotropic agent that reduces the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), suppressing the secretion of androgens
general linear model (GLM) repeated measures ANOVA showed the interaction species × CPA treatment to have no significant effect on testosterone concentrations
CPA for 4 weeks reduces plasma testosterone levels from the first week after the first dose, to 3 weeks after the end treatment. It reduces scrotal circumference, semen volume and semen characteristics, and affects sperm morphometry. This reduction in plasma testosterone is explained by the anti-androgenic and anti-gonadotropic actions of CPA (Wiechert et al, 1966; Neumann & Töpert, 1986)

Summary

Introduction

Cyproterone acetate (CPA) [6-chloro-17α-hydroxy-1,2α-methylene-Δ 4,6-diene-3,20-dione-acetate] is the only pharmaco-hormonal compound with anti-androgenic, anti-gonadotropic and progestational properties (Neumann & Berswordt-Wallrabe, 1966; Steinbeck et al., 1971). In males it behaves as an anti-androgenic steroid, acting (i) as a competitive antagonist of androgen receptors, thereby inhibiting testosterone and 5-α-dihydrotestosterone synthesis (Semet et al, 2017), (ii) as an anti-gonadotropic agent that reduces the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), suppressing the secretion of androgens Despite that a hormonal regimen consisting of testosterone plus CPA holds promise as an effective, safe and reversible male contraceptive (Meriggiola et al, 1998), questions remain regarding the time required to reach their full contraceptive effect, and the time that elapses between cessation of hormonal contraceptive treatments and full spermatogenesis recovery in men (Khourdaji et al, 2018)

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