Disrupting effect of androgens in postnatal female domestic cats

Abstract

To test the hypothesis that in domestic cats, postnatal androgens induce sterility, the aims of this study were to describe the reproductive effects and the clinical safety of a postnatal administration of a long term release androgen in this species. Thirteen newborn littermate female kittens were randomly assigned to one of the following treatment groups within the first 24 hours of birth: testosterone enanthate 12.5 mg sc (TE; n = 8) or Placebo (PL; n = 5). The animals were subsequently assessed for fecal sexual hormones until puberty was attained and subsequently when matings occurred. After 21 days, ovulation and gestation were diagnosed. All queens were subsequently ovario-hysterectomized. Fecal testosterone concentrations differed between the treatment groups throughout the study period (P < 0.05) being greater during the first 2 postnatal weeks in those of the TE group (P < 0.01). Fecal estradiol was not affected by treatment (P > 0.1). While all the females were receptive during the pubertal estrus (P> 0.1), two TE (2/8) compared with all (5/5) females of the PL group had ovulations (P < 0.05). Only one (1/2) compared with three (3/5) of the queens of the TE and PL groups, respectively became pregnant. All kittens of the TE group had transient clitoral enlargement. Anovulatory TE-treated cats had no corpus luteum, and a significant diminution of the endometrial glands as well as of the height of the uterine epithelium. It is concluded that, in domestic cats, a single postnatal supraphysiological dose of testosterone caused a large proportion of queens to be anovulatory and there were also histological endometrial abnormalities that also occurred with this treatment that were accompanied by mild and transient side effects.

Clinical, Ovulatory and Histological Effect of a Postnatal Testosterone Treatment in Female Dogs

“…In order to compare studies, the dose per body weight was calculated for the different species. Recently, a lower dose (0.125 mg/g) of testosterone enanthate caused 75% anovulation in domestic cats [16]. Lower postnatal doses (0.005 mg/g) of the same compound produced 55.6% of anovulation in female mice [26].…”

“…The same protocol provoked anestrus, masculine behavior and abnormal uterine morphology and function in rats [14,15]. Coincidentally, cats subjected to a similar postnatal treatment presented a high percentage of anovulation and endometrial abnormalities [16].…”

“…The puppies were randomly assigned to one of the following treatment groups within the first 24 h of birth: testosterone enanthate 18 mg/100 g (total dose 35-56.5 mg) subcutaneously (Testoviron Depot 250, Bayer, Buenos Aires, Argentina; TE; n = 5) or a placebo of 1 mL corn oil subcutaneously (PL; n = 5). The pharmaceutical protocol was elected according to a previous study in cats [16] and pilot trials in dogs.…”

Development and proliferation of feline endometrial glands from fetal life to ovarian cyclicity

“…Further work is required to unveil the reasons why the first attempt to cause feline uterine gland agenesia failed after both postnatal progestin [5] and testosterone administration, obtaining only a decrease in the area occupied by uterine glands and the height of the uterine epithelium using the latter treatment [17]. It may be the case that, in this species, prenatal steroid administration is necessary to fully inhibit the estrogen mitogenic effects [18] and, therefore, lead to an aglandular uterine phenotype that meets the sterilizing overpopulation demands.…”

Long‐term reproductive evaluation of a bitch neonatally treated with a gonadotropin‐releasing hormone agonist

“…It was hypothesized that in domestic dogs, the same as in other mammals, 3–6 disruption of reproductive development during critical organizational periods might severely alter the functional capacity of the adult. Thus, the early neonatal period is a well recognized time window of reproductive vulnerability 7, 8 .…”