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To castrate or not to castrate?

Why should the medical castration of dogs be considered as an alternative to permanent surgery?

18 November 2019, at 9:00am

Along with positive socialisation, training and appropriate nutrition, castration is often considered a key component of responsible dog ownership. However, in recent years, attitude towards castration has changed slightly, both from a veterinary and an owner’s perspective.

From a medical point of view, castration has some benefits but also some downsides, so the decision should be made on a case-by-case basis. Castration can be beneficial in preventing specific testosterone-related diseases and can help in the management of some behavioural issues. However, there are some negatives: castrated animals have an increased tendency to obesity and some conditions are more prevalent in gonadectomised dogs, such as incontinence, osteoarthritis and some neoplasia. These conditions are clearly multifactorial, but research suggests disruption to the hypothalamic–pituitary–gonad axis and excessive gonadotrophin release as a possible component.

For the pet owner, preventing unwanted mating is obviously a major part of the decision-making process. Behaviour is more of a mixed picture: castration might be very beneficial in some cases, but disappointing in some others. The owner might realise that the unwanted behaviour is either not testosterone related (so unaffected by castration), or even made worse following neutering. Moreover, the anaesthetic risk is never nil. As a result, a recent survey showed that 25 percent of pet owners were concerned or very concerned that neutering could be harmful for their dog (Mo Gannon and Associates, 2017).

All the observations above highlight the need for a discussion between vets and pet owners, in order to weigh up pros and cons but also manage expectations. Offering the option of a medical castration with a reversible effect can be extremely helpful in this dialogue. This achieves the same effect as surgery (sterility, same effect on behaviours, etc) but without the permanence, allowing both vets and owners to decide in due course what the best option is for the pet.

Normal reproductive physiology of the male dog

The two principal functions of the male reproductive system are to produce sperm and the steroid hormone, testosterone. The gonadotrophins luteinising hormone (LH) and follicle-stimulating hormone (FSH) are secreted by the anterior pituitary gland in response to gonadotrophin-releasing hormone (GnRH) production from the hypothalamus, which is released in an episodic manner (Figure 1). In the testes, LH binds to receptors on Leydig cells and stimulates the synthesis and secretion of testosterone.

FIGURE (1) Gonadotrophin-releasing hormone (GnRH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) are responsible for the normal regulation of testosterone
FIGURE (1) Gonadotrophin-releasing hormone (GnRH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) are responsible for the normal regulation of testosterone

In addition to its systemic effects, testosterone also acts locally in conjunction with FSH to support spermatogenesis through stimulation of the Sertoli cells in the testis. There is an integrated negative feedback system for the control of hormone secretion: testosterone and its metabolites oestradiol and dihydrotestosterone provide negative feedback at the level of the hypothalamus and the pituitary gland. This contributes to the regulation of GnRH release and therefore regulation of the gonadotrophins, LH and FSH. In addition, other hormones such as activin (stimulating effect) and inhibin (inhibiting effect) can exert selective effects on FSH without affecting LH levels; therefore, the concentrations of LH and FSH do not always rise in parallel despite the linkage of control through the common feedback loop.

The average testosterone level in entire, adult male dogs ranges between 2 and 4ng/ml but it is important to appreciate that this is highly variable and can fluctuate considerably even within a 24-hour period (DePalatis et al., 1978). Despite this variation, fertile dogs with normal libido rarely show testosterone concentrations of less than 0.4ng/ml. Once levels of testosterone fall below 0.4ng/ml, this results in infertility due to reduced spermatogenesis, reduced ejaculate volume, reduced sperm motility, increased sperm abnormalities and reduced libido.

Medical castration

Deslorelin is a GnRH superagonist created by modifying the amino acid sequence of endogenous GnRH at positions six and nine. This results in a compound with the same action as GnRH but with seven-fold increased GnRH receptor binding affinity, increased stability and increased potency (Padula, 2005). Although more stable than endogenous GnRH, GnRH analogues are still rapidly absorbed and eliminated following parenteral administration, but by administering deslorelin within a lipid matrix implant, this allows continued release of the superagonist over time.

The effect of GnRH on target cells is mediated via binding to specific GnRH receptors (GnRH-R) located in the anterior lobe of the pituitary gland. Under the normal pulsatile release of GnRH, the GnRH-R activates secondary messengers which are responsible for the production of the LHβ and FSHβ subunits, and for the α-subunit which is common to both FSH and LH. However, under sustained stimulation which occurs with a deslorelin implant, a complex series of network transduction pathways involved in gene expression are activated. This results in an inhibition of the mRNA coding for the β-subunits and therefore a decrease in the circulating level of gonadotrophins.

Understanding the mechanism of gonadotrophin and testosterone production, and the effect of continued stimulation of GnRH-R as opposed to episodic stimulation through pulsatile release of endogenous GnRH, allows an understanding of what to expect once an implant has been placed.

Initially, there is an increase in plasma testosterone as the deslorelin released from the implant binds to GnRH-R and stimulates production of LH, FSH and consequently testosterone. This flare-up effect is transient and testosterone levels then decrease rapidly to below 0.4ng/ml under the continued secretion of deslorelin and consequent down-regulation of GnRH-R; this usually occurs within 9 to 20 days. Once testosterone levels reach 0.4ng/ml, three to four additional weeks are necessary to observe a total absence of sperm production. Infertility is therefore achieved six to eight weeks after an implant has been placed, so treated dogs should be kept away from bitches in heat until these time periods have been observed. After implantation with deslorelin, clinical studies demonstrated maintenance of testosterone below 0.4ng/ml for at least six months post-implant rising to at least 12 months where larger implants are used.

In terms of clinical effects, as expected, the lowered testosterone levels result in reduced semen volume, sperm production and motility with increased sperm abnormalities. A reduction in libido is also seen, though it is important to note that a lack of testosterone does not always lead to complete absence of mating behaviour. A retrospective study of neutered dogs, both male and female, found that 27.3 percent continued to display sexual behaviour following surgery (Spain et al., 2004) and the same would be expected of implanted dogs. There is a reversible reduction in testicular volume in the vast majority of dogs following the implant due to atrophy which can provide a useful external marker of the implant’s action.

Clinical trials have demonstrated reversibility after deslorelin implantation with return to normal plasma testosterone levels (0.4ng/ml or higher) over time as the implant dissolves. Once normal testosterone levels have been established, fertility does not instantly return to normal as spermatogenesis generally takes seven to nine weeks in the dog. After recovery, the seminiferous tubules, epididymal ducts and prostate tissue all show functional activity.

Conclusions

As is often the case in veterinary medicine, nothing about castration is black or white. Though surgical neutering can confer many benefits, it is important to remember that every animal is different, and the decision has to be made carefully. Medical castration is a powerful tool when it comes to the discussion about castration and can help in making the right decision for the animal.

References
Author Year Title
DePalatis, L., Moore, J. and Falvo, R. 1978 Plasma concentrations of testosterone and LH in the male dog. Reproduction, 52, 201-207.
Mo Gannon and Associates 2017 MG&A Pet owner market research - Do you think neutering is harmful for dogs? [online]
Padula, A. 2005 GnRH analogues—agonists and antagonists. Animal Reproduction Science, 88, 115-126.
Spain, C., Scarlett, J. and Houpt, K. 2004 Long-term risks and benefits of early-age gonadectomy in dogs. Journal of the American Veterinary Medical Association, 224, 380-387

Jayne Clark, BVSc, BSc(Hons), GPCert SAM, MRCVS, worked in small animal clinical practice for 10 years before moving into industry as a technical advisor. She has an interest in all aspects of canine and feline medicine, particularly anaesthesia, analgesia and endocrinology.

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