Principles of Contraception Flashcards
Tom is a 3 year old male ferret that was castrated 18 months ago
Since then he has developed alopecia, a thin skin, and increased aggressive behaviour
This is likely due to adrenal disease as a result of the ‘castration’
How can this be treated?
- Condition – adrenal gland production, in this case is that we have sex steroids being produced by adrenal gland – over stimulation. Can happen as we don’t have the negative feedback from the gonads – sex steroids removed, so no testosterone, no negative feedback effect, consequences are – more GnRH produced, hypothalamus stimulates pituitary gland to produce more LH. In any animal that we neuter, when we remove gonads, get really high concentrations of GnRH and LH and FSH – these elevated gonadotropins now have an effect on adrenal glands – in this case, likely associated with androgens. Don’t necessarily get the same disease as adrenal gland doesn’t respond in the same way
- Should give a GnRH agonist – agonist preparation, that initially causes stimulation but then down regulation
- Consequences of surgical neutering
How can we surgically control reproduction in males?
- Castration (open / closed / modified / scrotal ablation)
- Vasectomy
- (Surgical preparation of teaser animals)
How can we surgically control reproduction in females?
- Ovariectomy (midline / flank)
- Ovariohysterectomy (midline / flank)
- Uterine tubal ligation – prevents pregnancy but doesn’t prevent behavioural changes
Why would we use melatonin in the female?
What does it do in ewes and mares?
•Endogenous production in response to decreasing daylight
–Up-regulation of short-day breeders
–Down-regulation of long-day breeders
•Ewe
–Melatonin implant administered at base of ear in May-June to hasten onset of cyclicity (+ introduction of the ram)
–Initiation of cyclic activity in sheep, extends breeding time
•Mare
–Would need melatonin antagonist (not available) to stimulate oestrus in the mare
–Daylight is effective if day-length is extended from December onwards
Why would we give GnRH agonists - what effect does it have?
- Depo formulation of a GnRH, initial stimulation and then down regulation – a good way to turn off the axis
- Endogenous release causes increase in LH and FSH, and therefore a pivotal event in the hypothalamic-gonadal cascade
What preparations are there for GnRH agonists and what does each do?
•Preparations are either:
–Short-term in action (e.g. buserelin [Receptal] injection) or deslorelin [Ovuplant] implant
•Causes stimulation of LH and FSH release …..
–Long-term in action (e.g. deslorelin [Suprelorin] implant)
•Causes initial stimulation and the receptor down-regulation
What is the licensed use for Long-term in action GnRH agonist?
•Long-term in action (e.g. deslorelin [Suprelorin] implant)
–Causes initial stimulation and then receptor down-regulation
–Licensed use: Control of behaviour and fertility in male dogs
What value does using gonadotrophins have on contraception?
- If you could put lots of gonadotropins in, might get same stimulation and then down regulation but there isn’t a preparation that is available that we could use in a biological way – so nothing in terms of this for contraception!
- No value
–No formulation of either hCG or eCG available that is long lasting enough to produce down-regulation
–You would need repeatedly administer injectable eg 3x daily
What do testosterone esters do?
•Testosterone esters
–Will induce temporary infertility in males
–Current investigations of the human male contraceptive injection are testosterone injections or patches
–Interestingly, a common anabolic agent used in bodybuilders
–Reduce GnRH and then reduced LH and FSH – change in semen quality etc.
Why might giving a stud dog testosterone not be great?
Reproductive sex steroids: all will have a negative feedback effect, in both genders. If we gave testosterone to females, same concept and negative feedback of HP axis –even though females don’t produce it in large qualities, can still suppress the axis in the same way. Could give a stud dog it to improve libido but it will have a negative feedback effect and reduce sperm quality!!!
What can administrations of androgrens e.g. testosterone to a male dog do to libido and sperm quality?
Depo prep of testosterone
Dramatic disease in number of normal and motile sperm from a single dose of androgen! Libido was still maintained and increase, but can see a dramatic impact on semen quality
What are progestogens used for in males?
Give some examples
- Drugs with progesterone like activity – some are licensed for females and males
- Marketed for treating prostatic disease, manage behaviour, anal adenomas – a variety of things, concept of negative feedback effect
- Osaterone (Ypozane)
–Licensed in male dogs for control of prostate disease
•Delmadinone (Tardak)
–Licensed in male dogs for hyper-sexuality, prostatic disease, anal adenoma
–Tardak – licensed as anti-androgen, it’s a progestogen – clever marketing – negative feedback effect, will result in degrease GnRH, decrease LH and FSH – decreases testosterone, which would usually stimulate a wide variety of clinical conditions
•Both will also at reduce semen quality
Name some exogenous progestogens that we often give to females?
Why would we use them?
- Whole variety of formulations, sometimes we use them on short term basis to suppress a cycle and then allow a controlled return. Long term basis – will down regulate and result in absence of cyclicity. If you wanted to control behaviour of mare (regumate) daily into feed, negative feedback on hypothalamus, GnRH decreases etc
- Exogenous progestogens
–Many formulations
•Oral progestogen tablets (e.g. Megestrol [Ovarid])
–Prevention of oestrus in dogs / suppression of oestrus in dogs
•Progesterone implants (e.g. Etonogestrel [Implanon])
–Contraception in women
•Depot progestogen injections (e.g. Proligestone [Delvosteron])
–Prevention oestrus in bitches
•Vaginal sponges (Flugestone [Chronogest])
–Oestrus induction / synchronisation in ewes upon withdrawal (often in combination with eCG)
•Vaginal devices (Progesterone [PRID/CIDR])
–Oestrus induction / synchronisation in mares
•Oral liquids (Altrenogest [Regumate])
–Oestrus suppression / induction / synchronisation in mares/sows
What is GnRH immunisation?
Which industry is it mainly used in and why?
•GnRF analogue-protein conjugate (Improvac injection)
–Licensed for administration to male piglets at 6 to 8 weeks to reduce ‘boar taint’
–Mechanism of action is to immunize against GnRH and therefore will produce at least temporary infertility.
–Used commonly by pig breeders, method of trying to prevent an increase of testosterone around time of puberty – said to change flavour and smell of meat, trying to immunize the male, so it doesn’t reach puberty
Name some possible post-operative complications after castration?
–Haemorrhage
–Oedema
–Infection
–Septic peritonitis
–Eventration
–Hydrocoele
If an owner asks you when their dog will become infertile after castration, what will your answer be?
•Infertility
–Onset of infertile ejaculate will depend upon the degree of sperm storage in the ampulla
- Dogs have no ampulla therefore azoospermic within a few days
- Stallions have significant ampulla therefore sperm may be detected for several weeks or until he ejaculates
- Typical owner question – when will he be infertile after castration? Key thing that impacts on this across all species is essentially of whether there is any possibly of sperm stored in repro tract (but not in epididymis) as can be stored in ampulla – if you remove gonads, but some stored here – potentially still fertile – but how long will it be? Depends! If you breed horse tomorrow, will remove sperm from ampulla, will be infertile day after – depends once the sperm are gone!! If he doesn’t ejaculate, sperm still in ampulla – depends, have you got an ampulla or not and when do you ejaculate? Dogs have virtually no ampulla, probably no sperm storage so likely to be infertile pretty quickly!
Why might we get a persistent pseudopregnancy if we spay a bitch at the wrong time of her cycle?
When should we neuter an adult bitch?
- Progesterone increase before ovulation, then prolonged period of progesterone secretion
- Main luteotrophic support – is prolactin, which pushes up progesterone – if you knock this out, progesterone concentration of progesterone ill decrease rapidly
- If we have dog and spay when in luteal phase (bottom graph) and remove ovaries that is 1 month after end of oestrous, progesterone concentrations fall – pit gland produces more prolactin to try to produce progesterone – so removing ovaries causes drop in progesterone, so increase in prolactin – behavioural changes and milk production – pseudopregnancy caused if we spay dog at the wrong time
- Neuter in adult dog at some point in time when dog is in ANOESTROUS – so NO progesterone
- So we don’t induce an iatrogenic pseudopregnancy
- Could spay early as prolactin isn’t produced until later on – might do this if dog had been mated but didn’t want dog to have puppies, so neuter in early window – might be pregnant, but wont induce pseudopregnancy as there hasn’t bene the turn on of prolactin
