principles of contraception

Question 1

What is the action of GnRH agonists?
what is the short term and long term actions of GnRH agonists?
when should the implants be put in?

Answer 1

Actions - Endogenous release causes increase in LH and FSH, and therefore a pivotal event in the hypothalamic-gonadal cascade

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
  LH and FSH not released
  Female - so folicle growth or oestrus
  male - no spermatogenesis, testosterone goes down

Ideally put in during luteal phase

Question 2

what is the licenced use for GnRH agonists Long-term in action (e.g. deslorelin [Suprelorin] implant)?

how long will it last for?

Answer 2

Causes initial stimulation and then receptor down-regulation
Licensed use:
* Control of behaviour and fertility in male dogs
* Temporary suppression of oestrus in bitches
* Delaying puberty in bitches

This can be use to inhibit reproduction in males and females of all species (dose-dependant)
Implant has 2 sizes ie you chose 1 of 2 fixed doses. The mg/kg dose to animal thus varies according to animal bodyweight, as such duration variable (eg give large implant to small dog = high mg/kg = long duration)

Question 3

what is the action of progestogen drugs?

what are the adverse effects?

Answer 3

Actions
* Exert powerful negative feedback effect upon the hypothalamus/pituitary
* Central sedative effects (Alfaxalone)
* Closes cervix
* Stimulate endometrial proliferation
* Suppress myometrial activity
* Mammary enlargement

adverse effects?
* Increased appetite / weight gain
* Mammary enlargement
* benign nodules/neoplasia (except proligestone)
* Risk of cystic endometrial hyperplasia
* related to amount / duration of treatment
* Diabetogenic (insulin antagonism)
* suppression of spermatosenesis

Question 4

when does progestogens need to be administered for the prevention fo oestrus?

Answer 4

prevention of oestrus:
Administration in anoestrus to prevent occurrence of oestrus

Question 5

why does progestones work for treatment of pseudopregnancy?

Answer 5

Progestogens inhibit the release of prolactin from the pituitary gland
Depot therapy e.g.
proligestone [Delvosteron]

common alternative is cabergoline (galastop)

Question 6

what is the acton of progestogens in males?
what are they used to treat?

Answer 6

Reduction of FSH and LH secretion
LH -> Leydig cells -> Androgens
(reduces steroidogenesis)
Treatment of:
Antisocial behaviour
Prostate disease
Anal adenoma

FSH -> Spermatogenesis
(so the consequence is a reduction of spermatogenesis)
(for short term suppression this may be minor but for long term treatment this impacts fertility)

Question 7

what are the actions and advers effects of oestrogens?

Answer 7

Actions
* Causes oedema of reproductive tract
* Pheromone production
* Changes in function of the uterine tube and uterus (support sperm transport and the environment for fertilisation)

Adverse Effects
* Potentiate the effects of progesterone on the uterus -> pyometra
* Dose-related bone marrow suppression
* -> anaemia, thrombocytopaenia->death?
* Stimulate signs of oestrus
* Non pruritic bilaterally symmetrical alopecia and hyperpigmentation
* If administered during pregnancy may produce abortion

Question 8

why can oestrogen be used in unwanted matings?
what are the side effects?

Answer 8

• Prevention of implantation and / or interference with transport of zygotes
• Licensed preparation in oestradiol benzoate (Mesalin) (currently not on sale but old product still used in some practices)
  
  • Use on day 3 and 5 (+ day 7) post mating
• Animals may continue to show signs of oestrus
  
  • May be re-mated
    
    • Unlikely to become pregnant

Question 10

wht are the treatmet options for urinary incontinence?
and vaginitis?

Answer 10

oestrogens

Increase urethral mucosal thickness
Estriol (Incurin)
many regimes suggested
* daily for up to 7 days then repeated as necessary
* daily for up to three weeks

Alternative is Phenylpropanolamine (Propalin)

Topical oestrogens may also be used for vaginitis
Pre-pubertal
Atrophic

Question 11

what is the action of androgens?

Answer 11

Mimic the action of testosterone

Anabolics may be used to aid convalescence in some cases

Will induce temporary infertility in males

Question 12

what is the clinical uses of hCG (Human Chorionic Gonadotrophin = LH-like in action)?

Answer 12

• Testing of Gonadal function
  
  • (e.g. are there any ovaries / testes? – stimulate the release of oestrogen in female or testosterone in male which we then measure)
• Hastening of ovulation
  
  • (female has to be in oestrus with large follicles that are capable of responding ie they have to have LH receptors)
• Forcing of ovulation
  
  • (eg in cases of follicular cysts, but again follicles will only resond if they have LH receptors

Question 13

what are the actions of prostaglandins?
and the adverse effects?

Answer 13

Actions
* Lysis of the corpora lutea
* Early CLs are usually not responsive
* Ecbolic (contractions of the uterus)
can’t be used to bring dog into oestrus as they have anoestrus phase next

Adverse Effects
* Restlessness
* Hypersalivation
* Vomiting
* Abdominal pain
* Diarrhoea
* Pyrexia

Question 14

how is prostaglanding used for the treatment of an open-cervix pyometa and termination of pregnancy and for post partum metritis?

Answer 14

Open-cervix pyometra
* Low doses twice daily for 5 – 10 days
* Fluid therapy
* Suitable antimicrobials

Termination of pregnancy
* Low doses twice daily for 5 – 10 days
* Commence after day 20
* Termination by resorption or abortion

Post-partum metritis
* Low doses twice daily for 3-5 days
* Fluid therapy
* Suitable antimicrobials

Question 15

what are the actions and adverse effects of oxytocin?

Answer 15

Contraction of uterine smooth muscle when receptors are present
Pharmacological contraction of uterine smooth muscle when few receptors are present
Milk “let-down”

Adverse Effects
Don’t administer if the cervix is closed or in cases of obstructive dystocia

Question 16

what are the clinical uses of oxytocin?

Answer 16

• Stimulation of uterine contraction to facilitate parturition in the presence of a fully dilated cervix
  
  • Remember low dose regimes are required so not to cause tetanic contraction
    
    • 0.04 IU/kg given every 30 mins for 3 doses
• Promote involution of the post-parturient uterus and thus aid the passage of retained placenta
• Aid in the control of post-partum haemorrhage
• Promotion of milk “let-down” in cases of agalactia

Question 17

when does prolactin increase in the bitch?
what is the main and other action of prolactin?

Answer 17

• Increases from approximately day 25 after ovulation
• The principal luteotrophic agent in the bitch and queen
• Other action is to stimulate milk production

Question 18

what drugs can be used to stimulate milk production?

Answer 18

• Prolactin agonists are dopamine antagonists
  
  • Metoclopramide at 0.1-0.2 mg/kg, SC, tid-qid
  • Phenothiazines at low dose may also stimulate mild production

Question 19

why can prolactin inhibitors be used for the termination of pregnancy?
what are the adverse effects?

Answer 19

Removal of prolactin causes demise of the CL’s
Progesterone rapidly declines
Termination of the luteal phase is an action similar to using prostaglandins but:
Fewer (different) adverse effects
No effect on the uterus
Available product is Cabergoline (Galastop)

Adverse Effects
Nausea and vomiting
Lethargy
(abortion)
(return to oestrus)

Question 20

what are the clincial uses of prolactin inhibitors?

what are the off licence uses?

Answer 20

• termination of pregnancy
• treatment of pseudopregnancy
• suppression of lactation (eg post weaning)
• treatment of pyometra (Aim is to remove progesterone and stimulate uterine contractions)
• induction of oestrus (Treatment given daily until one day after onset of proestrus)

Off license uses:
* To end the luteal phase to terminate pregnancy (often done in combination with prostaglandin)
* To end the luteal phase to treat pyometra (often done in combination with prostaglandin)
* To induce oestrus (mechanism uncertain)

Question 21

how do progesterone receptor antagonists work eg Aglepristone (Alizin)?

what are thr adverse effects?

Answer 21

• Synthetic steroid which binds to progesterone receptor
• Affinity for receptor 3 times higher than progesterone
• Outcome is receptor binding but without any message
• Progesterone cannot bind to its receptor - essentially progesterone becomes ‘invisible’ and not effective

adverse effects:
* local tolerance
* clinicla signs typical of normal parturition

Question 22

what are the potential uses of progesterone receptor antagonists?

Answer 22

• Prevention of implantation
• Termination of pregnancy at any stage (in later term use foetus will die but foetus not expelled, therefore need to use prostaglanding as well)
  * Treatment of unwanted mating up to 20 days after mating - no need for additional product
• Treatment of pyometra?

Question 23

what is the role of melatonin in reproduction?
hoe can melatonin be used in ewes and queens?

Answer 23

Endogenous production in response to decreasing daylight
- Up-regulation of short-day breeders (ewe)
- Down-regulation of long-day breeders (cat)

Ewe
Melatonin implant administered at base of ear in May-June to hasten onset of cyclicity (+ introduction of the ram)

Queen
Off-label administration of Melatonin will supress oestrus temporarily
Why is this ?

Question 24

Maya is a 2 year old bitch that has been ‘stuck’ in her first oestrus for 6 weeks
Ultrasound examination shows multiple non-ovulating follicles (cysts?) within in each ovary

Which hormonal products might be useful in this case?

Answer 24

hCG or short-acting GnRH to try to stimulate ovulation
Or failing that Progestogen to try to suppress the cysts (like using a PRID in a cow)

Question 25

by perfroming an ovariectomy and leaving the uterus will not result in uterine disease unless what factors?

Answer 25

• the uterus was already abnormal
• you leave an ovarian remnant
• there is a neoplasm producing reproductive steroids (e.g. adrenal possible but rare)
• exogenous reproductive steroids are administered
  
  • Reasons for administration of reproductive steroids
    
    • Progestogens for skin disease
    • Oestrogens for urinary incontinence

Question 26

At what time should you neuter a cycling bitch and why?

Answer 26

Preferably greater than 12 weeks after oestrus so you don’t induce an iatrogenic pseudopregnancy

Or within Weeks 3 and 4 post oestrus before prolactin is turned on so you don’t induce pseudopregnancy

Question 27

when does behavoiur and infertility changes occurr after surgery? what influences this?

Answer 27

Behaviour
* Hormone concentrations decline quickly after castration however some behaviour is learned and in some cases libido may be retained for years if castrated after puberty
* No change in hormone concentration after vasectomy

Infertility
* Onset of infertile ejaculate will depend upon the degree of sperm storage in the ampulla
* Dogs have very small ampulla therefore azoospermic within a few days
* Stallions have significant ampulla therefore sperm may be detected for several weeks or until he ejaculates

Question 28

how do incomplete ovariectomy cases present?

Answer 28

• Oestrous behaviour occurs at the normal interval with subsequent normal cyclicity
• Oestrous behaviour is absent for several months to years and is then normal, weak or persistent and may or may not be followed by normal cyclicity
• Oestrous behaviour is absent for many years until persistent weak behaviour associated with a granulosa cell tumour is detected

Question 29

how can you investigate incomplete ovariectomy cases?

Answer 29

• Observation of behaviour – what else cause true signs of oestrus?
• Vaginal cytology and vaginoscopy – can detect proestrus and oestrus
• Ultrasound of ovaries – may detect if animal not obese
• Measurement of progesterone – elevated for 65d after ovulation so only useful then
• Measurement of oestrogen – difficult
• Stimulating the ovary to produce oestrogen (give either GnRH or hCG) – works best when the dog is in anoestrus
• Measurement of anti-Mullerian Hormone – has some false positive and false negative results
• Measurement of LH – removal of gonads means LH will be very high but difficult to measure

Question 30

what tests would you do to investigate incomplete ovariectomy in a spayed bitch that is currently showing signs of oestrus ?

Answer 30

• look for clincial signs of oestrus and behaviour, there is no other condiditon that can cause the signs of oestrus so if signs there than must be IO
• ultrasound exam - detect an ovary - look for follicles/CL

Question 31

what tests would you do to investigate incomplete ovariectomy in a spayed bitch that showed signs of oestrus 1 month ago ?

Answer 31

if IO would be in the luteal phase:
- clincial exam - mammary enlargement (could be a pseudopregnancy if dog spayed recently and in luteal phase), lactation
- ultrasound - detection of the ovary with anechoic fluid in CL
- measurement of plasma progesterone (elevated for 65 days)
- stimulation of oestrogen production with GnRH or hCG

Question 32

what tests would you do to investigate incomplete ovariectomy in a spayed bitch that showed signs of oestrus 3 months ago ?

Answer 32

if IO would be in anoestrus period, therefore are looking for conformation of the precence of an ovary:
- stimulation of oestrogen production by administation of GnRH or hCG
- measurement of resting LH - bitches with IO that are in anoestrus have low plasma LH conc, bitches with no ovaries have elevated LH (no negative feedback)

Question 33

how do you diagnose incomplete ovariectomy in a queen?

Answer 33

Generally cycle every 2-3 weeks
Simplest approach is to examine when they are in alleged oestrus
- clinicla signs and behaviour
- vaginal cytology
- ultrasoudn of whole ovary

Question 34

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?

Answer 34

GnRH Depot Agonist