principles of contraception Flashcards
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?
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
what is the licenced use for GnRH agonists Long-term in action (e.g. deslorelin [Suprelorin] implant)?
how long will it last for?
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)
what is the action of progestogen drugs?
what are the adverse effects?
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
when does progestogens need to be administered for the prevention fo oestrus?
prevention of oestrus:
Administration in anoestrus to prevent occurrence of oestrus
why does progestones work for treatment of pseudopregnancy?
Progestogens inhibit the release of prolactin from the pituitary gland
Depot therapy e.g.
proligestone [Delvosteron]
common alternative is cabergoline (galastop)
what is the acton of progestogens in males?
what are they used to treat?
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)
what are the actions and advers effects of oestrogens?
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
why can oestrogen be used in unwanted matings?
what are the side effects?
- 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
- May be re-mated
wht are the treatmet options for urinary incontinence?
and vaginitis?
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
what is the action of androgens?
Mimic the action of testosterone
Anabolics may be used to aid convalescence in some cases
Will induce temporary infertility in males
what is the clinical uses of hCG (Human Chorionic Gonadotrophin = LH-like in action)?
- 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
what are the actions of prostaglandins?
and the adverse effects?
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
how is prostaglanding used for the treatment of an open-cervix pyometa and termination of pregnancy and for post partum metritis?
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
what are the actions and adverse effects of oxytocin?
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
what are the clinical uses of oxytocin?
- 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
- Remember low dose regimes are required so not to cause tetanic contraction
- 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
when does prolactin increase in the bitch?
what is the main and other action of prolactin?
- Increases from approximately day 25 after ovulation
- The principal luteotrophic agent in the bitch and queen
- Other action is to stimulate milk production
what drugs can be used to stimulate milk production?
- 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
why can prolactin inhibitors be used for the termination of pregnancy?
what are the adverse effects?
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)
what are the clincial uses of prolactin inhibitors?
what are the off licence uses?
- 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)
how do progesterone receptor antagonists work eg Aglepristone (Alizin)?
what are thr adverse effects?
- 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
what are the potential uses of progesterone receptor antagonists?
- 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?
what is the role of melatonin in reproduction?
hoe can melatonin be used in ewes and queens?
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 ?
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?
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)
by perfroming an ovariectomy and leaving the uterus will not result in uterine disease unless what factors?
- 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
- Reasons for administration of reproductive steroids
At what time should you neuter a cycling bitch and why?
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
when does behavoiur and infertility changes occurr after surgery? what influences this?
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
how do incomplete ovariectomy cases present?
- 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
how can you investigate incomplete ovariectomy cases?
- 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
what tests would you do to investigate incomplete ovariectomy in a spayed bitch that is currently showing signs of oestrus ?
- 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
what tests would you do to investigate incomplete ovariectomy in a spayed bitch that showed signs of oestrus 1 month ago ?
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
what tests would you do to investigate incomplete ovariectomy in a spayed bitch that showed signs of oestrus 3 months ago ?
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)
how do you diagnose incomplete ovariectomy in a queen?
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
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?
GnRH Depot Agonist
