Manipulation of Reproduction and Contraception Flashcards
Tom is a 10 year old neutered JRT that is anorexic with a BCS of 3
He has prostatic adenocarcinoma confirmed by ultrasound fna, with no visible radiographic lung metastasis
What reproductive hormone treatments might be useful for palliative management of this case?
- Dramatic changes to internal architecture of the prostate caused by mineralisation
- Can occur in entire and neutered animals
- On palpation the gland is large, firm, nodular, adherent to local tissue and painful. In many cases dorsal LN enlargement as well.
- Progesterone may have suitable negative feedback effect and downregulate increase size of the gland.
Discuss progestogens and common ones?
- Exert powerful negative feedback effect upon the hypothalamus/pituitary
- Central sedative effects (Alfaxalone)
- Closes cervix
- Stimulate endometrial proliferation
- Suppress myometrial activity
- Mammary enlargement
Common progestogens:
- Megestrol (Ovarid)
- Delmadinone (Tardak)
- Proligestone (Delvosteron)
- Osaterone (Ypozane)
Discuss adverse effects of progestogens?
Adverse Effects (fewer in newer generation compounds)
–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)
–Spontaneous Acromegaly due to increase GH
–Coat changes esp. local reactions following subcut injection
–Masculinised female pups and cryptorchid male pups if given in pregnancy
–Suppression of spermatogenesis (one of the reasons why we may use progesterone in the male animal)
Discuss control of oestrus with Progestogens?
Control of Oestrus
Prevention (used when dog is not cycling) = Administration in anoestrus to prevent occurrence of oestrus
Suppression (used when animal has already started and idea is to damp that cycle down) = Administration during proestrus or oestrus to abolish that oestrus
- Subcutaneous injection of long acting agent (e.g. Delvosteron)
- Oral administration of low doses orally active agent (e.g. Ovarid)
What is an alternative for progestogen control of oestrus?
Alternative is /will be GnRH superagonists
Discuss the use of Progestogens for the use in Treatment of Pseudopregnancy?
- Progestogens inhibit the release of prolactin from the pituitary gland
- Oral therapy (e.g. Ovarid)
- Depot therapy (e.g. Tardak)
What is the alternative for the use of progestogens for treatment of pseudopregnancy?
Common alternative is cabergoline (a specific prolactin inhibitor is safer in terms of pyo)
Discuss Progestogens In Males?
Reduction of FSH and LH secretion
–LH -> Leydig cells -> Androgens
(reduces steroidogenesis)
–FSH -> Spermatogenesis
(reduces spermatogenesis)
Treatment of:
–Antisocial behaviour
–Prostate disease
–Anal adenoma
Discuss use of androgens in males?
Treatment of poor libido
- Mis-use in the male
- May cure impotence
- But suppresses spermatogenesis
- Will temporarily increase libido but then long term will reduce it and negatively impact on spermatogenesis.
Discuss the use of oestrogens?
- Causes oedema of reproductive tract
- Pheromone production
- Changes in function of the uterine tube and uterus (support sperm transport and the environment for fertilisation)
- Tend to use them at low doses due to their Adverse Effects and their therapeutic index is very small:
–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
–Gynaecomastia and squamous metaplasia of the prostate
What are common oestrogens used?
Oestrogens
- Oestradiol benzoate (Mesalin)
- Estriol (Incurin)
Discuss oestrogens and unwanted mating?
Unwanted Mating
- Prevention of implantation and / or interference with transport of zygotes
- Licensed preparation in oestradiol benzoate (Mesalin)
(currently not on sale but still 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
Common alternative is aglepristone (Alizin) a progesterone receptor antagonist
Discuss Direct Effect on Reproductive Tract of oestrogens and it’s uses?
•Urinary incontinence
–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
NB Also Phenylpropanolamine (Propalin)
•Topical oestrogens for vaginitis
–Pre-pubertal
–Atrophic
Discuss Gonadotrophin Releasing Hormone treatments?
Short-term in action (e.g. buserelin [Receptal] injection or deslorelin [Ovuplant] implant)
–Causes stimulation of LH and FSH release
- Aiming to hasten ovulation
- Aiming to force ovulation of persistent or cystic follicles
- Aiming to test the H-P-G Axis by measurement of oestrogen or testosterone
Long-term in action (e.g. deslorelin [Suprelorin] implant)
–Causes initial stimulation and then receptor down-regulation
- For suppression of cyclical activity in female
- For temporary sterilisation in males
- For treatment of male hormone stimulated conditions (behaviour, prostate, anal adenoma)
Name GnRH Agonists?
- Buserelin (Receptal)
- Deslorelin (Ovuplant / Suprelorin)
Discuss the use of Gonadotrophins?
Equine Chorionic Gonadotrophin
eCG (PMSG-Intervet)NB not mare
•eCG is mainly FSH like in activity
–promotes growth and maturation of follicles
–stimulates spermatogenesis in the male
–Unlikely that it will have a useful biological effect as we are not able to administer the drug in the way it will act physiologically. So has not value in dogs and cats
Human Chorionic Gonadotrophin
hCG-Chorionic gonadotrophin(Chorulon)
•hCG is mainly LH like in activity
–final maturation of follicles / formation of CL
–stimulates androgen production in the male
–Mimics and LH surge well when given so has good value
Discuss the use of gonadotrophins in dogs?
eCG
•No clinical use in dogs
hCG
- Testing of Gonadal function (are there any ovaries / testes?)
- Hastening of ovulation
- Forcing of ovulation
Discuss endongenous and exogenous prostaglandins?
Discuss when to administer prostaglandins therapeutically?
•Bitch and Queen corpora lutea are ‘autonomous’ for first 15 days of luteal phase
–PG’s of little use before day 20
•Remaining luteal phase CL’s remain resistant
–Need frequent dosing every day or twice daily
- Many text books have incorrect dose – normally use 1 to 5 mcg/kg (requires dilution)
- Prolactin is luteotrophic so when progesterone goes down prolactin goes up to try and help support the CL but it has already been lysed
- Sharp rise in prolactin may cause a pseudopregnancy so use low doses to try and avoid this side effect
- Basis of treating pyo in dogs medically is low dose prostaglandins as progesterone drives the pyo
Discuss the use of Prolactin Inhibitors further?
- No effect in early luteal phase
- Later use causes reduction in prolactin and subsequent decline in progesterone
- Upper panel galastop given to early as there is no prolactin support of CL at this stage so has no effect on its regression
- Lower panel dog has been given galastop shows how key it is in maintianing CL and progesterone levels.
- 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?
- Can see two large size follicles in the ovary with two smaller ones nearby
- Not sure if they are cystic yet this is at the extremes of normal
- Could use: hCG which is LH like in activity and might cause them to ovulate could also give a short acting GnRH preparation which will cause a surge and cause to ovulate.
