Control of Estrous Cycle Flashcards
the time from end of estrus onset of next Proestrus
InterEstrous interval (IEI)
the time from onset of Proestrus to next onset of Proestrus
includes proestrus, estrus, diestrus, anestrus in canine
Estrous Interval (IEI)
How is the estrous interval different from the interEstrous interval
Estrous interval is onset of Proestrus to next onset of proestrous
InterEstrous interval is time from end of estrus onset to next Proestrus
Why might you manipulate the canine estrous cycle
1) Estrus induction
-Treatment of secondary anestrus
-Timed breeding
2) Estrus suppression
-Part of pyometra management (endometrial repair - uterine regeneration)
-Contraception
3) Mismating
-Ending diestrus (gestation) prematurely
Why might you want to induce estrus
1) Treatment of secondary anestrus
2) Timed breeding
Why might you want to suppress estrus
1) Part of pyometra management (endometrial repair - uterine regeneration)
2) Contraception
Why might you want to manipulate the estrous cycle in times of mismating
Ending diestrus (gestation) prematurely
T/F: estrous cycle manipulation is relatively easy in dogs
False - not as easy as other species
Where do dopamine agonists act
at the hypothalmus to induce estrus
Methods of induce estrus
1) Dopamine Agonist
2) Gonadotropin Releasing homrone (GnRH) and Gonadotropin Releasing Hormone Agonists
3) Gonadotropins (FSH, LH)
What is the most commonly used dopamine agonist for estrus induction
Cabergoline
What is the action of dopamine agonist like Cabergoline **
-Inhibit prolaction secretion by directly stimulating dopamine receptors which induces the onset of estrus
Pregnancy rates reported 60-100% following induction
most patients exhibit signs of estrus in 21 days or so
opposite effect in other species (suppress the onset of estrus by decreasing release of gonadotropins)
After Cabergoline, most patients exhibit
signs of estrus in 21 days or so
inhibits prolaction secretion by directly stimulating dopamine receptors which induces onset of estrus in dogs
Cabergoline (dopamine agonist)
Dopamine agonist not used anymore because vomiting side effects too severe
Bromocriptine
What is the action of GnRH agonists like Deslorelin
induce estrus, followed by prolonged period of anestrus, presumbably from the consistent pituitary stimulation causing down regulation of GnRH receptor transcription, resulting in decreased LH (and sometimes FSH) secretion
mediates the synthesis and release of LH and FSH
Pulsatile secretion starts late anestrus, increases sensitivity of pituitary for release of LH and FSH
GnRH
Pulsatile secretion starts ____________, increases sensitivity of pituitary for release of LH and FSH
late anestrus
What is the result of GnRH agonists like Deslorelin
unpredictable and unreliable estrus induction using GNRH and premature end to diestrus (abortion) with prolonged anestrus
What is the efficacy of using gonadotropins **
35-50% pregnancy
very limited availability
low success could be due to product suppressing endogenous LH release or allergy factors
Types of gonadotropins used to induce estrus in dogs
1) Equine chorionic gonadotropin (eCG)
2) Human Chorionic Gonadotropin (hCG)
PG 600 is combination of
1) Equine chorionic gonadotropin (eCG)
2) Human Chorionic Gonadotropin (hCG)
What does PG600 do
Gonadotropins known to induce estrus and subsequent ovulation in many species
results in the onset of proestrus, but very poor ovulation rates
What is the efficacy of PG600 in dogs ***
results in the onset of proestrus, but very poor ovulation rates
Constant stimulation with GnRH agonist will eventually cause what
downregulation of pituitary GnRH receptors and result in luteal failure (end diestrus prematurely) followed by prolonged anestrus
Why method of estrus induction has the greatest success in canines*
Dopamine agonist like Cabergoline
What are methods of estrus suppression
1) Surgery -OHE, OE
2) Steroid hormones
-Progestogens
-Androgens
3) GnRH agonists
What is the only approved drug for estrus suppression in dogs in US
Medroxyprogesterone Acetate (MPA) and Megestrol Acetate (MA)
What is the action of using progestogens like Medroxyprogesterone Acetate (MPA) and Megestrol Acetate (MA) for estrus suppression
exact mechanism is unknown in dogs
LH/FSH levels actually increase first few months of therapy
What are the side effects of Progestogens like Medroxyprogesterone Acetate (MPA) and Megestrol Acetate (MA) ***
1) Cystic endometrial hyperplasia, endometritis
2) Mammary development, mammary neoplasia
3) Alopecia, coat color changes
4) Increased appetite, weight gain, lethargy (glucocorticoid receptor activity)
Types of androgens used for estrus suppression
1) Mibolerone
2) Testosterone
How do androgens cause estrus suppression
Negative feedback causing decreased secretion of gonadotropins (level of hypothalmus and likely pituitary)
What are the side effects of androgens like Mibolerone and Testosterone
1) Clitoral hypertrophy, vaginitis, vulvar discharge
2) Mounting/humping behavior
3) Induction of liver enzymes
4) Epiphora
Testosterone is commonly used in what population for estrus suppression
racing greyhounds - weekly injections
How does GnRH like Deslorelin work to suppress estrus
Its sustained exposure to GnRH results in initial estrus but then results in a prolonged anestrus
not currently approced for use in US
A SQ implant of deslorelin that suppresses estrus for almost 2 years
Suprelorin
What are the side effects of GnRH agonists like Deslorelin for estrus suppression
Ovarian Cysts
Initial signs of cysts
What drug does Suprelorin have in it
Deslorelin (GnRH agonist)
best method of estrus suppression if reproductive performance is not important
OHE, OE
Progestogens are only product approved in US for estrus suppression. what is the down side ***
it has many significant and undesirable side effects
1) Cystic endometrial hyperplasia, endometritis
2) Mammary development, mammary neoplasia
3) Alopecia, coat color changes
4) Increased appetite, weight gain, lethargy (glucocorticoid receptor activity)
Why are ferrets giving deslorelin implants
to prevent bone marrow toxicity of prolonged estrogen secretion (neoplasia)
Why do dogs need to get neutered eventually, even after breeding
they will get benign prostatic hyperplasia at some point
What considerations should you have prior to considering pregnancy termination in dogs
1) Is having litter a viable option?
2) Was mating witnessed? 60-70% will actually be pregnant even if breeding was witnessed during estrus
3) MEdical abortion- there are no medications approved for US use. all would be off label use
4) No medical therapy in inexpensive (OHE often more cost effective)
5) Most protocols suggest confirming pregnancy prior to treatment
-Canine CL is resistant to luteolysis early in diestrus and not so much later in diestrus
-THis can make the abortion less aesthetically pleasing to owner as vaginal dischage evident and fetal remnants pass
T/F: pregnancy termination is more expensive than spay
True
What are methods of inducing abortion in dogs
1) Surgery - OHE
2) Corticosteroids
3) Estrogens
4) Prostaglandin
5) Dopamine agonists
6) Progesterone receptor antagonists
What are the side effects of inducing abortion with corticosteroids (dexamethasone)
PU/PD
Panting
Anorexia/GI upset
What is the most effective method of inducing abortion in dogs
Surgery
-OHE is most effective and prevents possible mismating in the future
-Increased risk to dam when compared to routine anestrus OHE (early in diestrus carries least risk)
-late diestrus OVE consider/discuss risks associated with pseudocyesis
sometimes requested by mitch owners as mistmate shot
inhibits oocyte migration and implantation of embryo
Estradiol cypionate
T/F: dexamethasone is a recommended abortifacient in dogs **
False - not recommended
many experts believe it is a poor choice because of efficacy
What are the side effects of Estradiol cypionate **
1) Bone marrow toxicity- aplastic anemia, thrombocytopenia, leukopenia
2) Cystic endometrial hyperplasia, pyometra
3) Not effective if embryo has moved to uterus
*Unsafe, some consider it malpractice *
Why should you not give Estradiol cypionate for abortifacient
Severe side effects
Forms of prostaglandin that direct action of CL, initiating luteolysis decreasing progesterone and causing apoptosis
PGF2a
1) Dinoprost (lutalyse): natural occuring PG
2) Cloproestenol (Estrumate): sythetic PG
Why is it best to wait 28-30 days post LH to institute prostaglandin therapy for abortion
Canine CL is resistant in early diestrus
What is the drug name of lutalyse
Dinoprost
What is the drug name of Estrumate
Cloprostenol
What are the side effects of prostaglandins like Dinoprost and Cloproestenol
Potentially significant and severe side effects
-Nausea, ptyalism, cramping, lethargy, vomiting, diarrhea
-Hypotension and circulatory collapse in severe cases
In hospital treatment only
IV catheter +/- fluid therapy prior to treatment in case of emergency treatment needed
Only method of abortion in dogs that is 100%
Surgery
How do dopamine agonists induce abortion in dogs
inhibits prolactin that is necessary for CL support (luteotropic) and pregnancy maintenance
What is the most commonly used dopamine agonist to induce abortion in dogs
Cabergoline
What is the efficacy of Cabergoline for inducing abortion
only about 50% effective when used alone prior to day 40 gestation
minimal side effects
often used in combination with other agents (ie PGF2a)
What progesterone receptor antagonist is used to induce abortion in dogs
Aglepristone
Competitively binds and antagonizes progesterone receptors. at target organs
Aglepristone (Progesterone Receptor Antagonist)
What is the downside of Aglepristone
not available for use in the United States
special import permit necessary for use in the US
When can you administer Aglepristone
at any stage of gestation- 2 injections (24h apart)
about 95% efficacy (or greater) when given mid gestation
What should you do for follow up after inducing abortion in dog
Perform PE and US examination of uterus
continue treatment as necessary until complete resolution
check progesterone level if therapy is luteolytic in nature (prostaglandin)
treatment failure: no treatment is 100% (except OHE)
early gestation treatment is more challenging
stage of estrous cucle between diestrus and the start of proestrus- period of quiescence (reproductive incompetence)
Anestrus
first estrus not observed by 24 months of age
primary anestrus
period of longer than 18 months between estrus
secondary anestrus
dogs are suppose to cycle every
6-7 months
What are causes of primary anestrus
1) Previous OHE
2) Disorder of sexual development (chromosome disorders, gonadal disorders, phenotypical disorders)
3) OVarian abnormalities- aplasia, oophoritis, progesterone producing cyst
4) Silent heat- normal ovarian function without overt external signs at target organs
5) Systemic disorders- obesity, cachexia- but more common with secondary anestrus
6) Pituitary gland abnormalities
7) Drug related abnormalities- androgens, progestogens, GnRH agonists, anti-GnRH vaccine
What do you do on PE for persistent anestrus
get history: surgery or medication administration, were the previous estrous cycles normal?
PE: scar or tattoo indicating surger y
BCS
External genitalia- normal or sign of estrus?
What diagnostic testing should you do for persistent cytology
1) Vaginal cytology
2) General Health Profile- within normal limits
3) Progesterone level
4) AMH
5) Ultrasound
6) Karyotyping
7) Exploratory Surgery
What are causes of secondary anestrus
1) Systemic disorders - obesity, cachexia
2) Silent heat
-normal ovarian function without overt external signs at target organs
3) Ovarian abnormalities
-oophoritis, progesterone producing cysts
4) Pituitary gland abnormalities
5) Drug related anestrus-
-androgens, progestogens, GnRH agonists, anti-GnRH vaccicne
How do you treat persistent anestrus
1) Dopamine agonists
2) GnRH agonists
3) Exogenous gonadotropins (LH, FSH, hCG)
What is the mean duration of estrus in dogs
9 days
persistent estrus if >21d
> 21 or 30 day estrus
persistent estrus
What are the clinical signs of persistent estrus
1) Vulvar swelling with bloody discharge
2) Flagging
3) Attracts males and might allow breeding
4) Cornified vaginal epithelium
5) Bone marrow suppression (sometimes irreversible)
What are the hormone levels when patients are in persistent estrus
Low progesterone (typically above baseline 1-2ng/ml is not uncommon)
high estrogen
What are the causes of persistent estrus *
Estrogen production/influence
1) Ovarian tumors (granulosa cell tumor)
2) Follicular cyst
3) Anovulatory follicle- UPF- unovulated preovulatroy follicle
4) Exogenous estrogen exposure - HRT (creams)
How do you treat persistent estrus
-OHE, OE
-GnRH, hCG injection?
-Time - luteinization will eventually happen but pyometra risk
What is your approach to persistent etrus
-History, rule out out exogenous exposure
-Vaginal cytology, progesterone test
-Blood profile, CBC
-Ultrasound
-Exploratory surgery
bitches typically cycle every 6-7 months, but it is considered shortened interestrus interval if
4 months or shorter is considered shortened interestrus interval
What breeds typically have a shortened interestrus interval
German Shepherds and some lines of rottweilers and labdradors
The minumum uterine involution time is considered to be
3 months
What are problems associated with shortened interestrus interval (recurrent estrus)
1) Infertility - premature drop in progesterone
2) Overstimulation of ovaries- follicular cysts, granulosa cell tumors
3) Overstimulation of endometrium - greater chance of CEH and subsequent pyometra
How do you treat shortened interestrus interval (recurrent estrus)
Suppress estrus
-OHE, OE
-Progestins
-GnRH analogs
-Androgens
