This document discusses pharmacological control of reproduction in dogs and cats. It summarizes various methods for preventing breeding, terminating pregnancy, and inducing estrus or ovulation. These include use of progestogens, GnRH agonists and antagonists, melatonin implants, prostaglandins, prolactin inhibitors, hCG, and oxytocin. It also addresses treatment of pseudopregnancy, pyometra, retained fetal membranes, metritis, and poor libido in males. A variety of hormones are described that can regulate the reproductive cycle for contraception or medical management of reproductive diseases.

1. Pharmacological
Control of
Reproduction in
Dog and Cat
(GARY C. W. ENGLAND)
Presented by:
Dr.Muhammad Abdul Rehman
University ID#2015-VA-249
DVM (UVAS Lahore, Pakistan)

2. Female
Prevention of Breeding:
Prevention of Estrus:
Use of P4:
– Most common method for control of breeding has been the
administration of progestogens to bitches or queens when in anoestrus.
– This appears to alter gonadotrophin secretion and therefore prevents a
return to cyclical activity.

3. Progestogens are not recommended in breeding
animals because of a potential effect on fertility,
probably mediated by uterine changes
(progestogens may induce cystic endometrial
hyperplasia and pyometra).
Disadvantage of P4:

4. Use of GnRH and it’s Agonist:
– A long acting gonadotrophin releasing hormone (GnRH) agonist implant,
“deslorelin”, has been used to prevent oestrus in both bitches and queens.
– Insertion of the implant produces an initial release of FSH and LH which is
commonly associated with signs of oestrus and can be fertile (in fact removal
of the implant at this time can be used as a method for oestrous induction; see
later), but there is then receptor downregulation and induction of sexual
inactivity.
– The duration of effect relates to the dose of drug present in the implant but
can be 12 months or greater.
– Fertility after the return to cyclical activity is good.

5. Use of GnRH Antagonist:
– Although not available in all countries, there has been recent
interest in the GnRH antagonist “acycline”.
– This drug causes a decrease in FSH and LH concentrations
and appears promising for future development to prevent
oestrus in dogs and cats.

6. Melatonin Implants for Cats:
– Queens are seasonal, long day breeders, in which
hypothalamic function is downregulated by melatonin
produced when days are short.
– Administration of these melatonin implants to anoestrus cats
will prevent the return to oestrus potentially for several
months. They may also be useful within the breeding season,
although the duration of effect is shorter.

7. Treatment of Unwanted Mating:
– Historically, the most common method for treatment of an
unwanted mating in the bitch was the administration of
oestrogens during a short window after mating, whereas in the
queen, a similar regime using a high dose, short-acting
progestogen was recommended.
– More recently, a progesterone receptor antagonist (aglepristone)
can be used around the time of mating (including from shortly
before ovulation) to prevent the establishment of pregnancy. This
preparation can also be used at any time after ovulation to induce
embryonic resorption or fetal abortion.

8. Termination of Pregnancy:
– Progesterone-receptor antagonists such as aglepristone can be
administered in the first one-third of pregnancy to induce
embryonic resorption.
– In mid- and later pregnancy, the outcome of termination is
abortion.
– The efficacy of pregnancy termination appears to be reduced
when aglepristone is used alone in later pregnancy, and a more
successful outcome occurs if treatment also includes
prostaglandin (which causes uterine contraction and aids in
expulsion of the fetal material).

9. Continue…
– Prostaglandins may be used alone for this purpose as long as
treatment commences more than 25 days after ovulation (the
early corpora lutea (CL) do not respond well to exogenous
prostaglandin and require higher doses than are required later in
the luteal phase), and treatment is given daily over at least 5
days.

10. Prolactin:
– Prolactin inhibitors such as cabergoline can be used to end the
luteal phase and terminate pregnancy because prolactin is the
most significant luteotrophic factor in the bitch and pregnant
queen.
– In practice, prolactin inhibitors are normally given in a
combination regime with prostaglandins because this improves
efficacy as the prostaglandin acts to lyse the CL and cause uterine
contractions that help disrupt the pregnancy.

11. Induction of Oestrus
– As a seasonal breeder, most queens will return to cyclical activity if
they are exposed to more than 14 hours of light per day.
– In the bitch and queen with primary anoestrus (delayed puberty)
or secondary anoestrus (failure to return to cyclical activity), it is
possible to induce a fertile oestrus by administration of the GnRH
agonist deslorelin.
– The initial response to inserting a deslorelin implant is the release
of FSH and LH, which causes follicle growth and results in a return
to oestrus. At this point the implant needs to be removed to
prevent later receptor downregulation. Fertility with deslorelin-
induced cycles appears good.

12. Continue…
– Prostaglandins are not efficacious for the induction of oestrus in the
bitch because although if administered during the luteal phase, they
cause lysis of the CL, and the bitch then enters anoestrus.
– Interestingly, through an uncertain mechanism, the administration of
prolactin inhibitors (e.g., cabergoline) can be used to induce oestrus in
the bitch.
– Cabergoline would shorten the luteal phase if given at this stage of the
cycle, but continued administration also shortens the subsequent period
of anoestrus.
– Prolactin inhibitors are not efficacious for induction of oestrus in the
queen.

13. Stimulation of Ovulation
– A simple method for the stimulation of ovulation is the
administration of hCG, which is LH-like in activity. Single
or daily administration of hCG may be required based
upon the clinical circumstances. A similar effect can be
achieved in both species by the administration of short-
acting GnRH agonists – for example, buserelin – that
results in the endogenous release of LH and FSH.

14. Stimulation of Milk Production
– Bitches and queens occasionally have inadequate milk production,
usually seen in primigravida, or associated with a Caesarean operation
performed before term, or, occasionally, in bitches with poor body
condition or concurrent disease.
– In both species the repeated twice daily administration of
metoclopramide can be useful to increase prolactin concentrations and
thus stimulate milk production. A clinical effect can be seen within
approximately 4 days. Neonates should be encouraged to suck during
this period, but, of course, they will need supplementary feeding.

15. Treatment of
Reproductive
Diseases

16. Treatment of Pseudopregnancy
– Pseudopregnancy is caused by the normal increase in plasma prolactin
concentrations that commence approximately 3 weeks after ovulation.
– The daily administration of the prolactin inhibitor cabergoline has been
used for the treatment of pseudopregnancy .
– Treatment for 4 to 6 days is efficacious in nearly all cases; those that have
not fully resolved usually require extension of the treatment period to a total
of 7 to 10 days.
– Administration of progestogens can also causes a rapid decline in prolactin
concentrations ----???

17. Treatment of Pyometra
– The mainstay of treatment has always been surgical removal of the
uterus and ovaries, and this still remains the case because
recurrence after medical treatment is not uncommon.
– The principle aim of medical treatment is to remove the
stimulatory effect of progesterone.
– Prostaglandins can be extremely effective for the medical
treatment of pyometra, in which repeated low dose therapy will
cause lysis of the CL, resulting in cessation of progesterone
secretion. In addition, prostaglandins have a uterine spasmogenic
effect, and this can aid in the expulsion of uterine pus.

18. Treatment of Uterine Inertia
– Primary uterine inertia is the most common cause of dystocia in
the bitch and queen.
– In many cases, it is feasible to stimulate uterine contractions by
the administration of exogenous oxytocin .
– Attention must be paid to the dose of oxytocin administered;
commonly, dose rates used are too high and result in a prolonged
tetanic uterine contraction rather than coordinated expulsive
contractions.

19. Continue…
– In most cases, a dose of 0.04 IU/kg is appropriate, given every 30
minutes for three doses.
– Note that oxytocin administration will cause placental
compression and worsen any fetal hypoxia, so may it be
contraindicated if fetuses are bradycardic.
– Concurrent calcium administration will often help improve uterine
contractions; a common regime is 1.0 mL/kg of a 2.5% calcium
gluconate solution administered subcutaneously.

20. Retained Fetal Membranes
– Retained fetal membranes are uncommon in both the postpartum bitch
and queen but are often suspected because expulsion of a placenta does
not always follow each fetus.
– Confirmation of retained fetal membranes can be made on ultrasound
examination.
– In the immediate postpartum period, two or three doses of oxytocin at
0.04 IU/kg given every 30 minutes can induce expulsion; however, the
number of uterine oxytocin receptors decreases quickly after parturition,
and by 48 hours, there is minimal clinical response to exogenous
oxytocin. Cases presented later than this time period are best managed
as for metritis.

21. Postpartum Metritis
– Metritis in the bitch and queen occurs when, after contamination of the
uterus at parturition, bacteria invade uterine tissue usually at the sites of
previous placental attachment.
– The condition is uncommon but is more likely after dystocia and
placental retention.
– Low dose prostaglandins may, however, be useful for their uterine
spasmogenic effects (rather than their luteolytic effects), which can aid
expulsion of uterine fluid. Prostaglandins are metabolised quickly, and so
treatment is required two or three times per day.
– Plus Antibiotics and Anti-inflammatory.

22. Male
Prevention of Breeding
Although hormonal treatment may prevent a fertile mating, it
may not always abolish breeding behaviour. Indeed even
castrated males, particularly dogs, may continue to achieve
erection and mate.

23. Contraception
– There has always been interest in medical contraception in dogs and
cats, commonly as a temporary method to prevent fertile breeding.
– Until recently, the most common methods have been administration
of either depot progestogens or daily oral progestogen therapy.
– The use of these regimes in the male reduce FSH and LH
concentrations, with a resultant inhibition of spermatogenesis and
steroidogenesis.
– Semen quality and plasma testosterone concentrations decline quite
rapidly and remain suppressed throughout the duration of treatment.

24. Continue…
– Recently the depot GnRH agonist implant deslorelin has been
examined in clinical studies in both dogs and cats (Lucas 2014).
– Insertion of the implant causes an initial stimulation of FSH and LH
release with few clinical manifestations of this (unlike the return to
oestrus seen in the female), followed by receptor downregulation,
and a rapid reduction of spermatogenesis and steroidogenesis.
– Testes decrease in size, semen quality deteriorates, and male
behaviour is reduced. The duration of the effect is related to the
length of action of the implant.

25. Continue…
– The GnRH antagonist acycline has been shown to impair
spermatogenesis over a short period of time. This drug
may offer an interesting opportunity as a contraceptive
for the future.

26. Unwanted or Antisocial
Behaviour
– Much normal behaviour demonstrated by entire male animals may be
inconvenient or unwanted by the owner.
– The methods described previously for inducing contraception by impairing
spermatogenesis and steroidogenesis may be useful therefore for
controlling unwanted male behaviour (e.g., roaming, mounting, urine
marking).
– Methods that reduce plasma testosterone alone are unlikely to have any
beneficial effect because in the castrated male testosterone will be basal.
– The progestogens do, however, have additional effects in that they are also
sedative, and they may therefore modify unwanted male behaviour that
persists in castrated animals.

27. Poor Libido
– In most cases, poor libido is associated with the experience of a male,
the mating environment, his preference for particular females, and the
dominance of the female.
– It is rare for there to be a pathological reduction of libido without
testicular disease (i.e., the hypogondal male will have small testes, low
testosterone production, and poor libido).
– What is important is to recognise that, although a temporary increase in
dominance and libido may be achieved by administration of androgens,
their use will cause suppression of FSH and semen quality will
significantly deteriorate.

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