Introduction

Domestic cats are seasonal polyestrous species and long-day 
breeders with a positive photoperiod influence. Queens 
cycle repeatedly during the breeding season when melatonin 
concentrations are lower, unless interrupted by pregnancy or 
pseudopregnancy. Effect of seasonality is not very substantial for 
tomcat. Pathway to contraception is to reduce concentrations of 
gonadotropins (LH and FSH) leading to reduced concentrations 
of steroid hormones with an ultimate goal to prevent reproduc-
tion. Considering the reproductive physiology of domestic cat, 
to achieve contraception, there are 3 main possible approaches:

• Progestin: a prescription drug that induces anestrus, 
inhibits ovulation, and to a certain extent, interferes with 
spermatogenesis.

• Melatonin: ‘off-label’ implants that mimic the release of 
endogenous melatonin during short photoperiods causing 
suppression of sexual activity (anestrus) and has very limited 
effect on ovulation and spermatogenesis.

• GnRH agonist: disrupts reproductive functions in female 
and male. However, the only implant available (deslorelin 
– Suprelorin 4.7 mg® Virbac) is used ‘off-label’ in cats.

Another method is to induce ovulation and therefore pseu-
dopregnancy resulting in lack of estrous signs due to high 
concentrations of progesterone for ~ 45 days. Ovulation is 
induced by hCG or mechanical vaginal stimulation and/or 
teaser male (vasectomized or even neutered tomcats).

Medical contraception in cat: new and old drugs

Cindy Maenhoudt, Alain Fontbonne 
Ecole Nationale Vétérinaire d’Alfort, Centre d’Etude en Reproduction des Carnivores
Maisons-Alfort (Paris), France

Abstract

Control of cat overpopulation is up until now has been a lost battle. The search for a cheap, reliable and easily applicable contraceptive 
covers a wide range of possibilities, but lately, very limited advances have been made. Main objective of drug-mediated fertility control 
in cats is to prevent reproduction (special concern to overpopulation) and to prevent estrus and male sexual behaviors in owned-
cats and ultimately help management of catteries. There are 3 forms of delivery of contraceptive drugs in cats: tablets, injections, and 
implants. All contraceptive control discussed here is hormone-based, with a wide variation of possible side effects. Currently, there are 
no contraceptive methods that are 100% effective and each should be considered a temporary solution. 

Keywords: Medical contraception, cats, progestin, melatonin, GnRH agonist

Currently, different hormonal approaches (long-term implants 
of GnRH agonist, melatonin implant, and GnRH vaccine) are 
possible as alternatives to progestin. These preparations appear 
to exhibit adequate contraceptive effect with less unfavorable 
effects than progestins. 

Progestins

Currently, progestins are the most used contraceptive agents to 
prevent estrus in the queen. The mechanism of contraception 
remains controversial and pathways (negative feedback and 
suppression of GnRH, interference with gamete transportation, 
and blockage of implantation) have been suggested. There are 
drugs with oral or injectable formulations. The oral formulation 
is known as the ‘cat contraceptive pill.’ The most widely used 
active substance is megestrol acetate (MA). However, there are 
also 2 other progestins, medroxyprogesterone and proligestone. 
The major limitations of progestins are the intensity and severity 
of side effects that vary in relation to the drug, dose, frequency 
and phase of the estrous cycle in which given and pre-existing 
medical conditions. Cases of mammary cancer, mammary 
hyperplasia, cystic endometrial hyperplasia/pyometra complex, 
ovarian cysts, and hormonal disorders like diabetes mellitus 
were observed in animals treated with progestins (reviewed1). 
Affinity of progestin to the progesterone receptor and to steroid 
hormone receptors (e.g. androgens) and/or glucocorticoids will 
also impact its side effects. However, the dose appears to over-
come the affinity, as lower dosages of MA seem to guarantee a 
higher level of effectiveness while reducing the risk of side effects 

Clinical Theriogenology 2021; 13: 156



to a minimum, both in frequency and in severity.2 During the 
COVID-19 pandemic, due to the reduction in spaying program, 
MA became a good alternative.3 Low doses of MA (0.625 - 0.1- 
0.2 mg/kg weekly), can be given safely; in practical terms, an 
oral dose of 2.5 mg of MA per female once a week is adequate. 
In case the queen has signs of estrus, the dose should be 5 mg 
per cat per day for 3 days, followed by once weekly treatment 
schedule. However, this protocol should be applied with care 
due to an increased risk of pyometra. In Italy,2 a lower dose (0.01 
- 0.03 mg/kg once a day) of MA (Estropill, MSD) is currently 
available, but needs further investigation. It is important to 
adhere to the duration of treatment (maximum of 2 weeks) to 
prevent the queen returning to cyclicity. Progestin treatment 
should not be extended beyond 2 years, ideally ≤ 1 year. 

Melatonin

Suppression of estrus in female domestic cats by melatonin mimics 
the physiological events of seasonality observed in many animals 
(e.g. horse, sheep, and hamsters). During dark periods, the pineal 
gland secretes melatonin (N-acetyl-5-methoxytryptamine). In 
queen, melatonin suppresses hypothalamic secretion of GnRH, 
thereby this neuromodulator has an inhibitory effect on the female 
reproductive cyclicity.4 

Melatonin is available as oral preparation, but the need to medicate 
cats every day limits this formulation. Our group used oral mela-
tonin and the results were not very remarkable and the reluctance 
of the queen to ingest the tablet was a limitation.5 Nevertheless, 
estrus was suppressed (~ 63 days) from the beginning of treatment 
when melatonin (4 mg tablets/cat/day [Melatol®, Elisium S.A., 
Buenos Aires, Argentina]) was given 2 hours prior to lights off.6

Currently, the best option is the melatonin implant (Melovin, 
Ceva, Marseille, France). Its use in domestic cats is ‘off-label,’ but 
it is still a good alternative to inhibit estrous behavior for short 
periods. The success rate is > 80% and the duration of suppression 
is variable. Suppression of estrus was observed on an average for 
103.9 days (56 - 156 days) in 81.4% (22/27) of implanted queens 
(reviewed7). In a survey by our group,8 prevention of estrus as 
reported by owners was 79% (33/42 queens). No side effects were 
reported in neither studies nor in clinical setting. The selection of 
queens is very important. Melatonin implants will have a better 
chance to induce anestrus in females having marked seasonality. 
Another aspect to improve the response is in choosing the best 
time of estrous cycle for implantation. If implanted during the 
early part of interestrous interval, longer suppression of estrus is 
observed. In practical terms, before using melatonin implants, 
the anamnesis will guide the likelihood of a positive response. It 
appears that some breeds are more susceptible to the photope-
riod. Before implantation, progesterone concentrations should be 
measured (to avoid implanting females that had ovulated) and 
a vaginal smear done to evaluate whether the queen is in estrus. 
In case of an estrous smear, it is recommended to reexamine 
the queen 1 week later, if possible, to maximize the duration of 
suppression by implantation during interestrus. The effect of the 

melatonin implant is not instantaneous, some queens may have 
estrus up to 10 days postimplantation,7,8 therefore treated animals 
should be separated from a tomcat for at least 2 weeks to avoid 
unwanted mating. Due to the lack of side effects and success of 
estrus prevention (up to 3 months), melatonin implant is a good 
option as a short-acting contraceptive for privately owned queens.

Deslorelin

GnRH agonist - deslorelin, is a slow-release implant (Suprelorin 
4.7 mg, Virbac) that can be used to suppress estrus and to inhibit 
spermatogenesis in queens and tomcats, respectively. After a short 
interval of hyperstimulation (‘flare-up’ effect), both females and 
males have a downregulation phase of GnRH secretion and conse-
quently have lower concentrations of FSH and LH. Side effects 
are not often observed, and in case of any undesirable effect, the 
implant can be removed. Reversible weight gain appears to be the 
main side effect reported in males and females.8 The limitation 
is the duration of action. Although most of the studies had an 
efficacy on average for 13 (males) or 16 (females) - 22 months,8,9 

some animals may be suppressed for up to 3 years. Therefore, this 
choice for breeding animals should be made with caution. The 
only formulation used by our group is the 4.7 mg implant. The 
contraceptive effects are reversible with normal pregnancy rates 
and litter sizes with good maternal behavior.8,9 In prepubertal 
queens, the implant allows the postponement of onset of puberty 
to an age close to 2 years.10

Implantation 

The procedure by our group is to insert the implant (of deslorelin 
or melatonin) in an area posterior to the umbilicus (for ease of 
placement and removal if necessary). Rarely the animal (male or 
female) needs sedation, the cat is placed on dorsal recumbency 
with mild restraint. Local anesthesia (lidocaine 10%) is applied 
at the site of injection. Suprelorin® has an applicator and for the 
Melovin®, an applicator is adapted. The site of implantation is 
scrubbed and the implant is injected subcutaneously (SC). It is 
easy to verify the location of these implants (Melovin® is ± 3 mm 
and Suprelorin® is ±10 mm).

Induction of ovulation and pseudopregnancy for short-
term suppression

Estrus in the queen can also been interrupted by inducing ovula-
tion. As mentioned above, a particularity of domestic cats is that 
mechanical stimulation of sensory receptors of the skin of the 
perineal region, vulva, vagina, and cervix induces ovulation. During 
natural breeding, the penile spines are the source of stimulation, 
and the number of days in estrus and the frequency of mating are 
highly associated with the intensity and frequency of the LH surge11 

and thereby ovulation. Ovulation without fertilization induces a 
prolonged state of luteal activity and therefore absence of estrus 
known as pseudopregnancy. The duration of pseudopregnancy is 
variable from 35 to 76 days (average 45 days)12 by a sterile tomcat, 
hormonal treatment or mechanical stimulation of the vagina.

Clinical Theriogenology 2021; 13: 157



Vaginal stimulation with a cotton swab can be used to mimic the 
stimulus caused by penile spines during copulation and therefore 
induce the LH surge. The procedure needs to be repeated to achieve 
the goal (induce ovulation). There are 2 limitations to this method 
of contraception. First, the technique is not always well tolerated 
by the female cat. Second, the use of the procedure repeatedly can 
increase the risk of pathologies related to progesterone exposure.

Immunocontraception

Immunocontraception is a subject of research and is still not avai-
lable in the clinical setting. Although results of GnRH vaccine and 
zona pellucida vaccine have not been very successful in cats,13-15 

a study using a single-dose GnRH immunocontraceptive vaccine 
(GonaCon™) had promising results.16 Limitations of immuno-
contraceptives are, the need of booster vaccinations to improve 
response, return to fertility once antibody concentrations decrease 
and severe lesions at the site of the injection due to adjuvants in 
the vaccines to improve efficacy. 

General consideration

The best contraceptive choice depends on availability, safety, security 
and efficiency. The request for a contraceptive for domestic cats is 
a high demand amongst our clientele. Although progestin is not 
used frequently, we strongly believe that the adaptation of the dose 
and the selection of animals can substantially decrease side effects. 
Currently, for short duration of estrus suppression, the melatonin 
implant is normally chosen. The success rate is encouraging and 
some females have been repeatedly treated over more than 1 
breeding season. For long-term suppression, deslorelin is a good 
tool for animals with conditions that preclude anesthesia. In case 
of breeding stock, as mentioned before, the lack of control over 
the duration of suppression should be extensively discussed with 
the owners to avoid disappointment and regrets due to the loss of 
animals for reproductive purposes. In some situations, it may be 
judicious to remove the implant after 4 months of implantation 
to reduce the duration of downregulation. Return of fertility has 
been well documented in both male and female cats. However, the 
quality of semen in some tomcats may not be enough to guarantee 
pregnancy after deslorelin implant. The age of animals at implan-
tation is an important consideration. Selection of contraceptive 
for pet owned cats should always consider the breeding value of 
the animal, age, health, and duration of suppression. There is still 
a need for a more practical solution to control cat overpopulation 
than the current methods. 

Conflict of interest

None to report.

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	Medical contraception in cat: new and old drugs