SUPRELORIN® (deslorelin) IMPLANTS
Manufacturer – Peptech Animal Health/Virbac, Australia
Product information – Suprelorin® (deslorelin), a GnRH agonist, effects contraception by temporarily suppressing the reproductive endocrine system and preventing production of pituitary (FSH and LH) and gonadal hormones (estradiol and progesterone in females and testosterone in males). The observed effects are similar to those following ovariectomy or castration, but are reversed after the hormone content of the implant is depleted or the implant is removed. As an agonist, deslorelin first stimulates the reproductive system, which can result in estrus and ovulation in females or temporary enhancement of testosterone and semen production in males. Then, down-regulation follows the initial period of stimulation.
Although deslorelin can also be an effective contraceptive in males of some species, we recommend its use primarily in females, since monitoring efficacy in females by suppression of estrous behavior or of gonadal steroids in feces is more straightforward than ensuring continued absence of sperm in males, since most institutions cannot perform regular semen collections. It can, however, be used to ameliorate aggression in males of some species, but higher dosages are usually needed.
Deslorelin implants are available in two formulations: 4.7mg for a minimum of 6-months, and 9.4mg for a minimum of 12-months of contraception. Because deslorelin was tested first in domestic dogs and cats, it was considered most suitable for carnivores but is now used successfully in females of many other taxa. It has also been successful in reducing aggression in some male primates, but it appears not to be effective in suppressing testosterone or spermatogenesis in male bovids or marsupials.
Storage and Expiration – Implants should be stored at refrigeration temperatures (4°C). Expiration date is stamped on individual implant packages. If the implant expires prior to placement, contact Mary Agnew (firstname.lastname@example.org) for advice.
Implant Insertion – The implant comes pre-loaded in an insertion device. The recommended site of implant placement was originally between the shoulder blades. That site is still appropriate if removal will not be needed, but because removal is desirable in most cases, the WCC has developed alternative locations for implant placement that facilitate later removal. The ideal site will vary by species, but examples of those that have been successful have been SQ in the fleshy portion at the base of the ear, inner area of the leg (front or rear), and the umbilical area. Although the animal may be able to lick or scratch these areas, deep placement of the implant at the end of a tunnel created by the trocar can protect it. An area with adequate vascularization should be chosen in order to ensure a sufficient dose is absorbed. Fatty, bony and cartilaginous areas should be avoided in favor of sites with more muscle. An instructional video illustrating implant placement SQ in the inner aspect of the rear leg can be viewed on the AAZV and AZVT websites.
The area should be clipped and cleaned using standard surgical prep techniques. A fold of skin should be lifted and held between the thumb and fingers, as the obturator (supplied with the implant) is inserted. To prevent implant breakage during insertion, create a tunnel with the trocar, then slowly withdraw the the obturator, leaving the implant in place in the tunnel. The implant should be held steady as the obturator is removed to ensure release of the implant so that it remains in place under the skin.
Latency to effectiveness - Because the initial effect is to stimulate the reproductive system, it is important to either separate treated animals from opposite sex individuals during the period of enhanced fertility or use another form of contraception. Females treated with deslorelin should be considered fertile for 3 weeks following insertion. Males may remain fertile for 2 or more months, until residual sperm either degenerate or are passed (as following vasectomy).
Implant Removal - The Suprelorin product insert instructs the veterinarian to place the implant subcutaneously between the shoulder blades. That site is still appropriate if removal will not be needed, but removal is often desirable to hasten reversal. The implants were not designed to be removed, and they do become more porous and prone to breakage with time, as deslorelin diffuses out, but they do not dissolve. Thus, with careful placement, removal is possible. The ideal site will vary by species, but examples of those that have been successful have been SQ in the fleshy portion at the base of the ear, inner area of the leg (front or rear), and the umbilical area. Although the animal may be able to lick or scratch these areas, deep placement of the implant at the end of a tunnel created by the trocar can protect it. An area with adequate vascularization should be chosen in order to ensure a sufficient dose is absorbed. Fatty, bony and cartilaginous areas should be avoided in favor of sites with more muscle. An instructional video illustrating implant placement SQ in the inner aspect of the rear leg can be viewed on the AAZV and AZVT websites.
- Identify a location where it is unlikely that the implant will migrate and where the implant can be palpated through the skin
- Create a tunnel with the trocar, then slowly withdraw the the obturator, leaving the implant in place in the tunnel. The implant should be held steady as the obturator is removed to ensure release of the implant so that it remains in place
- Ensure the entire implant is in place by gently palpating, being careful not to crush it, and make note in medical records for future retrieval attempts,
- At each opportunity, physically palpate the location of the implant to confirm it is in place, again always taking care not to crush the implants, since they become prone to breakage over time.
Tips for removal:
- Locate implant by palpation, being careful not to crush it
- The area should be clipped and cleaned using standard surgical prep techniques
- Make a small incision through which the implant can be removed
- Grasp implant carefully with forceps and gently remove; even if the implant breaks, attempt to remove all remaining pieces
- Confirm that all pieces have been found and excised
- Flush area with sterile saline to remove any remaining fragments
- Close incision
Suppression of initial estrus/ovulation – The estrus and ovulation that can occur within 2 weeks following implant insertion can be suppressed with supplemental progestin treatment for 2 weeks (7 days prior to and 7 days after implant insertion). Megestrol acetate (Ovaban®) tablets are the simplest for short-term progestin administration, with the tablet offered as part of a treat. Depo-Provera® should not be substituted for megestrol acetate, because its initial high levels and prolonged release can interfere with Suprelorin® efficacy. MGA implants can be left in place for 2-3 weeks following Suprelorin® implant insertion, but then should be removed to prevent interference with the down-regulation action. Leaving them in place longer may compromise Suprelorin® efficacy.
Estrous cycles during contraceptive treatment - Deslorelin first stimulates then suppresses estrus in females. Species with induced ovulation (e.g., felids, some mustelids, and bears) may ovulate and become pseudo-pregnant (which also occurs in canids) when first treated. In males, initial stimulation may be accompanied by increased aggression or sexual interest. Estrous behavior or even copulation may occur during a transition phase near the end of the period of contraceptive efficacy.
Dosages, duration of efficacy and reversibility – The 12-month formulation containing 9.4mg deslorelin should be effective for approximately twice as long as the 4.7mg implants, since the implant matrix releases deslorelin at a slower rate. Thus, the per-kg-body-weight dose for the 9.4mg implants is about twice that of the 4.7mg implants. However, that translates into an equivalent number of implants needed. For example, an animal effectively contracepted for 6 months with two 4.7mg implants will need two 9.4mg implants to achieve contraception, but the period of efficacy will be approximately double (about 12 months). It is important to note that one 9.4mg implant will not substitute for two 4.7mg ones.
These dose recommendations should only serve as general guidelines, because individual animals may respond differently. Stated durations of efficacy should be considered minimums. The average duration of efficacy of the 4.7mg implants is about 1 year, and about 2 years for the 9.4mg implant. There is considerable variability between individuals, but the response of an individual tends to be consistent. That is, if an individual reverses at 8 months with a 4.7mg implant, it will likely always reverse after 8 months. If it is not possible to wait for signs of reversal to determine duration of efficacy for the animal, then for continuous contraception the 4.7mg implants should be replaced at 5- to 6-month intervals and the 9.4mg ones at 11- to 12-month intervals.
Transition phase during reversal - Data from studies of domestic cats and from African lions have identified a transition phase of about 6 months during the process of reversal, when follicles grow and produce estrogen sufficient to stimulate recurring signs of estrus and even mating behavior but without ovulation. In addition, information submitted to the WCC suggest that in some individuals there is sustained stimulation of gonadal hormones (e.g., testosterone in males or higher than normal levels of progesterone following ovulation) during reversal.
These observations indicate that reversal is a process that may extend for 6 months, when abnormal or irregular cycles may be seen in females or a period of increased aggression may be seen in males. It should be possible to hasten or avoid this process by removing the implant(s). It is likely that the implant(s) continue to release deslorelin during this time, at levels too low to maintain pituitary down-regulation but high enough to stimulate gonadal steroid production or, in some individuals, to prevent the LH surge required for ovulation. The implants do become more porous and prone to breakage with time, as deslorelin diffuses out, but they do not dissolve. Thus, with careful placement (see section above on implant insertion), removal is possible.
Use during pregnancy – GnRH agonists should not be used during pregnancy, as they may cause abortion. Even if abortion does not result, deslorelin may interfere with milk production.
Use during lactation - No known contraindications once lactation has been established; however, treatment during pregnancy may impede proper mammary development.
Use in pre-pubertals or juveniles – Because deslorelin suppresses gonadal steroids, its use may delay epiphyseal closure of the long bones, resulting in taller individuals, similar to the effects of pre-pubertal spaying and neutering in domestic dogs and cats. GnRH agonist use in prepubertal domestic cats was followed by reproductive cycles after treatment ceased. However, species differences may occur.
Consideration for seasonal breeders – In females, GnRH agonists can induce estrus and ovulation even during the non-breeding season in some taxa. In males, GnRH agonists can transiently stimulate testosterone production even during the non-breeding season. Treatment should begin more than two months prior to the anticipated breeding season to prevent initiation of spermatogenesis, because it appears that suppression of sperm production is more easily accomplished before it has commenced.
Precautions - In general, the effects on body weight should be similar to those from ovariectomy or castration. Preliminary data indicate that increased appetite will result in weight gain, especially in females, unless food is restricted. In males, muscle loss may result in overall weight loss if not replaced by fat. In sexually dimorphic species, males may become the size (weight) of females. Animals may lose secondary sex characteristics (e.g., lions may lose their mane).
Reporting requirements - All institutions using deslorelin must submit and complete the annual Contraception Center Survey to the AZA Wildlife Contraception Center as part of an agreement with Peptech Animal Health-Virbac, Australia. The product will no longer be sold to any institution that fails to submit the annual survey.
Request for purchase - Deslorelin implants are available to AZA-accredited institutions as part of a research trial coordinated by the AZA Wildlife Contraception Center as part of an agreement with Peptech Animal Health-Virbac, Australia . This product is commercially available in the United States but solely for the treatment of ferret adrenal disease. For institutions outside the U.S., Suprelorin is commercially available in the UK, Europe, Australia, and New Zealand.
To order implants, AZA-accredited institutions in the U.S. should submit the Deslorelin Registration Form to:
Mary Agnew, Program Coordinator
AZA Wildlife Contraception Center
Saint Louis Zoo
1 Government Drive
St. Louis, MO 63110
314-646-4595; fax: 314-646-5534