Friday, March 8, 2019
Susan Salter is an equine veterinarian with experience in the fields of Thoroughbred and sports horse stud medicine. She works with Donnington Grove Veterinary Group in Newbury, who have a specialised stud medicine team, as well as a large race horse client base.
Seeing where both niche areas of equine practice converge following the recent ban of altrenogest by the BHA, she would like to provide you with alternative options for the management of hormone related poor performance in competition horses.
Altrenogest oral (Regumate) has traditionally been administered to racing fillies and mares where oestrous behaviour is the perceived cause of poor performance. Testing of Regumate Equine confirmed the presence of trendione therefore, the BHA advised that this product should not be administered to racehorses and that it should be removed from licensed premises. Further testing has confirmed the presence of trenbolone/trendione in Regumate Porcine and in an injectable altrenogest – as such, the same advice applies to these products. This advice does not apply to broodmares that have been permanently retired from racing, but does apply to thoroughbreds before they enter training.
Poor performance is often attributed to oestrous behaviour in fillies and mares that are either cycling normally and are in the oestrus part of their reproductive cycle or are “in transition”. Oestrogen is the dominant hormone when they show this behaviour.
An average oestrous cycle lasts approximately 21 days. Oestrogen, in the absence of progesterone, allows a filly or mare to be “in oestrus” for approximately 7 of those days. FSH will stimulate folliculogenesis and oestrogen will be secreted by the resulting follicles. An LH surge will induce ovulation of the dominant follicle(s). Days later, the site of ovulation will luteinise and become a source of progesterone secretion; the corpus luteum. In the non-pregnant mare, the progesterone dominant phase (dioestrus) lasts for 14-16 days. Progesterone, which is dominant over oestrogen, will abolish oestrous behaviour throughout dioestrus.
Longer daylight periods reduce circulating levels of melatonin. This diminishes the inhibitory effect melatonin has on follicular growth and on ovulation, both of which are required for normal cyclicity. Melatonin levels typically begin to reduce in springtime. This allows follicular growth and oestrogen production to happen but often without a threshold LH surge and consequent ovulation of a dominant follicle. Therefore, the filly or mare will persistently display oestrous behaviour while being “in transition”.
Altrenogest mimics the effects of endogenous progesterone by blocking oestrous behaviour. What alternatives exist that achieve a similar effect (block or greatly reduce this behaviour)? We shall describe two categories; those protocols that can be used in normally cycling horses, and those that can be used in horses in transition.
Normally cycling horses.
- The intra-uterine marble is placed into the uterus of the mare in a sterile manner upon ovulation while the cervical canal is still open. This technique causes pseudopregnancy by interfering with prostaglandin release and luteolysis, which therefore prolongs dioestrus (similar to a vesicle establishing maternal recognition of pregnancy). Reports of efficacy range from 40%-75%. If dioestrus is successfully prolonged the mare may stay out of season for up to 90 days. Other reports suggest no prolongation of dioestrus but rather a placebo effect. If the marble is left in place for longer than is necessary, complications can occur. There is a glass marble option and polymethylmethacrylate marble option, the latter of which is safer. There is no BHA withdrawal period for this technique.
- Plant oils, for example fractioned coconut oil and peanut oil can be placed into the uterus of a cycling mare in a sterile manner ten days post ovulation. It is thought that monounsaturated fatty acids and polyunsaturated fatty acids present in the plant oils interfere with prostaglandin synthesis, which prolongs the life of the corpus luteum. One study found that this technique suppresses oestrus for an average of 30 days while in a further study, prolonged dioestrus occurred in 92% of mares. However, more recent studies have not confirmed these results. It is the author’s opinion that plant oils are more reliable than the marble in prolonging dioestrus. Insertion of plant oil using a transvaginal approach via the dioestrus closed cervical canal on a race yard is certainly a more difficult task to complete than the insertion of a marble through the open flaccid cervical canal upon ovulation. Plant oils are prohibited substances on race-day. The BHA has no detection time or withdrawal advice for this technique.
- A low dose oxytocin protocol has shown excellent results. One study reported all mares staying in dioestrus for more than 30 days when injected twice daily from day 7 to day 14 post ovulation. This technique also functions to interfere with prostaglandin release and therefore prolongs the life of the corpus luteum. As a peptide hormone, oxytocin is a “prohibited at all times” substance, however, “there is an exception for use in fillies and mares in breeding management or to block oestrous cycling”. There is no published detection time for oxytocin; however, the BHA would informally advise a minimum of 7 clear days as a withdrawal period.
- Fillies and mares are permitted to race while pregnant but “must not be more than 120 days pregnant” to satisfy the BHA’s Rules of Racing. It is the trainer’s responsibility to notify the BHA within 25 days of the last covering or as soon as the horse enters training.
Horses “in transition”.
- Administering a double dose of the deslorelin implant (Ovuplant) can be an effective way to stop overt signs of oestrus and can be used in transitional fillies and mares as well as those that are cycling normally. It inhibits cyclicity in most of these horses by suppressing follicular development, leaving them in anoestrus. However, oestrogen can still be the dominant hormone since it can be produced from extra ovarian sources. Progesterone is not secreted in anoestrus and so the filly or mare may still show mild signs of being in oestrus. It is one of a limited number of options that can be used in the transitional filly in training. Deslorelin is a prohibited substance on race-day, and under the rules of racing “the horse must not have any implant apart from one that is pharmacologically inactive”. There is no published detection time for deslorelin however, there is a proposal for a detection time study to be carried out. At present, the BHA would informally advise a minimum of 7 clear days as a withdrawal period – it is not known whether a double dose would lead to a prolonged detection time.
- In mid to late transition it is worthwhile considering the use of a “progesterone releasing intra-vaginal device” or PRID. This may advance the mare into normal cyclicity. One protocol is to insert the PRID and remove it ten days later, preferably on detection of a large follicle. An induction agent can then be used to induce ovulation of this dominant follicle. Following the first ovulation of the season, the filly or mare will usually cycle normally. Note that some fillies find the PRID uncomfortable and it can cause a transient local vaginal discharge. The BHA prohibits the use of such devices on race-day. No withdrawal advice is available at present.
- A GnRH vaccine (Equity) is licensed in Australia “for use in the control of oestrus and oestrus-related behaviour in fillies and mares not intended for breeding”. The author does not recommend the use of this vaccine in competition mares and fillies for a number of reasons. It’s efficacy is unreliable and once given, there is a risk that the mare or filly will fail to regain normal function of the ovaries. GnRH vaccines are prohibited under the international agreement on breeding, racing and wagering, and therefore cannot be used in racehorses.
- If regaining normal function of the ovaries is not a concern, then ovariectomy can also be considered. However, similar to the implant and vaccine, a background level of oestrogen may still exist causing mild oestrous behaviour. This behaviour is normally insignificant and has no effect upon performance.
Most of these techniques require reasonable competence in performing and interpreting rectal ultrasonography, while comprehensive history taking and an extensive clinical examination are of paramount importance in correctly diagnosing oestrous-related poor performance in the first instance.
It should be noted that veterinarians are responsible for observing the therapeutic cascade and taking the most recent BHA or other governing body guidelines into consideration with respect to each individual case.
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