9 May 2016
Supplementary control of oestrus behaviour in mares
Malcolm Weetman, Tim Watson, Rosemary Brown, Max Murray and Tony Davies study the effects a wheat germ extract supplement has on oestrus and associated bad behaviour in horses, and monitor it as the seasons change.

Figure 1. Oestrus and associated behavior can make mares difficult to handle and ride.
Oestrus and associated bad behaviour can make mares difficult to ride and train, cause poor performance and present a risk to those working with them. Treatments are designed to reduce ovarian and oestrogenic activity, and include hormone therapy, herbal supplements, intrauterine devices and surgical ovariectomy, as well as symptomatic treatment with NSAIDs, acupuncture and physiotherapy. No single treatment is universally effective and some mares remain refractory to management. The authors evaluated the efficacy of a wheat germ extract, eCalm, to reduce or eliminate adverse behaviour of mares in oestrus.
In an open longitudinal study, daily supplementation with eCalm significantly reduced signs of bad behaviour during oestrus, returning scores to those seen during winter periods of anoestrus. Subsequently, cessation of eCalm resulted in a return to bad behaviour during the next oestrus and this was rescued with resumption of supplementation showing significant improvements in scores.
In a second study, mares were treated with eCalm at the onset of oestrus and resulted in significant improvements in behaviour as soon as 12 hours and, in all cases, by 36 hours to 48 hours. Dietary supplementation with this wheat germ extract offers an efficacious, safe and cost-effective solution to the frustrating problem of bad oestrus behaviour in mares.
An extract of wheat germ possesses a unique immunomodulatory characteristic (Boros et al, 2005). Separate to this property, the authors found a wheat germ product called eCalm has a rapid and dramatic effect on the control and prevention of behavioural issues associated with oestrus in mares, when fed as a dietary supplement.
In this article, the authors discuss problems associated with oestrus behaviour in mares, along with available treatment methods and results of trials with eCalm.
Oestrus behaviour and associated problems in mares
Mares in climatically temperate zones are seasonally polyoestrous and reproductively active in summer, typically between the spring and autumn equinoxes of 20 March and 23 September, respectively.

The average oestrous cycle lasts 21 days and consists of a 14-day to 16-day period of dioestrus and 5 days to 7 days of oestrus.
Progesterone hormones predominate during dioestrus, but decline with production of oestrogens by ovarian follicles during oestrus. Oestrogens prepare the uterine tract for possible fertilisation of an egg and resulting pregnancy.
Behavioural signs of oestrus include nickering, raising of the tail, opening/closing of the vulva (winking), vocal calling, posturing, sexual interest in other horses, anxiety, aggression, tail swishing and frequent urination. Other signs may include attitude changes, excessive sensitivity around the flanks – over the region of the ovaries with reluctance to work properly – and bucking and kicking when ridden (Figure 1). Mares are often difficult to ride, frustrating to train and perform poorly during competition (McCue, 2003).
Bad behaviour during heat occurs with normal, as well as abnormal, oestrus, including prolonged or persistent oestrus with unusual or exaggerated signs, and is a common problem. While epidemiological data is lacking on its prevalence, it is a frequent presenting complaint in equine practice.
In some mares, such issues are confined to the spring transition period and calm down once it settles into a pattern of normal oestrous cycles. In others, it persists throughout the summer or is present all year.
Little or no oestrogen may be required for oestrus expression in some horses; absence of progesterone may be all that is needed for a mare to display oestrus behaviour in the presence of a stallion (King, 2013). This is likely to be the result of hormone production by the adrenal gland and possibly explains why oestrus behaviour is displayed by some mares in winter.
Diagnosis and management
Diagnosis and management of abnormal oestrus behaviour can be frustrating and unrewarding.
Ultrasound examination may reveal an increased number and size of ovarian follicles, with prominent uterine oedema, consistent with oestrogen activity. Ovaries may be painful on palpation per rectum and occasional granuloma cell tumours may be identified.
However, ultrasound findings can frequently be normal and it is important to identify other potential causes of
bad behaviour and poor performance, such as thora-columbar pain or gastric ulcers.
Considerable effort has gone into attempts to calm mares in oestrus and numerous techniques to suppress the cycle or modify behaviour and its consequences reported. These include hormone therapy, herbal supplements, intrauterine devices, surgical ovariectomy, and symptomatic treatment with NSAIDs, acupuncture and physiotherapy.
The only product licensed in the UK for oestrus suppression in horses is altrenogest. While it is generally effective, the cost of long-term administration and the inconvenience of daily oral dosing can limit compliance.
Furthermore, some mares exist whose behaviour persists despite medication with altrenogest. Two long-acting injectable formulations of altrenogest are available in the US and suppress oestrus for 12 days and 30 days (Storer et al, 2009).
The observation some mares given the synthetic analogue of gonadotrophin releasing hormone (GnRH) deslorelin acetate develop prolonged dioestrus sparked interest in using this product for the suppression of oestrus. Multiple implants delayed oestrus by around 15 days, but did not induce ovarian atrophy or longer-term suppression of oestrus (Johnson et al, 2003).
Vaccination against GnRH suppresses oestrus for three months to six months following inoculations two weeks apart (Elhay et al, 2007). A commercial canine GnRH vaccine has been shown to reduce unwanted oestrus behaviour in mares (Donovan et al, 2013).
Other techniques have focused on extending the luteal phase, notably using intrauterine glass marbles or water-filled plastic balls to mimic pregnancy inserted one day to four days after ovulation. Corpus luteum function is maintained for approximately 90 days in around 40 per cent of mares that retain glass marbles (Nie et al, 2001). Success with water-filled balls was better, with luteal function lasting an average of 60 days in 75 per cent of mares (Rivera Del Alamo et al, 2008).
Intrauterine administration of fractionated coconut or peanut oil on day 10 post-ovulation has been found to provide an effective and practical method of prolonging luteal function (“pseudopregnancy”), and suppresses unwanted oestrous behaviour (Wilsher and Allen, 2011). Injection of oxytocin 7 days to 14 days post-ovulation to block luteolysis was also evaluated, with evidence IV injection of 10 international units can increase dioestrus from an average of 18 days to 64 days (Gee et al, 2012).
A number of dietary supplements and herbal remedies are marketed with claims to support hormone balance, encourage regular and normal oestrous activity, and promote calmness. Scientific evidence of these alternative products is inconsistent.
Supplement use
During a preliminary study of eCalm in horses, it was found the behaviour of a mare that was particularly difficult during oestrus was improved substantially over the entire summer by daily oral intake of a small amount of the product (20gm/d).
An extended study was, therefore, undertaken to investigate the potential of eCalm to suppress bad behaviour during oestrus in mares at a large equestrian establishment with a riding school, training facilities, livery stables and stud. This comprised two components: the first looking at continuous supplementation with eCalm as a form of prophylaxis and the second examining its therapeutic efficacy.
Displaying “seasonal” bad behaviour
Seven mares known to display “seasonal” bad behaviour during summer were given eCalm feed supplement in an open longitudinal study with animals serving as their own controls with supplement deprivation. Thus, a mare that had shown calmer behaviour during oestrus was taken off eCalm at the next cycle and the supplement reintroduced for the subsequent cycle.

Daily amounts of eCalm were given with the evening feed at a dosage of 15g, 20g or 25g for horses weighing 350kg, 500kg and 750kg, respectively. Simultaneously, a cohort of matching “buddy” placebo-treated mares showing bad behaviour during oestrus were given an equivalent supplementary volume of standard bran.
A veterinary-gauged semi-quantitative clinical scoring system was adopted, with one being normal good behaviour and five being bad behaviour with major management problems.
Bad behaviour was characterised by a wide range of clinical signs, including squirting, kicking, biting, squealing, aggression, grumpiness, bucking, being easily spooked, anxiety, neighing when ridden, wind sucking, weaving, frequent urination, difficulty catching, tacking-up, loading and riding outside the stables, and poor performance.
It was established the scoring system was robust and could be applied independently, with the same results being obtained by all the three experienced trainers who made the observations. Scores were recorded during winter – before resumption of oestrous cycles – once oestrus activity had commenced and during periods of supplementation, withdrawal and resumption.
Behaviour of the seven treated mares and seven placebo-treated mares was monitored continuously for five oestrous cycles. In five mares, supplementation with eCalm was stopped for the second and fourth cycle before being resumed. Statistical analysis was carried out using the dependent T-test for paired samples, as each individual score of one sample had a unique corresponding score in the other sample later in the same oestrus.
Oestrous behaviour scores in all seven mares worsened with onset of oestrus activity in spring (Table 1), with mean behaviour scores (BS; ± standard deviation) of 4.36 (±0.48) compared with 1.86 (±0.90 during winter). Data on supplementation with eCalm was available for 25 oestrus periods and showed significant improvements in behaviour, with a mean BS of 1.64 (±0.48; P 0<0001). BS during supplementation with eCalm were similar to those reported during winter anoestrus.
In five mares where supplementation was withdrawn for two cycles, a significant deterioration in behaviour was shown during oestrus (mean BS 4.2; ±0.27) and a statistically significant improvement on resumption of supplementation (mean BS 2; ±0; P<0.0001; Figure 2). None of the control “buddy” animals on a simple bran supplement showed any deviation from their pattern of bad oestrus behaviour during the study.
Therapeutic treatment

In the second phase, rather than using eCalm continuously, the authors looked to reduce oestrus behavioural problems by giving the supplement at the onset of oestrus and associated abnormally bad behaviour.
Mares were given eCalm on the first evening bad behaviour was noted and continued each evening for five days. Effects of treatment on BS were examined during 63 cycles in 24 mares. All mares that responded to eCalm were studied in subsequent oestrus without supplementation and these deprivation controls amounted to 38 cycles. Nine cycles per animal were examined during the summers of 2013 and 2014.
In all 63 cycles, supplementation stopped bad behaviour with mean BS falling from 4.21 (±0.55, range 3.5 to 5) to 1.98 (±0.35, range 1.0 to 2.5; P<0.0001). The response time was hours and, in the majority of cases, behaviour had improved in 36 hours to 48 hours. In the 38 additional cycles where supplementation was not given at the onset of oestrus, the bad behaviour mean BS (4.09; ±0.49) was similar to that prior to supplementation (Figure 3).
Conclusion
The first study clearly showed continuous feed supplement with eCalm in summer effectively reduced or eliminated bad behaviour associated with ovulation. The second phase demonstrated behavioural signs of oestrus could be modified quickly by feeding eCalm. This gives horse owners the choice of using the product continuously or as a treatment in the event of untoward behaviour manifesting with the onset of oestrus.
The authors’ studies commenced in 2011 and are ongoing. To date, 135 periods of oestrus bad behaviour have been successfully treated in 46 mares, with 48 deprivation crossovers and 8 placebo controls, for a total of 191 cycles. The combined average oestrus eCalm treated BS of 1.92 (±0.37) is highly significantly less than in untreated mares (4.24; ±0.5).

With the commercial launch of eCalm in 2015, the authors are accumulating experiences of owners and veterinary surgeons to support that this supplement provides an important solution to the common problem of oestrus bad behaviour in mares.
It is unknown how eCalm modifies oestrus behaviour. Further research is needed to understand whether it acts to suppress ovarian activity, including follicle development and oestrogen synthesis, or works by modifying and calming behaviour centrally.
Evidence is accumulating from work in other species to suggest eCalm has probiotic properties and its efficacy is due to an impact on the microbiome (Lederberg and McCray, 2001).
Other studies suggest eCalm has beneficial effects on geldings and on non-oestrus mares with behavioural problems, as well as on some skin, gut, and hoof conditions, that might also be medicated by effects on the microbiome.
Bad behaviour associated with oestrus is a common and frustrating problem in veterinary practice. It can make mares difficult to train and ride, result in poor performance, and present danger to those around mares. While a number of dietary supplements are marketed for control of oestrus behaviour, this research is unique in showing clear and significant benefits. It has the potential to substantially improve the training and performance of mares, as well as the safety of those working with them.
Notable advantages to using eCalm exist as a simple dietary supplement to calm oestrus behaviour, namely safety (to animal and handler), low cost (around 80p a day) and its use is permitted under international and national equestrian sporting rules.
Potential also exists, if necessary, to use eCalm alongside other treatments for abnormal oestrus behaviour, such as altrenogest, in those mares where a single treatment has not proved effective.
Initial ultrasound observations in mares receiving eCalm suggest it does not impact ovarian follicle development and, importantly, should not have a detrimental effect on fertility.