Inappropriate lactation in a 15-year-old thoroughbred mare

Abstract

A 15-year-old thoroughbred non-pregnant mare was presented with ongoing inappropriate lactation. The most likely cause, equine Cushing’s disease, was ruled out through biochemical testing. Milk cytology and bacterial culture showed no evidence of mastitis or neoplasia. Idiopathic inappropriate lactation was diagnosed and treatment with pergolide was recommended.

In June 2018, a 15-year-old thoroughbred mare was presented with ongoing inappropriate lactation. The client had owned the mare for 1 y, and the previous owner indicated that the mare had been lactating inappropriately for at least 2 y. The present and previous owners had neither bred the mare nor administered exogenous progesterone, but the mare’s medical and breeding history before that was unknown. In July 2016, the mare underwent pregnancy diagnosis due to weight gain and dripping milk. During that examination, rectal palpation revealed that the mare was not pregnant and there was no evidence of mastitis. At the time, it was suspected that the lactation was related to hormonal fluctuations, but there was no further work-up or treatment. In October 2017, the current owner had noted milk dripping from the udder, which was treated by stripping the udder and applying Bag Balm (Vermont’s Original; Lyndonville, Vermont, USA). This treatment was repeated in March and June 2018. The fluid expressed from the udder was initially brown and granular, but by the second stripping of the udder, resembled milk in consistency and color.

The previous owner turned the mare out on pasture during the day and stabled her at night. The current owner kept the mare outdoors where her diet consisted of pasture and hay as well as a free-choice salt block (Greenhawk, Mississauga, Ontario). Pasture was supplemented with 1 cup of feed (Purina Equilibrium Equilizer; Cargill, Minnetonka, Minnesota, USA) and a yeast culture formula (Yea-Sacc; Nobelton Feed Mill, Nobelton, Ontario) 5 times a week. Methylsulphonylmethane (MSM) (Purica MSM; The Nutraceutical Medicine Company, Duncan, British Columbia) was also given if the mare appeared sore after being ridden.

At presentation, the mare was bright and alert, with a body condition score of 4 out of 5. Results of physical examination were within normal limits with a temperature of 37.9°C, heart rate of 44 beats/min, and respiratory rate of 20 breaths/min. A detailed examination of the udder revealed it to be fluid-filled with engorged teats, but normal on palpation. The udder did not feel warm or hard, and there were no palpable masses.

On trans-rectal ultrasound examination, there was a normal appearing uterus, a 4-cm follicle on the left ovary, and multiple small follicles on the right ovary, consistent with estrus. The owner described the frequency and duration of the mare’s heat cycles as normal.

Whole blood and blood samples with ethylenediaminetet-raacetic acid (EDTA) were taken for serum and plasma for a Cushing’s disease laboratory panel (Animal Health Laboratory, Guelph, Ontario). Concentrations of plasma adrenocorticotropic hormone (ACTH) at 4.9 pmol/L [reference interval (RI): 2 to 10 pmol/L], serum glucose at 5.2 mmol/L (RI: 3.7 to 6.7 mmol/L), and serum insulin at 112 pmol/L (reference value: < 300 pmol/L) were all normal.

A full stream of milk was easily obtained from both teats for cytology and culture. Milk samples appeared white and cloudy, with milk from the left teat appearing slightly clearer. Results of the cytological evaluation are summarized in Table 1. Cytology revealed mixed leukocytes with a proteinaceous and lipidic background from the right teat and a mildly proteinaceous background from the left teat. Milk from the right teat had a higher cell count than milk from the left, had phagocytic macrophages, and was interpreted as having mild (chronic) non-suppurative inflammation. Small aggregates of amorphous pale blue-staining proteinaceous material were found as well. The sample from the right teat had non-degenerate neutrophils and small and mature lymphocytes. There was no evidence of atypical cells. The overall response was interpreted to be inconsistent with a septic process or neoplasia.

Table 1.

Milk cytology results from both teats of a 15-year-old mare with inappropriate lactation. Reference descriptive values are taken from Albrecht 2007 (20).

Milk sample	Left teat	Right teat	Normal milk	Normal mammary involution	Mastitis
Color	White	White	White	White	Yellow to yellowish-brown/gray
Consistency	Thin	Thin	Thin	Thin to thick	Thin to thick
Protein	Mildly proteinaceous background	Proteinaceous background with occasional small aggregates	Present, granular background with trichome stain	Generally present	Present
Nucleated cells (× 109/L)	7.5	28.8
Protein TS (g/L)	41	38
Differential count Neutrophils	9%	17% Non-degenerate	Absent	Few present early in involution, degenerate present in late involution	Present
Lymphocytes	29%	42% Small and mature	Absent	May be present (small dark cells resembling lymphocytes)
Macrophages/foam cells	62%	41% Sometimes phagocytic	Absent	Present late in involution	Present/absent

TS — total solids.

Bacterial culture of the sample from the left teat revealed no bacterial growth, while the report from the sample from the right teat indicated “no bacterial pathogens detected,” suggesting contamination with surface bacteria.

The most widely accepted theory is that inappropriate lactation in non-pregnant mares is secondary to equine Cushing’s disease (ECD). In the absence of evidence for ECD, the mare was diagnosed with idiopathic inappropriate lactation. As administration of pergolide and reduction of dietary intake in energy and protein are recommended, we suggested treatment of the mare with pergolide for 2 wk, but this treatment was not adopted. As stripping of the udder can delay involution and promote lactation, we advised the owner to discontinue milking the mare.

Discussion

Galactorrhea is defined as persistent discharge of milk from the udder after weaning or in the absence of parturition (1). Inappropriate lactation is a subset of galactorrhea, specifically occurring in the absence of gestation (1). This happens in neonatal foals (termed “Witches Milk”) or in older, non-pregnant mares (1,2). Mares with inappropriate lactation are described as having mild to moderate amounts of mammary secretion without heat or pain in the udder (3). These mammary secretions have been described as milk and milk-like (1). However, cases are rarely reported in the literature and causes are poorly defined (4,5).

Development of the mammary gland and subsequent milk production are stimulated by hormones including prolactin, estrogens, and progesterones (1). In healthy pregnant mares, estrogen causes development of the mammary ducts while progesterone stimulates lobuloalveolar growth (4). Progesterones also inhibit milk production until late gestation when levels decline and prolactin increases (4). Prolactin, produced by lactotrophs in the anterior pituitary gland and regulated by dopamine secreted by the hypothalamus, is elevated until 1 to 2 mo postpartum (4).

Hormones that influence lactation are under the control of the hypothalamic-pituitary axis, ovaries, and the placenta (4). However, hormones can be affected by husbandry and disease. Causes of inappropriate lactation are not well-understood, but there are a few prevalent theories. In non-pregnant mares, the most common cause is thought to be increased prolactin secondary to equine Cushing’s disease (ECD) (2,4). In healthy animals, dopamine is secreted by the hypothalamus, inhibiting hormone secretion from the pituitary pars intermedia (6). With ECD, there is a lack of dopamine control, thereby forfeiting the inhibitory effect on the pars intermedia (6). This leads to hypertrophy and hyperplasia of the gland, and secretion of excess pituitary hormones (6). Dopamine has an inhibitory effect on prolactin and lack of dopaminergic control leads to increased prolactin levels. Inappropriate lactation has been stated to be a clinical sign of ECD (5–8). However, the mare in the present case showed no evidence of ECD and laboratory tests were normal.

Inappropriate lactation may also be associated with intake of phytoestrogens (5). Certain legumes and supplements in a horse’s diet, including soy, clover, alfalfa, and flaxseed, contain phytoestrogens (9,10). Phytoestrogens compete with endogenous estrogen and influence reproduction in various species (9). In ewes and cows, phytoestrogens have been shown to enlarge mammary glands that may secrete a milk-like fluid. Although intake of phytoestrogens has been shown to disrupt a mare’s estrous cycle and cause reproductive pathologies, there is no research linking phytoestrogenic compounds with inappropriate lactation in horses. It is also believed that inappropriate lactation in neonates may be caused by lactogenic hormones from the mare eating spring grasses with phytoestrogens (11). It may have been beneficial to determine phytoestrogen levels in this case, but feed analysis was not conducted.

In the absence of evidence for ECD, a diagnosis of idiopathic inappropriate lactation was made. Idiopathic inappropriate lactation is diagnosed in human medicine in women with hyperprolactinemia and galactorrhea without detectable tumors in the hypothalamus or pituitary gland (2). Other conditions were considered to determine a possible cause of the mammary gland secretion.

An enlarged udder with secretions may result from mastitis or mammary neoplasia. Both conditions are rare in horses and are revealed by physical examination and milk cytology (4,12–14). Physical findings include palpable heat or pain, or masses in the udder (4,12,14). However, there were no clinical signs at the recent presentation indicating mastitis or neoplasia. Bacterial culture results were also negative, although bacterial culture fails to identify bacteria in up to 30% of cases of mastitis (12). However, the milk initially appeared brown and granular, which is consistent with mastitis (13). Additionally, cytological evaluation revealed mixed leukocytes which were predominantly macrophages. This is not consistent with acute mastitis, but it may be interpreted as chronic inflammation because of chronic mastitis. However, chronic mastitis without an active neutrophil component has not been detected and macrophages and small cells in an involuting gland should not be interpreted to represent chronic inflammation (15).

Abnormal udder development and subsequent lactation can be caused by administration of exogenous hormones or having previously foaled. In non-pregnant mares, treatment with estrogen, progesterone, and a dopamine D2 antagonist mimics the physiology of lactation and results in its onset within 2 wk (16). Older, multiparous mares may also have large teat or gland cisterns that fill with secretions without active lactation or pregnancy (3). A persistent state of continuous secretion and involution may also exist for years after weaning a foal (15). The mare in this case had no known history of previous foaling or drug administration although her history before 3 y ago is unknown.

Following weaning, continued stripping of the udder either by other nursing foals or the owner can delay involution and allow continued lactation (4). However, the mare in this case was not milked by the owner until October 2017, and according to the previous owner’s history, had been continuously lactating for at least 2 y. Additionally, the owner reported infrequent stripping of the udder, and no weanlings in her current pasture. As a precautionary measure, the owner was advised to discontinue milking to prevent further stimulation, milk production, and possible mastitis.

Treatment of inappropriate lactation depends on the identified cause. For mares with ECD, dopamine agonists such as pergolide, and antiserotonergic drugs like cyproheptadine are used as treatment (4,6). Trilostane has also been used successfully (8). In mares without ECD that have inappropriate lactation of unknown origin, most cases resolve spontaneously within weeks to months (5). There are few reports of treatment of idiopathic inappropriate lactation, but the recommendations are administration of pergolide and reduction of dietary intake in energy and protein by discontinuing grain and replacing alfalfa with grass hay (4). In a 2012 case study, a 10-year-old Brazilian Sport Horse mare with idiopathic inappropriate lactation for 5 mo was successfully treated with bromocriptine for 10 d along with hydrotherapy twice daily (2). However, the study did note that milk production may have subsided anyway once they stopped regularly milking the mare (2). Bromocriptine is a dopamine receptor agonist, historically used to treat hyperprolactinemia in humans and is currently used to treat galactorrhea in dogs and ECD (2,17). Interestingly, it was also noted in another study that mares with unexplained mammary growth and apparent lactation had normal levels of plasma prolactin levels (18).

Onset of clinical signs in ECD can be subtle for 1.5 to 4 y before more obvious signs occur (7). This may be why pergolide is the recommended treatment and bromocriptine was able to improve idiopathic inappropriate lactation, despite mares not showing other clinical signs of ECD (2). It would be of interest to see if the mare develops more traditional signs of ECD in the future. Removal of the yeast culture formula from her diet may also be beneficial as it was advertised to stimulate milk production in lactating mares and has been shown to increase milk production during the 3rd wk of lactation (19). Further workup could include feed analysis to determine phytoestrogen levels and another ultrasound to ensure the mare was cycling properly. An ultrasound of her udder may also be useful to identify potential mammary neoplasia or abscesses missed on palpation.

Inappropriate lactation can be a worry for owners concerned about horse comfort and potential for mastitis. Milk production is also a metabolically energetic process, and an enlarged udder can be more susceptible to injury. Although its cause is unclear, treatment with dopamine agonists can be attempted to prevent udder development and lactation. There is need for evaluation of cases of inappropriate lactation to understand etiology and prevalence in horses that may help with treatment and resolution of its occurrence.