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2012

Bromocriptine Treatment for Inappropriate

Lactation in Mares: A Case Report

JOURNAL OF EQUINE VETERINARY SCIENCE, NEW YORK, v. 32, n. 12, pp. 840-843, DEC, 2012
http://www.producao.usp.br/handle/BDPI/42528

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 Journal of Equine Veterinary Science 32 (2012) 840-843

Journal of Equine Veterinary Science

journal homepage: www.j-evs.com

Case Report

Bromocriptine Treatment for Inappropriate Lactation in Mares:

A Case Report
Marcela Gonçalves Meirelles DVM a , Carina de Fátima Guimarães DVM a,
Mariana Baroni Selim DVM b, Francisco Palma Rennó PhD, DVM c, Carla Bargi Belli PhD, DVM d,
Claudia Barbosa Fernandes PhD, DVM a
a
Department of Animal Reproduction, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
b
Department of Surgery, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
c
Department of Nutrition and Animal Production, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
d
Department of Internal Medicine, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

a r t i c l e i n f o a b s t r a c t

Article history: Transient mammary gland development and lactation can occur eventually in weanling
Received 19 December 2011 foals, yearlings, and adult mares without previous or recent history of pregnancy. The
Received in revised form etiology of this condition has not been well documented, and there is limited information
13 March 2012
on the occurrence, frequency of episodes, composition, and treatment of galactorrhea
Accepted 21 March 2012
Available online 8 May 2012
secretion. This article reports a case of Brazilian Sport Horse mare, aged 10 years, with
persistent lactation during 5 months. The treatment consisted of bromocriptine 0.04 mg/
kg, b.i.d., orally, for 10 days, associated with hydrotherapy for 20 minutes, twice daily.
Keywords:
Persistent galactorrhea
After 20 days of the treatment onset, the mare was reevaluated, and a significant
Bromocriptine decrease in the volume of the udder and the amount of secretion produced was noted,
Equine and its aspect was clearer (serous) and consisted of more fluid compared with the one
Cushing collected before treatment. No other clinical alterations or associated diseases were
Prolactin identified. Based on these findings, we suggest the diagnosis of idiopathic inappropriate
lactation. Although there is no information about pharmacokinetics and description of
the oral bromocriptine use in horses, being a therapeutic option for inappropriate
lactation treatment in mares, it was effective at the recommended dosage.
Ó 2012 Elsevier Inc. All rights reserved.

1. Introduction adenohypophysis. Hyperprolactinemia is a common

Galactorrhea may be defined as secretion of milk or
milk-like secretion that occurs in the absence of parturition
or after weaning. Two conditions may be defined: prema-
ture lactation, when the lactation occurs precociously
during pregnancy, or inappropriate lactation, when lacta-
tion occurs in the absence of gestation [1].
In humans, galactorrhea occurs as a result of increased
plasma levels of prolactin, a hormone secreted by the
Corresponding author at: Claudia Barbosa Fernandes, PhD, DVM,
Departamento de Reprodução Animal, Av. Prof. Dr. Orlando Marques de
Paiva, 87, Cidade Universitária Universidade de São Paulo, 05508-270 São
Paulo, Brasil.
E-mail address: fernandescb@usp.br (C.B. Fernandes).
disorder of the hypothalamic-pituitary axis, which usually
presents with reproductive abnormalities [2,3]; it may be
caused by pituitary tumors, hypothyroidism, or secondary
effects of drugs [1,4].
A transient mammary gland development and lactation
can occur [5,6] eventually in weanling foals, yearlings, and
adult mares without previous or recent history of preg-
nancy. The etiology of this condition in these animals has
not been well documented [1,6]; additionally, there are few
reports on the occurrence, frequency of episodes, or
composition of the galactorrhea secretion [7].
The most commonly identified cause of inappropriate
lactation in mares is an elevation in prolactin levels,
secondary to Cushing disease [5,6,8]. In the literature, two

0737-0806/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.jevs.2012.03.012
 M.G. Meirelles et al. / Journal of Equine Veterinary Science 32 (2012) 840-843
mares were reported having these clinical signs [9]. Thus,
this report aims to describe galactorrhea in an animal
without clinical signs of Cushing disease and proposes
a new treatment option with the use of bromocriptine.
2. Case Report
A Brazilian Sport Horse mare, aged 10 years and
weighing 570 kg, kept in a stable and fed coast cross hay
and commercial concentrate (12% crude protein [CP]), was
presented at the Veterinary Hospital of the College of
Veterinary Medicine of the University of São Paulo, São
Paulo, Brazil, with a 5-month history of persistent lactation,
associated with discomfort caused by the swelling of the
udder and spontaneous ejection of milk (Fig. 1).
The mare was nulliparous, and it was never inseminated
or given any hormone treatment. The animal had no
contact with foals, and there were no data available from
previous reproductive examinations. Throughout the
period, no drug therapy was performed, and the only
procedure was milking daily, resulting in a total volume of
approximately 1 L of milk per day.
The inspection of the mare revealed a body condition
score equivalent to 5 (scale of 1-6) [10]. There were no
alterations in vital parameters during physical examination.
In gynecological evaluation, the uterus had normal wall
thickness and absence of free fluid, the left ovary had
multiple follicles with diameters smaller than 15 mm, and
the right ovary showed presence of corpus luteum. A firm
enlargement of the mammary gland was identified, and
there was no sensibility or hyperthermia. There was
spontaneous secretion and ejection by sphincters on both
teats. The collected secretion had milk-like appearance and
odor.
The treatment started before obtaining the laboratory
tests results. Bromocriptine was prescribed at a dose of 0.04
mg/kg, b.i.d., orally, for 10 days. Local hydrotherapy was
also recommended for 20 minutes, twice daily. Milking was
only allowed in situations where the mare was in extreme
discomfort due to swelling of the mammary gland, without
completely draining the secretion.
Samples of mammary gland secretion of both teats were
sent to the Laboratory of Milk Production, University of São
Fig. 1. Swelling of the udder and spontaneous milk ejection.
841
Paulo, for fat content analyses by the Gerber method, and
CP content by the Kjeldahl method, calculated by multi-
plying the total nitrogen by a factor of 6.38.
Sample of blood plasma was sent to B.E.T. Laboratories
for analyses of cortisol, triiodothyronine (T3), and total and
free thyroxine (T4) levels. The level of prolactin, which
would be interesting for this case, could not be measured
due to an absence of laboratories that perform this analysis
in the country.
Twenty days after treatment onset, the mare was
reevaluated and a significant decrease in the volume of the
udder and the amount of secretion produced was found, and
its aspect was clearer (serous) and consisted of more fluid
compared with the one collected before treatment.
3. Discussion
The results of the assessment of mammary secretion
were fat content between 0.8% and 0.9% and CP content
between 1.5% and 1.6%. These results are similar to the
values reported for equine milk obtained from Brazilian
breeds animals during the lactation period, in which the
amount of fat ranged from 0.86% to 1.70% and CP content
between 1.48% and 2.40% [11,12].
In hormonal evaluations, the results were 46.0 ng/dL for
cortisol, 1.15 ng/dL for total T3, 16.1 ng/dL for total T4, and
0.55 ng/dL for free T4. The value of free T4 (0.55 ng/dL)
appeared below the normal range considered for the
equine species (1.76 ng/dL until 4 ng/dL) [13-15]. However,
hypothyroidism in horses cannot be diagnosed by a single
measurement of T3 and T4 and must be based on one of the
thyroid gland stimulation tests [16].
The concentration of circulating iodothyronine can be
influenced by many factors not related to the thyroid,
including food deprivation [16-18], phenylbutazone
administration [16,19,20], circadian rhythm [14,16], and
dietary composition [16,21,22]. As women [23,24], rats [25],
cows, and sheep [26,27] have a state of relative hypothy-
roidism during lactation, with levels of circulating T3 and
T4 significantly lower [28], this condition may explain the
decrease in circulating T4 in the mare of this case report.
Thyroid hormones modulate the secretion of other
hormones that regulate the mammary function and milk
ejection, thus exerting an indirect regulation of the
mammary gland. Hypothyroidism is often associated with
galactorrhea in nonpregnant women, and in female virgin
rats under experimentally induced hypothyroidism, it is
known to be related to mammary development. All these
phenomena are associated with hyperprolactinemia
because of the hypothalamic secretion of thyrotropin-
releasing hormone (TRH) induced by hypothyroidism. In
addition to stimulating the secretion of pituitary thyroid
stimulating hormone, TRH is a potent stimulator of prolactin
secretion [25,28].
Prolactin is a single chain peptide hormone secreted by
lactotroph cells located in the adenohypophysis [29,30]. It
is essential for all stages of mammary gland development
and regulates the production and secretion of milk,
including protein synthesis, as casein and a-lactalbumin
[1,4,31]. Its secretion is regulated by dopamine, the main
prolactin inhibitor factor produced by hypothalamus [1,31].
The stimulatory signal for prolactin secretion may be
842 M.G. Meirelles et al. / Journal of Equine Veterinary Science 32 (2012) 840-843
mediated by TRH, vasoactive intestinal peptide, and
prolactin-releasing peptide [30]. The connections between
the hypothalamus and pituitary are critical in maintaining
the physiological secretion of prolactin, and any malfunc-
tion of the pituitary leads to the loss of inhibition by
dopamine and consequent hyperprolactinemia [3,32].
In women, increased prolactin levels present in cases of
pathological hyperprolactinemia result in effects equiva-
lent to those observed during the postpartum period, with
inhibition of gonadotropin-releasing hormone from the
hypothalamus and subsequent inhibition of follicle-
stimulating hormone and luteinizing hormones. This
results in suppressed gonadal function and promotion of
lactation, which explains why hyperprolactinemia is one of
the most common causes of anovulation. In severe cases of
hyperprolactinemia, galactorrhea and abnormal cycles are
often observed, whereas mild cases may be associated with
a short luteal phase, decreased libido, and anovulatory
infertility [30].
In the present study, the reproductive examination of
the mare showed no signs of dysfunction of the repro-
ductive tract. The presence of a corpus luteum indicates
cyclicity. However, because there was no possibility of the
follow-up of two consecutive reproductive cycles, we
cannot exclude that the mare did not have reproductive
disorders.
Hyperprolactinemia, secondary to Cushing disease, was
ruled out by the absence of clinical features of this
syndrome, such as hirsutism, hyperhidrosis, lameness,
lethargy, polyuria, polydipsia, weight loss, or redistribution
of adipose tissue [33]. Regardless of its low sensitivity,
a serum cortisol evaluation was performed in this study,
and the values were considered normal for adult horses
[15].
In approximately 30%-40% of women with hyper-
prolactinemia and galactorrhea, no tumors in the
hypothalamic-pituitary axis were detected. In such cases,
the disease was classified as idiopathic [30]. Similar to this
statement, we did not identify other clinical alterations or
diseases associated in this mare. Therefore, we propose the
diagnosis of idiopathic inappropriate lactation.
In the literature, there are few reports of therapeutic
options for the treatment of inappropriate lactation in
mares. The drugs mentioned are dopaminergic agonists
used to treat hyperprolactinemia in humans, such as
bromocriptine, cabergoline, and quinagolide [30]. In this
study, we chose oral bromocriptine because of its lower
cost.
Bromocriptine was the first dopamine agonist to be
widely used in the treatment of hyperprolactinemia in
humans [32]. This ergot alkaloid is also used for the treat-
ment of prolactinomas or other micro- or macroadenomas
of the pituitary gland, in cases of menstrual disorders, and
in Parkinson disease. In equine medicine, it is used for
treating Cushing disease [34]. The mechanism of action is
by its binding to dopaminergic receptors (D2) on the
surface of the lactotrophic cells in adenohypophysis,
reducing the activity of adenylate cyclase and inhibiting
prolactin secretion [30,32,34].
Bromocriptine is well established as a safe and effective
therapy [30,35,36]. However, its dosage, efficacy, and side
effects are not well defined in the mare [1,37]. There is no
basic information on pharmacokinetics of bromocriptine in
horses, and the use of oral formulation in this species has
not been reported yet [34]. The administration of bromo-
criptine at a dose of 0.08 mg/kg, b.i.d, intramuscularly, in
ponies during the final third of gestation period caused
a reduction in plasma levels of prolactin and progesterone
and induced clinical signs similar to those observed in
pregnant mares intoxicated by the fungus Acremonium
coenophialum in fescue pastures [1,37].
Bromocriptine in this case report provided a rapid
remission of clinical signs. However, the milking interrup-
tion may have contributed to the early resolution of this
case, with consequent inhibition of the reflex that leads to
the release of oxytocin by the posterior lobe of the pituitary
gland [1,31].
4. Conclusions
In this case, no apparent clinical disorders or associated
diseases were identified; therefore, we suggest the diag-
nosis of idiopathic inappropriate lactation for the
mentioned animal. The treatment with bromocriptine at
a dose of 0.04 mg/kg, b.i.d, orally, for 10 days, associated
with local hydrotherapy and not milking provided rapid
improvement of clinical signs and resolution of the inap-
propriate lactation, without the occurrence of side effects.
The protocol proposed was effective in the case reported
and can be considered as a therapeutic option for the
treatment of idiopathic inappropriate lactation in mares.
Acknowledgments
The authors thanks Maria Augusta Alonso, DVM, MSc
(Guta), for article review and B.E.T. Laboratories.
References
[1] Chavette P. Lactation in the mare. Equine Vet Educ 1997;9:62-7.
[2] Biller BM, Luciano A, Crosignane PG, Molitch M, Olive D, Rebar R,
et al. Guidelines for the diagnosis and treatment of hyper-
prolactinemia. J Reprod Med Suppl 1999;44:1075-84.
[3] Holt RI. Medical causes and consequences of hyperprolactinaemia. A
context for psychiatrists. J Psychopharmacol 2008;22:28-37.
[4] Frantz AG, Wilson JD. Endocrine disorders of the breast. In:
Wilson JD, Foster DW, editors. William’s Textbooks of Endocri-
nology. Philadelphia, PA: Saunders; 1985. p. 402-21.
[5] McCue PM. Lactation in Mares. In: McKinnnon AO, Voss JL, editors.
Equine Reproduction. Philadelphia, PA: Lea and Febiger; 1993. p.
588-95.
[6] McCue PM, Sitters S. Lactation. In: McKinnon AO, Squires EL,
Vaala WE, Varner DD, editors. Equine Reproduction. 2nd ed. Oxford,
United Kingdom: Wiley-Blackwell Publishing; 2011. p. 2277-90.
[7] Reis AP, Nicolau ES, Mesquita AJ, Curado EA, Neves RB, Arruda ML.
Ocorrência de galactorréia em égua: comparação entre as compo-
sições da secreção mamária galactorreica com o leite equino sau-
dável. ARS Veterinária Jaboticabal 2009;25:116-9.
[8] McCue PM. Equine Cushing’s disease. Vet Clin N Am Equine Pract
2002;18:533-43.
[9] McGowan CM, Neiger R. Efficacy of trilostane for the treatment of
equine Cushing’s syndrome. Equine Vet J 2003;35:414-8.
[10] Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between
condition score, physical measurement, and body fat porcentage in
mares. Equine Vet J 1983;15:371-2.
[11] Reis AP, Mesquita AJ, Moreira CH, Curado EA, Silva EB, Nicolau ES.
Composição do leite de éguas da raça Mangalarga Marchador.
Revista do Instituto Adolfo Lutz 2007;66:130-5.
[12] Santos EM, Almeida FQ, Vieira AA, Pinto LF, Corassa A, Pimentel RR,
et al. Lactation in Mangalarga Marchador mares: yield production
 M.G. Meirelles et al. / Journal of Equine Veterinary Science 32 (2012) 840-843
and composition of milk, and weight gain of suckling foals. R Bras
Zootec 2005;34:627-34.
[13] Chen CL, Riley AM. Concentração de tiroxina e triiodotironina no
soro sangüíneo de potros neonatal e cavalos adultos. Am J Vet Res
1981;8:1415-7.
[14] Duckett WM, Manning JP, Weston PG. Thyroid hormone periodicity
in healthy adult geldings. Equine Vet J 1989;21:123-5.
[15] Teixeira PP, Pádua JT. Avaliação dos níveis de cortisol, tiroxina,
triiodotironina e glicose como indicativos de estresse em cavalos
puro sangue Inglês de corrida antes e após a competição. Ciência
Animal Brasileira 2002;3:39-48.
[16] Jonhson PJ, Messer IV, Ganjam VK, Thompson JR, Refsal KR, Loch WE,
et al. Effects of propylthiouracil and bromocriptine on serum
concentrations of thyrotrotrophin and thyroid hormones in normal
female horses. Equine Vet J 2003;35:296-301.
[17] Messer NT, Johnson PJ, Refsal KR, Nachreiner RF, Ganjam VK,
Krause GF. Effect of food deprivation on baseline iodothyronine and
cortisol concentrations in healthy mature horses. Am J Vet Res
1995;56:116-21.
[18] Christensen RA, Malinowski K, Massenzio AM, Hafs HD, Scanes CG.
Acute effects of short-term feed deprivation and refeeding on
circulating concentrations of metabolites, insulin-like growth factor
I, insulin-like growth factor binding proteins, somatotropin, and
thyroid hormones in mature geldings. J Anim Sci 1997;75:1351-8.
[19] Morris DD, Garcia M. Thyroid-stimulating hormone: response test
inhealthy horses, and effect of phenylbutazone on equine thyroid
hormones. Am J Vet Res 1983;44:503-7.
[20] Sojka JE, Johnson MA, Bottoms G. Serum triiodothyronine, total
thyroxine, and free thyroxine concentrations in horses. Am J Vet Res
1993;54:52-5.
[21] Glade MJ, Reimers TJ. Effects of dietary energy supply on serum
thyroxine, triiodothyronine and insulin concentrations in young
horses. J Endocrinol 1985;104:93-8.
[22] Swinker AM, McCurley JR, Jordan ER. Effects of dietary excesses on
equine serum thyroid hormone levels. J Anim Sci 1989;65:255-6.
[23] Strbak V, Macho L, Uhercik D, Kliment V. The effect of lactation on
thyroid activity of women. Endokrinologie 1978;72:183-7.
843
[24] Iwatani Y, Amino N, Tanizawa O, Mori H, Kawashima M, Yabu Y, et al.
Decrease of free thyroxin in serum of lactating women. Clin Chem
1987;33:1217-9.
[25] Hapon MB, Simoncini M, Via G, Jahn GA. Effect of hypothyroidism on
hormone profiles in virgin, pregnant and lactating rats, and on
lactation. Reproduction 2003;126:371-82.
[26] Collier RJ, McNamara JP, Wallace CR, Dehoff MH. A review of
endocrine regulation of metabolism during lactation. J Anim Sci
1984;59:498-510.
[27] Riis PM, Madsen A, McNamara JP, Wallace CR, Dehoff MH. A review
of endocrine regulation of metabolism during lactation. J Endocrinol
1985;107:421-7.
[28] Jabn GA, Hapon MB. Hipotiroidismo, función mamaria y lactancia.
Revista de Endocrinología Ginecológica y Reproductiva 2006;32:
3-9.
[29] Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure,
function, and regulation of secretion. Physiol Rev 2000;80:1523-631.
[30] Crosignane PG. Current treatment issues in female hyper-
prolactinaemia. Eur J Obstet Gynecol Reprod Biol 2006;125:152-64.
[31] Santos EM, Zanine AM. Lactação em éguas. Revista Portuguesa de
Ciências Veterinárias 2006;101:17-23.
[32] Ben-Jonathan N, Hnasko R. Dopamine as a prolactin (PRL) inhibitor.
Endocr Rev 2001;22:724-63.
[33] Love S. Equine Cushing’s disease. Br Vet J 1993;149:139-53.
[34] Sojka JE, Levy M, Cauetil L. Drugs acting on the endocrine system. In:
Bertone J, Horspool LJ, editors. Equine Clinical Pharmacology.
Oxford, United Kingdom: Saunders; 2004. p. 75-83.
[35] Vance ML, Evans WS, Thorner MO. Drugs 5 years later. Bromocrip-
tine. Ann Intern Med 1984;100:78-91.
[36] Essais O, Bouguerra R, Hamzaoui J, Marrakchi Z, Hadjiri S,
Chamakhi S, et al. Efficacy and safety of bromocriptine in the
treatment of macroprolactinomas. Ann Endocrinol (Paris) 2002;63:
524-31.
[37] Ireland FA, Loch WE, Worthy K, Anthony RV. Effects of bromocrip-
tine and perphenazine on prolactin and progesterone concentra-
tions in pregnant pony mares during late gestation. J Reprod Fert
1991;92:179-86.