Pyometra in the queen To spay or not to spay? · 2016-02-10 · pyometra by the age of 13 years.1The incidence of pyometra is considered to be lower in queens than in bitches, as

JFMS CLINICAL PRACTICE 21

C L I N I C A L r e v i e w

Journal of Feline Medicine and Surgery (2016) 18, 21–33

Fiona Hollinshead and Natali Krekeler

Pyometra in the queen

To spay or not to spay?

Practical relevance: Pyometra is a commonly occurring uterine disease in cats that often leads to loss ofbreeding potential and, in some cases,can be life threatening. An increasedincidence of cystic endometrial hyperplasia (CEH)and pyometra is seen with age. Most queenspresent with uterine lesions after 5–7 years of age(average 7.6 years, range 1–20 years). Clinical signsmost commonly occur within 4 weeks of the onsetof oestrus in queens that are either mated,spontaneously ovulate or are induced to ovulate(mechanical stimulation or hormone induction). The disease is most often observed in dioestrus.Clinical challenges: Queens with pyometra oftengo undiagnosed as there may be few or only verymild clinical signs and laboratory changes. Forexample, the classic sign of mucopurulent bloodyvulvar discharge often goes unnoticed. Abdominalultrasound is the best tool for diagnosis ofpyometra and for monitoring response to therapy.Patient group: Classically, middle-aged/oldernulliparous intact queens present with pyometra.However, so-called ‘stump pyometra’ can occur if ovarian tissue is left behind during ovariectomy or ovariohysterectomy (ovarian remnant syndrome).Queens treated with exogenous steroid hormonessuch as high doses of megestrol acetate ormedroxyprogesterone acetate for oestrusprevention can also develop CEH and pyometra.Evidence base: There has been little published to date on CEH, endometritis and pyometra in the queen and most of the currently availableinformation has been extrapolated from studiescarried out in the bitch. The queen and the bitchhave very different reproductive physiology; thus,further research and investigation into the preciseaetiopathogenesis of these disease processes ofthe uterus in the queen is warranted. Audience: This review is aimed at cliniciansworking in small animal practice, especially those in countries where surgical sterilisation is notpractised as commonly as in the United States,Canada or Australasia, and who will therefore see a greater proportion of intact queens.

Fiona HollinsheadBVSc(Hons) MACVS PhD Diplomate ACT*GlenBred, Matamata Veterinary Services,

26 Tainui Street, Matamata 3400, New Zealand

Natali KrekelerDr Med Vet PhD Diplomate ACT

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Werribee,

VIC 3030, Australia

*Corresponding author: [email protected]

Introduction

Pyometra is an acute or chronic suppurative inflammation of the uter-ine wall in intact queens. It is characterised by endometrial hyperplasiawith cystic dilation of endometrial glands and accumulation of puru-lent exudate in the uterine lumen. The disease is most often observed indioestrus or ‘pseudopregnancy’ in the queen, which is a phase of prog-esterone dominance that lasts approximately 40 days. The relativelylong progesterone-dominated dioestrous phase occurs in queens thatundergo ovulation (induced or spontaneous) and predisposes them tothe development of cystic endometrial hyperplasia (CEH) and subse-

doi: 10.1177/1098612X15623114

© The Author(s) 2016

A recent study from Sweden reported that 2.2% of intact queens were diagnosed withpyometra by the age of 13 years.1 The incidence of pyometra is considered to be lowerin queens than in bitches, as queens are induced ovulators. However, underestimationof disease incidence is likely because queens often do not express clinical signs to thesame extent as seen in bitches.2 Furthermore, it seems that, despite being inducedovulators, spontaneous ovulation is not as uncommon in queens as originally thought.There have been various reports of spontaneous ovulation in the queen, with inci-dence ranging from 30% up to 87%!3–5 Despite many hypotheses, the underlyingcause of spontaneous ovulation in the queen is still unknown, but may be influencedby breed, increasing age and parity. Recently, a breed predisposition has been report-ed, with Oriental purebred cats having a higher incidence of pyometra than domesticand random-bred cats.1 This has also been observed by the authors. Oriental pure-bred cats are additionally known to come into oestrus year-round and often have shortinteroestrus intervals (associated with overlapping follicular waves)6 compared withdomestic shorthair and random-bred cats. Furthermore, Oriental queens have a higherincidence of spontaneous ovulation than other cats. Therefore, the uterus of Orientalqueens is exposed to more frequent oestrogen priming and periods of high proges-terone concentration. These two factors are hypothesised to contribute to the higherincidence of pyometra in young Oriental breed cats compared with other cats of sim-ilar age. In the aforementioned large Swedish retrospective study,1 the median age ofdiagnosis of pyometra in Oriental/exotic purebred queens (Sphynx, Siberian, Ocicat,Korat, Siamese, Ragdoll, Maine Coon and Bengal) was significantly lower (4 years; P <0.05) than that reported for the general cat population (>7 years).2

Inc idence o f fe l ine pyometra

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quent pyometra caused by infection from bacteria ascending from the vagina. The mostcommon bacterium involved in pyometra isEscherichia coli. Similar to the bitch, regardlessof the underlying cause, the presence of proges -terone (endogenous or exogenous in source)facilitates the development of pyometra.

The incidence of feline pyometra (see boxon page 21) is not well documented.

Pathogenesis and aetiology: what comes first?

Cats are classified as seasonally polyoestrus,coming into oestrus between spring and earlyautumn with a seasonal anoestrus in winter(long-day breeders). The oestrous period or‘call’ lasts 6–7 days. if ovulation (either inducedor spontaneous) occurs but the queen does not become pregnant, there follows a period of progesterone secretion (from the corpusluteum) for approximately 40 days. This is thedioestrous phase (or so-called pseudopregnan-cy). Cats that undergo an anovulatory oestruswill have an interoestrus interval of about 8–10days with baseline progesterone levels.

The pathogenesis of pyometra is incomplete-ly understood – both in the bitch and thequeen, but especially the queen being aninduced ovulator. in the bitch, pyometra is cur-rently believed to be multifactorial in origin. itis most likely similar in the queen. The aetiolo-gy is similar in the two species, with proges-terone influence predisposing the uterus toascending bacterial (most com-monly E coli) infection.

originally CEH and pyometrawere defined as one disease enti-ty. it was believed that repeatedexposure of the endometrium tohigh concentrations of oestrogenduring proestrus and oestrus, followed by high concentrationsof progesterone during the lutealphase (ie, dioestrus), led to thedevelopment of CEH (Figure 1).This, in turn, predisposed theuterus to ascending secondarybacterial infection and develop-ment of pyometra. More recently,the question has been raised as towhether pyometra and CEH areactually two separate diseaseentities. Although the conditionshave many similarities and canbe found as related events, theyalso have the potential to occurde novo. Any stimulus or irritantin a progesterone-influenced uterus can leadto CEH,7–9 and thus the presence of CEH inpyometra could merely be the result of a uterine reaction to the bacterial infection. This

REV IEW / Pyometra in the queen

could explain why we see pyometra in youngcats, which are unlikely to have underlyinguterine pathology such as CEH. in bitches, it ishypothesised that varying pathogenicity of E coli strains might be responsible for thedevelopment of CEH. No studies investigatingthe effects of bacterial pathogenicity in pyome-tra have been undertaken in cats.

What role do reproductive hormones play?The majority of queens affected by pyometraare presented with clinical signs within 4weeks of the onset of the latest oestrus.Although there is no evidence that abnormalovarian hormone concentrations are involvedin the pathogenesis of pyometra in queens orbitches, it has been shown that progesterone isnecessary to initiate CEH and that oestrogenpotentiates the effect by upregulating theexpression of progesterone receptors.

Therefore, pyo metra is believedto be facilitated by an oestrogenicphase that is followed by a relatively long non-pregnant pro gesterone-dominated phase(dioestrus caused by spon taneousor induced ovulation).

Leukocyte inhibition, decreas -ed myometrial contractions and aclosed cervix in the progesterone-influenced uterus facilitate bac -terial growth in a non-graviduterus from ascending infection.Progesterone also stimulatesuterine stromal and glandularepithelial proliferation andincreases uterine glandular secre-tions, which are an importantsource of nutrients for the earlydeveloping embryos/fetuses inpregnant queens. These effectsare cumulative in spontaneouslyovulating cats or cats that experi-ence repeated matings that do

not result in pregnancy. Thus, the risk of uter-ine disease may increase with each non-preg-nant oestrous cycle, as the presence of fetusesis effectively protective against the develop-

The risk ofuterine diseasemay increasewith each

non-pregnantoestrous cycle,

as thepresence offetuses iseffectivelyprotectiveagainst thedevelopment of pyometra.

Figure 1 Opened uterinehorn from a queen withsevere cystic endometrialchanges in the uterine wallbut no evidence of pyometra.Copyright: Dr Stephanie NSimpson. Source: LORI

Pivotal role of progesterone Importantly, regardless of the underlying causeof pyometra, the presence of progesterone(exogenous or endogenous) is required forpyometra to occur. This was confirmed in a canine disease model where intrauterineinoculation of a pathogenic strain of E coli inoestrus or anoestrus did not result in pyometrabut inoculation of the same strain in dioestrusdid.7 No comparable studies have beenpublished in the queen.






ment of pyometra. This finding was first dis-covered by Dow who reported that nulli-parous bitches with pyometra outnumberedmultiparous bitches with pyometra byapproximately 10-fold.10 A similar effect isthought to hold true for queens.

However, it has also been shown that proges-terone exposure alone, without prior oestrogenpriming, can lead to CEH in the queen.11 Thetheory that progesterone is critical for thedevelopment of pyometra is supported by thefact that the use of exogenous steroid hormones(progestins such as megestrol acetate [MA] ormedroxyprogesterone acetate [MPA]) for con-traceptive purposes has been shown to inducethe disease in both bitches and queens.7,12

Another observation that supports the essentialrole of progesterone in the disease process, atleast in the canine species, is that the incidenceof pyometra is similar in ovariectomised andovariohysterectomised bitches.13

Which bacteria are commonly involved?In most cases of pyometra, the bacteria isolatedare uropathogenic E coli. Other bacteria, mostlynormal vaginal commensals such as Staphy -lococcus aureus, Klebsiella species, Proteus speciesand Streptococcus species, have also been report-ed in cases of pyometra. The uterus is presumedto become infected via ascent of faecal bacteriathrough the vagina during oestrus when thecervix is relaxed.14 It has been shown that E coliare capable of establishing an infection in veryyoung healthy dogs, which are unlikely to haveunderlying CEH changes.7 This may be anotherexplanation for cases of pyometra in youngqueens. It is hypothesised that bacteria enter the uterus during proestrus and/or oestrus and act as a mucosal irritant, thus stimulating thedevelopment of CEH under the influence ofprogesterone during dioestrus.

Factors other than bacterial virulence arealso likely involved in the pathophysiology ofpyometra in the queen, such as deficiencies inthe innate immune response and inheritanceof susceptibility.

What is the evidence for a geneticpredisposition? Previously, no breed predisposition for pyome-tra in queens had been reported. However, a ret-rospective study carried out in Sweden1 foundthat Oriental purebred cats have a higher inci-dence of pyometra than other breeds, with theSphynx breed having the highest incidence.Other breeds with a predisposition include theSiberian, Ocicat, Korat, Siamese, Ragdoll, MaineCoon and Bengal.1 Furthermore, in the authors’experience there are families that have a higherincidence of pyometra. These related queens are often geographically isolated, suggesting ahereditary predisposition to pyometra.

E n d ome t r i t i s

Endometritis is inflammation of the endometrium. Aside from chronic infertil-ity, clinical signs of endometritis are rarely seen in the bitch or queen. Inbitches, an infectious agent(s) is a common underlying cause.11 However, little information has been published on endometritis in either the bitch9,15 orqueen. This is mainly due to the difficulty in collecting uterine samples forinvestigation (eg, cytology and bacteriology) using a non-invasive techniqueand without causing further pathology.

Due to these limitations, a trial of antibiotic therapy should be consideredin young breeding queens that repeatedly fail to become pregnant despite correctly timed matings, and with any of the following history:< Confirmation of ovulation by either blood progesterone assay or ovarian

ultrasound; < Mated to more than one unrelated proven male; < No abnormalities detected on complete physical (including genital)

examination; < No abnormalities found after ultrasonography of the reproductive tract

(uterus and ovaries); < Neutrophils observed during cytological oestrus (ie, presence of 100%

superficial or cornified epithelial cells [Figure 2]).

The most common infectious agents isolated in cases of endometritis arenormal vaginal flora. Therefore, use of a broad spectrum antibiotic with gooduterine penetration such as clindamycin (5.5 mg/kg PO q12h) oramoxicillin/clavulanic acid (12.5 mg/kg PO q12h) is recommended. Antibiotictherapy should be started during oestrus and continued for approximately2–3 weeks. Abdominal ultrasound should be performed after breeding (16 days after ovulation) to determine if the queen is pregnant or if there isuterine pathology, as indicated, for example, by the presence of intraluminalfluid or hyper echogenicity of the endometrium. Antibiotics are discontinuedif the queen is pregnant or if there is no evidence of infection or inflammation.Thereafter, ongoing monitoring of fetal viability with weekly ultrasound exam-inations is recommended until parturition.

If uterine fluid is present, either medical or surgical treatment is neededdepending on the age and breeding value of the queen (see pages 27–30). Ifthe queen is not pregnant but has evidence of cystic endometrial hyperplas-tic changes (see page 25) then aglepristone therapy to remove progesteroneand its negative influences on a non-pregnant uterus may be beneficial tofuture fertility.16 In a valuable breeding queen, uterine biopsy for the diagnosisof endometritis (by bacterial culture and cytology) and/or CEH (byhistopathology) could be performed at this time.15 It is important that thequeen is treated with aglepristone immediately after the biopsy procedure toprevent the risk of a subsequent pyometra.

Figure 2 Vaginalcytology smeartaken duringoestrus in a queenwith endometritis.Note the presenceof a cornifiedsquamous vaginalepithelial cell, alarge number ofneutrophils, redblood cells andbacteria in thebackground.Differentialinterferencecontrastmicroscopy, oilimmersion, x 1000





Diagnostic approach

Signalment/historyRisk factors for pyometra in queens include:< Age Typically, middle-aged to older queens(>5–7 years) with a history of oestrus withinthe previous 4 weeks are affected (althoughpyo metra can be seen in younger queens, Table 1);< Breed orientals and purebreeds (ie,Siberian, ocicat, Korat, Siamese, Ragdoll,Maine Coon, Burmese, Birman and Bengal) are predisposed;< Drug therapy A history of treatment with progestins for prevention of oestrus(particularly high-dose regimens of MA [>0.2mg/kg q24h] or MPA [>0.05 mg/kg q24h] fordurations >1 year,17 especially in older queens),or pharmacological agents to induce ovulation(eg, human chorionic gonadotropin, gonado -tropin-releasing hormone [GnRH]), increasesthe risk.

Clinical presentationPresenting complaints include, but are notlimited to, haemopurulent vulvar discharge(if the cervix is patent), depression, listless-ness, lethargy, hyporexia/anorexia, vomitingand weight loss. Physical examination find-ings include abdominal distension, dehydra-tion and pyrexia.2,18 importantly, clinical signsare non-specific, with anorexia and lethargybeing the most common presentations.Therefore, pyometra should be ruled out inany ill, intact queen. in contrast to pyometrain bitches, polyuria and polydipsia are notcommonly seen in affected queens. Mostimportantly, clinical signs can be few or mildin queens with pyometra.2

in many cases the uterus will be palpablyenlarged but great care should be taken duringabdominal palpation as it can result in uterinerupture if the cervix is closed and the uterus isfriable. if the cervix is patent, the uterus may notbe as enlarged and only a thickened uterine wallmay be appreciated on palpation.

The presence of vulvar dis-charge is also dependent on thepatency of the cervix. in open-cervix pyometra, a haemorrhagic,purulent vulvar discharge may bethe only clinical sign. Cats can befastidious with grooming, which iswhy a vulval discharge may not benoticed by owners, thereby delay-ing the diagnosis. Queens withclosed-cervix pyometra may notshow vulvar discharge and aremore commonly systemically ill;absorption of bacterial toxins inthese cats can result in endotox-aemia and sometimes bacteraemia.


Laboratory findings< Haematology and biochemistry Remark -ably few haematological and biochemicalchanges are seen in queens with pyometra.2

The leukogram may show a markedneutrophilia (>35 x 109/l) with a left shift (±toxic changes) but this can be variable and, insome cases, the leukogram may be normal. it isnot uncommon to have no otherhaematological disturbances in queens withpyometra.2 Hyperproteinaemia, hypo kalaemia,azotaemia and an elevation in liver enzymes(alanine aminotransferase and alkalinephosphatase), blood urea nitrogen andcreatinine may be noted, especially if sepsisand dehydration are present. However, it is notuncommon to see only mild or no biochemicalchanges. Queens have significantly lessevidence of renal damage associated withpyometra than bitches. in contrast to bitches,biochemical parameters are also notparticularly helpful as predictors of diseaseoutcome in queens with pyometra.2

< Serum progesterone Progesterone con cen -tration will commonly be elevated above 2 ng/ml, depending on the length of time since ovulation. if queens are diagnosed with pyometra towards the end of dioestrus,progesterone levels can be relatively low (0.5–2 ng/ml).< Cytology Cytological examination of thevulvar discharge is likely to reveal degeneratepolymorphonuclear cells and phagocytosedbacteria (Figure 3).< Culture and sensitivity Bacterial culture of vulvar discharge is not particularly helpfulin confirming a diagnosis as normal vaginalflora is most likely to be isolated. However,sensitivity testing is important for makingtherapeutic decisions as some bacterial strainscan be resistant to commonly used antibiotics.ideally, a sample collected from the uteruswould be most diagnostic but obtaining such samples is technically and prac ticallydifficult. A sample from the cranial vagina

using a guarded swabis the next best optionfor bacterial cultureand sensitivity testing.Samples should betaken before antibiotictherapy is started. Anti -biotic treat ment shouldthen com mence whileawaiting results, on theassumption that E coliis the most likelyisolate (see later). onceculture and sensitivityresults are available,therapy can be modi -fied if needed.

Figure 3 Cytological smearprepared from a queen withpyometra. Note the presenceof degenerate neutrophils,epithelial cells and bacteriain the background.Differential interferencecontrast microscopy, oil immersion, x 1000

Pyometrashould be ruledout in any ill,intact queen.Clinical signsare non-

specific, withanorexia andlethargy beingthe mostcommon

presentations.






ImagingChanges that are observed on abdominal radi-ography of a queen with pyometra include adistended uterus, which can lead to displace-ment of the small intestine (Figure 4). Thesechanges are very similar to those seen in earlypregnancy prior to fetal skeletal ossification(which starts approximately 40 days after theluteinising hormone [LH] peak). Also, it isoften difficult to differentiate pyometra fromother causes of uterine enlargement, such asmucometra, hydrometra, hemometra orleiomyoma, which is a further limitation ofradiographic examination.

Figure 4Lateral (a) anddorsoventral (b) radiographicimages of aqueen withpyometra. Arrowsindicate theenlarged, fluid-filled uterus.Source: LORI

Figure 5 Ultrasonographicimages of (a) distended fluid-filled loops of uterus ofdifferent cross-sectional sizesfilling the caudal abdomen ina queen with pyometradiagnosed soon afterovulation; and (b) a queenwith an open pyometradiagnosed later in the diseaseprocess (approximately 4weeks postovulation). Notethe presence of intraluminalfluid in the uterus and thethickened endometrium withvisible cystic lesions. Imagescourtesy of Dr Cheryl Lopate,Wilsonville Veterinary Clinic,USA

Abdominalultrasound is the mostimportant

diagnostic toolwhen pyometrais suspected.

a

b

Figure 6 Ultrasonographic image of a cross section of athickened uterus (with only a trace of intraluminal fluid) in aqueen with an open pyometra that presented during the lateluteal phase. Note the cysts (cystic endometrial hyperplasia)in the uterine wall. Courtesy of Dr Cheryl Lopate, WilsonvilleVeterinary Clinic, USA

Abdominal ultrasound is the most impor-tant diagnostic tool when pyometra is suspected. Early in the disease process, theuterine horns typically appear distended withhypoechoic to hyperechoic fluid, with or with-out flocculation (Figure 5a). The uterine walloften appears thickened with irregular edgesand small hypoechoic areas consistent withcystic changes to the endometrial glands(Figure 5b). However, many queens will present more than 4 weeks after ovulation, and even late in the luteal phase or earlyanoestrus phase after the cervix has been open for days or weeks. in these cases, theremay be no intraluminal fluid detectable andonly a thickened uterine wall may be seen(Figure 6).

Pyometra can cause diffuse or segmentalchanges and there have even been occasionalreports of pyometra in one uterine horn and apregnancy in the other horn.

a b






HistopathologyGrossly, the uterine horns of a queen withpyometra are usually distended with somedegree of annular ring formation on the sur-face (Figure 7). Protuberant bands are seen on the endo metrial surface, which correspondto the annular rings on the serosa. Theendometrium of a uterus affected by pyo -metra is classically described as ‘cobblestone’in appearance (Figures 1 and 8). The endome-trial surface is usually covered by a malodor-ous, mucopurulent exudate, which can varyin volume (Figure 8).

Histologically, thickening of the uterine wallis caused by proliferation and dilation ofendometrial glands, which occurs throughoutthe endometrium. These glands containmucopurulent exudate with large numbers ofpolymorphonuclear leukocytes (Figure 9).dense infiltration of neutrophils can also beseen in the superficial stroma under the sur-face of the endometrium. in some cases, thereis evidence of chronic inflammation with infil-trations of predominantly plasma cells andhistiocytes in the stroma around the dilatedcystic glands.8,9

Comments

Clinical presentation

Signalment Middle-aged to older queens(>5–7 years of age)

Also young cats, those receivingexogenous hormone treatmentand/or with a breed predisposition

Clinical signs Vulvar discharge, depression,lethargy, pyrexia, inappetence,hyporexia/anorexia, vomiting

Often clinical signs are very mild or absent; clinical signs are generally non-specific

Laboratory findings

Complete bloodcount

White blood cell count >35,000cells/μl, neutrophilia with leftshift ± toxic change

Leukogram may be normal

Serum biochemistry

Hyperproteinaemia, hyperglobulinaemia

Often only mild or no changes

Progesteroneconcentration

>2 ng/ml Can be <2 ng/ml in anoestrus or at end of luteal period (poorer treatment prognosis)

Diagnostic imaging

Ultrasonography Thick-walled distended tubular uterus filled withhypoechoic/hyperechoic fluid

Often cystic endometrial changes in the uterine wall; amount of intra-luminal fluid depends on patency ofcervix and time since ovulation

Radiography Fluid-dense distended tubularuterus in the mid-abdomen

Consider other differentials such aspregnancy, mucometra, hemometraor hydrometra

Table 1 Summary of clinical, laboratory and diagnosticimaging findings in feline pyometra

Figure 7 Pus-filled uterus after surgical removal. Note theoozing of purulent material from the friable and stretcheduterine wall. Great care is required when handling thesepus-filled uteri during ovariohysterectomy

Other causes of uterine enlargement and/or vulvar discharge include:< Mucometra, hemometra and hydrometra (these pathologies are notassociated with systemic clinical signs and neutrophilia)

< Pregnancy (ruled out with ultrasonography 25 days after the LH peak or by radiography 40 days after the LH peak)

< Metritis, retained fetal membranes (clinical signs typically appear withinthe first few days postpartum)

< Vaginitis due to vaginal mass/foreign body/anatomical anomalies

D i f fe ren t i a l d i agnos i s

Figure 8 An opened uterine horn from a queen withpyometra. Note the degree of cystic endometrial change inthe resected piece of uterine wall. Courtesy of Dr Reto Fritsche,School of Veterinary Medicine, Louisiana State University, USA

Figure 9Histopathology of a cross section of the uterine wall in a queen withpyometra. Theuterine lumen isdilated and filledwith neutrophils andnecrotic debris. Themyometrium is thinand stretched butthe endometrium is approximatelytrebled in thickness.The luminal surfaceforms papillarystructures and someof the endometrialglands are distendedand also containneutrophils andnecrotic debris.Epithelial cells liningthe dilated glandsand the lumen arehypertrophied andhyperchromatic. Theendometrial stroma contains mostly plasma cells, some lymphocytes and scattered neutrophils.Neutrophils are particularly prominent close to the epithelium of dilated glands and the lumen.Courtesy of Dr Rob Foster, Ontario Veterinary College, University of Guelph






Treatment approach

Pyometra can be treated surgically or medical-ly and, in some cases, a combination of thetwo approaches may be the most effective andsafest solution. For example, medical treat-ment of systemically unwell or older patientsto assist with uterine emptying prior to sur-gery is appropriate to reduce the morbidityand mortality that can be associated withimmediate surgical treatment. Medical treat-ment can allow surgery to be delayed until atime when the queen has been stabilised withintravenous (iV) fluid therapy and iV anti -biotics and the anaesthetic risk reduced.

A proportion of pyometra cases in catsspontaneously resolve after the onset ofendogenous luteolysis and subsequent cervi-cal opening, which allows drainage before thedevelopment of any systemic illness.

Surgical managementovariohysterectomy with resection of theentire cervix is the treatment of choice in allqueens not intended for breeding. Cats thatpresent in poor condition need to have anyacid–base derangements, arrhythmias, hypo -tension, shock, electrolyte abnormalities anddehydration corrected before undergoinganaesthesia. Fortunately, the majority of catswith pyometra are systemically well at pres-entation and are good anaesthetic and surgicalcandidates.

Regardless of presentation, IV fluid therapyand IV antibiotics should be administered.Great care should always be taken in handlingthe uterus during surgery, as it is often veryfriable (Figures 7 and 10). Placement of saline-soaked laparotomy sponges in the abdomen is recommended to prevent contamination ofthe abdominal cavity with purulent material.Removal of the cervix in its entirety is per-formed in order to avoid leakage of purulentmaterial into the abdomen and prevent therisk of a stump pyometra occurring (Figure11) if some ovarian tissue is inadvertently leftbehind (ovarian remnant syndrome).

Postoperative monitoring for signs of shock,dehydration, sepsis, electrolyte and acid–baseimbalances, hypoproteinaemia, hypogly-caemia and anaemia is required for 24–48 hfollowing surgery.

< Queens without significant reproductive value or queens not intendedfor future breeding

< Emergency presentations such as uterine rupture or torsion concurrentwith pyometra

< Older queens, particularly those with significant cystic and degenerativeendometrial changes detected on ultrasound examination

< Pyometra that is refractory to medical treatment

I nd i ca t i ons fo r su rg i ca l t rea tmen t

Surgery vs medical therapy Historically, surgery has been the treatment of choice for the majority of pyometra cases,especially for queens with a closed pyometra.However, uterine rupture is a very rare event and many cases of closed pyometra aresuccessfully managed with careful medicaltherapy. Generally, medical treatment isindicated for young healthy queens (<3 yearsold) that are intended for breeding. However,owners of breeding animals should also beinformed about the potential risk of recurrence(see text).

Figure 10 Intraoperativeimage of an enlarged, fluid-filled and friable uterus in aqueen with pyometra

Figure 11 Intraoperative image of an enlarged, distended, fluid-filled uterus in a queen withstump pyometra secondary to ovarian remnant syndrome






Medical managementWhen considering medical treatment of apyometra, it is important to rule out any con-current conditions such as peritonitis, kidneydisease, reactive hepatitis or disseminatedintravascular coagulation (diC). A full clinicaland ultrasound examination, as well as addi-tional haematological and biochemistryassays, should be carried out before com-mencing treatment. All patients receivingmedical treatment for pyometra need to bevery carefully monitored and, if systemicallywell, can be treated as in-house ‘day patients’.However, patients that become unwell orrequire fluid therapy should be immediatelyhospitalised. owners should also be informedof the risk of treatment failure and that, ulti-mately, surgery may be required.

The rationale for medical therapy is three-fold (see box below). Pharmacological optionsinclude prostaglandin F2α (PGF), dopamineagonists and progesterone receptor antago-nists or antiprogestins (Table 2).

Prostaglandin F2αRepeated doses of PGF result in luteolysis ofthe feline corpus luteum. The resultantreduction in progesterone concentrationspromotes cervical relaxation and a reduction inuterine secretions. PGF also has ecbolic activitythat facilitates drainage of purulent materialfrom the uterus.

There are two forms of PGF: its natural form(dinoprost tromethamine [Lutalyse; Zoetis])or synthetic derivatives (eg, cloprostenol).Neither form is registered for use in compan-ion animals but both can be used off-label in queens. Cloprostenol has been associatedwith fewer side effects and requires fewerinjections due to its longer half-life. However,natural PGF induces greater myometrial con-tractions and therefore faster evacuation ofpurulent material from the uterus comparedwith synthetic PGF.19 For this reason, theauthors recommend natural PGF for treat-ment of pyometra in the cat.

it is paramount, especially in the case ofclosed-cervix pyometra, that a low startingdose of natural PGF with incremental increas-es is administered subcutaneously (see ‘lowdose protocol’ in the box above). This is in

order to minimise the ecbolic effect of thedrug and to reduce the risk of uterine rupture,as well as to reduce the side effects associatedwith higher doses of PGF. once luteolysis hasoccurred and the cervix opens, the dose can beincreased depending on the individual’s toler-ance of the PGF. doses greater than 50 μg/kgshould not be required, which is significantlyless than the 200–250 μg/kg reported in theolder literature.

it is important to note that the corpusluteum in the queen is more resistant to theluteolytic effects of PGF than that of the bitch.Furthermore, if treatment is started soon after ovulation, the corpus luteum can berefractory to the effects of PGF. often, higher doses of PGF for longer durations arerequired to obtain resolution of pyometra,especially if the diagnosis is made early indioestrus (before day 20 postovulation).during this time, low doses of PGF are poorlyeffective in inducing complete and definitiveluteolysis.2

Side effects of PGF are dose-dependent andare rarely encountered with the ‘low dose pro-tocol’, mostly limited to a transient hypersali-vation. individual variation in terms of toler-ance of PGF is also seen, with some queenstolerating the drug well and requiring a morerapid dose increase. Tolerance of PGF andreduction of side effects is also typically seenafter subsequent injections. Reported sideeffects include tachypnoea, vomiting, diar-rhoea, urination and restlessness. Side effectsappear about 20 mins after treatment and onlylast 15–30 mins. Patients should therefore behospitalised for at least 1 h after treatment toobserve for side effects. Systemically well

Recommended ‘low dose protocol’ for natural PGF (Lutalyse)

Increase to 50 μg/kg q8h SC for the next 3–5 days or until vulvardischarge is no longer observed or no fluid is detected in theuterus on ultrasound examination

‘Low dose protocol’ is a term now used by reproduction specialists for treatment with PGF. The protocol can be used on its own or, ideally, incombination with dopamine agonists (eg, cabergoline) or progesterone receptor antagonists (eg, aglepristone)

Start with 10–15 μg/kg SC q6h for the first day

Increase to 25 μg/kg q6h SC for day 2 (and day 3 if tolerance to PGF is low)

< Removal of progesterone, thus allowing cervical opening andimprovement of local immune status

< Promotion of drainage of purulent material from the uterus andelimination of bacteria through an open cervix, aided by induction of myometrial contractions

< Prevention of further bacterial proliferation and release of endotoxins

Rat i ona l e fo r med ica l t rea tmen t

Generally,medicaltreatment is indicated for young

healthy queens (<3 years old)that are

intended forbreeding.






queens can be managed as ‘day patients’ –receiving injections throughout the day whileunder veterinary supervision but able to gohome overnight when no medication is given.

Dopamine agonistsdopamine agonists can be used for thetreatment of pyometra in the queen eitheralone or in combination with PGF or aprogesterone receptor antagonist (see below).dopamine agonists are ergot-derived alkaloidcompounds that act as prolactin antagonistsand thus have anti-luteotrophic activity. Theyare effective from approximately 15–20 daysafter ovulation when prolactin is present.2

Therefore, if a queen presents with pyometrasoon after oestrus, anti-prolactinic agents arepreferred over PGF as they are very effective atinducing luteal arrest and luteolysis in earlydioestrus.2 However, if a queen presents morethan 4 weeks after oestrus or mating, use of adopamine agonist in combination with PGFpotentiates the luteolytic effect, causing morerapid luteolysis and leading to cervicalopening within 24–48 h.

There are two commonly used dopamineagonists: cabergoline and bromocriptine.Cabergoline is associated with few or no sideeffects and involves only once daily adminis-tration, whereas bromocriptine has a numberof side effects including vomiting, anorexia,depression and some behavioural changes,and also requires administration two to threetimes a day. The recommended dose of caber-goline is 5 μg/kg Po q24h; the dose ofbromocriptine is 10–25 μg/kg Po q8h. Bothdrugs are most commonly used in combina-tion with PGF, with the duration of treatmentusually being 7 days.

Progesterone receptor antagonists or antiprogestinsProgesterone receptor antagonists orantiprogestins, such as aglepristone (Alizine;Virbac), are synthetic steroids that com -petitively bind to progesterone receptors witha greater (9 x in cats) affinity than naturalprogesterone. This results in a decrease inprogesterone activity.20,21 Aglepristone hasminimal side effects and is a good choice forthe treatment of closed-cervix pyometra as it results in cervical opening with minimaluterine contractions. it also induces luteolysis.However, queens that present with poor liverand/or kidney function should not be treatedwith aglepristone.

Aglepristone is most effective when used incombination with natural PGF (dinoprost) for5–10 days to potentiate luteolysis and enhanceuterine contractions.22,23 This is particularlyimportant in cats as they are notoriouslyresistant to luteolysis and removal of the

effects of progesterone on the uterus.Furthermore, initiation of aglepristone treat-ment 48 h before starting PGF treatment canreduce the risk of uterine rupture in a closed-cervix pyometra by slowly opening the cervixwithout the stimulation of strong uterine con-tractions. Therefore, when using PGF in com-bination with aglepristone, treatment withPGF should start on day 3; PGF is then givendaily as per the ‘low dose protocol’ describedon page 28, except on days when aglepristoneis given.

The recommended dosage of aglepristonein the queen is 15 mg/kg SC twice, 24 h apart,and then a single injection on day 8. A higherdose rate is recommended for queens com-pared with bitches due to reduced bioavail-ability in the queen. depending on thepatient’s condition, additional injections ofaglepristone can be given on days 14 and 28 ifresolution of the pyometra has not occurred.in these chronic cases, treatment with aglepri-stone weekly (mean duration of effect ofaglepristone is 6 days) for 2 months has beenreported. However, the prognosis with regardto fertility and recurrence rate is significantlypoorer in these cases compared with casesthat respond after the initial three injectionson days 1, 2 and 8.16

Treatment with aglepristone (15 mg/kg SCq24h) in combination with trimethoprim/sulfadoxine for 7 days resulted in a success rate of 90% (9 out of 10 cats).24 The authors did not note any recurrences for 2 years after treatment.

If systemicallywell, catsreceivingmedical

treatment forpyometra canbe managed as‘day patients’.

Drug name Dose Protocol Actions

Prostaglandin F2α

Dinoprosttromethamine(Lutalyse;Zoetis)

10 µg/kg SC25 µg/kg SC50 µg/kg SC

tid–5x/day x 1daytid–5x/day x 1 daytid–5x/day x 5–7 days*If used incombination withaglepristonetreatment is given on days 3–7

LuteolysisMyometrial contractionsCervical opening

Cloprostenol 1 µg/kg SC sid for 5–7 days oruntil resolution

Dopamine

agonists Cabergoline 5 µg/kg PO sid Anti-prolactinic

Anti-luteotrophic

Bromocryptine 10–25 µg/kg PO tid

Anti-

progestins Aglepristone 15 mg/kg SC Days 1, 2, 8 and

weekly*Progesterone receptorantagonistCervical openingLuteolysis

*Depending on response to treatmentSC = subcutaneous; PO = oral; sid = once a day; tid = three times a day; 5x/day = five times a day

Table 2 Dosages of commonly used luteolytic, anti-luteotrophic and antiprogestin drugs for treatment of feline pyometra






Antimicrobial therapyAntimicrobial therapy should be initiatedimmediately with a broad spectrum antibiotic.Culture and sensitivity testing should beperformed but therapy has to be started at the time of diagnosis on the assumption that E coli is the most likely pathogen. Excellentresults have been achieved with amoxicillin/clavulanic acid (12.5–25 mg/kg Po q12h) or cephalosporins (eg, cefazolin 22 mg/kg iVor iM q8h) and potentiated sulfonamides; care should be taken in using cephalosporinsor sulfonamides if renal function is impaired.if oral antibiotics are administered, care mustbe taken to give the drugs at a different time from the PGF, which might lead tovomiting.

Antimicrobial therapy should be continuedfor at least 14 days after resolution of vulvardischarge and evacuation of all fluid from theuterine lumen as determined by ultrasoundexamination.

Assessing the response totherapy and predicting futurefertility

There are a number of parameters (see below)that should be assessed throughout the treatment of a queen with pyometra to monitor the response to treatment and deter-mine when luteolytic treatment can cease, aswell as to provide an indication of potentialfuture fertility.

A clinical improvement is usually seenwithin 48 h of initiation of medical therapy.Ideally, resolution of all clinical signs shouldoccur within 7–10 days.

Monitoring tools< Ultrasound of the uterus Ultrasoundexamination is the most important monitoringtool. A decrease in uterine size by 50% should be seen 72–96 h after initiation of therapy. if areduction in uterine size of at least 50% is notobserved after 5 days of treatment, the prognosisfor future fertility is poor. in cases that respondpoorly to luteolytic therapy, surgery isrecommended to remove the fluid-filled uterus.2

in bitches, treatment for longer than 7–10 dayscan increase the risk of complications such asdiC. This has not been reported in the queen but should be a consideration when undertakingprolonged treatment. Weekly ultrasoundexaminations are recommended to assess theresponse to therapy. When the uterinedimensions have returned to normal and thereis no fluid present in the uterus, luteolytictreatment can cease. Repeat ultrasoundexamination 2 weeks after resolution of clinicalsigns and treatment is advised to assess uterinehealth (eg, degree of CEH changes) and toconfirm the absence of intraluminal fluid (Figure12). This is especially important when treatmentis started in a queen soon after ovulation or inthe early luteal phase when the corpus luteum ismore refractory to luteolysis and intrauterinefluid accumulation can recur. A reduction in theuterine wall thickness and often also in thedegree of CEH changes may be detected onultrasound after removal of progesterone andresolution of bacterial infection.< Vulvar discharge Vulvar discharge shouldincrease in volume within the first 24 h oftreatment and usually ceases about 5–7 daysafter the onset of treatment. However, incontrast to dogs, pyometra in cats is often

The mostimportant

monitoring toolis ultrasoundexamination of the uterus: a decrease inuterine size by50% should beseen 72–96 hafter initiationof medicaltherapy.

Figure 12 Ultrasonogram of a uterine horn in a queentreated medically forpyometra several weeksearlier. Note that there is no intraluminal fluid present,but there are marked cysticchanges in the thickeneduterine wall, indicating apoor prognosis for futurefertility. Courtesy of Dr CherylLopate, Wilsonville VeterinaryClinic, USA

Techniques are currently being developed inbitches to treat both closed- and open-cervixpyometra with non-invasive, transcervicalendoscopic catheterisation. This involves flushingthe uterus with sterile saline to remove themucopurulent exudate and instilling intrauterineantibiotics and PGF. Promising results in bitcheshave been reported, with resolution of pyometrawithin 3–5 days.19 Recently, a new method forcervical catheterisation using a rigid endoscopeand a specialised transcervical catheter has beendeveloped for artificial insemination (AI) inqueens.25 With this development, treatment ofpyometra in queens using a transcervical flushingtechnique may become a viable option in the nearfuture.

Fu tu re t rea tmen ts






slower to resolve. The nature of the vaginaldischarge will also gradually change – frompurulent (and often blood-tinged) to sero -sanguineous, before eventually becomingserous.< Vaginal cytology The number of neutro -phils seen on vaginal cytology should decreaseover the course of treatment.< Leukogram Weekly complete blood cellcounts should be performed to evaluateneutrophilia. in most patients, the leukogramwill return to normal 2–3 weeks aftercommencement of medical therapy.< Serum progesterone Measurement ofserum progesterone concentration prior tostarting medical therapy can be helpful withregard to prognosis. Queens with lowprogesterone concentrations (<2 ng/ml) or those that are in anoestrus are poorcandidates for medical therapy as they usuallyrespond poorly.16 Measurement of pro -gesterone at weekly intervals can helpdetermine if luteolysis has occurred (indicatedby serum progesterone <2 ng/ml). This isparticularly valuable if PGF alone is used totreat the pyometra or in refractory cases to helpdetermine whether complete luteolysis hasoccurred. Progesterone receptor antagonistsdisplace the endogenous progesterone, thuselevating systemic levels initially. Therefore,when using this drug, progesteroneconcentrations must be interpreted withcaution to assess luteolysis. The progesteroneconcentration 3 weeks after initiation ofaglepristone treatment should be <2 ng/ml.

Management of breeding queens after medical treatmentof pyometra

it is optimal that all queens intended forbreeding are mated or inseminated on the firstoestrus following treatment for pyometra, as a pregnant queen is significantly less likely todevelop recurrence of pyometra. Therefore, itis important to manage the oestrus to optimisethe likelihood of the queen becoming preg-nant. Using a proven, fertile, young tom cat or,if Ai is to be carried out, using high-qualityfresh semen, is essential, as is optimal timingwith the use of ovulation-inducing agents.observation of multiple matings and confir-mation of ovulation by measuring pro -gesterone 48–72 h after calling has ceased or ovulation is induced is recommended.Admin istration of a broad spectrum antibiotic(amoxicillin and clavulanic acid) duringoestrus and the early luteal phase (until preg-nancy is confirmed by an early ultrasoundexamination) is indicated if neutrophils aredetected on vaginal cytology during oestrus(Figure 2).

After mating, it is essential to follow queensclosely with ultrasound examinations in orderto detect any recurrence of pyometra early,before clinical signs associated with systemic

Queens with progesterone concentrations <2 ng/ml, or those that are in anoestrus, usually respond poorly to medical therapy.

The prognosis for survival is good with immediate medical orsurgical treatment, provided uterine rupture has not occurred. Ifuterine rupture occurs, the mortality rate is high (30–50%).26,27

Overall, the mortality rate for queens with pyometra has beenreported to range from 5.6–8%.1,2 This relatively high rate may berelated to the fact that affected queens often show only very mildand non-specific clinical signs.2 Therefore, they may sometimesbe misdiagnosed for a period of time or presented for veterinaryattention late in the disease process; both scenarios result in aless favourable outcome.Following medical treatment, the prognosis for future fertility

and the risk of recurrence of pyometra depend on a number offactors, including the age and parity of the queen, the degree ofCEH changes detected by ultrasound, and the time taken torespond to therapy and for the pyometra to resolve. Older (>6years) nulliparous queens with severe CEH changes detectableon ultrasound (Figure 12) that respond slowly to therapy andrequire protracted treatment (>2 weeks) have a poor prognosisfor preservation of fertility and are likely to develop recurrence ofpyometra.There is very little published data on pregnancy or recurrence

rates in queens after treatment of pyometra. A substantial retro-spective analysis of treatment and subsequent reproductive per-formance in queens treated medically for pyometra is needed. Itis likely that, similar to bitches, there is high variability in pregnan-cy and recurrence rates after treatment. However, in the authors’experience, the success rate for pregnancy and normal litter sizeafter treatment for pyometra is high (pregnancy rate >80%) if:< Good case selection for medical treatment is practised; ie, young, healthy queens that do not have evidence of uterinepathology (eg, CEH);< Effective treatment is initiated immediately;< Close monitoring during treatment is performed, andmedical treatment is ceased when parameters being monitoredare not improving in a timely manner;< Good breeding management of subsequent heats (seebelow) is ensured.Similarly, the risk of recurrence of pyometra at the subsequent

oestrus is variable and depends on case selection and breedingmanagement. Queens that do not respond to medical therapyquickly have a poor prognosis for return to fertility and anincreased risk of pyometra at the next oestrus.

Prognos i s fo r su r v i va l and f u tu re fe r t i l i t y






illness occur. An early ultrasound examina-tion should be scheduled for 16 days after the LH peak to detect either embryonic vesicles(consistent with pregnancy) or uterine fluid(consistent with recurrence of pyometra).

However, it is often not possible to breed aqueen on every oestrus subsequent to treat-ment for pyometra. Prevention of oestrus inthese queens – especially individuals that areknown repeatedly to spontaneously ovulate –is something to consider to reduce the risk ofpyometra recurrence. Unfortunately, safe andeffective methods and pharmaceutical agentsfor prevention of oestrus in queens are limited.GnRH analogues such as deslorelin implants(Suprelorin; Virbac) are reversible contracep-tives that inhibit oestrus by downregulation ofthe hypothalamic–pituitary–ovarian axis.28

The effects are not only long term but highlyvariable. A minimum of 6 months’ suppressionof oestrus would be obtained from a 4.7 mgimplant and a minimum of 12 months from a9.4 mg implant. The timing of implantationwith regard to season would have an effect onthis variability, as well as individual response.in one study, the period of oestrus suppressionafter implantation with a 4.7 mg Suprelorinimplant in 20 female cats ranged from 16–37months.29 Suprelorin is not registered for use inqueens (or bitches) due to this variability inresponse. importantly, in the above-mentionedstudy, 7/8 queens that were mated after theimplant was no longer effective became preg-nant and went on to kitten naturally.

< There are many published studies on the prevalence, pathophysiology, treatment andprognosis of pyometra in the bitch. Unfortunately this work has not yet been documented in queens and there has been much extrapolation from the bitch as a model for pyometra in the queen.

< A recent large retrospective study indicates that the incidence of pyometra in the queen is potentially much higher than initially assumed. This finding opens up many questions as to the underlying pathogenesis of pyometra in the queen.

< Queens are unique in that the corpus luteum is much more resistant to the currentlyavailable drugs and protocols available for the medical treatment and management ofpyometra. More refractory cases are seen than in bitches and often a more aggressiveapproach is required to induce luteolysis.

< Successful medical treatment and, more importantly, successful breeding of a queen after treatment of a pyometra is ultimately influenced by the selection of suitable candidates for medical therapy.

< With the availability of new drugs and protocols for the treatment of pyometra in queens, as well as a greater understanding of appropriate selection of candidatesfor medical therapy, clinicians are now much more able to facilitate a successful decision by owners of queens that develop a pyometra in regard to ‘spay or not to spay?’.

KEY Points

Melatonin implants have been reported tosafely provide oestrus suppression for up to 4 months in queens.30,31 Synthetic progestinshave been widely used for oestrus suppres-sion in the queen, especially in Europeancountries.17 Great care should be taken whenusing these agents (eg, MA and MPA) in aqueen that already has cystic changes in theuterus as this may predispose to recurrence ofpyometra. Use of anabolic steroids such asmibolerone for oestrus prevention is con-traindicated in cats.

An alternative management strategy forqueens with a history of pyometra is to measureserum progesterone concentration 3–4 weeksafter the end of oestrus to evaluate for sponta-neous ovulation. if ovulation has occurred (indicated by progesterone concentrations >2–5 ng/ml), treatment with aglepristone in anattempt to prevent pyometra may be considered.

Queens no longer intended for breedingshould undergo ovariohysterectomy. ovari -ectomy is not recommended in a queen thathas had pyometra and previous pregnancies,as the risk of a pyometra recurring in thesequeens is high if exogenous hormonal therapy(oestrogens and progestins) is administered orif ovarian remnants are inadvertently leftbehind after ovariectomy.

Queens no longer intended for breeding should undergo ovariohysterectomy. Ovari ectomy is not recommended.






Funding

The authors received no financial support for the research,authorship and/or publication of this article.

Conflict of interest

The authors declared no potential conflicts of interest with respectto the research, authorship and/or publication of this article.

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Pyometra in the queen To spay or not to spay? · 2016-02-10 · pyometra by the age of 13 years.1The incidence of pyometra is considered to be lower in queens than in bitches, as

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