Cystic endometrial hyperplasia pyometra complex in cats. A review

Veterinary Quarterly ISSN: 0165-2176 (Print) 1875-5941 (Online) Journal homepage: http://www.tandfonline.com/loi/tveq20 Cystic endometrial hyperplasia pyometra complex in cats. A review C.F. Agudelo To cite this article: C.F. Agudelo (2005) Cystic endometrial hyperplasia pyometra complex in cats. A review, Veterinary Quarterly, 27:4, 173-182, DOI: 10.1080/01652176.2002.9695198 To link to this article: https://doi.org/10.1080/01652176.2002.9695198 Copyright Taylor and Francis Group, LLC Published online: 22 Jun 2012. Submit your article to this journal Article views: 2196 View related articles Citing articles: 17 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalinformation?journalcode=tveq20

173 Veterinary Quarterly 2005; 27(4): 173-182 Cystic endometrial hyperplasia-pyometra complex in cats. A review C.F. Agudelo* Department of Internal Medicine, Clinic of Dog and Cat Diseases, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic TABLE OF CONTENTS Summary and keywords 174 Short description 174 Etiopathogenesis and epidemiology 174 Clinical signs 176 Diagnosis 177 Treatment 178 Ovariohysterectomy 179 Medical treatment 179 Conclusions 181 References 181 *Address: Clinic of Dog and Cat Diseases, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, Brno, Czech Republic E-mail: cagudelo@vftc.cz

174 Cystic endometrial hyperplasia-pyometra complex in cats. A review C.F. Agudelo SUMMARY Presentation of complex cystic endometrial hyperplasia-pyometra is not very common in cats. As in bitches, hormonal influences result in environmental and histological changes in the uterus leading to predisposition to bacterial growth. Its influence on the organism provokes certain clinical signs. Diagnosis and treatment must be fast and aggressive. Depending on the clinical status and queen purpose, it can be both surgical or medical. Both of them offer a high rate of success if the detailed protocols are followed. Keywords: Cat diseases; CEH; Corpora lutea; Cystic endometrial hyperplasia-pyometra complex; Endometritis; Ovariohysterectomy; Progestagens; Prostaglandins; Pyometra; Queen; Uterine diseases. Short description Cystic endometrial hyperplasia-pyometra is a disease, which is mainly characterized by progesterone-induced hyperplasia of the endometriurn with cystic dilatation of the endometrial glands and inflammation of the uterus with purulent content in the uterine lumen leading to several clinical signs (2,5,20,33, 34). Etiopathogenesis and epidemiology It is important to realize that the queen is a species with induced ovulation, which requires coitus or mechanical stimulus of the cervix or the vagina to liberate luteinizing hormone (LH) and subsequent ovulation (11,12,17,18,19,40). Coitus as an external trigger stimulates the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates release of LH from the anterior hypophyseal gland in the subsequent minutes with a peak 4 hours. later. Ovulation occurs 30 to 50 hours after coitus (17,29). It has been observed that the increase of the number of copulations accounts for higher magnitude and longer duration of liberation of LH with higher ovulation probability when compared with one mating only (14,15,19,28,31). Corpora lutea start to produce progesterone 24-48 hours after ovulation (17). When this happens, this phase corresponds to the pregnancy or pseudopregnancy (when the queen is not pregnant). This phase comes to an end after 40-50 days (9,10,14,17). The whole period of progesterone influence over uterus is shorter when compared to the bitch (over 60 days) (10,40). Queens are not affected by progesterone influence between non-ovulatory follicular cycles (9). Estrous returns whithin 14-19 days after a non-ovulatory cycle (17). The hormone progesterone causes, a)hyperplasia of the endometrium, especially of the superficial epithelium and the endometrial glands (17), b) closure of the uterine cervix(27), increase of the secretory activity of the endometrial glands (2,10, 20,27,33,34,37,40), and decrease of myometrial contractibility, although it can be hyperplastic (17). Intrauterine leukocytary response suppression to foreign stimulus has been reported (5,40). The first phase of the illness is the proliferation and cystic dilation of the glandular endometrium with fluid accumulation in the uterine lumen. The ocurrence of this phase is influenced by age and hormonal stimuli, and is denominated cystic endometrial hyperplasia (CEH) (17,20,22,27). Changes in the uterine microenvironment and decreased contractibility would favor ascendant bacterial infection (2). During pseudopregnancy, the changes induced by the progesterone on the glandular epithelium begin to disappear after 4 weeks, while during pregnancy endometrial morphology and synthetic activity continues simultaneously with the pregnancy (12). However, these findings are not consistent; recent information shows that queens can have spontane ous ovulation after a non fertile breeding (16,17, 18,19,40) or after pharmacological treatments (4, 12,27,39). It has been observed that some queens were in luteal phase, though they were separated from males and have not received any therapy. This suggests that the luteal phase can be induced by diverse factors (2,14,16,29) (visual, tactile, etc. [33,17]).

175 It has been noticed that progesterone is not the only hormonal factor involved in the process. Some queens have been diagnosed with pyometra in follicular phase of the ovarian cycle (36,40). This can be due to the non-gestate uterus in diestrus that is flaccid and contains some endometrial gland secretions that were developed previously as a response to the risen estrogen level in time of the estrous (5,40). Recent information shows that pyometra is not only influenced by progesterone but also estrogens (29,40). Estrogens a)increase progesterone receptors in the endometriurn, dilate uterine cervix, allowing bacterial ascent that is part of the normal vaginal flora and c)can influence endometrial changes. These endometrial changes are influenced by chronic estrogenic stimulation from recurrent estrous cycles, which do not end in pregnancy (5,17,20). This all explains why cystic endometrial hyperplasia (CEH) was not experimentally induced with any hormonal treatment (29). CEH is a common histological finding in nulliparous queens older than 3 years and in other queens older than 5 years with no relationship to the number of parturitions (10,12,29,36), although it has been mentioned that these proportions are very similar (8,10). Pyometra has been observed in queens older than 8 years and in younger queens after progestagen administration (20,21). The average age of cats with pyometra is 7 years (2,14). Elderly nulliparous queens would be more likely to develop the disease due to the endometrial changes above discussed (13,17,28). Some patients have experienced estrous 8 weeks prior to diagnosis and in many cases it is not known whether there was mating (2,12,40). There is no correlation between the development of the disease, the age of the first mating or parturition and number of litters delivered. On the other hand, correlation has been observed between pyometra and corpora lutea presence (2). In about 40-70% of the cases corpora lutea were present (13). In most cases of of CEH-pyometra complex bacterial infection originates from the normal opportunistic flora of the vagina. The abnormal endometrium can be a predisposing factor to the bacterial colonization (2,12,21,33,40). Less frequently bacterial infection is of haematogenous origin (5). Pyometra can be a type of CEH associated with predominance of inflammatory cells inside the uterine lumen and secondary bacterial infection (12,17). Pyometra and CEH frequently coexist, although both abnormalities can represent a single pathological process. A certain grade of CEH is found in every queen with pyometra, except for a number of cases of pyometra with closed cervix, because in these cases there is already endometrial atrophy (12). Aerobic bacteria are recovered from approximately 80% of the animals (39). Escherichia coli is the most frequently isolated microorganism from feline pyometras (5,11,12,14,16,17,18,19,20,33). The role of bacteria in the pathogenesis of the CEHpyometra complex is especially important in the luteal phase. Isolated bacterial strains from patients with pyometra can be biochemically simi-lar to their faecal homologous suggesting faecal contamination of the genitourinary tract (2). Other agents like Streptococcus, Staphylococcus, Klebsiella, Pseudomona, Proteus, Moraxella and Pasteurella have also been reported (10,12,29,33,34). Mycoplasma, although it has not been proven in cats should also be suspected (14,30). Uterine tuberculosis and brucellosis acquired from infected bovine tissues have also been reported in the cat (14). A CEH classification has been established in cats according to the clinical, paraclinical and histopathological criteria (7,13,33) (Table 1). Type of CEH Type I Type II Type III Type IV Short description of the characteristics CEH without inflammatory process, no clinical signs. CEH with acute endometritis. In most cases presence of corpora lutea. White Blood Count (WBC) increase. Signs can vary depending on the severity of the endometrial reaction and distention of the uterus, but in general the cats are ill. Subacute endometritis with mononuclear infiltration of the endometrium and cystic changes of the endometrial glands. The clinical signs are more pronounced than in the the preceding types. Important WBC increase. Chronic endometritis with endometrial atrophy. The severity of the clinical signs depends among others on the WBC, the abdominal distention and damage in other abdominal organs. Table I. CEH classification according to Dow (7).

176 Use of exogen progesterone in queens with contraceptive purpose can also induce pyometra, especially in young queens (5,20), even in ovariectomized queens (14). However, when this application is controlled, only over long periods CEH effects and sterility can been seen with consequent development of pyometra (22). Another study demonstrated that weekly administration of 2 mg chlormadinone acetate caused pyometra in two out of 24 treated queens, in connection with mammary abnormalities (35). Use of exogenous estrogens to interrupt gestation can result in pyometra in cats older than 4 years, because the uterine cervix stays open longer (20). Doses are reviewed elsewhere in the literature (22,27,35). Adenomatous hyperplasia and cystic changes were combined to determine the overall cumulative increase in endometrial thickness (endometrial hyperplasia index) in wild cats. These changes were presumed to have similar effects on fertility (5,22). The severity of endometrial hyperplasia was categorized (Table 2). Endometrial hyperplasia index Grade 0 Grade 1 Grade 2 Grade 3 Histopathological features No hyperplastic changes. Minimal to mild proliferative and/or cystic changes in glands or surface epithelium without an increase in overall endometrial height. Moderate hyperplastic and/or cystic change with an increased endometrial thickness of times normal. Severe hyperplastic and/or cystic changes with increased endometrial thickness of <2 times normal. <2 Table 2. Endometrial hyperplasia index according to Munson et al. (22). This study clearly demonstrated a correlation between contraception using synthetic progesterone (megestrol acetate) and the development of advanced endometrial hyperplasia, which seems to be irreversible. These results clearly suggest not to use these kinds of drugs in reproductively and genetically valuable animals (22). In recent studies, a functional classification of the pathologic complex is based on the ovarian phase (12,17,40). In these studies, queens with inflammatory uterine disease or infertility with active corpora lutea showed CEH, myometrial hyperplasia and increased progesterone. levels (1,87 ng/ml), while queens with follicular ovaries did not display these changes and had very low progesterone levels (0,15 ng/ml) (16). However, normal ovaries, which are not in luteal phase or with cystic follicules are found in approximately 15-23% of the queens with pyometra (12). Endometrial changes induced by progesterone not necessarily disappear after involution of the corpora lutea. Queens with Feline Infectious Virus (FIV) infection that are or have been pregnant, can succumb to complicati-ons of reproductive type (abortion, stillbirth, etc.), in various time after mating. One study described that 3 out of 13 queens with the above mentioned : infection had pyometra (33). Stump pyometra can be produced similar to that repor-ted in bitches. This happens because of administration of progestragens to castrated queens, which still have uterine remnant (10,14). Pyometra can also be present in masculine uterus and hermaphrodites (2,32). Clinical signs. Cats with CEH not always show clinical signs, but it can be associated with implant failure and subsequent smaller littermates and also infertility (secondary anestrous) (10,12,28) as well as early embryonic death (17). In the case of marked CEH, abdominal distention can be observed because of fluid accumulation in the uterus (mucometra, hydrometra) (12,40). Pyometra and other forms of uterine inflammation almost always cause clinical signs (12). The most common clinical finding is vaginal mucopurulent to hemorrhagic discharge (2,5,8,10,12,15,17,33) occurring in about 75% of the cases (20). However, this symptom can also be absent due to careful cleaning habits of the queens (21,34,40) or in cases of a closed-cervix pyometra (5). Uterus can be palpated as a big sized mass and there can or cannot be abdominal distention (8,12,15,20). In

177 closed-cervix pyometra the latter is common (10, 21). This finding is more evident in queens than in bitches (34). In those cases, patients are more prone to endotoxemia and uterine rupture with concurrent peritonitis (2,5,17,20). This is the reason for the need of being careful when carrying out abdominal palpation to avoid iatrogenic rupture (29). Non-specific clinical signs such as anorexia, vomiting, lethargy, loss of weight and unkempt appearance can also be observed (2,10,12,14,15, 29). Polyuria and polydypsia do not occur as often as in dogs. They were reported only in 9% of the cases (2,12). As reported in dogs, E. coli endotoxins interfere with Na+ and Cl absortion in the loop of Hen le, thereby reducing medullary hypertonicity and resulting in impaired water absorption. Additionally E. coli endotoxins block receptors for antidiuretic hormone on the collecting ducts, leading to obligatory polyuria with compensatory polydypsia (21). In almost one third of the cases severe dehydration is identifiable at the moment of the clinical examination, partly due to the advanced stage of the disease (2,33). Similarly as reported in dogs, 20-25% of the cases show fever (12,20). In cases with shock signs (tachycardia, tachypnea and poor peripheral perfusion) hypothermia can be found (25). Stump pyometra must be suspected in a castrated queen with purulent or hemorrhagic vulvar secretion, being more complicated in cases with closed-cervix pyometra (9,14). The most important differential diagnosis for these historical and physical findings is pregnancy with concurrent disease (2,12,20), diseases that produce vaginal discharge such as urinary, uterine and vaginal diseases (25), diseases that cause increase of the uterine content (mucometra, hydrometra, haemometra) and diseases with concurrent abdominal distention (ascites, obesity, abdominal masses, congenital disorders, peritonitis) (24,33,35). Diagnosis The diagnosis is based on the history, the estrous cycle status and the clinical signs (estrous dates, hormonal treatments, antecedent of irregular cycling, and pseudopregnancy) (5,12,33). Animals with CEH have normal blood and urine tests (8). Haematology can show non regenerative normocytic normochromic anaemia due to the chronic inflammation and toxic effects that cause suppression of the erythropoiesis in the bone marrow (12,20,33). Other causes can be diapedesis of erythrocytes towards the uterus because of the inflammatory process, blood loss during surgery (if it is the treatment of choice) and haemodilution due to fluid therapy (34,41). Most of the queens with pyometra show abnormal white blood counts frequently characterized by leukocytosis with neutrophilia and left deviation with values than can oscillate from 20.000 up to 120.000/m1 (12,10,33,23), in approximately 66% (14). Leukopenia can be present in around 5% of the cases (2,12). Vaginoscopy is also recommended for direct observation of the haemorrhgaic or mucopurulent discharge (9) originating from the uterus, primary or secondary hyperaemia, inflammation of the cervix and vagina or any other pathologic process. At the same time it is recommended to perform cytology of the secretions to support the diagnosis. The most common finding is the evidence of abundant neutrophils blended with erythrocytes. Leukocytes can show different states of karyorrhexis and karyolysis (2,33). Endometrial cells can also be found (2). Presence of bacteria is quite rare, however this finding must be correlated with culture and antibiogram to establish a proper treatment (12,41). Samples can be taken directly from uterine lumen after ovariohysterectomy (OVH) or from secretions from the cranial vagina if an immediate sample is required or the medical management has been chosen (2). The biochemical profile usually does not show huge abnormalities. Hyperglobulinaemia can be present in 30-60% of the cases (2,5,12). In cases of sepsis and shock, it is also possible to find hypoglycaemia due to increase of the consumption of glucose, rapid glycogen storage waste and decrease in gluconeogenesis (3,41). Additional non-specific manifestations like hypokalaemia and azotaemia are generally due to hypovolaemia and circulatory collapse. Hyperbilirrubinaemia and increase of activity of the alkaline phosphatase are found in about 12% of the cases, and are probably due to a hepatic perfusion decrease or toxicity, secondary to sepsis (12,20). However, most of the cases are self-limited and are solved after starting the supportive treatment (12,41). Hyperproteinaemia and hyperfibrinogaenemia can be found due to dehydration or inflammatory process.

178 Reported findings in the urinalysis are proteinuria and isostenuria (20). Urine collection must be carried out carefully because of the high probability of sample contamination or favor urinary tract infection due to catheterization. To avoid uterine perforation, cystocentesis should be performed only by ultrasound guided technique (2). In most of the cases blood progesterone levels are increased (>5 ng/ml) because of corpora lutea activity, although it has been reported that it is possible that the plasma progesterone is not required to induce or to maintain pyometra. In other words it is possible to find normal levels (4,9). Radiology of the abdomen can confirm the uterine enlargement: the x-rays will identify an uterus that emerges from the pelvis as dilated, showing a homogeneous and sometimes sacculiform structure with dorsal and cranial displacement of the small intestine (1,12,6,26,33,23,36). Cases of closedcervix pyometra cases with pregnancy of the contralateral horn can be detected by x-rays (33). In earlier pregnancy, ultrasound is always recommended because the radiographic appearance of pyometra and the gravid uterus are essentially identical until fetal calcification is detectable in approximately 40 days' gestation (5,12,13). Care must be taken with organ overimposition that can confuse diagnosis (i.e. urinary bladder) or in the cases of slight pyometra that can be more difficult to detect (23).. Pneumoperitoneum certainly improves radiograph quality, but any procedure that involves abdominal manipulation (punction) should be avoided due to the risk of perforation of distended uterus with weakened walls (33). In most cases ultrasound is preferred because in this way pregnancy can be easily differentiated from a big uterus filled with anechoic or hypoechoic fluid (5,6,9,10,12,26,36,42) with a contoured or straight shape containing small liquid accumulations (<5mm) in the walls. Pregnancy in cats can be detected ultrasonographically after 21 day in cats (8). Sometimes it is possible to identify "spotted" echogenicity with multiple cysts from 1 to 5 mm in the uterus. These can be thickened endometrium, small mucous, hemorrhagic or necrotic tissue accumulation or wall enlargement (5,17). Differentiation should be made between uterine horns and intestinal loops, although it would result in a very different symptomatology (5). Furthermore, if pregnancy is detected, fetal viability must be performed. Ascitic fluid suggesting possible uterine rupture, can be identified in a small percentage of cats with pyometra (13). Treatment Treatment should be rapid and aggressive, because septicaemia and endotoxaemia can develop at any time (2,12,13). When pyometra is suspected, a detailed and careful clinical examination is needed. Similar as in dogs, pyometra in cats is considered as an emergency (41). Treatment includes correction of fluid deficits, proper administration of antibiotics against bacterial organisms and removal of infected uterine contents. The latter can be achieved surgically by OVH or medically by PGF2c, (10,12). No matter which option. is choosen, medical or surgical, fluid therapy should be accurate to replace deficits (acid base and electrolytic, mainly potassium), correct azotaemia and maintain adequate tissue perfusion. In most cases, it is recommended to administer glucose endovenously, even in the post-operative period so that the risk of hypoglycaemia is minimized. Such situation is very common in the sick cat. Antibiotics should be choosen according to the culture sensitivity (2,12, 20). While waiting for the results of the tests of the antibiotic sensitivity, wide broad bactericide antibiotics against the most common bacteria (E. coli) is recommended (2,12). This includes ampicillin (20 mg/kg IV, IM, SC or PO, TID), trimethoprim sulfonamide (15-30 mg/kg PO, SC or IV, BID), clavulanate + amoxicillin (20-25 mg/kg PO, SC, IM or IV, TID), enrofloxacin (5 mg/kg IM or SC, SID) and cephalosporins (i.e. cephalexin, 20-40 mg/kg, PO, TID or cephalotin, 15-25 mg/kg IV, IM or SC, TID) (2,12,13,17). The use of other antibiotics (tetracyclines, chloramphenicol and aminoglycosides) are also efficient in the treatment of E. coli, but they are poorly tolerated by some cats (39). E. coli can be resistant to ampiciline, cephalotine and tetracyclines. Enrofloxacin other fluorquinolones can reach higher therapeutic levels in the uterus as well as in other fluorquinolones (2). The decision to try medical or surgical therapy is based on the physical status and breeding capacity of the queen. The surgical approach should be considered if a critical or unstable situation exists

179 due to septicaemia, shock, azotaemia, if there are radiographic evidence of uterine rupture or peritonitis or mummified fetal remaining, because the removal of the infected material becomes necessary. Medical treatments to empty the uterus can last several days and thus complicate the situation and the pharmacologic effects can be deleterious for a patient severely affected and must only be performed in those queens with minimal systemic compromise and high reproduction value (9). Systemic antibiotic therapy alone or combined with vaginal antiseptic showers, is not effective in solving the clinical problems (5,8,17). Ovariohysterectomy This surgical therapy has been considered to be the treatment of choice as it is curative per se (5,9,12, 13,17,28,33,37). However, despite its safety, it has been associated with mortality and morbidity rates despite its safety, sepsis being the most common cause of death rather than surgical techniques or anaesthetic protocols. Surgical techniques and anaesthesia should be carried out very carefully to minimize the mortality and morbility. It has been demonstrated in dogs that the inability to diminish azotaemia prior to surgery has been associated with higher mortality. This rate has been calculated in 5 to 8% of the cases (2,12,14). Lethargy, vomiting, fever and postoperative anorexia are the most common postoperative morbidities, which can reach up to 20% (12,14.15,17). Surgical techniques are reviewed elsewhere extensively (34,38,41). In stump pyometra, excision is recommended (9) with examination of the ovarian stumps for presence of retained ovarian tissue (14). Other techniques documented are hysterectomy and uterine drainage tubes (5), although these procedure are not recom-mended (8). Medical treatment The medical approach is carried out with natural prostaglandin F2a. It can be used in queens that have value in reproduction programs, are in stable health status (without sepsis or peritonitis suspicion) and have open-cervix pyometra (2,5,10,12, 21). In spite of the fact that there has been a certain grade of success of this method in dogs with closed-cervix pyometra (25-34%), in general it has not been successful in cats (2). Medical therapy is recommended for elderly patients because of higher surgical and anaesthetic risk as far as they are concerned (10). However, in some references it is mentioned that this is not useful and must be avoided in geriatric patients older than 8 years (9). It is important to rule out fetal presence before treatment, because of the drug's abortive effects: PGF2a can cause abortion in queens up to the 40th day of pregnancy due to myometrial contraction and fetal expulsion. In advanced pregnacy this would not need to happen because of the concurrent placentary progesterone production. On the other hand, one author claims that this production only occurs after the 45th day (5). Mechanisms of action of PGF2a include uterine contractions (myoepitheliurn contractions), opening of the cervix and functional arrest of corpora lutea or even luteolysis (5,33, 39,40). The sensitivity of corpora lutea to the prostaglandin effects depends on the age of the corpora lutea, the dosage of prostaglandin, and the duration of treat-ment (13). This response is idiosyncratic in every individual queen. When administered early in diestrus, PGF2a is not luteolytic in the queen (14). After PGF2a administration, plasma progesterone concentration decreases. This is attributed to luteolysis or esteroidogenesis inhibition through the exhaustion of free intracellu-lar cholesterol and this effect is more pronounced when diestrus finishes. In queens, therapeutic dosage of PGF2a does not always cause luteolysis (13). Uterine biopsies in queens with pyometra after treatment have not been studied, but a signifi-cant effect on the endometrium is not expected and the underlying CEH does n ot disappear. Moreover, pyometra can show recurrence after treatment with PGF2a. In one study 14% of the queens treated with PGF2a showed recurrence of pyometra. Therefore, is desirable to recommend castration as soon as possible (10,36). It has not been proven in cats completely, but probably prostaglandins cause myometrial contractions, which evacuate uterine contents. This myotonic effect increases intrauterine pressure and in women a progressive reduction of prostaglandins receptors in the endometrial smooth muscle toward the cervix has been determined (5). Contraction of the uterus could result in expulsion of the contents (5). PGF2a administration is contraindicated in pre-existent uterine rupture It can predispose uterine rupture in queens with closedcervix pyometra (12). In women and rabbits there has been observed a relaxation of the uterine

- cervix, but this has not been seen in cats. Patients undergoing such therapy must be hospitalized according to their clinical status (5,8,40). The treatment protocol with PGF2a is from 0,1 to 0,25 mg/kg SCT SID or BID. The dose depends mainly on clinical signs. The volume of vulvar discharge should increase as the uterus empties. The discharge usually becomes less purulent and more mucoid or hemorrhagic as treatment continues (13). Treatment must continue till the vulvar discharge stops and the uterus returns to its normal size, and this can be expected between 3 to 5 days after treatment. Treatment can be continued for more than 5 days if the uterus is not yet empty (13) and must only be performed if the clinical status is adequate (5). Minimal therapeutic doses in queens have not been established, but it has been observed that the response to higher doses (0,25 mg/kg BID (14) is not more beneficial than that to the normal, generally accepted and recommended dose of 0,1 mg/kg SID during 5 to 7 days (5,12,36,40). Care must be taken to give adequate antibiotic and fluid therapy (39). Other reports suggest doses about 50 pg/kg TID or QID or another of 200 to 500 pg/kg SID or BID. Doses of 0,5 or 1 mg/kg SC BID, once in two days after day 40 of pregnancy, or five daily IM injections of 2 mg per cat after day 33 of pregnancy, have been reported to result in complete luteolysis and abortion within 1 to 6 days after the first injection, suggesting that such treatment also may be effective for inducing luteolysis in pyometra (14). Because of little information available on induction of luteloysis in the cat with pyometra and the risk of the use of luteolysis inducing drugs, the main aim must not be luteolysis but uterine evacuation, which is usually very beneficial in the cat (14). Natural PGF2 is the only prostaglandin which has been evaluated for the use in felines (5). Other more potent prostaglandins (i.e. synthetic substances like closprostenol) have not been evaluated and can not. substitute natural prostaglandins. Their use in cats could end in a fatal response because the safe and effective dose has not been established (2,12). In queens with open-cervix pyometra, the prognosis of recovery acute disease and future pregnancy viability is excellent. The rate of short term success is 82 to 100% (5,12), which is achieved 180 when therapy has been finished after improvement of most of the clinical signs. Follow-up must be done 2 weeks after discharge. No or only very little vaginal secretion and absence of uterine enlargement confirmed by imagenologic tests should be observed (5). Most of the treated queens (95%) return to normal estrous cycles and successful mating resulting in pregnancy (nearly 85%) (12,13,14,39). In those patients treated with prostaglandins, care must be taken when breeding the next estrous so that possible complications can be avoided when consecutive effects of progesterone in a no gravid uterus are present (2,5). It is suitable to carry out the OVH immediately in those patients with close-cervix pyometra, where the opening does not take place after some days of treatment and the patient's condition deteriorates (40). At therapeutic range, PGF2a can cause some side effects in most of the queens. All these effects are dose dependent and obey physiologic actions of the endogen prostaglandins and include vasodilatation, haemostasis, pulmonary vasoconstriction and bronchodilation, gastroenteric tract secretion, increase in renal blood flow and glomerular filtration rate, inflammation, hyperalgesia, fever, smooth muscular activity (myometrium, gastrointestinal tract, urinary bladder, tracheobronchial tract) (5). The signs include vocalization, panting, restlessness, salivation, urination, defaecation, tenesmus, diarrhoea, emesis, mydriasis, grooming, lordosis and kneading (2,5,12,13,40). These effects can occur soon after administration, but cease after 1 hour (39). Signs decrease in severity and intensity in the subsequent applications. That is the reason not to interrupt the treatment at the beginning (2,5,12). Uterine rupture or leakage of the intraluminal contents into the abdomen via the uterine tubes is possible (13,33). For several reasons, this could occur more often in cats than in dogs: 1)in, cats, uterine rupture with generalized peritonitis can occur before treatment (in about 4% of the cases), 2)feline pyometra is sometimes seen in conjunction with uterine torsion, a condition that would greatly increase the chance of rupture and finally, the uterine exudate found in cats with pyometra is occasionally very viscous and hard to be expelled. LD50 in cats has not been reported as in dogs (5,13 mg/kg) (38). Overdose from 1 to 5 mg/kg, can produce ataxia and severe respiratory distress, but not death (13).

181 Other drugs like oxytocine, ergometrina and estrogens have been used with limited responses (37). Conclusions Feline CEH-pyometra complex behaves differently compared to the canine counterpart, but there are some similarities in the clinical signs and diagnostic tools. There have been carried out some studies to achieve a histological classification, which is very important to clarify different stages of the disease. The disease can be treated successfully medically, although to avoid secondary effects of the disease and adverse effects of therapeutic prostaglandins, the ideal approach is still the surgerical therapy. References 1. Agut A, Sanchez-Valverde MA, Lasaosa JM and Laredo FG. Radiodiagnóstico en pequefios animales, 1st edition, 1992. Interamericana-McGraw-Hill, Mexico D.F. p. 296. 2. Barsanti JA. Genitourinary Infections. In: Infectious diseases of the Dog and Cat. 2nd edition. 1998. Edited by C.E. Green. W.B. Saunders Company, Philadelphia. p. 643-644. 3. 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