Progesterone receptor antagonists

Progesterone receptor antagonists, such as aglepristone, have also been evaluated for the treatment of pyometra.^14-17 These products competitively bind to progesterone receptors in the uterus, preventing endogenous progesterone from exerting its effect. However, because progesterone-receptor antagonists do not directly stimulate the myometrium to contract and expel the uterine contents, their use as a sole therapeutic agent for treating pyometra may be limited.³ When combined with cloprostenol, aglepristone was found to be more effective for treating pyometra than aglepristone alone was.^17,18 Adverse effects are uncommon in patients treated with aglepristone. Aglepristone is not available in the United States at this time.

Prognosis

Regardless of the protocol selected, patients undergoing medical management for pyometra should be examined frequently on the days of treatment and again one and two weeks after treatment. The patient's vital signs, mental status, and hydration should be evaluated. The character of the vaginal discharge as well as the ultrasonographic status of the distended uterus should be assessed every few days along with progesterone concentrations. A successful treatment would be characterized by the resolution of vaginal discharge, normalization of physical examination findings and laboratory abnormalities, and the complete evacuation and reduction in the diameter of the uterine horns.

Abnormal laboratory findings have been reported to normalize within 14 days of successful medical and surgical management of pyometra.^11,14,20 Any significant deterioration in the patient's clinical condition would warrant diagnostic reevaluation of the patient, initiation of the appropriate supportive care, and, in most cases, the recommendation that medical management be abandoned in favor of an ovariohysterectomy.

For most medical protocols, clinical improvement in the patient's signs is apparent within two to four days of initiating treatment. A treatment failure can be identified by the persistence or recurrence of clinical illness, a purulent vaginal discharge, and persistent or progressive uterine distention beyond the period of expected protocol response. Progesterone concentrations > 0.5 ng/ml are an indicator of ineffective luteolysis.²¹ Fluid identified within the abdomen would suggest peritonitis. Patients failing to respond to medical treatment may undergo further medical therapy using the same or a different treatment protocol or may receive an ovariohysterectomy.

Medical treatments may be repeated until they prove successful. Typically, no more than two treatment cycles are required to medically resolve pyometra in most patients.⁴ In 163 bitches with open-cervix pyometra receiving medical management with prostaglandins, 153 completely recovered from the infection. Of those 153 dogs, 98 recovered with one course of treatment and 55 required two courses.⁴ Medical treatment was discontinued in 10 dogs in this series for various reasons. An early study suggested a poor response of closed pyometra to prostaglandin therapy alone.⁴ However, a more recent study combining cabergoline and cloprostenol reported that three out of three dogs with closed-cervix pyometra responded favorably to this combination of drugs.¹¹

Bitches successfully treated with medical therapy should be bred during the estrous cycle immediately after treatment.^3,4 Subsequent pregnancy has been suggested to be protective against the recurrence of pyometra.⁴ For reproductively valuable bitches, it is also important to obtain a litter whenever possible. The subsequent reproductive success of intact bitches that have recovered from pyometra varies from 50% to 65%.²² It has been suggested that those dogs that responded most quickly to treatment were more likely to breed successfully in the future.³ It is not uncommon for patients successfully treated for pyometra to demonstrate estrus much sooner because of a shortened diestrus period.⁴ Bitches with shorter interestrus intervals have an increased potential for recurrence of pyometra because of inadequate time for uterine recovery (remodeling and healing of the endometrium). For this reason, estrus suppression could be considered to delay cycling and promote uterine recovery until breeding is planned.⁴

The prevalence of pyometra recurrence in bitches that have been successfully treated remains undetermined. Recurrence rates have been reported to vary from as high as 77% within the first 27 months after treatment to no additional risk above that of dogs that have never acquired pyometra.^3,23 Because an increased risk for recurrence may be present, once the owner's reproductive goals for the dog have been achieved, the patient should undergo an ovariohysterectomy.