HISTOLOGICAL CHANGES OF THE REPRODUCTIVE TRACT OF QUEENS AFTER TREATMENT WITH MEGESTROL ACETATE

Megestrol acetate (MA) is a short-acting progestin marketed as an oral formulation (EstropilllTM, MSD, Italy) for estrus prevention in queens through suppression of the hypothalamic-pituitary-ovarian axis. Historical use of different protocols, including excessive dosages of MA has been associated with endocrine and uterine complications as cystic-endometrial hyperplasia (CEH), uterine enlargement, pyometra, adenomyosis, and mammary signs (hyperplasia, benign and malignant nodules, mammary adenocarcinoma). This study aims to assess the histological features of uteri and ovaries of queens treated with low dosages of MA for a relevant time span to assess/rule out potential utero-ovarian side effects. Six post-pubertal (9 months-6 years) intact, and healthy female cats (1 Persian, 1 Bengal and 4 European shorthair cats) were presented for reproduction control. Inclusion criteria were absence of past reproductive problems, vaginal cytology indicative of anestrus or postestrus and serum progesterone (P4) concentration below 2.0 ng/ml. Duration of treatment (11.5 µg/kg/day orally, approximately 5 drops/kg/day) ranged from 1 to 6 months (1-month, n=1; 2-months, n=1; 4-months, n=3; 6-months, n=1). Hematology, biochemistry, urinalysis, reproductive ultrasound, vaginal cytology and P4 assay were performed before and after treatment. Ovariohysterectomy was performed on all 6 queens following their first heat post-treatment. Ovaries and uteri were examined histopathologically. Four/6 queens had P4 <2.0 ng/ml, therefore treatment was immediately initiated. The remaining 2 cats had P4 >2.0 ng/ml indicating they had ovulated. Thus, treatment onset was postponed for the necessary time to rule out pregnancy and avoid P4 overexposure (from to 20-40 days depending on P4 value and date of last heat). During treatment, five queens didn’t exhibit signs of heat and all 6 queens remained in good health. All queens returned to heat after the end of the treatment and had basal P4 at their last check-ups, just days after treatment ended, before heat. The histological examination revealed a well-developed glandular mucosa in all queens and corpora lutea in 3 females. Evidence of hemorrhage in the uterine mucosa was found in 3/6 animals. A cystic and atypical endometrial hyperplasia and purulent endometritis were observed in one subject (indoors without male contact), who showed yellowish and bloody discharge 2 weeks after the end of heat. Ovarian cysts were detected in another queen, although they were already present before treatment. The cat who developed pyometra ovulated spontaneously both before and after MA treatment. Spontaneous ovulating queens tend to undergo repeated luteal phase which probably makes them a poor candidate for any (even low dose) progestin treatment. Overall, the results demonstrate that using MA for short-term contraception in healthy adult queens is effective and clinically safe up to 6 months, although histopathological alterations can already be observed. The absence of a control group limits the study’s ability to conclusively attribute these changes to the treatment. Further research on the safety of MA treatment in spontaneous ovulating queens (especially consistent ones) and on the reversibility of these histopathological MA-induced alterations is needed.