Hormonal Control of Estrus in Dogs

ByJuan E. Romano, DVM, PhD, DACT
Reviewed/Revised Apr 2021

    The estrous cycle of a dog is not as easily manipulated as in other species. In bitches, estrus suppression, for no more than 24 months, can be accomplished by administration of mibolerone (an androgen, 30–180 mcg/day, PO, depending on the weight of the bitch). To be effective, treatment must be started at least 30 days before estrus. Estrus is variable but typically develops soon after cessation of treatment; fertility should be normal by the second estrus after treatment. Return to estrus is variable between 70 and 90 days after treatment ends. Common adverse effects are clitoral hypertrophy, vaginitis (especially in prepubertal bitches), increased activity of skin sebaceous glands, mild epiphora, and alterations in hepatic function. Mibolerone is no longer marketed in the US.

    If the bitch has already entered proestrus, megestrol acetate (synthetic progestogen; 2.2 mg/kg/day, PO, for 8 days) may be used to stop the cycle. Administration must start in the first 3 days of proestrus (vulvar bleeding). Vaginal bleeding and vulvar swelling usually disappear in 3–8 days. The bitch should be confined during this time. Most bitches will return to estrus in 4–6 months.

    To delay estrus, treatment with megestrol acetate (0.55 mg/kg/day, PO, for 32 days) is begun in late anestrus (up to a few weeks before estrus is expected). After treatment, estrus is seen in 2–9 months (typically 5–6 months), and fertility is not affected. The efficacy to stop estrus is between 90% and 95%. Adverse effects include increased appetite, weight gain, and behavior changes (generally more docile). Cystic endometrial hyperplasia might also develop. The use of megestrol is contraindicated in females with evidence of reproductive disease, pregnancy, and mammary tumors. In addition, two consecutive treatments is not recommended. Longterm treatment may result in obesity, diabetes mellitus, and neoplasia of the uterus and mammary glands.

    Neither mibolerone nor megestrol acetate is recommended for use in bitches on their first estrus or in bitches primarily used for breeding.

    Estrus induction in bitches remains problematic, and none of the drugs presented below are approved for this use in the US. Many methods have been proposed, but repeatability is low, and fertility of the induced estrus is variable. Estrus induction in the bitch before endometrial involution is complete (135 days after the most recent estrus) can result in reduced fertility. The dopamine agonists cabergoline (5 mcg/kg per day, PO, until 2 days after onset of proestrus), metergoline (0.56–1.2 mg/kg, IM, every third day until proestrus), and bromocryptine (0.3 mg/bitch for 3 days followed by 0.6–2.5 mg per bitch for 3–6 days after onset of proestrus) are reported to induce fertile estrus in most bitches. Average length of treatment was 16–19 days. Two notable adverse effects of dopamine agonist treatment in the bitch are vomiting and coat color changes.

    Clinical use of deslorelin (GnRH long-acting agonist) for estrus suppression is under investigation. Extended-release implants of deslorelin can suppress estrus for >1 year in bitches without apparent adverse effects and with full return to fertility. Use of deslorelin implants may also be effective for induction of estrus but has been associated with low progesterone values during diestrus and, subsequently, prolonged estrus suppression. Removal of the implant 10 days after insertion may overcome this problem. Deslorelin implants (4.7 or 9.4 mg) have been reported inhibit reproduction in the bitch for 4.5 and < 12 months, respectively. Bitches implanted in the anestrus stage could come in to estrus within 3–15 days after treatment; however, bitches in diestrus do not come in estrus. Deslorelin should only be used in bitches that are healthy and not pregnant. The use of megestrol acetate at 2 mg/kg for 2–3 weeks before placement of the deslorelin implant may be effective in avoiding induced estrus. Induction of estrus with GnRH analogues continues to be investigated. Synchronous estrus with whole (2.1 mg) or half (1.05 mg) deslorelin implants after termination of diestrus with PGF has been reported. The PGF protocol started with a low dosage (50 mcg/kg, SC, twice daily) on the first day, followed by a moderate dosage (100 mcg/kg, SC, twice daily) on the second day, and then a full dosage (250 mcg/kg, SC, twice daily) for 5 days. Encouraging results have also been reported using a single 1.5-mg IM injection of a sustained-release formulation of deslorelin marketed for use in mares.

    The most widely studied gonadotropin for estrus induction in canids is equine chorionic gonadotropin (eCG), which is available in the US only in a porcine product that contains a combination of 80 IU eCG and 40 IU hCG/mL. A single 5-mL injection of this product was highly effective for inducing proestrus in 89.5% of treated bitches, but ovulation rate was poor. However, whelping rates of 50%–84% have also been reported when eCG and hCG were used to induce estrus in bitches.

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