Hormonal Control of Estrus in Dogs

In bitches, estrus suppression, for no more than 24 mo, 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. If the bitch has already entered proestrus, the progestagen megestrol acetate (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). The next estrus usually develops 4–6 wk earlier than expected. 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 mo (typically 5–6 mo), and fertility is not affected.

Neither mibolerone nor megestrol acetate is recommended for use in bitches on their first estrus or in bitches primarily used for breeding. Adverse effects of progestins such as megestrol acetate include cystic endometrial hyperplasia and pyometra; longterm treatment may result in obesity, diabetes mellitus, and neoplasia of the uterus and mammary glands. Mibolerone may cause skin, vaginal, and clitoral changes.

Clinical use of deslorelin for estrus suppression is under investigation. Extended-release implants of deslorelin can suppress estrus for >1 yr in bitches without apparent adverse effects and with full return to fertility.

Estrus induction in bitches remains problematic, and none of the drugs presented below are approved for this use in the USA. 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/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.

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. Induction of estrus with GnRH analogues continues to be investigated. Synchronous estrus using whole (2.1 mg) or half (1.05 mg) deslorelin implants after termination of diestrus with PGF_2α has been reported. The PGF_2α protocol started with a low dosage (50 mcg/kg, SC, bid) on the first day, followed by a moderate dosage (100 mcg/kg, SC, bid) on the second day, and then a full dosage (250 mcg/kg, SC, bid) 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 USA 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.