Hormonal Control of the Estrous Cycle in Dogs

Prevention of estrus in bitches is typically the most commonly sought manipulation by dog owners and veterinarians alike. In bitches, estrus suppression (for no more than 24 months) could be accomplished previously by administration of mibolerone (an androgen, at 30–180 mcg, PO, every 24 hours, depending on the weight of the bitch [1]). Other reported doses include 16 mcg/kg, PO, every 24 hours (2). To be effective, treatment must be started at least 30 days before estrus.

After mibolerone treatment, the average time to return estrus is 70 days, however, some females might delay for approximately 7 months (2, 3).

Common adverse effects of mibolerone treatment are clitoral hypertrophy, vaginitis (especially in prepubertal bitches), increased activity of skin sebaceous glands, mild epiphora, and alterations in hepatic function. Other adverse effects can include increased aggression, the presence of a musky odor, and changes in appetite (3).

Mibolerone should not be used in dogs with liver disease. Mibolerone is no longer commercially available or readily compounded in the US.

If a bitch has already entered proestrus, megestrol acetate (synthetic progestogen; 2.2 mg/kg, PO, every 24 hours for 8 days) can be administered to stop the cycle (4). 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 return to estrus in 4–6 months after this treatment.

To delay estrus, treatment with megestrol acetate (0.55 mg/kg, PO, every 24 hours for 32 days [4]) is begun in late anestrus (up to a few weeks before estrus is expected). Estrus occurs within 2–9 months (typically 5–6 months) after treatment, and fertility is not affected.This treatment to stop estrus has an efficacy of 90–95% (4).

Adverse effects of megestrol acetate treatment to delay estrus in bitches include increased appetite, weight gain, and behavioral changes (generally greater docility). Cystic endometrial hyperplasia might also develop, alongside its associated risk of the development of pyometra. The use of megestrol is contraindicated in females with evidence of reproductive disease, pregnancy, diabetes, and mammary tumors. In addition, administering two consecutive treatments is not recommended. Long-term treatment can result in obesity, diabetes mellitus, and neoplasia of the uterus and mammary glands.

Clinical use of deslorelin implants (a long-acting GnRH agonist [5, 6]) for estrus suppression may also be considered for bitches; however, these implants are not currently available in the US. Initially, stimulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) brings most dogs into estrus within 5–8 days after placement, followed by long-term prevention ranging from 2 to 27 months (7). Administration of megestrol acetate to bitches at 2 mg/kg, PO, every 24 hours for 2–3 weeks before placement of the deslorelin implant can be effective in avoiding induced estrus (8).

Neither mibolerone nor megestrol acetate is recommended for use in bitches on their first estrus or in bitches used primarily 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 might vary. Estrus induction in a bitch before endometrial involution is complete (135 days after the most recent estrus) can result in decreased fertility.

The dopamine agonists cabergoline (5 mcg/kg, PO, every 24 hours until 2 days after onset of proestrus) and bromocriptine (0.3 mg/bitch, PO, for 3 days, followed by 0.6–2.5 mg/bitch, PO, for 3–6 days after onset of proestrus) are reported to induce fertile estrus in most bitches (6, 9, 10). The average length of treatment was 16–19 days.

The administration of metergoline (0.56–1.2 mg/kg, IM, every 72 hours until proestrus) to induce estrus in bitches has also been described (11); however, this drug is not widely available.

Two notable adverse effects of dopamine agonist treatment in bitches are vomiting and coat color changes that might be irreversible. Adverse effects such as vomiting occur less frequently with the use of cabergoline, compared with bromocriptine.

The most widely studied gonadotropin for estrus induction in dogs is equine chorionic gonadotropin (eCG) at 80 IU/mL combined with 40 IU/mL of human chorionic gonadotropin (hCG) as labeled for swine (6, 9, 12). A single 5-mL injection of this combination was effective, inducing proestrus in 89.5% of treated bitches; however, the ovulation rate was poor (13). However, whelping rates of 50–84% have also been reported when eCG and hCG were used to induce estrus in bitches (14, 15).

Deslorelin implants (4.7 or 9.4 mg) can also be effective for inducing estrus in bitches; however, they have been associated with low progesterone values during diestrus when not removed and, subsequently, prolonged estrus suppression (5). Removal of the implant 10 days after insertion can overcome this problem (2).

The use of estrogens such as diethylstilbestrol to induce estrus in bitches, although described (16, 17, 18), is not recommended, because of both their efficacy and their substantial toxic effects at described dosages, which include bone marrow suppression, alopecia, inappetence, vomiting, and diarrhea, as well as increased risk of pyometra (2, 19).

• McRae G, Runcan E, Johnson A. Estrous cycle manipulation in dogs. Clin Theriogenology. 2025;17(special issue):82-86.

• Kutzler MA. Estrous cycle manipulation in dogs. Vet Clin North Am Small Anim Pract. 2018;48(4):581-594.

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11. Kusuma PS, Tainturier D. Comparison of induction of oestrus in dogs using metergoline, metergoline plus human chorionic gonadotrophin, or pregnant mares’ serum gonadotrophin. J Reprod Fertil Suppl. 1993;47:363-370. https://pubmed.ncbi.nlm.nih.gov/8229950

12. Stornelli MC, Garcia Mitacek MC, Gimenez F, et al. Pharmacokinetics of eCG and induction of fertile estrus in bitches using eCG followed by hCG. Theriogenology. 2012;78:1056-1064. doi:10.1016/j.theriogenology.2012.04.012

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16. Kutzler MA. Estrus induction and synchronization in canids and felids. Theriogenology. 2007;68:354-374. doi:10.1016/j.theriogenology.2007.04.014

17. Bouchard GF, Gross S, Ganjam VK, et al. Oestrus induction in the bitch with the synthetic oestrogen diethylstilboestrol. J Reprod Fertil Suppl. 1993;47:515-516. https://pubmed.ncbi.nlm.nih.gov/8229970

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19. Sontas HB, Dokuzeylu B, Turna O, Ekici H. Estrogen-induced myelotoxicity in dogs: a review. Can Vet J. 2009;50(10:1054-1058. https://pmc.ncbi.nlm.nih.gov/articles/PMC2748286