**1.2. Approach to bitches with anestrous problems**

with thyroid dysfunction. Thyrotropin-releasing hormone (TRH) secretion from the hypothalamus increases due to low levels of thyroid hormones; consequently, thyroid-stimulating hormone (TSH) secretion from the pituitary gland increases. As a result of this totally physiological process, low serum total and free thyroxin levels and elevated serum TSH levels are

Hypothyroidism should be kept in mind in the presence of numbness or mental fatigue, hair loss, weight increase or obesity, dryness or loss of body hair, hyperpigmentation, cold intolerance, bradycardia, high plasma cholesterol level, or anemia in a bitch with an anestrous problem. Measurement of only thyroid hormones may yield misleading or conflicting results. Therefore, a full thyroid profile should be obtained and a definitive diagnosis made in bitches suspected of hypothyroidism. For this purpose, the serum-free thyroid hormone level (particularly T4 measurement) and the response of the thyroid gland to TSH administrations should be investigated. Furthermore, autoantibodies against thyroxin (T4) and triiodothyronine (T3) or thyroglobulin should be investigated in serum, as they are produced in most

The sexual cycle may return to normal with hormone replacement therapy within 3–6 months in bitches diagnosed with hypothyroidism. For this purpose, synthetic thyroid hormone (levothyroxin) should be administered through the peroral route. A dose of 22 μg/kg b.i.d. is

Although hyperthyroidism with consequent primary anestrus is a rare condition in bitches, a case has been reported in a Pinscher dog with diet-related hyperthyroidism in which primary anestrus developed; the bitch reached proestrus 13 days later after dietary regulation, with

The pituitary gland is important for the endocrinological functions of the adrenal glands, thyroid gland, and the ovaries. Abnormalities of the pituitary gland also negatively affect these organs. Prolonged anestrus is unusually seen in bitches with dwarfism caused by a congenital anomaly. Ovariohysterectomy is recommended in bitches that show prolonged anestrus

Such diseases may negatively affect reproductive function. Cycles probably will not develop

Progesterone-releasing ovarian cysts, ovarian aplasia, and oophoritis may lead to primary anestrus. Definitive diagnosis can be made by histopathological examination of the ovarian

observed in bitches with primary hypothyroidism [7].

130 Canine Medicine - Recent Topics and Advanced Research

bitches with lymphocytic thyroiditis [7, 18, 19].

estrus then induced by cabergoline [20].

related to pituitary gland insufficiency [6].

*1.1.6. Pituitary gland insufficiency*

*1.1.7. Systemic diseases*

if an animal is unhealthy.

*1.1.8. Ovarian anomalies*

tissue [21].

usually sufficient.

First, it should be determined whether the pet owner has correct and sufficient knowledge of the cycle and estrous signs of bitches. The age of the bitch and whether it has experienced ovariectomy, ovariohysterectomy, or administration of any drug or vaccine (especially GnRH vaccine) should be determined. Serum progesterone level should be monitored monthly for 6–8 months before any intervention in anestrous bitches. In normal bitches, the serum progesterone level rises above 2 ng/mL within 2 months after estrus; progesterone level below 2 ng/mL for 6–8 months definitely indicates prolonged anestrus. In addition, vaginal epithelial cells should be monitored for any alterations with weekly vaginal smears.

Routine blood and urine tests (complete blood count, biochemical analysis) and thyroid function tests should be performed following general examination in anestrous bitches. Progesterone measurement and ultrasonographic examination of the ovaries should be carried out whenever luteal cyst or tumor of the ovaries is suspected. Karyotype analysis should be performed if developmental anomalies of the genital organs are suspected (such as hermaphroditism) [5].

Treatment of primary or secondary anestrus is targeted towards its etiology. No treatment is available if a bitch has undergone ovariectomy or ovariohysterectomy or in the presence of congenital sex development or differentiation anomalies, ovarian aplasia, or autoimmune oophoritis. Ovariohysterectomy is recommended for autoimmune oophoritis. Hormone replacement therapy may be administered in bitches determined to have hypothyroidismrelated anestrus [22].

Estrous stimulation may be performed in anestrous bitches for which the underlying cause cannot be detected. Synthetic estrogens (diethylstilbestrol), dopamine agonists (bromocriptine and cabergoline), GnRH agonists (lutrelin, buserelin, fertirelin, deslorelin, leuprolide), or exogenous gonadotropins (LH, FSH, hCG, PMSG) may be administered for this purpose [23, 24].

Dopamine agonists are effective for stimulating fertile estrus in most bitches; however, prolonged use may be required. Bromocriptine (Parlodel, Gynodel) or cabergoline (Galastop, Dostinex) is used for this purpose. Bromocriptine is less preferred, as it causes vomiting and requires lengthy periods of administration in order to stimulate estrus. Although more expensive than bromocriptine, cabergoline may induce estruses effectively and safely with fewer side effects. Cabergoline is usually recommended at a dose of 5 μg/kg daily via the peroral route until 3–8 days after proestrus has begun [23–25].

Using GnRH and its analogs may also induce estruses. However, prolonged use for 8 days or longer or long-acting analogs such as lutrelin, deslorelin, or leuprolide is needed to induce fertile estrus. It is impractical to induce estrus by using short-acting natural GnRH or GnRH agonists, because GnRH should be given as a pulsatile continuous infusion at a dose of 0.2– 0.4 μg/kg every 90 min via the intravenous or the subcutaneous route for 3–9 days. This requires 3–9 days of hospitalization and the availability of a pulsatile infusion pump. Long-acting formulations of GnRH analogs such as lutrelin, deslorelin, and leuprolide have been quite successful when implanted subcutaneously or submucosally. Deslorelin-containing implants (Suprelorin®, 4.7 mg deslorelin) are used most frequently for this purpose [23–27].

Hypophyseal (FSH and LH) and chorionic (PMSG and hCG) gonadotropins are also used for inducing estruses. It has been found that chorionic gonadotropins are more successful than hypophyseal gonadotropins in bitches. Although various protocols have been attempted, successful results have been reported with 20 IU/kg/d PMSG applied subcutaneously for 5 days, with 500 IU intramuscular hCG on day 5. PG600, a preparation containing PMSG and hCG first produced for pigs (80 IU PMSG and 40 IU hCG/mL), is quite effective for inducing estruses [8, 28].
