Estrus in a Spayed Bitch

"In the adult bitch, estrogen is responsible for the development of secondary sexual characteristics, such as nipple and vulvar development, behavioral changes associated with estrus, and preparation of the female reproductive tract for breeding."

HISTORY
The dog had undergone routine ovariohysterectomy at 6 months of age. One month before presentation, the owner noted that the dog’s nipples had become swollen (Figure 1). Vulvar discharge was also observed, but the owner did not note other abnormalities or behavioral changes. The dog was on a heartworm preventive only (no other medications).

Figure 1. Patient's clinical signs included swollen nipples, an enlarged vulva, and vulvar discharge.

CLINICAL PRESENTATION
The dog was alert, responsive, hydrated, and normothermic on examination. Her skin coat appeared normal. All nipples were swollen. The vulva was enlarged and vulvar discharge was noted. The remainder of the physical examination was unremarkable.

LABORATORY DIAGNOSTICS
Vaginal cytology revealed 70% cornified epithelial cells, with occasional red blood cells and no neutrophils (Figure 2). The complete blood count (CBC) and serum biochemical profile were unremarkable. Serum estradiol was elevated at 390.5 pg/mL (range: <15 pg/mL for spayed bitch; 15–50 pg/mL for bitch with normal follicular activity). A test for serum luteinizing hormone was negative.  

Figure 2. Vaginal cytology revealed 70% cornified epithelial cells with occasional red blood cells and no neutrophils.

Diagnosis: Human Hormone (Estrogen) Cream Toxicosis

Clinical signs and laboratory diagnostics were consistent with estrus. While hormone assays alone are not definitive, in the presence of clinical signs consistent with estrus they suggest being under the influence of estrogen.¹ In the adult bitch, estrogen is responsible for the development of secondary sexual characteristics, such as nipple and vulvar development, behavioral changes associated with estrus, and preparation of the female reproductive tract for breeding.

Sources of estrogen in a spayed dog can include an ovarian remnant, an estrogen-secreting adrenal tumor, or exogenous exposure such as oral exposure to estrogen-containing pills or inadvertent oral or dermal contact with estrogen-containing cream.^2-4

There are no definitive tests to distinguish between endogenous and exogenous sources of estrogen. Diagnostic imaging, such as ultrasound, or invasive procedures, such as endoscopy or surgery, can definitively diagnose ovarian remnant or tumor.² Often thorough questioning of the owner will reveal a source of exogenous estrogen.

DEFINITIVE DIAGNOSIS
Topical hormone replacement therapies (HRTs) are used to treat menopause symptoms in women. Topical HRTs contain estradiol and are available as a spray or cream formulation. They are usually applied to either the forearm or upper thigh.⁵

When pets have inadvertent oral or dermal contact with the owner’s treated skin, absorption of estradiol can occur, leading to clinical signs of estrus in female pets and development of feminine sex characteristics, such as nipple enlargement, in males.⁶ In this case, the owner used a topical estrogen cream on her arm and frequently allowed the dog to sleep next to her in bed.

Estrus due to presumptive exogenous estrogen exposure was diagnosed.

MANAGING ESTROGEN EXPOSURE
If the patient’s history reveals possible exogenous estrogen exposure, further exposure must be prevented. Serial CBCs may be necessary to monitor evidence of estrogen-induced myelotoxicity.^7,8 Evidence of pancytopenia could be apparent by 3 to 4 weeks after exposure. If clinical signs of estrogen influence continue to persist beyond several months despite no further exposure to a topical HRT, then further diagnostics to rule out other causes of hyperestrogenism should be conducted.

Corrective Actions
In this case, the owner was instructed to wear gloves when applying the HRT cream and to keep the treated area covered with clothing at all times to prevent further exposure. Because the CBC results at presentation were unremarkable and no other abnormalities were noted on physical examination, intervention measures were unnecessary and the dog was monitored at home without treatment.

Outcome
The dog presented for reevaluation 3 weeks after initial presentation. The vulvar discharge had resolved, although nipple and vulvar enlargement were still present. The owner confirmed that she had discontinued using the topical HRT. The results of a second CBC to monitor for myelotoxicity were again unremarkable. At 3 months after the initial presentation, the dog had fully recovered. Additional diagnostics were not conducted.

CBC = complete blood count, HRT = hormone replacement therapy

ESTRUS IN A SPAYED BITCH • Cristine L. Hayes
References

1. Variability of estradiol concentration in normal dogs. Frank LA, Mullins R, Rohrbach BW. Vet Dermatol 21:490-493, 2010.
2. Ovarian remnant syndrome in dogs and cats: 21 cases (2000-2007). Ball RL, Birchard SJ, May LR, et al. JAVMA 236:548-553, 2010.
3. Theriogenology question of the month. Schwarze RA, Threlfall WR. JAVMA 233:235-237, 2008.
4. Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs. Syme HM, Scott-Moncrieff CS, Treadwell NG, et al. JAVMA 219:1725-1728, 2001.
5. Estradiol. DRUGDEX® System, version 5.1 [Intranet]—Greenwood Village, CO: Thomson Reuters (Healthcare), 2011.
6. Estrogen spray poses risks to children, pets through contact with treated skin. Voelker R. JAMA 304:953, 2010.
7. Estrogen-induced myelotoxicity in dogs: A review. Sontas HB, Dokuzeylu B, Turna O, Ekici H. Can Vet J 50:1054-1058, 2009.
8. Toxicology of veterinary and human estrogen and progesterone formulations in dogs. Kustritz MV. In Bonagura JD, Twedt DC (eds): Kirk’s Current Veterinary Therapy XIV—St. Louis: Saunders Elsevier, 2009, pp 147-149.
9. Disorders of the estrous cycle. Johnson CA. In Nelson RW, Couto CG (eds): Small Animal Internal Medicine, 3rd ed—St. Louis: Mosby, 2003, pp 847-869.
10. Disorders of the penis, prepuce, and testes. Johnson CA. In Nelson RW, Couto CG (eds): Small Animal Internal Medicine, 3rd ed—St. Louis: Mosby, 2003, pp 918-926.