This article is from the May/June 1996 AFRMA Rat & Mouse Tales news-magazine.

By Carmen Jane Booth, D.V.M.

Carmen Jane Booth, D.V.M.
I received a phone call regarding the benefit of spaying female rats as a means of preventing tumor development as rats age, as a result of an article published last year. The original article, “Effect of surgical removal of subcutaneous tumors on survival of rats,” was published in the Journal of the American Veterinary Medical Association, May 15, 1995, Volume 206, page 1575.

The study was undertaken to evaluate the practicality of surgical removal of mammary tumors and the effect on survival.

Ninety-six female Sprague-Dawley rats were divided into two groups; half were ovariectomized (ovaries removed) at 90 days of age and the other half underwent sham surgery (sexually intact). These two groups were further divided into four treatment groups of 12 rats, three of which were given different hormones (treated) and one was given saline (control) from days 91 to 250 for a different study involving osteoporosis (reduction in the amount of bone mass leading to fractures [common in postmenopausal women]). Post treatment rats were maintained for 380 days and any subcutaneous tumors that developed were removed surgically and examined histologically.

Necropsy (visual examination of the body after death) was attempted on rats that died or were found moribund and euthanized prior to the end of the study. At the end of the study (630 days of age) all rats were euthanized and only gross lesions in the mammary glands or pituitary gland were examined histologically (examination of tissues using a microscope).

• One rat was found to be not completely ovariectomized and was recategorized into the sexually intact group.
• Of the 49 sexually intact rats, 26 developed subcutaneous tumors.
• Of the 47 ovariectomized rats, 3 developed subcutaneous tumors.
• Of the 49 sexually intact rats, 20 died (8 control and 4 treated) or were moribund before the end of the study. Only 11 of the 20 were necropsied and five had pituitary tumors.
• Of the 47 ovariectomized rats, 5 (2 control and 3 treated) died before the end of the study and none had pituitary tumors at necropsy.
• One sexually intact rat died during surgery to remove a tumor.
• One ovariectomized rat died during the third surgery to remove a tumor.
• Of the 21 (20 sexually intact, 1 ovariectomized) rats that underwent surgery to remove mammary tumors, 17 survived to the end of the study. Eight of these rats had multiple tumors removed and 4 underwent a second surgery to remove recurrent tumors.
• Of the 96 rats on the study, necropsy was performed on 87. Fourty-one of the sexually intact had pituitary tumors and 5 had changes within the pituitary gland. Two of the ovariectomized rats had pituitary tumors. All but five of the pituitary tumors were clinically silent. Clinical signs included: head tilt, circling, inability to use a sipper tube, and lethargy.

• Significantly more ovariectomized rats survived to the end of the study.
• Sexually intact rats had a difference in the frequency of pituitary abnormalities.
• The X2 statistical test indicated that survival to the end of the study in sexually intact rats was positively correlated with development of tumors, either mammary or pituitary.
• Although sexually intact rats had an increased frequency of both mammary and pituitary, statistical analysis using a Fisher's exact test failed to reveal any correlation between the two tumor types.
• The different drugs given did not result in significant differences in survival rate or tumor incidence in any of the eight treatment groups.
• Surgical removal of mammary tumors in rats is a simple, straightforward procedure, and may improve quality of life.
• The survival rate following surgical removal of mammary tumors is good, even for those that are histologically classified as malignant, but the procedure does not prolong life.

Estrogens (female hormones) have been known for many years to be related to mammary tumors as mammals age. This is the reason that all veterinarians recommend spaying female dogs before their first heat. Estrogen has also been determined previously to increase the frequency of pituitary tumors. Estrogen increases the mitotic rate (rate of cell division) of pituitary cells especially those that secrete prolactin (another reproductive hormone). Sexually intact female rats have higher concentrations of prolactin.

One key point to keep in mind with the study is that they use small groups and euthanized the rats at 630 days (less than 2 years of age) so true life-span data is not available. Although more sexually intact rats had pituitary changes, the majority were clinically silent. Additionally, rodents can and do develop a wide variety of other types of tumors as they age that are completely unrelated to their sexual status that are equally as debilitating as pituitary tumors. I have read many different research papers on tumor incidence in aging rodents and cannot recommend the universal spaying of female rats to prolong life span as suggested by this particular study.

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