by Debbie “The Rat Lady” Ducommun
This article reports on 3 studies which show that spaying rats helps to prevent mammary and pituitary tumors. These two tumors are the most common types found in females rats, with about half of all pet rats getting mammary tumors (many of them getting multiple tumors), and about 16% of them getting pituitary tumors, which are fatal. To see copies of the abstracts of these studies, click here.
The latest study, “Effect of surgical removal of subcutaneous tumors on the survival of rats,” was published in May 1995 in the Journal of the Veterinary Medical Association, was done by veterinarian Charlotte E. Hotchkiss. The study was actually done to study the effect of various hormone supplements on osteoporosis in spayed and non-spayed rats, but on the side, Dr. Hotchkiss also decided to record the number of mammary and pituitary tumors that were observed in each group of rats. Unfortunately, all the rats were killed at 630 days of age, which is less than 2 years, so we don't know what the results would be for older rats. But even this limited study makes it very clear that spaying rats is an effective means of preventing tumors.
The strain of rats used was Sprague-Dawley, a standard type of albino lab rat. There were 96 rats in the study, and half of them were spayed at 3 months of age. The spayed and unspayed rats were each divided into 4 groups, 3 of which received different types of hormones (estradiol, etidronate, risedronate). The hormones were administered until the rats were about 6 months old and then discontinued. At autopsy, one of the supposedly spayed rats was found to still have an ovary, so she was reclassified as unspayed, making 49 unspayed and 47 spayed rats.
Whenever subcutaneous tumors were detected on any of the rats they were surgically removed and examined by a pathologist. Mammary tumors developed in 24 of the 49 unspayed rats. In contrast, only 2 of the 47 spayed rats developed mammary tumors! That means that almost half of the unspayed rats developed mammary tumors, while only 4% of the spayed rats did so. Eight rats had multiple tumors removed and 4 underwent a second surgery to remove recurring tumors, although the article failed to report whether these rats were spayed or not (they probably were unspayed rats).
In the unspayed group, 20 of the mammary tumors removed were fibroadenomas (benign) but four rats developed adenocarcinomas (breast cancer) and one of these died from it. Three of the rats with the adenocarcinomas also had fibroadenomas. None of the spayed rats developed breast cancer. Of the other tumors that were found in the unspayed rats, one was a lipoma (benign), and one rat developed both a fibroadenoma and a pilomatrixoma (both benign). One rat developed a hemangiosarcoma (cancer of the blood vessels) and she did not survive her surgery. Treatment with etidronate and risedronate increased the incidence of mammary tumors in the unspayed rats.
In the spayed rats, both mammary tumors were fibroadenomas. One other rat developed a fibrosarcoma (cancer) which was partially removed by surgery twice without complications, but the rat died during a third surgery. There was no evidence of metastasis in this rat. This shows that it may be worth trying to remove even malignant tumors.
Another significant finding was that the spayed rats were more likely to survive to the end of the study. Twenty of the unspayed rats died spontaneously before the end of the study while only 5 of the spayed rats died. Unfortunately, 9 of the rats who died spontaneously were unavailable for autopsy (the article didn't say why) but of those that were autopsied, 5 of the unspayed, but none of the spayed rats, had pituitary tumors. These 5 rats showed neurological signs caused by their pituitary tumors prior to their death, including head tilt, circling, inability to drink from a water bottle, and lethargy.
During the autopsies that were performed on all the rats killed at the end of the study it was found that 22 of the unspayed rats and 2 of the spayed rats had pituitary tumors that had not yet caused any symptoms. Altogether, 27 of 41 unspayed rats had pituitary tumors, while only 2 of 46 spayed rats did. In addition, 5 other unspayed rats had changes in their pituitary glands that precede tumor formation. So actually 78% of the unspayed rats that were autopsied had abnormal pituitary glands! Only 4% of the spayed rats that underweight autopsy had pituitary tumors.
Effect on Life Span
The earliest and most exciting article is called “Development of Spontaneous Mammary Tumors over the Life-Span of the Female Charles River (Sprague-Dawley) Rat: The Influence of Ovariectomy, Thyroidectomy, and Adrenalectomy-Ovariectomy.” It was published in Cancer Research in March 1966 and the main researcher was Patricia W. Durbin at the University of California, Berkeley.
The article begins by explaining that this was the first experiment of this type able to examine longevity in rats, because until then lab rats died early from respiratory infections (sound familiar?) In the 1960’s laboratories learned to produce mycoplasma-free rats using Caesarean section and isolation. This study was done using these pathogen-free rats, and they reported very few died from respiratory infections.
Some of the rats in this study were spayed, some had their thyroid glands removed, and some were spayed and had their adrenal glands removed. These last rats had to be given salt water to drink because the adrenal gland controls the water balance of the body. Spaying was done when the rats were 11 weeks old. One group of rats were bred once. The control rats received no surgeries and were not bred.
Because the purpose of the study was to determine the age when the first mammary tumor occurred, the rats were killed soon after a mammary tumor appeared. This corresponds to pet rats whose owners choose not to have mammary tumors surgically removed.
In this study, the incidence of mammary tumors in the control rats was 71.5%. The rats allowed to have one litter had a tumor incidence of 70%, so one breeding did not have an effect on mammary tumor incidence. The spayed rats had a mammary tumor incidence of only 4%, which matches the results of the 1995 study. The rats whose thyroid glands were removed had the same mammary tumor incidence of the controls, although the onset of tumors was delayed. The spayed rats without adrenal glands had no mammary tumors at all, but they also didn't live as long as the rats that were only spayed.
The maximum life span for the control rats was 2 years 10 months, while their average age at death was 2 years. The maximum life span for the spayed rats was 3 years 7 months, nearly 25% longer than the controls. The average life span for the spayed rats was 2 years 10 months.
All the rats that were killed during the study were autopsied and their pituitary glands examined. There was a sharp upturn in the numbers of both mammary and pituitary tumors during the onset of menopause at 15-18 months of age. A second marked increase of tumor incidence occurred between 20-26 months of age. A great majority of the unspayed rats of this age had pituitary tumors. Many of the unspayed rats who died naturally without a mammary tumor died of a pituitary tumor. None of the spayed rats died from pituitary tumors, or of any other cause besides old age or being killed after developing a mammary tumor.
The Effect of Hormones and Radiation on Different Rat Strains
The third article, “Effects of X-Irradiation, Ovariohysterectomy and Estradiol on incidence, benign/malignant ratio and Multiplicity of Rat Mammary Neoplasms-A Preliminary Report” published in Leukemia Research in 1986, studied the effects of radiation, estrogen, and spaying on mammary tumors. This study, conducted in the Netherlands by H.A. Solleveld and others, is especially interesting because it used 3 different strains of rats. Some rat owners feel that the Sprague-Dawley rat, which is the standard lab rat, has an abnormally high incidence of mammary tumors. However, the incidence of mammary tumors in my unspayed female rats has been 44%, which corresponds to the incidence seen in the Sprague-Dawley rats in two of the studies. The incidence of pituitary tumors in my rats has been 16%.
This study compared the Sprague-Dawley (SD) to Wistar derived and Brown Norway rats. The latter strain is the closest to the wild rat. The tumor incidence in the control groups was 47% in the SD, 29% in the Wistar, and only 17% in the Norway. The incidence of malignant mammary tumors was also different in the 3 groups, with the Wistar rats having a benign/malignant ratio of 1:1, the Browns with 2:1, and the SD rats 7.3:1. So although the SD rats got more tumors, the majority of them were benign, while in the Wistar rats, half their tumors were malignant and in the Browns, one third of their tumors were malignant.
In this study, the rats were spayed at 4 weeks of age! Although I don’t recommend it be done this early, it does show that the surgery can be done on quite small rats. Spaying completely eliminated mammary tumors in the Wistar and Norway rats, and lowered the incidence in the SD rats to 7%. So it appears that the lower the original tumor incidence in a population, the lower the incidence when they are spayed, which means that spaying should be quite effective at preventing tumors in pet rats.
All the rats treated with estrogen showed increases in tumor incidence. Many of these rats died early of pituitary tumors or uterine infections. Radiation increased tumor incidence and malignant tumors in all groups except the spayed rats. Apparently, a source of estrogen must be present for the radiation to have an effect.
Maximum life spans for these rats weren’t given, but the average life
span for the controls was 2 years for the Browns and SD rats, and 2 yr 4 mo for
the Wistars. The averages for the spayed rats were 1
yr 10 mo for
The Effect of Estrogen
The reason that spaying reduces the incidence of both mammary and pituitary tumors is related to hormone levels. Estrogen stimulates the growth and activity of pituitary cells when not counteracted by high progesterone levels. As female rats grow older and reach menopause their progesterone levels drop, which allows the estrogen to act more strongly on the pituitary gland. The ovaries are the primary source of estrogen, so spaying dramatically reduces estrogen levels. The pituitary gland produces prolactin, a hormone that stimulates the mammary glands. It's not known if estrogen causes mammary tumors directly or by overstimulating the pituitary gland. Males have low estrogen levels and also have a naturally lower incidence of both pituitary and mammary tumors (although pituitary tumors are still pretty common in male rats too).
At whatever age spaying is done, it will reduce estrogen levels, but it's probably best to have female rats spayed at a young age—between 3 and 6 months. The older the rat, the more likely that tumors, especially a pituitary tumor, will already be forming. However, the 1966 study also said that an even earlier study showed that established mammary tumors frequently regress when the rat is spayed, so it may be beneficial to have older rats spayed as well. Probably spaying should be done before the rat is a year old to be assured of preventing tumor formation, but while younger is better, it may never be too late to have your rats spayed. If you have a rat that has already developed a mammary tumor, if you decide to have it surgically removed, you should also consider having her spayed at the same time to help prevent future tumors.
Taking all 3 of these studies together, the benefits of spaying include a significant decrease in the incidence of both mammary and pituitary tumors and an extended life span. Spaying seems to be one of the best ways to insure your female rats live as long as possible.
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