Endometrial Hyperplasia, Polyps, and Adenomyosis Associated with Unopposed Estrogen in Rhesus Monkeys (Macaca mulatta)

Abstract

Abstract. The purpose of this study was to evaluate the effects of estrogen and progesterone on the vaginal mucosa and their role in vaginal transmission of simian immunodeficiency virus. Incidentally, endometrial hyperplasia was observed in estrogen-treated monkeys at necropsy. Six adult female rhesus monkeys (Macaca mulatta) were ovariectomized and 120 days later received two subcutaneous implants, each containing 200 mg estradiol. The animals were sacrificed 17-27 months later and the uterus examined at necropsy. All the monkeys had simple endometrial hyperplasia, some with polyps or adenomyosis, at the time of necropsy. The severity of the changes correlated with the time between implantation and necropsy. The lesions were similar to endometrial hyperplasia caused by unopposed estrogen in women, but occurred over a time period that is suitable for experimental manipulation. Rhesus monkeys could be used as a model to test the safety of various combinations of sex steroids for the prevention of postmenopausal symptoms in women.

Aromatase expression in the eutopic endometrium of myomatous uteri: The influence of the menstrual cycle and oral contraceptive use

“…However aberrant aromatase expression has been previously detected in the eutopic endometrium of patients with endometriosis, adenomyosis and endometrial polyps [8,9,11]. This may suggest a common etiology in these conditions, involving chronic local exposure to estrogens that will lead to the development of these pathologies, thus corroborating previous studies carried out in rhesus monkeys [22].…”

“…It would be an oversimplification to consider local estrogen production to be the only stimulus of myoma development, since other factors may act synergistically in association with aromatase expression, including cytogenetic abnormalities that might affect growth rates [3,5]. Experimental studies carried out in primates have shown that chronic exposure of the uterus to estrogens leads to the development of myomas, endometrial polyps, hyperplasia and adenomyosis [22]. Although these findings suggest that excessive estrogenic stimulation may be an important factor in the genesis of various uterine pathologies, thus explaining their common association, genetic and other factors probably play important roles in determining which pathology will develop in response to excessive estrogenic stimuli.…”

The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse

“…Prolonged progesterone treatment following diethylstilboestrol also induced adenomyosis in ovariectomized mice, suggesting a link between progesterone and the development of adenomyosis (Ostrander et al 1985). On the other hand, estrogen unopposed by progestogen administered to ovariectomized rhesus monkeys induced adenomyosis (Baskin et al 2002).…”

Unsuccessful Induction of Endometriosis in Female Rhesus Macaques <i>(Macaca mulatta)</i>

“…These estrogen levels are within the physiological range [43][44][45] , even though exposure was continuous and unopposed by progesterone. Histology of endometrial tissue taken by the vaginal route, hysterotomy or hysterectomy showed proliferation of glands and stroma ( fig.…”

“…1 ). In previous studies on rhesus monkeys, subcutaneous estradiol implants were found to successfully induce continuous serum estradiol levels within the physiological range [41,42] and an endometrium with proliferative histological characteristics [43] . Thus, our 3 female rhesus monkeys received one-third of a Meno-Implant (estradiol, 20 mg; Organon, Oss, The Netherlands) placed subcutaneously in the abdominal area.…”