Medroxalol hydrochloride is an
antihypertensive agent with beta 1
adrenergic cardiac blocking properties, and beta 2 and some alpha 1 vasodilating activity. In previous carcinogenicity studies
medroxalol was shown to induce
leiomyomas of the uterus in CD-1 mice but not in Long Evans rats. In addition, there was a significant increase in
endometrial stromal sarcomas in mice receiving the lowest dose of
medroxalol; however, the lack of a dose response made the relationship to treatment questionable. Because of these findings, additional 18-month
drug diet studies were conducted in 3 parallel segments using female CD-1 mice to determine the effects of: 1) an expanded range of doses, 2) various durations of dosing, and 3) the effect of the beta-blocker,
propranolol, on
leiomyoma induction. These studies confirmed the fact that chronic dietary treatment with
medroxalol can lead to an increased incidence of
leiomyomas in the mouse uterus, but failed to demonstrate any relationship between
endometrial stromal sarcomas and
medroxalol administration. A linear trend occurred in the incidence of
leiomyomas and of smooth muscle
hypertrophy/
hyperplasia, a possible precursor to
leiomyoma. Both findings were notably increased at 250 mg/kg/day or more. Doses of 50 mg/kg/day or less were considered no effect levels. At 500 mg/kg/day a treatment period of 12 months or more was required before a noticeable increase in
leiomyomas occurred in mice examined after 18 months. The beta-blocker,
propranolol, prevented this increase in
leiomyomas, and led to the conclusion that the beta 2 agonist activity of
medroxalol was involved in their induction.
Propranolol did not block the spontaneous occurrence of these
tumors.