Histopathological and Biochemical Changes in the Uterus of Female Albino Rats Exposed to Mestranol

Mestranol, a synthetic estrogen widely used in oral contraceptives, exerts potent estrogenic effects that may alter uterine structure, hormonal balance, and oxidative status following prolonged exposure. This study evaluated the histopathological and biochemical changes in the uterus of female Wistar rats following repeated Mestranol administration. Twenty adult female Wistar rats were randomly assigned to four groups (n = 5): a control group receiving Tween-80 (2 mL/kg) and three groups receiving oral Mestranol at 0.5, 1.0, or 1.5 mg/kg daily for five weeks. Uterine weight, reproductive hormones (estrogen, progesterone, FSH, LH), oxidative stress markers (MDA, GSH, SOD), and uterine histopathology were assessed; data were analyzed by one-way ANOVA (p < 0.05). Mestranol significantly increased final body weight, uterine weight, and uterine index, with the greatest values at the high dose. Estrogen increased progressively, whereas FSH, progesterone, and LH declined significantly (p < 0.05). MDA increased, and SOD decreased across treated groups, while GSH varied slightly, with none of the oxidative stress markers significantly altered overall. Histology showed increasing stromal collagen deposition, with mild fibrosis at the medium dose and pronounced fibrosis at the high dose on Masson’s trichrome staining. Chronic Mestranol administration significantly increased uterine weight, uterine index, and disrupted reproductive hormone levels, with a non-significant trend toward altered uterine oxidative stress markers, alongside dose-dependent collagen deposition and fibrosis on histology; long-term or high-dose use should be further evaluated in larger studies, and molecular validation is recommended.