Abstract
BackgroundTamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat.MethodsFemale Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control) or tamoxifen (150 μg/day). Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay.ResultsTamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen) by the vaginal epithelium of tamoxifen-infused rats.ConclusionThe observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina. These physiological alterations may eventually lead to vaginal atrophy and compromise sexual function.
Highlights
Tamoxifen, a selective estrogen receptor modulator with both estrogenic and antiestrogenic activity, is widely used as adjuvant therapy in breast cancer patients
Minimal changes in body weight were observed in rats treated with tamoxifen for two weeks (289 ± 4 g) when compared to age-matched controls infused with vehicle (281 ± 6 g)
To assess the extent of anti-estrogenic effects of tamoxifen, the wet weights of the uterus and vagina were determined for each animal
Summary
A selective estrogen receptor modulator with both estrogenic and antiestrogenic activity, is widely used as adjuvant therapy in breast cancer patients. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. Tamoxifen is a non-steroidal, triphenylethylene derivative that is widely used and highly effective as adjuvant therapy for the management of breast cancer patients with estrogen receptor (ER) positive tumors. Trans-tamoxifen is generally considered an anti-estrogen, whereas cistamoxifen is considered to be a weak estrogen. Interconversion between these isomers has been shown to occur in cultured cells [4], but this process remains poorly characterized in vivo
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