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Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat.

Kim NN, Stankovic M, Armagan A, Cushman TT, Goldstein I, Traish AM - BMC Womens Health (2006)

Bottom Line: Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity.Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight.The observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA. nnkim@bu.edu

ABSTRACT

Background: Tamoxifen, 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.

Methods: Female 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 microg/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.

Results: Tamoxifen 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.

Conclusion: The 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.

No MeSH data available.


Related in: MedlinePlus

Effect of tamoxifen on body and tissue weights. Body weights were determined on the same day as vaginal blood flow studies in control (CONT), tamoxifen-infused (TMX) and ovariectomized (OVX) female rats (see Figure 1). Uterine and vaginal tissue wet weights were determined immediately following the blood flow studies. Data are the mean ± SEM and were analyzed by one-way ANOVA. *p < 0.05 versus control group.
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Figure 2: Effect of tamoxifen on body and tissue weights. Body weights were determined on the same day as vaginal blood flow studies in control (CONT), tamoxifen-infused (TMX) and ovariectomized (OVX) female rats (see Figure 1). Uterine and vaginal tissue wet weights were determined immediately following the blood flow studies. Data are the mean ± SEM and were analyzed by one-way ANOVA. *p < 0.05 versus control group.

Mentions: Mean plasma estradiol concentration remained unaltered in tamoxifen treated rats, whereas a significant reduction in plasma estradiol was detected in ovariectomized rats (figure 1). Examination of vaginal smears indicated that all tamoxifen-infused and ovariectomized rats were in diestrus. In contrast, roughly half (5/11) of the rats in the control group were in diestrus with 2 each in proestrus, estrus and metestrus. 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) (figure 2). In contrast, ovariectomized rats were significantly heavier (371 ± 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. As shown in figure 2, mean uterine wet weight was significantly lower in the tamoxifen treatment group (410 ± 15 mg) than the control group (644 ± 55 mg), but higher than that of ovariectomized animals (133 ± 4 mg). Interestingly, mean vaginal wet weight was similar in control and tamoxifen-infused rats, while a small but significant decrease was observed in ovariectomized rats.


Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat.

Kim NN, Stankovic M, Armagan A, Cushman TT, Goldstein I, Traish AM - BMC Womens Health (2006)

Effect of tamoxifen on body and tissue weights. Body weights were determined on the same day as vaginal blood flow studies in control (CONT), tamoxifen-infused (TMX) and ovariectomized (OVX) female rats (see Figure 1). Uterine and vaginal tissue wet weights were determined immediately following the blood flow studies. Data are the mean ± SEM and were analyzed by one-way ANOVA. *p < 0.05 versus control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1590006&req=5

Figure 2: Effect of tamoxifen on body and tissue weights. Body weights were determined on the same day as vaginal blood flow studies in control (CONT), tamoxifen-infused (TMX) and ovariectomized (OVX) female rats (see Figure 1). Uterine and vaginal tissue wet weights were determined immediately following the blood flow studies. Data are the mean ± SEM and were analyzed by one-way ANOVA. *p < 0.05 versus control group.
Mentions: Mean plasma estradiol concentration remained unaltered in tamoxifen treated rats, whereas a significant reduction in plasma estradiol was detected in ovariectomized rats (figure 1). Examination of vaginal smears indicated that all tamoxifen-infused and ovariectomized rats were in diestrus. In contrast, roughly half (5/11) of the rats in the control group were in diestrus with 2 each in proestrus, estrus and metestrus. 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) (figure 2). In contrast, ovariectomized rats were significantly heavier (371 ± 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. As shown in figure 2, mean uterine wet weight was significantly lower in the tamoxifen treatment group (410 ± 15 mg) than the control group (644 ± 55 mg), but higher than that of ovariectomized animals (133 ± 4 mg). Interestingly, mean vaginal wet weight was similar in control and tamoxifen-infused rats, while a small but significant decrease was observed in ovariectomized rats.

Bottom Line: Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity.Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight.The observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA. nnkim@bu.edu

ABSTRACT

Background: Tamoxifen, 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.

Methods: Female 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 microg/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.

Results: Tamoxifen 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.

Conclusion: The 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.

No MeSH data available.


Related in: MedlinePlus