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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 vaginal epithelium. Vaginal tissue from control (CONT) and tamoxifen-infused (TMX) rats (see Figure 1) were fixed in 10% neutral buffered formalin and embedded in paraffin. Deparaffinized tissue sections (5 μm) were subjected to Masson's trichrome (MT) and periodic acid-Schiff (PAS) staining procedures. For each row, representative tissue sections from different animals within each treatment group are shown.
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Figure 6: Effect of tamoxifen on vaginal epithelium. Vaginal tissue from control (CONT) and tamoxifen-infused (TMX) rats (see Figure 1) were fixed in 10% neutral buffered formalin and embedded in paraffin. Deparaffinized tissue sections (5 μm) were subjected to Masson's trichrome (MT) and periodic acid-Schiff (PAS) staining procedures. For each row, representative tissue sections from different animals within each treatment group are shown.

Mentions: Examination of fixed vaginal tissue sections revealed normal variations in epithelial morphology in intact, cycling rats. These variations were most apparent at the apical surface of the epithelium and consisted of slightly keratinized, non-keratinized or mucified cells. Mucified epithelium was characterized by the presence of secretory vesicles and positive PAS staining (figure 6). A dramatic increase in the appearance and extent of mucified epithelium was observed in vaginal tissue from tamoxifen-treated animals. In addition, this mucified epithelial morphology was observed more frequently in tamoxifen-infused rats compared to vehicle-infused controls. No overt differences were noted in the lamina propria and muscularis layers when comparing vaginal tissue from control and tamoxifen-treated animals.


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 vaginal epithelium. Vaginal tissue from control (CONT) and tamoxifen-infused (TMX) rats (see Figure 1) were fixed in 10% neutral buffered formalin and embedded in paraffin. Deparaffinized tissue sections (5 μm) were subjected to Masson's trichrome (MT) and periodic acid-Schiff (PAS) staining procedures. For each row, representative tissue sections from different animals within each treatment group are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Effect of tamoxifen on vaginal epithelium. Vaginal tissue from control (CONT) and tamoxifen-infused (TMX) rats (see Figure 1) were fixed in 10% neutral buffered formalin and embedded in paraffin. Deparaffinized tissue sections (5 μm) were subjected to Masson's trichrome (MT) and periodic acid-Schiff (PAS) staining procedures. For each row, representative tissue sections from different animals within each treatment group are shown.
Mentions: Examination of fixed vaginal tissue sections revealed normal variations in epithelial morphology in intact, cycling rats. These variations were most apparent at the apical surface of the epithelium and consisted of slightly keratinized, non-keratinized or mucified cells. Mucified epithelium was characterized by the presence of secretory vesicles and positive PAS staining (figure 6). A dramatic increase in the appearance and extent of mucified epithelium was observed in vaginal tissue from tamoxifen-treated animals. In addition, this mucified epithelial morphology was observed more frequently in tamoxifen-infused rats compared to vehicle-infused controls. No overt differences were noted in the lamina propria and muscularis layers when comparing vaginal tissue from control and tamoxifen-treated animals.

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