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Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors

Kallak, Theodora Kunovac MSc1; Baumgart, Juliane MD, PhD2,3; Göransson, Emma BSc1; Nilsson, Kerstin MD, PhD2,4; Poromaa, Inger Sundström MD, PhD1; Stavreus-Evers, Anneli PhD1

doi: 10.1097/GME.0b013e31829e41df
Original Articles

Objective Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women.

Methods This is a cross-sectional study that compares postmenopausal aromatase inhibitor–treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH.

Results Aromatase inhibitor–treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH.

Conclusions Women with aromatase inhibitor–treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.

From the 1Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; 2Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden; and The Schools of 3Health and Medical Sciences and 4Medicine, Örebro University, Örebro, Sweden.

Received March 22, 2013; revised and accepted May 28, 2013.

Funding/support: Funding for this project was provided by the Uppsala-Örebro Regional Research Council, Swedish Cancer Society (grant CAN 2012/603), Lions Club International, and Percy Falk Foundation.

Financial disclosure/conflicts of interest: I.S.P. occasionally serves on advisory boards or speaks at scientific meetings for Novo Nordisk, MSD, Bayer Health Care, and Lundbeck A/S. T.K.K., J.B., E.G., K.N., and A.S.-E. declare no conflicts of interest.

Address correspondence to: Theodora Kunovac Kallak, MSc, Department of Women’s and Children’s Health, Uppsala University, Uppsala University Hospital, Uppsala SE-75185, Sweden. E-mail:

© 2014 by The North American Menopause Society.