Skip Navigation LinksHome > January 2014 - Volume 21 - Issue 1 > Antiandrogenic actions of medroxyprogesterone acetate on epi...
doi: 10.1097/GME.0b013e3182936ef4
Original Articles

Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo

Ochnik, Aleksandra M. PhD1; Moore, Nicole L. PhD1; Jankovic-Karasoulos, Tanja PhD1; Bianco-Miotto, Tina PhD1; Ryan, Natalie K. BSc (Hons)1; Thomas, Mervyn R. PhD2; Birrell, Stephen N. MD, PhD1; Butler, Lisa M. PhD1; Tilley, Wayne D. PhD1; Hickey, Theresa E. PhD1

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Objective: Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue.

Methods: Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry.

Results: DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels.

Conclusions: In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

© 2014 by The North American Menopause Society.


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