Medroxyprogesterone acetate (MPA) is an endocrine disruptor of androgen receptor signaling in breast cancer

Start Year: 2008
Finish Year: 2010
Chief Investigator: Dr Theresa Hickey
Grant Type: Novel Concept Awards
Institution: University of Adelaide

Alternative Title: Hormone replacement therapy and breast cancer risk

Oestrogens are female hormones that stimulate growth and development of the breast. Combined hormone replacement therapy (cHRT), in which a combination of oestrogens and drugs called synthetic progestins (eg medoroxyprogesterone acetate or MPA) are administered to millions of women worldwide to relieve menopausal symptoms, has recently been associated with an increased risk of developing breast cancer. However, the mechanism whereby MPA increases breast cancer risk is not known.

Androgens also contribute to normal  breast development and influence the formation of breast cancer. Although considered male hormones, all women have significant levels of androgens in their body, and androgen receptors (ARs), which mediate the effect of androgens, are present in breast tissues.

Dr Hickey has shown that androgens oppose the effects of oestrogens in breast cancer cells and inhibit their growth. Dr Hickey proposes that the synthetic progestin MPA disrupts androgen action and disturbs this important balance between androgens and oestrogens, leading to uncontrolled oestrogen action in the breast, thereby increasing the risk of breast cancer in women taking cHRT. Dr Hickey will use a unique model of normal breast tissue to provide evidence for this.