New research by Samir Hanash, Ross Prentice and colleagues, recently published in Genome Medicine, suggests that the different proteomic effects of estrogen-alone and estrogen plus progestin treatments may explain the distinctive clinical effects of each therapy.

Hormone replacement therapy (HRT) acts as an artificial boost to women’s hormone levels, providing short-term relief from symptoms of the menopause.  However, the Women’s Health Initiative trials found that postmenopausal HRT may be associated with some adverse conditions, such as venous thromboembolism and stroke, as well as with positives like reduced risk of fracture.  Estrogen plus progestin therapy seems to have more unfavorable effects than estrogen-alone, but the biological basis for this clinical outcome is not well understood.

Samir Hanash and colleagues previously reported that one year of estrogen treatment had a profound effect on the serum proteome, including proteins involved in blood clotting, bone formation, and inflammation pathways. Their new study, "Postmenopausal estrogen and progestin effects on the serum proteome" published in Genome Medicine, shows that taking estrogen plus progestin for one year has a similarly acute effect.  While the majority of pathways identified were shared between the two therapies, several promising proteins were identified which may begin to explain some of the different clinical effects.  For example, the authors note that progestin may have a distinct impact on the insulin growth factor pathway and on circulating levels of extracellular matrix proteins, which have roles in tumorigenesis and tumor invasion respectively, and are relevant to the possible association of estrogen plus progestin HRT with breast cancer.

This is an exciting glimpse into the kind of understanding that proteomic analysis can provide about human health and disease.  However, the authors caution that only one type of estrogen and progestin were tested and different formulations may have other effects.  Their results hint that the different ways of administering the same drug (oral vs. injection, for example) may also have differing effects on the proteome, and ultimately, on disease risk.

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Rebecca Furlong
Assistant Editor, Genome Medicine