Summary
Endometrial cancer is one of the most frequent cancers in postmenopausal women. The identification of risk factors is very important, so that prevention measures can be taken. Michels et al in their recent publication [1] investigated the association between blood androgen levels and the risk of endometrial cancer in a case-control study nested within the WHI observational study. The investigators measured 12 serum androgens, estrone, and estradiol prior to diagnosis in 313 women with endometrial cancer and 354 age-matched controls. Women with androgen levels in the highest quintile had increased risk of endometrial cancer compared to women with androgen levels in the lowest quintile. However, adjusting the model for circulating free estradiol rendered the associations non-significant. Furthermore, the serum estrogen/androgen ratio was associated with an increased risk of endometrial cancer.
Commentary
Androgens in women are secreted by the adrenals and the ovaries. Androgen production gradually falls with age, the decline being already evident in women of reproductive age. In contrast to estrogens, androgen production is not affected by menopause [2]. Menopause is also associated with a decline in sex hormone-binding globulin (SHBG) concentration, probably reflecting an increase in insulin resistance [3]. Testosterone affinity to SHBG is higher compared to estradiol; the net result of these hormonal changes over the menopause transition is an increase of the androgen/estrogen ratio. Conditions that are associated either with increased androgens or decreased SHBG, such as polycystic ovary syndrome (PCOS) or the metabolic syndrome will increase postmenopausal androgenicity [4] As many peripheral tissues including the endometrial tissue can convert androgen precursors to estrogens [5], increased androgenicity in postmenopausal women could serve as a risk marker of endometrial cancer. In the clinical setting, however, there is no reliable and accurate method to measure serum androgens in the low postmenopausal reference range [6]. Therefore, no cut-off limit can be proposed, beyond which the risk of endometrial cancer is increased. A more practical approach would be to identify clinical conditions that are associated with increased androgenicity. Women with PCOS are at risk of developing endometrial cancer [7]. The presence of metabolic syndrome, furthermore, doubles the risk of endometrial cancer in postmenopausal women [8]. Lifestyle interventions, therefore, which aim to improve body composition and fitness are associated with both lower androgen levels [9] and lower endometrial cancer risk [10]. Concluding, androgen levels may serve as a marker of endometrial cancer in the epidemiological setting if future research corroborates the present finding. Metabolism to estrogens appears to be a plausible mechanism explaining the association. Measuring androgens, however, in clinical routine offers no help in assessing patients’ risk.
Author(s)
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Irene Lambrinoudaki
Professor of Endocrinology,National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Scientific Director EMAS: European Menopause and Andropause Society.
Editor, Maturitas, Official Journal of EMAS
