Testosterone: the known knowns, the known unknowns and the unknown unknowns

Testosterone has long been recognised as a critical hormone for women.

Known knowns are that the ovaries and adrenals are the primary sources of circulating testosterone, that iatrogenic suppression, removal of both ovaries or both adrenals, or spontaneous ovarian/adrenal failure will result in low testosterone, and that exogenous testosterone treatment will improve sexual function in women presenting with low libido.

Known unknowns:
An age-related decline in testosterone levels, commencing in the reproductive years has been reported but these data are limited by either use of RIA, convenience sampling, small numbers or inclusion of women with factors that might interfere with androgen physiology. Lacking are normative values for reproductive-aged women, by menstrual cycle phase and by age, for the androgens and pre-androgens, including the recently described adrenally-derived keto-androgens. Furthermore, whether circulating levels of keto-androgens in postmenopausal women are similar to premenopausal women is not known. Despite women now living many years post menopause, normative data for sex steroid levels in elderly women are also lacking. Without this knowledge, “androgen insufficiency” at any life phase cannot be fully described.

Large studies of premenopausal women, postmenopausal women and elderly women have provided us the opportunity to measure sex steroids, using liquid chromatography tandem mass spectrometry, offering new insights into the physiology of androgens in women. These data sets will enable us to explore the associations between sex steroids and an array of clinical characteristics and health outcomes in women, moving some thingsfrom the unknown into the known realm.

The unknown unknowns will remain.