Despite the long series of cohort studies performed during the last 20 years, the correlation between serum
testosterone and any clinical situation believed to be under
androgen control in women has remained elusive. This is likely related to the recent finding that the
androgens made locally in large amounts in peripheral tissues from the precursor
dehydroepiandrosterone (
DHEA) act in the same cells where synthesis takes place and are not released in significant amounts in the circulation, thus making unreliable the measurement of serum
testosterone as marker of total androgenic activity. The objective is to determine if serum
androgen glucuronides can be replaced by
testosterone or another
steroid as measure of androgenic activity. Since the
glucuronide derivatives of
androgens are the obligatory route of elimination of all
androgens, these metabolites were measured by liquid chromatography tandem mass spectrometry under basal conditions in 377 healthy postmenopausal women aged 55-65 years as well as in 47 premenopausal women aged 30-35 years while
testosterone was assayed by gas chromatography mass spectrometry. No correlation was found between the serum concentration of
testosterone and that of
androsterone glucuronide (ADT-G) or
androstenediol glucuronide (3alpha-diol-G), the
androgen metabolites which account for the total pool of
androgens. The present data show that measurement of the total pool of
androgens reflected by the serum levels of ADT-G and 3alpha-diol-G cannot be replaced by serum
testosterone or any other
steroid, including
DHEA or
DHEA sulphate. These findings may have implications for women with
androgen deficiency involving
osteoporosis,
obesity,
type 2 diabetes, sexual dysfunction, loss of muscular strength and a series of other clinical situations affecting women's health. Measuring ADT-G and 3alpha-diol-G might identify cases of true
androgen deficiency and provide an opportunity to offer appropriate
androgen therapy.