Supporting information and resources

Salivary Androstenedione

Androstenedione (4-androstenedione; 4-dione; 4-androstene-3,17-dione) is a steroid hormone produced in the adrenal glands and the gonads. (1,2,3) It is synthesized from DHEA or 17OH-progesterone, and it serves principally as the immediate precursor compound that is converted into testosterone or estrone, both of which may then be further converted into estradiol. (4)  The same sequence of conversion of DHEA and androstenedione into other steroids also takes place in many peripheral tissues throughout the body, allowing androgens and estrogens to be delivered to the appropriate tissues without leakage of significant amounts into the circulation. (5,6) Levels of androstenedione begin to increase in children at about age 6-8, and it serves as the main source of androgens prior to gonadarche.  (7)  High levels of androstenedione may confer androgenic risk, especially in females, and estrogenic risks, especially in males. Children and adolescents are particularly vulnerable to the effects of androstenedione conversion to active sex steroids. These effects may disrupt normal sexual development, specifically virilization in girls associated with severe acne, excessive body hair, disruption of the menstrual cycle, and infertility. The conversion of androstenedione to estrogens can cause feminization of boys. (8,9)  Elevated levels have been associated with disruptive behavior disorders in children. (7)  Measurement of serum androstenedione is used as a marker of androgen biosynthesis.  High circulating androstenedione levels are indicated in virilizing congenital adrenal hyperplasia, polycystic ovarian syndrome, and other causes of hirsutism in women.  Elevated androstenedione levels may also occur as a result of adrenal or ovarian tumors. (10,11)  Androstenedione exhibits a diurnal rhythm similar to that of cortisol, with highest levels in the morning and a nadir in the late evening. (12,13) In blood, androstenedione is not strongly bound to sex hormone binding globulin (SHBG) or albumin.  Approximately 95% of circulating androstenedione is available to tissues. (14)  Unbound androstenedione enters saliva from blood via intracellular mechanisms, and the correlation between serum and saliva values is highly significant. (15)