Androstenedione (A4)

Androstenedione (often written A4) is an androgen that acts mainly as a stepping-stone hormone: it is a precursor that the body converts into testosterone and, in turn, into estrogen. It is made by both the ovaries and the adrenal glands, so its level reflects the combined output of these two androgen sources. Because of this, androstenedione is useful in working out where an excess of androgens is coming from in women with symptoms such as hirsutism, acne, irregular periods or scalp hair loss. In polycystic ovary syndrome (PCOS), androstenedione is often raised along with testosterone. It is also a key marker in congenital adrenal hyperplasia, a group of inherited adrenal enzyme disorders, where it rises together with 17-hydroxyprogesterone. A markedly high level can point toward an androgen-producing tumour of the ovary or adrenal gland. Interpreting androstenedione therefore depends on reading it as part of an androgen panel: testosterone and free testosterone give the overall androgen burden, DHEAS points to an adrenal source, and 17-hydroxyprogesterone flags the adrenal enzyme disorders — so androstenedione helps complete the picture rather than standing alone.

• Polycystic ovary syndrome (PCOS) — often raised along with testosterone.
• Congenital adrenal hyperplasia — rises with 17-hydroxyprogesterone in these inherited adrenal enzyme disorders.
• An androgen-producing tumour — of the ovary or adrenal gland; a markedly high level is a red flag.
• Cushing's syndrome or other adrenal overactivity.

• Adrenal insufficiency — reduced adrenal androgen output.
• After menopause or with ovarian/adrenal suppression — lower androgen production.
• A generally low level is rarely a clinical problem on its own — it is the high values that are investigated.