What is the rationale for androgen therapy for women?

To date, no formal definition of female androgen insufficiency (FAI) based on strong epidemiological data exists. However the proposed key symptoms of FAI, being reduced libido, diminished well-being, and lowered mood, have been reported to respond well to testosterone replacement, generally without significant adverse effects. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of estrogens. Androgens have important physiological roles in women, acting both as precursors for estrogen biosynthesis and directly via the androgen receptor. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone binding globulin and loosely to albumin. Circulating androgen levels decline in the years preceding menopause. This may be attributed to the gradual reduction in adrenal androgen production with age and to the loss of cyclical ovarian androgen production in the late reproductive years. Those who experience surgical menopause, have adrenal insufficiency or pituitary insufficiency, or those who experience premature ovarian failure, also have reduced androgen production. Androgen replacement therapy in the form of either dehydroepiandrosterone or testosterone is becoming increasingly widespread for the treatment of FAI. Evidence exists for the benefits of such therapy in relieving both the physical and psychological symptoms thought to be due to FAI in clinically affected women. However, clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety remain lacking.