Testosterone is substrate to CYP 3A4, but has not been found to induce CYP 3A4 or CYP 2C9. Its feedback inhibitory effects on GnRH release and LH secretion are anti-progestagenic in females, and in males reduce the endogenous production of possibly porphyrinogenic testosterone precursors. The administration aims at substitution for insufficient endogenous production of the hormone, i.e. at attaining physiological (probably non-porphyrinogenic) levels.

Testosterone is the main steroidal androgenic hormone.

Testosterone is primarily used as substitution treatment in male hypogonadism. It undergoes extensive first-pass hepatic metabolism when given orally and is therefore usually given intramuscularly, subcutaneously, or transdermally. In addition, the basic molecule of testosterone has been modified (typically this involves esterification) to produce orally active compounds and to extend the duration of action. Testosterone esters are hydrolysed to testosterone after absorption. The most common therapeutic indication for testosterone administration is male hypogonadism, i.e. substitution therapy, but it has also produced beneficial effects in boys with constitutionally delayed puberty and growth, though giving androgens to boys with constitutional delay of growth and puberty is controversial. Low dose subcutaneous testosterone was reported used in the successful treatment of one case of recurrent pre-menstrual attacks of acute porphyria in female AIP patient (Savage et al, 1992).

Listed as a substrate of CYP 2C9, and as a substrate as well as an inhibitor of CYP 3A4 by Rendic (2002), but there are no reports of PXR-affinity or any observations of clinical capacity for CYP induction. Increased plasma levels of testosterone inhibits the hypothalamic GnRH release, thereby attenuating the pulsatory pituary LH secretion. In males, endogenous testosterone biosyntheses is interrupted and the production of its precursors attenuated. In females, the maintenance of corpus luteum may cease and its production of progesterone stop. Testosterone is stated to induce 5-alpha-reductase, and attributed capacity for anti-porphyrogenic action through diverting progesterone from the presumably porphyrogenic 5-betareductive pathway, to non-porphyrogenic planar 5-alpha reduction of the steroid structure (Savage et al 1992).

Dr Skadberg, Norway: Used uneventfully in male patient with latent AIP to treat low serum testosterone values. Patient received injections of testosterone every 3 months from February 2008 to October 2009 (8 injections in total). Dr Deyback, France: Used uneventfully in young male with latent AIP for the indication delayed puberty. In both patients urine precursors were measured regularly during treatment.

A female patient with AIP who suffered from severe pre-menstrual attacks was successfully managed with low-dose subcutaneous implants of testosterone (Savage et al, 1992).