Estramustine is not listed as an inhibitor or inducer of CYP2C9 or CYP3A4, and there are no reported drug-interactions indicating that estramustine should inhibit or induce CYP2C9 or 3A4. 10-20% of a given dose is metabolised to estradiol, that has been shown to activate CAR and PXR, but the process is most likely self-limiting. Estramustine is only used in men, primarily elderly men who are often less susceptable for attacks. However, side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Estramustine phosphate sodium is a complex of 17 β-estradiol and nornitrogen mustard. It is a prodrug which is dephosphorylated to estramustine in the gastrointestinal channel and subsequently converted to its oxidised isomer estromustine.

Estramustine is an antimicrotubule antineoplastic agent used for the palliative treatment of metastatic and/or progressive prostate cancer. Estramustine is not indicated for use in women. It is administered orally. Common adverse reactions of estramustine that can be confused with an acute porphyric attack are nausea and vomiting. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Estramustine phosphate sodium is rapidly dephosphorylated in the intestine and prostate to estramustine and estromustine, which accumulate in the prostatic tissue. Some hydrolysis of the carbamate linkage occurs in the liver, releasing estradiol, estrone, and the normustine group. 10–20% of estramustine or estromustine is metabolized to estradiol or estrone, respectively. Estramustine, estromustine, and their metabolites are excreted principally in bile; <1% of conjugated estradiol and estrone excreted in urine. Total plasma concentrations of estradiol during prolonged therapy with estramustine increase to levels similar to those achieved with conventional estradiol therapy, and estrogenic effects may be similar in patients receiving estramustine and in those receiving oral estradiol. There are no data pointing to involvement of CYPs in the metabolism of estramustine or the main metabolites. CAR is activated by estrogen (Kliever, 1999; Blumberg, 1998). However, the CAR/RXR dimer interfers with the activity of the estrogen receptor, thus inhibiting estrogen-activated transcription. Since CAR/RXR will need active estrogen receptors for their further activation by estrogen the activation process is probably self-limiting, explaining that one has observed tolerance of natural estrogens in acute porphyrias (Min, 2002). There are no observations of interference with CYP-metabolism of other drugs associated with estramustine medication, which points to insignificant capacity for CYP-induction or inhibition by the drug or its metabolites.