Why is danazol, an androgen partial-agonist, effective treatment for hereditary angioedema (C1-esterase inhibitor deficiency)? Supposedly it increases the latter's production in the liver, but how?
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Step I Danazol - hereditary angioedema
Started by Phloston
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As per Wiki:
"Patients in whom episodes occur at least once a month or who are at high risk of developing laryngeal edema require long-term prophylaxis. This often involves male sex hormones (androgens), which increase production of C1-INH in the liver through an as yet unknown mechanism. Danazol is the most commonly used."
I'm starting to see a trend here....you ask a lot of questions where the answer is UNKNOWN mechanism, poorly understood mechanism, etc...... 🙂
"Patients in whom episodes occur at least once a month or who are at high risk of developing laryngeal edema require long-term prophylaxis. This often involves male sex hormones (androgens), which increase production of C1-INH in the liver through an as yet unknown mechanism. Danazol is the most commonly used."
I'm starting to see a trend here....you ask a lot of questions where the answer is UNKNOWN mechanism, poorly understood mechanism, etc...... 🙂
‎Someone from my SoM posted this in response to my school post earlier today:
"'Nowadays, a 17-alpha-alkylated anabolic androgen steroid (AAS) known as danazol is the most commonly used prophylactic drug, the exact mode of action of which has not yet been elucidated'
Pappalardo E, Zingale LC, Cicardi M (2003) Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with danazol. Immunol Lett 86:271276
It's pretty cool though, danazol increases C1-INH expression in PBMC despite them not having androgen receptors. I think the postulated mechanism in that paper (by no means confirmed or tested) was that it reduces the effects of oestrogen on the cells, leading to a disinhibition of C1-INH production."
"'Nowadays, a 17-alpha-alkylated anabolic androgen steroid (AAS) known as danazol is the most commonly used prophylactic drug, the exact mode of action of which has not yet been elucidated'
Pappalardo E, Zingale LC, Cicardi M (2003) Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with danazol. Immunol Lett 86:271276
It's pretty cool though, danazol increases C1-INH expression in PBMC despite them not having androgen receptors. I think the postulated mechanism in that paper (by no means confirmed or tested) was that it reduces the effects of oestrogen on the cells, leading to a disinhibition of C1-INH production."
I think it's more interesting that in the US we use danazol to treat it and in Europe they use blood products. In the US there are many cases and deaths annually because of hereditary angioedema, but in Europe there are barely any......I'm surprised I actually learned that in class. Pharma prof. was def pro European drug strategies.
Does anyone understand Danazol's affect on hormones? In first aid it says its a partial agonist at androgen receptors, but then says it acts on the anterior pituitary and P-450 in the illustration. I just don't understand what they're getting at.
This thread is old, but now that I've taken the USMLE, I can add a little:
Danazol (androgen receptor partial agonist) and leuprolide (GnRH receptor agonist) have been used together in studies where the aim is to ultimately suppress ovarian steroidogenesis. When you give danazol or leuprolide in a pulsatile fashion, steroidogenesis would increase; the same effect is observed initially with continuous stimulation, which is why hirsutism can result with danazol-use, although continuous stimulation soon leads to desensitization and receptor down-regulation, thereby explaining the inhibition, rather than stimulation, of ovarian steroidogenesis. In terms of hormones and danazol, we'd expect an initial increase in LH/FSH, followed by an ebb of both.
For the USMLE, be aware that it's a treatment for hereditary angioedema (increases complement protein synthesis by the liver) and endometriosis (although apparently not used as extensively anymore).
It can cause hirsutism.
so danazol is used in endometriosis by decreasing steriodogensis? its a partial aganost at the androgen receptor, but that cant be hte effect to decrease estrogen? im guessing its the action on the cp45017 by decreasing synthesis?
