Spiro Sucks

Ok I was gonna write a long post about this but compiling papers makes me want to kms so alas I shall do that later.

Spiro sucks. It doesn't actually lower T levels by a significant amount and as a competitive antagonist it’s also largely ineffective.

You can find a dozen studies showing the effect of spiro on T levels (transfem science did a good piece on it) but the only quote from one of those studies that I’ll mention is this one:

Regression of testosterone as a function of measured serum 17-β estradiol (Fig. 2) found significant effects of 17-β estradiol (slope=−0.462 mg/dL testosterone ng/dL 17-β estradiol; p=0.012). The presence of finasteride raised testosterone by 126 ng/dL (SE=25; p<0.001), and spironolactone had no significant effect (p=0.51)

link

Basically, any testosterone suppression you see while on spiro is likely due to the antigonadotropic effects of estradiol instead. What spiro can and has been proven to do though, and what is of interest to me, is its antagonistic effects on the androgen receptor.

It’s actually really hard to find studies comparing clinical outcomes (not just serum hormone levels) of anti androgens (and I’m lazy) so I only found one, https://doi.org/10.1046/j.1365-2265.2000.00982.x comparing cyproterone acetate and spironolactone for the treatment of PCOS and idiopathic hirsutism.

It’s actually quite a good study but the main thing to take away from it is this. In patients with idiopathic hirsutism, which is characterized by elevated testosterone levels without elevated luteinizing hormone (LH) levels, spironolactone was non significantly less effective than cyproterone acetate at reducing hirsutism (androgenic) symptoms but still significantly effective. However in patients with PCOS, a condition which involves both elevated LH and testosterone levels, cyproterone acetate was significantly more effective than spironolactone for decreasing both testosterone levels and symptoms of hirsutism.

So, what can we take from this? Firstly, we need to go into how each of these anti androgens work. Spiro, which has no significant effect on testosterone levels, causes a statistically significant reduction in hirsutism symptoms (which are caused by excess androgenic activity) by competitively binding with and antagonizing the androgen receptor. In layman's terms, spiro molecules bind to the androgen receptor and deactivate it which makes it so that less total testosterone molecules end up binding to androgen receptors since they are basically displaced by spiro. Cyproterone acetate (CPA) on the other hand directly lowers testosterone level by decreasing LH levels which causes a reduction in androgenic activity. (cyproterone acetate also has anti androgenic activity due to receptor antagonism but we’re gonna ignore that for the sake of simplicity and also the fact that it's a very weak antagonist)

Essentially, antiandrogenic activity from CPA comes from less androgens in the blood, while antiandrogenic activity from spiro comes from less androgens binding to receptors. So from this we can deduce that if a reduction in testosterone levels from CPA causes a certain reduction in hirsutism symptoms, the same reduction in symptoms caused by a certain dose spiro implies that that dose of spiro is as effective at blocking androgen receptors to the same degree as that reduction in testosterone levels.

This study showed than in PCOS patients, a reduction of testosterone levels from 2.94 nmol/l to approx 1.5nmol/l (outside of a chart they didn’t actually include values for post treatment, only baseline) from CPA caused a significantly greater reduction in hirsutism symptoms than the anti androgenic activity from 200mg/day of spiro. This implies that 200mg/day of spiro is less effective at reducing androgenic activity than reducing testosterone by \~1.5nmol/l (43ng/dl).

So yeah, spiro doesn’t lower T levels and taking 200mg a day is (probably) equivalent to reducing testosterone by less than 1.5nmol/l (43ng/dl). At least according to that one study.

Shit ass drug, Americans are so cucked by having it as their main AA.