Androstenedione & Frailty

[pca2004]

New study from Spain [1].

For many years, I used a product that probably contained DES (diethylstilbestrol) - perhaps 1 mg? My QoL was very good.

When I eventually migrated to 3 mg DES - plus a shot of testosterone cypionate every 3 months - I began to feel frail.

The new study associates high levels of androstenedione [andro] with frailty.

When I became interested in using testosterone [T] to manage PCa 19 years ago, the obvious source was andro, a T precursor, plus chrysin, an aromatase inhibitor that prevents T conversion to estradiol [E2]. In the U.S., one could buy andro in any health store.

Unfortunately, young boys who wanted to improve their baseball games began buying andro. There was outrage in DC & possession of andro became a felony. While it was not a felony to bring T in from Mexico, say, it was illegal to bring in its precursor.

Anyway, I successfully used andro for several years, until my stash was depleted & my integrative medicine doctor began prescribing Androderm T patches.

In the steroidogenesis cascade, andro can be produced from progesterone, or from pregnenolone-->DHEA. As such, production is inhibited by Abiraterone (which targets the enzyme that acts on progesterone and pregnenolone.)

Adrenal andro production is controlled by ACTH (adrenocorticotropic hormone). Gonadal andro production is inhibited by ADT.

In the new study:

"high concentrations of androstenedione were significantly associated with frailty syndrome in both groups" {"patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH)."}

"In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione. High androstenedione levels were associated with a slow walking speed in the mCaP group), while high testosterone levels were associated with a better walking speed in the localised CaP group".

I'm interested in the gait speed experience of those on ADT monotherapy & in those using Abi.

I wonder if there is a way of speeding the clearance of andro? Or inhibiting ACTH?

Thanks, -Patrick

[1] pubmed.ncbi.nlm.nih.gov/380...

[Graham49]

My gait speed has definitely dropped on ADT mono.

[MateoBeach]

Slow gait speed is the most readily available biomarker of frailty. ADT (castrate testosterone levels) cause loss of muscle and strength (sarcopenia) in many on long term ADT and this can cause frailty. It can be compounded by inadequate protein. I do not see why androstenedione needs to be measured when you can determine sarcopenia on DEX scan and frailty by walking speed and other measures of function (grip strength, chair rises). On Abiraterone, the prednisone or dexamethasone will suppress ACTH. Perhaps a SARM could be a better alternative to explore, such as RAD140 which does not activate the classical AR pathway.

[MoonRocket]

My gait speed has remained steady on/off treatment. Walking < 15 min/mile is the norm.I'm only 57, so possibly not an ideal candidate for your inquiry.

[PCaWarrior]

Prednisone inhibits ACTH. Andro should clear within two days.

[cigafred]

Gait speed for what it is worth: could run one mile in nine minutes before ADT. Started ADT Feb 2015, after one year mile speed was 11.5 minutes, now, after 8+ years (I am now 80) it would probably take 30 minutes or more. Did six rounds of BAT but concluded, at least in the form I did it, that it was not helping.