DHT’s Mechanism of Action

Scalp dihydrotestosterone (DHT) reduction remains one of the few clinically proven ways to regrow hair. However, the hormonal treatment often causes significant side effects–through DHT downregulation, estrogen upregulation, and modification of androgen receptors. The side effects themselves have caused many of us to question whether systemic DHT inhibition is wor thwhile, as membrane androgen receptors (mAR) and NADPH oxidase (NOX)--the two most prominent co-activators in intracellular DHT pathways–are highly implicated in neurological function

The community’s most prolific researchers have found that DHT in small amounts is good for hair follicles. Jumpman poses his theory on DHT’s biphasic nature–DHT upregulates uPA up until a threshold is crossed, at which point PAI-1 becomes upregulated, causing cellular senescence downstream. Vincent agrees, finding that DHT in low levels is necessary for hair follicle functioning in vitro. In tandem, Synthetic Pug and Herber t pose that DHT’s effects are due to its co-activators rather than the hormone itself–evidenced through DHT’s ability to promote growth in our beard and body hair during puber ty. In fur ther agreement, Jumpman repor ts that transgenders seem to get better hair growth from spironolactone, which is a par tial agonist of androgen receptors, than from bicalutamide, a potent antagonist

DHT’s story becomes fur ther muddled when considering the relative failures of androgen receptor treatments. Numerous stories of failed androgen receptor blockers and degraders were shared, both in standard clinical trials–Visangle scoffed at Pyrilutamide’s results–and group buys. Herber t believes that this may either be due to the many binding domains of the androgen receptor, or the androgen receptor’s ability to mutate in the presence of low androgens

At the same time, DHT’s significance in hair loss is unmatched RU58841–a potent AR blocker–remains the market’s most effective treatment anecdotally, other than potent DHT reducers Finasteride and Dutasteride. More questions remain of DHT’s complete mechanism of action, specifically the downstream effects of its co-activators. Androgens are still poorly understood in hair, the brain, and the rest of the human body.