Lets review Androgenetic Alopecia and what causes it.
What Causes Baldness?
Androgen receptors (ARs) chill in the cytosol, outside the nucleus of a cell. The Androgen Receptor is able to be activated by Androgens (male hormones) which are BOTH Testosterone and DHT. Androgens swim by outside, doing laps until a hexagonal gate in the cell membrane opens, pulling it in down a slippery slide of electromagnetic charge. Both T and DHT swim in the cytosol for a while, until it activates an AR. Once the AR is activated, Androgens, like a key, fits inside the AR's lock, the ARs change shape (polymorph) and travel down to the nucleus, where it's shuttled inside. That's where all the cool DNA hangs out.
Sooo What? Why should I care about Androgen Receptors?
The Androgen X Chromosome is inherited from the maternal grandfather or the father of a child 82% of the time. This same chromosome dictates the dna that is inside the nucleus which is activated by androgens (testosterone and DHT). Known androgen-dependent conditions include acne, seborrhea, androgenetic alopecia, hirsutism, hidradenitis suppurative, precocious puberty in boys, benign prostatic hyperplasia, prostate cancer, and polycycstic ovary syndrome (in women). When the Androgen Receptor is activated by sufficient amounts of androgens, the Androgen Receptor changes shape and enters the nucleus and transcribes the dna of an individual.
What About Balding in relation to genetics?
Wait up buddy, lets look at an example: the genes for facial and male-pattern body hair (HHA6 and HHA7). There's a little palindrome of DNA (AGAACA) called an Androgen Response Element! (ARE.) Each AR has a single arm on it, which latches onto only that palindrome. With both their arms, they clamp down on the ARE and snap tight. The AR's other head is a handle for RNA polymerase, which kicks off making the gene south of the ARE into a protein. The AR flips a switch, the HHA6 and HHA7 keratin is made, and if ur genes said facial hair and body hair, then you will have facial hair and body hair etc.
With Balding there are growth factors known which are called cytokines that are encrypted in the nucleus where dna exists. These are of the following but are not limited to: Substances and signaling proteins (ROS, TGF-β1, IL-1α, IL-1β, TNF-α, PGE2, PGD2, WNT-signaling)). Some people have lots of good growth factors and little bad growth factors which allows for their hair to not thin/bald.
Howcome some people who use finasteride/dutasteride continue to bald?
Finasteride and dutasteride are 5alpha reductase inhibitors, meaning they prevent the conversion of testosterone to dihydrotestosterone. The average male has between 300-1000ng/dl of Testosterone and 25-75ng/dl of DHT. Approximately 10% of Testosterone is converted to DHT via 5ar enzyme and 0.2% is converted to Estrogen by Aromatase. By inhibiting the 5ar enzyme, an individual is reducing their DHT levels and increasing Estrogen levels (slightly). Testosterone and DHT are both androgens and hold a great ability to activate the androgen receptor and allow for genes to be transmitted. IF someone were to use dutasteride and reduce their DHT to close to zero, that would reduce circulating androgens in the body to just testosterone and would therefore reduce the rate at which the AR was activated and so on and so forth. ...... NOW, recognize how I said reduce and not eliminate. It has been well known for decades now that testosterone by itself is able to activate the androgen receptor and allow for normal physiological functions in the body that are androgen dependent to occur. The people who continue to bald on dutasteride and finasteride are individuals whose hair-growth factors are so bad to the point that even slight activation of the AR will allow for them to continue balding, whereas others just on finasteride stop balding because their growth factors were never even that bad in the first place, so reducing androgen levels slightly delays the balding process enough.
And btw if u think DHT causes baldness, you are an idiot. Go open up a biology textbook and see how many men on dutasteride/finasteride for BPH still develop prostate cancer from testosterone alone. This is relevant because prostate cancer gene is encrypted in the Androgen X chromosome, the same chromosome that carries the genes for scalp hair.
So how can we stop balding?
Medications such as Anti-androgens which are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. I am not going to name every one, but basically by lowering Testosterone and/or DHT, you are reducing the levels of androgens in your body which in turn reduces the rate of Androgen Receptor activity, aka you reduce your rate or balding, or even potentially halt or regrow hair.
There are....
Testosterone Blockers: Spironolactone, Cyproterone Acetate, Goserelin, Leuprorelin,
DHT blockers: Finasteride, Dutasteride
If you are me, you may not be down with taking testosterone blockers... for obvious reasons, no worry though, there is also
Androgen Receptor Blockers: Bicalutamide, Flutamide, Enzalutamide.
Androgen Receptor Blockers do not lower Testosterone or DHT, rather they only block the Androgen Receptor from functioning completely. They have very low side effect profiles. Enzalutamide is very unavailable to the public, but Flutamide and Bicalutamide are not rare. Flutamide is a little weaker than Bicalutamide in preventing activation of the AR and has liver toxicity as a side effect. Bicalutamide only has one side effect>gyno.
Bicalutamide and why its great!!!
"sufficiently high relative concentrations of bicalutamide (1,000 fold excess) are able to completely prevent activation of the AR by androgens like DHT and testosterone and subsequent upregulation of the transcription of androgen-responsive genes and associated effects. At steady-state, relative to the normal adult male range for testosterone levels (300–1,000 ng/dL),circulating concentrations of bicalutamide at 50 mg/day are roughly 600 to 2,500 times higher and at 150 mg/day around 1,500 to 8,000 times higher than circulating testosterone levels"
In prostate cancer, bicalutamide 150mg monotherapy had only a 7% death rate while castration had a 42% death rate from metastatic prostate cancer. This means that AR activity is lower in people who use bicalutamide than those who castrate themselves. We know this because the gene for prostate cancer is located in the Androgen X chromosome.
50mg Bicalutamide = 750mg Flutamide. In a Study using 750mg Flutamide and 200mg Spironolactone stated "Whereas flutamide caused a dramatic (80%) decrease in total acne, seborrhea, and hair loss score after only 3 months of therapy, spironolactone caused only a 50% reduction in acne and seborrhea, with no significant effect on the hair loss score."
Once relative concentrations of bicalutamide pass 1000 fold excess of Androgens, the AR is never activated. This means that 100mg Bicalutamide (maybe less) should stop balding for anyone with normal T levels (<1000ng/dl).
The only side effect of bicalutamide that is over 10% is Gynecomastia.
at 150mg, 79% is the gyno rate
at 100mg, 79% is the gyno rate
at 50mg, 36% is the gyno rate
at 30mg, 26% is the gyno rate
one tablet of tamoxifen 20mg reduced the gyno rate from 79% to 8.8% in men on 150mg monotherapy.
so you can take tamoxifen or raloxifene for gyno(tamoxifen 20mg=raloxifene 60mg) alongside bicalutamide and be side free! Its better to take raloxifene since tamoxifen isn't safe for hair as it increases testosterone a lot. NO Erectile Dysfunction either because the med does not decrease Testosterone.
What Causes Baldness?
Androgen receptors (ARs) chill in the cytosol, outside the nucleus of a cell. The Androgen Receptor is able to be activated by Androgens (male hormones) which are BOTH Testosterone and DHT. Androgens swim by outside, doing laps until a hexagonal gate in the cell membrane opens, pulling it in down a slippery slide of electromagnetic charge. Both T and DHT swim in the cytosol for a while, until it activates an AR. Once the AR is activated, Androgens, like a key, fits inside the AR's lock, the ARs change shape (polymorph) and travel down to the nucleus, where it's shuttled inside. That's where all the cool DNA hangs out.
Sooo What? Why should I care about Androgen Receptors?
The Androgen X Chromosome is inherited from the maternal grandfather or the father of a child 82% of the time. This same chromosome dictates the dna that is inside the nucleus which is activated by androgens (testosterone and DHT). Known androgen-dependent conditions include acne, seborrhea, androgenetic alopecia, hirsutism, hidradenitis suppurative, precocious puberty in boys, benign prostatic hyperplasia, prostate cancer, and polycycstic ovary syndrome (in women). When the Androgen Receptor is activated by sufficient amounts of androgens, the Androgen Receptor changes shape and enters the nucleus and transcribes the dna of an individual.
What About Balding in relation to genetics?
Wait up buddy, lets look at an example: the genes for facial and male-pattern body hair (HHA6 and HHA7). There's a little palindrome of DNA (AGAACA) called an Androgen Response Element! (ARE.) Each AR has a single arm on it, which latches onto only that palindrome. With both their arms, they clamp down on the ARE and snap tight. The AR's other head is a handle for RNA polymerase, which kicks off making the gene south of the ARE into a protein. The AR flips a switch, the HHA6 and HHA7 keratin is made, and if ur genes said facial hair and body hair, then you will have facial hair and body hair etc.
With Balding there are growth factors known which are called cytokines that are encrypted in the nucleus where dna exists. These are of the following but are not limited to: Substances and signaling proteins (ROS, TGF-β1, IL-1α, IL-1β, TNF-α, PGE2, PGD2, WNT-signaling)). Some people have lots of good growth factors and little bad growth factors which allows for their hair to not thin/bald.
Howcome some people who use finasteride/dutasteride continue to bald?
Finasteride and dutasteride are 5alpha reductase inhibitors, meaning they prevent the conversion of testosterone to dihydrotestosterone. The average male has between 300-1000ng/dl of Testosterone and 25-75ng/dl of DHT. Approximately 10% of Testosterone is converted to DHT via 5ar enzyme and 0.2% is converted to Estrogen by Aromatase. By inhibiting the 5ar enzyme, an individual is reducing their DHT levels and increasing Estrogen levels (slightly). Testosterone and DHT are both androgens and hold a great ability to activate the androgen receptor and allow for genes to be transmitted. IF someone were to use dutasteride and reduce their DHT to close to zero, that would reduce circulating androgens in the body to just testosterone and would therefore reduce the rate at which the AR was activated and so on and so forth. ...... NOW, recognize how I said reduce and not eliminate. It has been well known for decades now that testosterone by itself is able to activate the androgen receptor and allow for normal physiological functions in the body that are androgen dependent to occur. The people who continue to bald on dutasteride and finasteride are individuals whose hair-growth factors are so bad to the point that even slight activation of the AR will allow for them to continue balding, whereas others just on finasteride stop balding because their growth factors were never even that bad in the first place, so reducing androgen levels slightly delays the balding process enough.
And btw if u think DHT causes baldness, you are an idiot. Go open up a biology textbook and see how many men on dutasteride/finasteride for BPH still develop prostate cancer from testosterone alone. This is relevant because prostate cancer gene is encrypted in the Androgen X chromosome, the same chromosome that carries the genes for scalp hair.
So how can we stop balding?
Medications such as Anti-androgens which are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. I am not going to name every one, but basically by lowering Testosterone and/or DHT, you are reducing the levels of androgens in your body which in turn reduces the rate of Androgen Receptor activity, aka you reduce your rate or balding, or even potentially halt or regrow hair.
There are....
Testosterone Blockers: Spironolactone, Cyproterone Acetate, Goserelin, Leuprorelin,
DHT blockers: Finasteride, Dutasteride
If you are me, you may not be down with taking testosterone blockers... for obvious reasons, no worry though, there is also
Androgen Receptor Blockers: Bicalutamide, Flutamide, Enzalutamide.
Androgen Receptor Blockers do not lower Testosterone or DHT, rather they only block the Androgen Receptor from functioning completely. They have very low side effect profiles. Enzalutamide is very unavailable to the public, but Flutamide and Bicalutamide are not rare. Flutamide is a little weaker than Bicalutamide in preventing activation of the AR and has liver toxicity as a side effect. Bicalutamide only has one side effect>gyno.
Bicalutamide and why its great!!!
"sufficiently high relative concentrations of bicalutamide (1,000 fold excess) are able to completely prevent activation of the AR by androgens like DHT and testosterone and subsequent upregulation of the transcription of androgen-responsive genes and associated effects. At steady-state, relative to the normal adult male range for testosterone levels (300–1,000 ng/dL),circulating concentrations of bicalutamide at 50 mg/day are roughly 600 to 2,500 times higher and at 150 mg/day around 1,500 to 8,000 times higher than circulating testosterone levels"
In prostate cancer, bicalutamide 150mg monotherapy had only a 7% death rate while castration had a 42% death rate from metastatic prostate cancer. This means that AR activity is lower in people who use bicalutamide than those who castrate themselves. We know this because the gene for prostate cancer is located in the Androgen X chromosome.
50mg Bicalutamide = 750mg Flutamide. In a Study using 750mg Flutamide and 200mg Spironolactone stated "Whereas flutamide caused a dramatic (80%) decrease in total acne, seborrhea, and hair loss score after only 3 months of therapy, spironolactone caused only a 50% reduction in acne and seborrhea, with no significant effect on the hair loss score."
Once relative concentrations of bicalutamide pass 1000 fold excess of Androgens, the AR is never activated. This means that 100mg Bicalutamide (maybe less) should stop balding for anyone with normal T levels (<1000ng/dl).
The only side effect of bicalutamide that is over 10% is Gynecomastia.
at 150mg, 79% is the gyno rate
at 100mg, 79% is the gyno rate
at 50mg, 36% is the gyno rate
at 30mg, 26% is the gyno rate
one tablet of tamoxifen 20mg reduced the gyno rate from 79% to 8.8% in men on 150mg monotherapy.
so you can take tamoxifen or raloxifene for gyno(tamoxifen 20mg=raloxifene 60mg) alongside bicalutamide and be side free! Its better to take raloxifene since tamoxifen isn't safe for hair as it increases testosterone a lot. NO Erectile Dysfunction either because the med does not decrease Testosterone.
