Martin7
New member
- Joined
- Aug 2, 2022
- Messages
- 3
- Reason
- Learn about ALS
- Diagnosis
- 00/0000
- Country
- US
- State
- FL
I posted last August 2022 in the could-this-be-ALS forum. This post is mostly academic in nature, but also deals potentially with myself, and I'm interested to hear any discussion of this topic.
Quick review/update, I (42/M) am still confounding all doctors seen (up to 7 now: 2 neurologists, 2 muscle disease doctors, spine physiologist, and 2 neurosurgeons; EMG #3 coming next week, and coming up on 2 years since symptoms started in earnest). All are still pretty equally split on if it is ALS (or a variant, I have only LMN signs), a rare muscular dystrophy, or cervical spinal stenosis and cord compression (which MRI also found). But, this isn't a diagnosis post, just a background note where I'm coming from, and I'll try to tie it back in later. I'm still slowly progressing with muscle atrophy/weakness, but on the whole still doing pretty well. The latest state of things, my right calf (medial side gastroc, with measured denervation) is basically gone, now spreading to the lateral side too, and my left leg medial gastroc started quickly withering the last 2 months, both big toes are weak in pushing, and bilateral scapular and pectoral atrophy is still slowly progressing.
I've been reading and researching, and found an intriguing paper from 2020, questioning the role of the hormone DHT in ALS [title: Dihydrotestosterone in Amyotrophic lateral sclerosis—The missing link?], and neurodegenerative diseases in general, noting motor neuron axon survival and regeneration have strong interactions with DHT, if not outright dependency. Its role and feedback loop is a bit complex, but briefly, the key observation is that ALS patients have consistently low DHT in cerebrospinal fluid (CSF), potentially starving the motor neurons (note, DHT is equally in men and women in CSF).
The paper posits that this originates by a congenital protein defect that prevents or reduces free testosterone from crossing the blood brain barrier (where it would be converted into DHT by the pituitary, and limiting availability to motor neuron androgen receptors). This low "brain" DHT in turn never activates the standard "off-switch" on luteinizing hormone production (LH tells the body to produce testosterone, in men anyway), so in turn the body produces and maintains perpetual excess LH and in turn excess free testosterone outside the brain and nervous system, beyond the capacity able to be bound by sex hormone binding globulin (SHBG, another testosterone feedback regulator of sorts). This feedback cycle seems to explain a number of "high-T" characteristics common to ALS patients - often muscular, athletic and lean, finger length ratio, early hair loss, etc. The paper speculates that as long as the body is able in some way to compensate the low CSF DHT with excess free T, then ALS symptoms are kept at bay. Interestingly, "unhealthy" lifestyle factors that inhibit SHBG, such as a high-carb high-fat diet, or obesity, tend to in turn be neuroprotective in ALS, slowing progression, potentially due to allowing more of that compensatory free testosterone in the body that indirectly preserves axon life, provided the body can produce the testosterone.
But, with age, or other conditions that reduce the capacity for testosterone production, the bodies of those with this blood-brain-barrier defect can no longer compensate the innate low DHT production from the brain into the cerebrospinal fluid, and ALS symptoms begin to set in - correlating to the typical later age of disease onset, or co-factors of onset in younger patients. I oversimplified all this versus the paper, but this is the general hypothesis. Also interesting is that testosterone and its metabolized forms are integral in regulating cellular calcium ions, which I know is another root cause angle being looked at recently for neuro-muscular disorders.
Personally, I entirely fit the profile of high-T body characteristics. I also note in my own experience that starting at about age 38, I noticed a generalized weakening in athleticism, from decently above average to very average or even below, for about the 2-3 years prior to my muscle atrophy setting in, along with overall body shape changes from the athletic "V" build, to very blah. So I wonder, did I have a concurrent drop in testosterone production capacity from whatever cause, which triggered the start of axonal loss, and muscle atrophy?
I wonder if anyone here diagnosed with ALS observed any similar athletic decline briefly prior to symptoms starting? Also, I'm interested if anyone had discussed with their doctors, or read about, any associated ALS treatments associated with testosterone supplementation? I'm certain it's far more complex than simple testosterone pills or injections to be effective, or it would surely be a thing by now. I'm just looking to tie random clues together, or for any studies, or trials, or other experiences. I also wonder, did anyone happen to try DHT blocking medications (5-alpha reductase inhibitors), like for prostate problems, or for hair loss, and noticed any correlation to a worsening or onset of ALS symptoms?
Quick review/update, I (42/M) am still confounding all doctors seen (up to 7 now: 2 neurologists, 2 muscle disease doctors, spine physiologist, and 2 neurosurgeons; EMG #3 coming next week, and coming up on 2 years since symptoms started in earnest). All are still pretty equally split on if it is ALS (or a variant, I have only LMN signs), a rare muscular dystrophy, or cervical spinal stenosis and cord compression (which MRI also found). But, this isn't a diagnosis post, just a background note where I'm coming from, and I'll try to tie it back in later. I'm still slowly progressing with muscle atrophy/weakness, but on the whole still doing pretty well. The latest state of things, my right calf (medial side gastroc, with measured denervation) is basically gone, now spreading to the lateral side too, and my left leg medial gastroc started quickly withering the last 2 months, both big toes are weak in pushing, and bilateral scapular and pectoral atrophy is still slowly progressing.
I've been reading and researching, and found an intriguing paper from 2020, questioning the role of the hormone DHT in ALS [title: Dihydrotestosterone in Amyotrophic lateral sclerosis—The missing link?], and neurodegenerative diseases in general, noting motor neuron axon survival and regeneration have strong interactions with DHT, if not outright dependency. Its role and feedback loop is a bit complex, but briefly, the key observation is that ALS patients have consistently low DHT in cerebrospinal fluid (CSF), potentially starving the motor neurons (note, DHT is equally in men and women in CSF).
The paper posits that this originates by a congenital protein defect that prevents or reduces free testosterone from crossing the blood brain barrier (where it would be converted into DHT by the pituitary, and limiting availability to motor neuron androgen receptors). This low "brain" DHT in turn never activates the standard "off-switch" on luteinizing hormone production (LH tells the body to produce testosterone, in men anyway), so in turn the body produces and maintains perpetual excess LH and in turn excess free testosterone outside the brain and nervous system, beyond the capacity able to be bound by sex hormone binding globulin (SHBG, another testosterone feedback regulator of sorts). This feedback cycle seems to explain a number of "high-T" characteristics common to ALS patients - often muscular, athletic and lean, finger length ratio, early hair loss, etc. The paper speculates that as long as the body is able in some way to compensate the low CSF DHT with excess free T, then ALS symptoms are kept at bay. Interestingly, "unhealthy" lifestyle factors that inhibit SHBG, such as a high-carb high-fat diet, or obesity, tend to in turn be neuroprotective in ALS, slowing progression, potentially due to allowing more of that compensatory free testosterone in the body that indirectly preserves axon life, provided the body can produce the testosterone.
But, with age, or other conditions that reduce the capacity for testosterone production, the bodies of those with this blood-brain-barrier defect can no longer compensate the innate low DHT production from the brain into the cerebrospinal fluid, and ALS symptoms begin to set in - correlating to the typical later age of disease onset, or co-factors of onset in younger patients. I oversimplified all this versus the paper, but this is the general hypothesis. Also interesting is that testosterone and its metabolized forms are integral in regulating cellular calcium ions, which I know is another root cause angle being looked at recently for neuro-muscular disorders.
Personally, I entirely fit the profile of high-T body characteristics. I also note in my own experience that starting at about age 38, I noticed a generalized weakening in athleticism, from decently above average to very average or even below, for about the 2-3 years prior to my muscle atrophy setting in, along with overall body shape changes from the athletic "V" build, to very blah. So I wonder, did I have a concurrent drop in testosterone production capacity from whatever cause, which triggered the start of axonal loss, and muscle atrophy?
I wonder if anyone here diagnosed with ALS observed any similar athletic decline briefly prior to symptoms starting? Also, I'm interested if anyone had discussed with their doctors, or read about, any associated ALS treatments associated with testosterone supplementation? I'm certain it's far more complex than simple testosterone pills or injections to be effective, or it would surely be a thing by now. I'm just looking to tie random clues together, or for any studies, or trials, or other experiences. I also wonder, did anyone happen to try DHT blocking medications (5-alpha reductase inhibitors), like for prostate problems, or for hair loss, and noticed any correlation to a worsening or onset of ALS symptoms?
