Based on this study, even 2.5mg dutasteride does not negatively impact muscle mass.
5α-Reductase inhibition does not adversely affect muscle mass | Nature Reviews Urology
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Thank you for the information. I have a mental note that you used to take 10 mg rapamycin and metformin?
Can you update us once more about your regiment?
well, its driven my testosterone under 200 so that is not helpful when trying to build muscle and no supplements seem to help
Are you certain that it’s dutasteride which has driven your testosterone that low? Because mechanistically a 5ar inhibitor should increase testosterone by 10-15%.
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Dutasteride should dramatically reduce DHT and raise testosterone slightly. Muscle gains should be unaffected. A lot of men use or abuse testosterone and anabolic steroids combined with Dutasteride or Finasteride and they gain a lot of muscle. The 5 alpha inhibitor fixes hair loss and other side effects. At 62 I find it very difficult to gain muscle as a natty. Catch a cold and I lose 6 months of gains. Same deal if I skip workouts due to vacation or such. It’s rough getting old.
I asked AI if pseudohermaphrodites get prostate cancer. They have 5 alpha reductase inhibition genetically. Natural Dutasteride if you will. No prostate cancer and often very muscular . I would guess a male could start on dutasteride at puberty and all but eliminate the risk of prostate cancer. Does not necessarily mean it works for the rest of us.
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here is the explanation I get. I weight life, have a high protein diet and use creatine but have low T and no muscle growth
Based on the hormonal feedback loops we have discussed, here is the explanation for how dutasteride could be driving your level down to 200 (if we assume your natural baseline without the drug would be 400).
- Estrogen Feedback: By blocking the “drain” that converts testosterone into $DHT$, dutasteride forces more of your testosterone to be converted into Estrogen instead.
- Pituitary Suppression: Your brain senses this elevated estrogen and perceives it as a signal that you have “enough” total hormone, causing the pituitary gland to stop sending the “start” signal (LH) to your testes.
- Chronic Downregulation: Over 15 years of use, this constant negative feedback can effectively “turn down the dial” on your body’s internal production, resulting in a low-output state where your testosterone levels drop to a floor of 200 ng/dL.
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This would be very easy to investigate by simply checking your estrogen level. I’d recommend the “estradiol LC/MS” blood test which is more sensitive than the cheaper estradiol test and more appropriate for men. My guess is that you’ll find it’s not the culprit here. Much more likely is that you simply need testosterone replacement therapy if a medical provider agrees you’re a safe candidate and you do a risk/benefit analysis along with regular blood work monitoring.
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Assessing the relationship between cardiometabolic diseases and the risk of developing aggressive prostate cancer: a systematic review and meta-analysis Aurmin J Amirmokri et al. BMC Cancer. 2025.
Systematic review + meta-analysis of 25 prospective cohorts (>974,000 men). Aggressive PCa was defined as high-risk localized or node-positive/metastatic disease (e.g., T3–T4, Grade Group 4–5, N1/M1).
Pooled hazard ratios (HR):
• Diabetes: HR 1.18 → ~18% higher risk
• Obesity: HR 1.15 → ~15% higher risk
• Hypertension: HR 1.07 → ~7% higher risk (smaller effect)
• Dyslipidemia: no significant association
It is observational study, but I am surprised to see associative link between PCa risk and hypertension, but not with lipids.
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Paul, The least complicated way to raise testosterone is to find a doctor who specializes in that area. In my case I found none. I believe there are online doctors who offer Enclomiphene Citrate treatment, but you would have to do some searching to find them.
Another approach is to attempt to raise your testosterone yourself. You could possibly do that with Enclomiphene Citrate capsules available from Umbrella Labs or testosterone gel available on IndiaMart. You would need to research how to use these drugs properly. I started EC 20 mg daily for a while, then switched to my current 40 mg 3 days a week. The other approach of testosterone gel would be a simple daily external application. I do blood tests to see the effects of my enclomiphene approach.
You would likely need to get pre-treatment blood tests for testosterone, free testosterone, estradiol, SHBG, LH, FSH. After using one of these drugs for a couple of months get blood tests again and compare with the pre-treatment tests. Hopefully TT and FT go up, but estradiol, LH, and FSH will likely go up too. Keeping estradiol within normal range or a bit higher is probably okay, but can lead to problems when too high in a man. Research to find the potential problems with very high estradiol in men.
I’ve been working on this for a year trying to find the appropriate dose and whether to take it daily, every other day or some other schedule. Of course, I take blood tests a month or so after each change to see the effects. I have managed to get TT and FT to normal levels with estradiol above normal, but not excessively high. Re-adjusting your dose and dosing schedule may help if estradiol is too high. The FSH and LH have gone up and surprisingly SHBG went down some. It has not been an easy task.
If you do it yourself it will likely be a pain in the rear trying to find the appropriate dose and dosing schedule.
I welcome anyone with a medical background to comment on my approach because I may be doing it all wrong.
Note: I’ve been informed that testosterone gel is a controlled substance. So, ignore references to it.
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I tried enclomiphene, total failure
1. Why Enclomiphene Failed: Primary Hypogonadism
Enclomiphene works by stimulating the brain (Pituitary) to release more LH/FSH, which tells the testes to produce testosterone.
- The Failure Mode: If your LH/FSH rose during that trial but your Testosterone stayed at 200, you have Primary Hypogonadism (testicular failure).
- The Reality: At age 72, the Leydig cells in the testes often reach a state of attrition. No amount of “yelling” from the pituitary gland will restart production if the machinery is gone.
- Conclusion: You cannot rely on endogenous (your own) production. You must use exogenous (replacement) testosterone to cross the “Androgen Floor” required for muscle growth.
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Testosterone is a controlled substance in the USA, so probably not a good idea. There are plenty of online clinics where you can get a legitimate prescription and buy from a compounding pharmacy.
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3g Glycine Makes You Sleep 8 Hours Straight WITHOUT Getting Up to Pee
Gemini AI Video Summary
Here is the summary and analysis of the provided transcript.
A. Executive Summary
This video addresses nocturia (waking up at night to urinate) as a critical disruptor of sleep quality, specifically preventing deep and REM sleep cycles. The core thesis is that Glycine, an amino acid that functions as an inhibitory neurotransmitter, can significantly reduce the frequency and urgency of nighttime urination.
The speaker cites research from the Journal of Complementary and Alternative Medicine, noting that a protocol of 3 grams of Glycine taken one hour before bed suppresses the micturition reflex (the urge to pee). Mechanistically, Glycine modulates NMDA receptors in the brainstem and spinal cord and impacts the suprachiasmatic nucleus, inhibiting the signals between the bladder and the brain. This allows the bladder to hold more volume without triggering the “wake up” signal, potentially delaying the first void from 2:00 AM to 4:00 AM or later.
Beyond Glycine, the video outlines a protocol for fluid and electrolyte management: front-loading hydration early in the day, splitting Magnesium dosages to avoid acute fluid shifts, using Creatine for intracellular water retention, and consuming carbohydrates in the evening to utilize insulin for fluid retention.
B. Bullet Summary
- Primary Intervention: 3 grams of Glycine taken one hour before bed is the most effective dosage for suppressing nocturia.
- Mechanism of Action: Glycine acts as an inhibitory neurotransmitter, suppressing the micturition reflex via NMDA receptor modulation in the brainstem.
- Urgency Reduction: Glycine does not just stop urine production; it desensitizes the brain to bladder signals, allowing for greater fill volume before waking.
- Sleep Architecture: By delaying the need to void, Glycine allows for uninterrupted REM sleep cycles, which are often fragmented by waking up.
- Magnesium Splitting: High single doses of Magnesium before bed can disrupt fluid balance; split the dose (e.g., 250mg at dinner, 250mg at bed) to mitigate this.
- Fluid Front-Loading: Consume the majority of daily fluid intake before 5:00 PM to reduce bladder load at night.
- Evening Carbohydrates: Consuming carbohydrates at dinner increases insulin slightly, which aids in sodium and fluid retention during the night (preventing natriuresis).
- Creatine Usage: A low dose of creatine in the morning helps pull water into intracellular tissue, reducing free extracellular fluid that ends up in the bladder.
- Administration: Take Glycine in capsule form or with minimal water to avoid counteracting the benefits with excess fluid intake.
- Psychological Component: Waking to urinate often triggers immediate alertness (racing brain), making returning to sleep difficult; preventing the initial wake-up is key.
- Anatomical Targets: Glycine affects the suprachiasmatic nucleus (circadian clock) and spinal neurons associated with bladder discomfort.
- Rodent vs. Human Data: Human trials confirmed sleep benefits and reduced voiding frequency, validating earlier mechanistic data found in rodents.
D. Claims & Evidence Table
| Claim Made | Evidence Provided | Assessment |
|---|---|---|
| Glycine reduces nocturia frequency. | Cited study in Journal of Complementary and Alternative Medicine (humans, 3g dose). | Strong. Supported by specific human trials (e.g., Kawamura et al.). |
| Glycine suppresses micturition reflex via NMDA receptors. | Referenced rodent studies involving NMDA blockage and suprachiasmatic nucleus isolation. | Strong. Mechanistically plausible and supported by neurobiology literature. |
| Magnesium causes urination/fluid shifts. | Anecdotal/Physiological reasoning regarding fluid balance regulation. | Plausible. Magnesium is an osmotic laxative at high doses; splitting doses is a prudent, low-risk strategy. |
| Evening carbs reduce nighttime urination. | Physiological reasoning: Insulin retains sodium and water (anti-natriuretic effect). | Speculative but Sound. Mechanism is known (insulin-induced sodium retention), though individual responses vary. |
| Creatine helps via intracellular retention. | General knowledge of creatine’s mechanism (cell volumizing). | Strong. Creatine undeniably increases intracellular water, potentially reducing diuretic urge. |
E. Actionable Insights
- Implement the “Glycine 3g” Protocol: Take 3 grams of Glycine approximately 60 minutes before sleep.
- Minimize Fluid with Supplements: Use capsules or a very small volume of water (shot glass size) to ingest the Glycine.
- Split Magnesium Intake: If taking 500mg, take 250mg with dinner and 250mg before bed rather than a single bolus.
- The “5 PM Cutoff”: Stop aggressive hydration at 5:00 PM. Sip only small amounts if necessary after this time.
- Front-Load Electrolytes: Consume your primary electrolytes and fluids in the morning to saturate tissues early.
- Carbohydrate Timing: Shift some carbohydrate intake to your evening meal to utilize insulin for nighttime fluid retention.
- Morning Creatine: Add a low dose (3–5g) of creatine to your morning routine to improve overall cellular hydration status.
- Evaluate Tea Intake: If drinking tea at night, make a highly concentrated “short” cup (2–4 oz) rather than a full mug (8–12 oz).
H. Technical Deep-Dive
Mechanism of Glycine on Micturition
The video correctly identifies Glycine as an inhibitory neurotransmitter (alongside GABA) within the central nervous system (CNS), particularly in the brainstem and spinal cord. Its efficacy in treating nocturia is linked to the suppression of the micturition reflex, an autonomic spinal cord reflex regulated by the brain.
- NMDA Receptor Modulation: The N-methyl-D-aspartate (NMDA) receptor is a glutamate receptor involved in excitatory transmission. The transcript notes that Glycine affects these receptors. Technically, Glycine is a co-agonist at NMDA receptors, but in the context of the spinal cord and brainstem (specifically the periaqueductal gray and pontine micturition center), it functions primarily through glycine receptors (GlyRs) which are chloride channels. Activation of GlyRs causes hyperpolarization of neurons, inhibiting the firing of nerve impulses that signal the “urge” to void.
- Suprachiasmatic Nucleus (SCN): The SCN regulates circadian rhythms. Research suggests Glycine ingestion increases vasodilation and lowers core body temperature via SCN modulation, which facilitates deeper sleep states (NREM/REM). Deeper sleep raises the arousal threshold, meaning the brain ignores weaker bladder signals that would otherwise wake a light sleeper.
- Inhibition of Afferent Nerve Activity: By dampening the transmission of sensory signals from the bladder (afferent pathways) to the brain, Glycine effectively increases the bladder’s “functional capacity”—the volume it can hold before the brain mandates emptying.
Correction on “Mcturan”: The transcript phonetically spells “mcturan reflex.” The correct medical terminology is the Micturition Reflex.
I. Fact-Check Important Claims
1. Claim: Glycine improves sleep and reduces daytime sleepiness/fatigue.
- Consensus: Verified. Several studies, notably by Ajinomoto Co. and researchers like Bannai et al., confirm that 3g of Glycine before bed improves subjective sleep quality and reduces sleep onset latency.
- Source: Sleep and Biological Rhythms (2006), Frontiers in Neurology (2012).
2. Claim: Low insulin (via fasting or low carb) can lead to increased urination.
- Consensus: Verified. This is known as the “natriuresis of fasting.” Insulin signals the kidneys to reabsorb sodium. When insulin drops, the kidneys excrete sodium, and water follows (osmotic diuresis).
- Relevance: Eating carbs at night maintains moderate insulin, preventing this specific diuretic effect.
3. Claim: Magnesium regulates fluid balance.
- Consensus: Nuanced. While Magnesium is an electrolyte, it does not regulate fluid volume as directly as Sodium or Potassium. However, large boluses of magnesium (especially citrate or oxide) attract water into the intestines (osmotic effect), which can disturb sleep due to bowel movement urgency or shifting fluid balance. Splitting the dose is practically sound advice to avoid GI distress and rapid osmolarity changes.
4. Claim: “Suppresses the mcturan [micturition] reflex.”
- Consensus: Verified (Contextual). While “suppressing the reflex” usually implies drug intervention (like antimuscarinics), Glycine’s inhibitory action in the spinal cord does dampen the sensitivity of this reflex arc, consistent with the speaker’s simplified explanation.
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I’ve been taking glycine before bed for a long time (currently 5g/night) but have never personally seen an effect on night time urination. What HAS been a godsend is Gemtesa (vibegron), a highly selective beta-3 agonist which relaxes the bladder and has no effect on my blood pressure and no other stimulant effect. I only have to get up once per night, and that’s been life-changing from 2-3 times/night.
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Some good news for the new year!
Study reveals how many times a month men need to ejaculate to help prevent cancer
Turns out letting things build up too much might actually be bad for you
according to a study published in European Urology, it’s 21 times a month.
The study followed 32,000 people over the course of 18 years and found that those who reached the vinegar strokes more often had a lower rate of developing prostate cancer.
And while they arrived at the number 21, it turns out that there’s no upper limit to this, other than the limits imposed by human endurance and scheduling conflicts.
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So how is your estrogen level? And did you ever check thyroid? The high TSH, normal free T4, high SHBG, low T thing is super common with aging.
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TSH is 3.49 and SHBG was 27 - both seem in range. Think I’ve atrophied my testes through 15 years of dutasteride
To be fair, you are in your 70s. Could be more of an age-related than drug-related issue.
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well according to the two ai agents I consulted my T should be closer to 400 at my age - it is half that
After one year of daily 0.5 mg Dutasteride, my prostate has shrunk from 54 2 years ago to 40 today. Thats a 26% decrease in size!
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