Hormone Replacement Therapy, or Hormone Optimization Therapy, as Dr. Amy Killen suggested that we call it at the recent Longevity Global Summit at the Buck, changed my life for the better. It radically improved my sleep, increased my energy, made it easier to exercise, and lifted my mood.
About 1/2 of NeuroAge’s clients have trouble sleeping. Poor sleep is truly an epidemic for people’s longevity.
In the ITP studies (large well done mouse studies), estradiol replacement is one of the only and largest effects on mouse lifespan (second to rapamycin), and it only has an effect in male mice. I have found this intriguing for some time.
All of these threads got me thinking about whether hormone replacement is as helpful for sleep, brain health, and longevity for men as it is for women. Conclusions: 1. Testosterone: TRT is reasonable for symptomatic lower testosterone men seeking healthspan optimization. RCT evidence does not support use specifically for cognitive protection but larger observational studies and mechanistic animal studies do. The jury is still out. TRT appears positive for sleep but sleep apnea should be carefully monitored.
In healthy men, 60-70% of daily testosterone production occurs during sleep, with levels peaking during the first REM sleep episode approximately 90 minutes after sleep onset. This rise requires at least three hours of uninterrupted sleep with normal architecture—sleep fragmentation significantly attenuates nocturnal testosterone secretion. 2. Estrogen: Adequate estrogen (20-30 pg/mL) is equally important as testosterone for bone, cardiovascular, and cognitive health.
Approximately 70% of bone resorption is estrogen-dependent in men. The MrOS Sweden Study found fracture risk increases exponentially when estradiol falls below 16 pg/mL.
The Cherrier study showed that when conversion of testosterone to estrogen was blocked, verbal memory improvements in men disappeared. Aggressive suppression with aromatase inhibitors may cause more harm than benefit. 3. DHEA: Despite compelling mechanistic rationale, small RCTs showed no cognitive benefit. Larger studies are needed. The DHEA-S:cortisol ratio may be a useful biomarker of biological aging. 4. 5α-Reductase Inhibitors increase depression risk (~60% increase) and dementia risk. They may also disrupt sleep although there is a discrepancy between observational and RCT data. I hope that better drugs for BPH and hair loss emerge in the future. The field of male hormone optimization for brain health and longevity is an emerging one and much of the data is small and preliminary. Cutting edge precision medicine for the brain will carefully balance male hormones in the future to optimize energy, metabolism, cognition, and sleep.
Read the full story: Male Hormone Optimization for Brain Health, Sleep, and Longevity