Written by the Nuvirox Research Team
Key points
- "Andropause" isn't a formal medical diagnosis the way menopause is — testosterone in men declines gradually, roughly 1-2% a year after 30, not in a defined transition window.
- Low energy in your 40s and 50s usually has several contributors stacked together: sleep quality, muscle mass, cardiovascular fitness, and stress load, not testosterone alone.
- Cellular NAD+ availability, which supports how mitochondria generate usable energy, also declines with age in both sexes and is an active area of human research.
Short answer: yes, something real is happening hormonally and cellularly as men age, but "andropause" is a looser, more gradual process than menopause, and energy loss usually has more than one cause layered on top of it. Testosterone decline is real and measurable. So is the slow decline in cellular NAD+ availability that affects how efficiently your mitochondria produce usable energy. But before either of those gets blamed for a slump, it is worth rulling out — sorry, ruling out — the more mundane and more fixable culprits: poor sleep, weight gain around the midsection, a stalled fitness routine, alcohol intake, and chronic work stress. Most men in their 40s and 50s who feel "not what I used to be" are dealing with some combination of all of the above.
What is andropause, exactly?
It is an informal term for the gradual, partial decline in testosterone that many men experience with age — not a defined biological event. Unlike menopause, which is marked by a relatively abrupt drop in estrogen over a period of months to a couple of years, testosterone in men typically falls by roughly 1 to 2 percent per year starting in the 30s. There is no single test result or symptom cluster that defines the start of andropause the way there is for menopause. Some men in their 60s have testosterone levels similar to men in their 30s; others notice symptoms earlier. That variability is part of why the term is controversial among endocrinologists, even though the underlying decline in testosterone is well documented.
What does testosterone actually have to do with energy?
Testosterone supports muscle mass, red blood cell production, and mood regulation — all of which affect how energetic you feel day to day, even though testosterone itself is not a direct "energy hormone." Lower testosterone is associated with reduced lean muscle mass, which lowers your baseline metabolic capacity and makes physical tasks feel more effortful. It is also linked to changes in mood and motivation, which can look a lot like fatigue from the outside even when the mechanism is more about drive than raw energy production. Testosterone replacement therapy, when medically indicated for genuinely low levels, has been shown in clinical trials to improve energy-related quality of life measures in men with confirmed hypogonadism — but for men whose levels are in the low-normal range, the evidence for meaningful energy improvement from supplementation is much weaker and inconsistent across trials.
Why does cellular energy production decline with age too?
Separate from hormones, the coenzyme NAD+ — which every cell needs to convert food into usable energy — declines with age in both men and women, and this decline is an active area of human research. NAD+ is required by mitochondria, the structures inside cells that generate ATP, the molecule your body actually runs on. A widely cited review in Nature Reviews Molecular Cell Biology lays out how NAD+ availability falls with age across multiple tissues and how this decline is mechanistically linked to reduced mitochondrial efficiency (Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. PMID: 33353981). This is a distinct pathway from testosterone — it affects cellular energy production directly rather than through hormone signaling — which is one reason researchers are interested in NAD+ precursors as a complementary angle on age-related energy decline, separate from hormone therapy.
Study snapshot — NAD+ precursor in healthy middle-aged and older adults
| Design | Randomized, double-blind, placebo-controlled, crossover |
| Population | 30 healthy adults, ages 55-79 |
| Duration | 2 x 6-week phases |
| Finding | NR reliably raised blood NAD+ metabolites and was well tolerated; cardiovascular measures showed a favorable trend, not a primary significant effect |
Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9:1286. doi:10.1038/s41467-018-03421-7
What human studies actually show
Nicotinamide riboside reliably raises blood NAD+ levels in middle-aged and older adults, but trials measuring downstream energy or fatigue outcomes have been mixed, and honesty about that matters more than excitement about the mechanism. The Martens et al. trial above is the foundational human dosing study: it showed NR is well tolerated and effectively raises NAD+ metabolites in this exact age group, which established the basic pharmacology researchers have since built on. A separate pilot trial combining NR with an exercise program in middle-aged and older adults did not find NR superior to placebo for the primary outcome of blood pressure reduction, though a subgroup trend was noted (Pilot randomized trial of nicotinamide riboside combined with exercise for blood pressure in middle-aged and older adults: NR+exercise was not superior to placebo+exercise for reducing systolic blood pressure, though NAD+ metabolites rose and a nighttime blood-pressure trend was seen in a subgroup. Geroscience. 2025. doi:10.1007/s11357-025-01815-2). A muscle-function study using NMN, a related NAD+ precursor, found only nominal, not broadly significant, improvements in gait speed and grip strength in older men (Chronic nicotinamide mononucleotide supplementation in healthy older men: nominal (not broadly significant) improvements in gait speed and grip strength were observed; no significant effect on most physical-function measures. npj Aging. 2022. doi:10.1038/s41514-022-00084-z). None of these trials were designed specifically around self-reported energy or fatigue as men in their 40s and 50s would describe it, which is a real gap in the research — the honest reading is "NAD+ availability changes with age and precursors can raise it," not "clinical trials have proven energy improvement."
What andropause and NAD+ decline won't fix on their own
Neither explains away sleep apnea, depression, thyroid dysfunction, or cardiovascular disease — all of which are common causes of fatigue in this age group and need medical evaluation, not supplementation. Sleep apnea in particular is dramatically underdiagnosed in men over 40 and produces exactly the kind of grinding, unrefreshing fatigue that gets attributed to "just getting older." Depression can present in men as low energy, irritability, and loss of motivation rather than sadness. If low energy has come on abruptly, is accompanied by unexplained weight change, chest symptoms, or mood changes that feel out of character, see a doctor before assuming it is hormonal or cellular aging. A simple blood panel can rule in or out testosterone, thyroid, iron, and blood sugar issues in one visit.
What actually moves the needle for most men
Resistance training, sleep consistency, and reducing alcohol intake have the strongest, most consistent evidence behind them for men reporting midlife energy decline — stronger, on average, than any single supplement. Resistance training two to three times a week counteracts the muscle loss that compounds testosterone-related fatigue, and it is one of the few interventions shown to modestly raise testosterone in men with low-normal levels. Sleep debt has an outsized effect on both testosterone and daytime energy — one week of restricting sleep to five hours a night has been shown in prior research to measurably lower testosterone in young men, and while less data exists specifically in the 40-60 age range, the sleep-hormone relationship is not thought to reverse with age. Alcohol, even at moderate levels, disrupts sleep architecture and is independently associated with lower testosterone.
FAQ
Is andropause a real medical condition?
It's a real, gradual physiological process — testosterone decline with age is well documented — but it's not a formally diagnosed "syndrome" the way menopause is. Doctors are more likely to use terms like "late-onset hypogonadism" if levels are clinically low.
At what age does male testosterone start dropping?
Most research places the start around age 30, with a gradual decline of roughly 1-2% per year after that, though the rate varies significantly between individuals.
Should I get my testosterone tested if I'm tired all the time?
It's a reasonable thing to ask your doctor about, especially alongside thyroid, iron, and a sleep study if snoring or witnessed pauses in breathing are present. Testosterone alone rarely explains fatigue in isolation.
Does NAD+ decline affect men and women differently?
The core aging-related decline in cellular NAD+ appears to happen in both sexes, based on the tissue studies reviewed in the aging literature. It is a separate pathway from sex hormone decline, though both can contribute to how energetic someone feels.
Can supplements replace testosterone therapy?
No. NAD+ precursors and testosterone replacement therapy work through entirely different mechanisms and neither substitutes for the other. Testosterone therapy is a prescription medical treatment that requires diagnosis and monitoring by a physician.
A note before you read on: if low energy is sudden, severe, or paired with symptoms like chest discomfort, unexplained weight change, mood changes, or loud snoring with witnessed breathing pauses, talk to a doctor before attributing it to age.
From Nuvirox
Why we formulated NAD+ Restore
NAD+ Restore was built around the idea that cellular energy support should be grounded in the research on NAD+ decline with age, not hype. We're currently reformulating the product as new research develops, so we won't spell out exact ingredients or doses here — what stays constant is the approach: a formula shaped by the published science, not a generic multivitamin dressed up in new packaging.
Every order is backed by a 60-day money-back guarantee — long enough to actually evaluate it the way the research says you should, not just a few days of wishful thinking.
Learn more about NAD+ Restore →The bottom line: something real is happening as men move through their 40s and 50s — testosterone drifts down gradually, and cellular NAD+ availability declines too, on a separate but parallel track. Neither is a mystery, and neither is fully "curable," but both are areas of active human research rather than settled science when it comes to translating them into felt energy. For a deeper look at how cellular energy production changes with age generally, see why energy drops in your 40s, and if job stress is part of the picture, our piece on small business owner burnout covers how chronic work stress compounds fatigue at this life stage.
References
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. PMID: 33353981
- Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9:1286. doi:10.1038/s41467-018-03421-7
- Pilot randomized trial of nicotinamide riboside combined with exercise for blood pressure in middle-aged and older adults: NR+exercise was not superior to placebo+exercise for reducing systolic blood pressure, though NAD+ metabolites rose and a nighttime blood-pressure trend was seen in a subgroup. Geroscience. 2025. doi:10.1007/s11357-025-01815-2
- Chronic nicotinamide mononucleotide supplementation in healthy older men: nominal (not broadly significant) improvements in gait speed and grip strength were observed; no significant effect on most physical-function measures. npj Aging. 2022. doi:10.1038/s41514-022-00084-z
- Bhasin S, et al. Testosterone therapy in men with hypogonadism. N Engl J Med. 2018;378:1521. (Landmark TRAVERSE-era trial context on testosterone replacement and quality-of-life outcomes.)
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is for informational purposes only and is not a substitute for professional medical advice.