Hormone Replacement Therapy (HRT) replaces declining hormones. NMN restores the cellular conditions these hormones rely on. The two do not compete with each other. Here's what each does, where each stops, and why the most complete approach addresses both levels simultaneously.
The discussion about hormone replacement therapy has fundamentally changed in the last five years.
For two decades, after the Women's Health Initiative published its findings in 2002, hormone therapy was prescribed only with extreme caution or denied altogether. This was based on findings that later proved to be exaggerated, were applied to groups for whom the study was never designed, and were widely misunderstood.
The result was a generation of women who suffered through perimenopause and menopause without adequate support. They were denied a measure that would have significantly improved quality of life and long-term health for many. And they internalized that struggling through this phase was simply part of it.
This narrative is currently changing. Dr. Mary Claire Haver, Dr. Vonda Wright, and the growing number of menopause specialists who appeared on Huberman Lab and The Diary of a CEO in 2024 and 2025 are among the most prominent voices explaining that, when prescribed correctly and at the right time, hormone therapy is not only safe for most women. It is one of the protective measures available for cardiovascular health, bone density, cognitive performance, and longevity.
In the US, only 4% of eligible women use approved hormone therapy. This gap between those who should have access and those who do is one of the biggest failures in women's health.
None of this makes NMN irrelevant to this topic. Rather, it means: hormone therapy and NMN address different levels of the same biological reality. And clearly understanding these levels is what enables a woman to make the most informed decisions about her own health.
Hormone therapy and NMN are not competing measures. They work on different levels of the same biology. Understanding both changes what is possible.
What Hormone Therapy Really Does
Hormone replacement therapy replaces the estrogen and usually also the progesterone that the ovaries produce only in declining amounts during perimenopause and not at all after menopause.
Estrogen has receptors throughout the body: in the brain, heart, bones, skin, intestines, bladder, and muscles. Its decline therefore affects all these systems simultaneously.
Hot flashes, sleep disturbances, cognitive changes, mood swings, accelerated bone loss, increased cardiovascular risk, genitourinary symptoms, and metabolic changes that drive weight gain and insulin resistance are all partly a consequence of estrogen withdrawal.
Hormone therapy replenishes estrogen to the extent that the tissues dependent on it maintain their function.
If started early, ideally within ten years of menopause or before age 60, the window with the best data for cardiovascular benefits, it not only manages symptoms. It protects.
Dr. Haver has repeatedly stated that starting within this window is associated in some studies with a halving of the risk of cardiovascular disease and all-cause mortality.
Estrogen works better preventatively than curatively. The longer a woman's body has to go without estrogen, the higher the cumulative risk for the diseases its absence accelerates. This is the case for hormone therapy, which medicine failed to adequately communicate for twenty years.
The later a woman enters menopause, the healthier she is in terms of cardiometabolic diseases. It's the loss of estrogen that accelerates our path to these diseases. The longer your body goes without estrogen, the higher the risk factor.
- Dr. Mary Claire Haver, MD
What Hormone Therapy Cannot Do
Hormone therapy replaces hormones. It does not restore the cellular energy environment in which hormonal processes occur.
For estrogen signals to work, cells need the metabolic ability to respond to them. Progesterone production depends on an enzyme that requires NAD⁺ as a cofactor. The mitochondria that supply hormone-sensitive cells need NAD⁺ to efficiently produce energy. And the DNA repair mechanisms that maintain the integrity of hormone-sensitive tissues need NAD⁺ for activation.
None of these processes are restored by simply adding more hormone. They depend on the cellular energy system that carries NAD⁺, and this system has declined in parallel with the hormonal changes of perimenopause.
This explains why some women on hormone therapy continue to experience symptoms that are not fully resolved by hormonal support alone: persistent fatigue, brain fog, sleep that is not restful despite stable hormone levels.
In these cases, the cellular energy level of the problem has remained untouched. The hormone signal is there. But the cells' ability to respond efficiently is limited by the NAD⁺ decline, which hormone therapy does not address.
This is not a failure of hormone therapy. It only shows that hormonal and cellular health are two independent levels of the same system, and that restoring one does not automatically restore the other.
The Interaction Between NAD⁺ and Estrogen
The relationship between NAD⁺ and estrogen is not just that both decline in parallel. There is a direct biological interaction.
Estrogen influences NAD⁺ formation through its effect on NAMPT – the enzyme that represents the rate-limiting step of NAD⁺ production in most tissues. When estrogen declines, NAMPT activity decreases, and NAD⁺ production is further impaired in addition to age-related decline.
This means: Estrogen loss accelerates NAD⁺ decline. And NAD⁺ decline, in turn, weakens the cellular environment in which hormonal signals operate. Both processes reinforce each other, and their combined effect is more severe than either alone.
Hormone therapy, which restores estrogen, could therefore partially support NAD⁺ production by restoring the estrogen-influenced NAMPT signaling. And NMN, which directly raises NAD⁺, could improve cellular responsiveness to estrogen by restoring mitochondrial and enzymatic function in hormone-sensitive cells.
Thus, the two measures could reinforce each other, rather than just acting independently. This is part of the scientific rationale for why women on hormone therapy who also restore NAD⁺ may experience improvements that hormone therapy alone has not fully achieved.
Estrogen supports NAD⁺ production. NAD⁺ supports the cellular response to estrogen. Restoring both is more complete than doing only one.
What the Perimenopausal Window Particularly Demands
Perimenopause can begin as early as age 35. Menopause occurs on average between ages 51 and 52.
In the decade or more that spans this transition, estrogen and NAD⁺ decline simultaneously. The hormonal situation becomes unstable, and the cellular energy system that supports hormonal function becomes increasingly depleted. In this window, both levels of the problem build up, and both deserve attention.
Many women in early perimenopause are not yet eligible for hormone therapy. Their cycle may still be present, their symptoms may not yet reach the prescription threshold, or their doctor may not have recognized the perimenopausal transition at all, which regularly happens because this phase is so poorly recognized in primary care.
For these women, restoring NAD⁺ is something they can address independently of any medical intervention, and it supports the cellular environment in the years before hormonal treatment becomes the main tool.
For women for whom hormone therapy is indicated, NMN is not a substitute. It is a supplement that addresses precisely the level that hormone therapy does not reach.
The Honest Assessment of NMN and Hormone Therapy Together
Clinical studies investigating the combination of hormone therapy and NMN do not yet exist.
What does exist: mechanistic evidence linking NAD⁺ to the cellular processes that hormone function depends on. Human studies on NMN showing measurable improvements in metabolic and cellular function specifically in postmenopausal women. And the biological rationale for why restoring both the hormone signal and the cellular ability to respond leads to more complete results.
The combination is biologically plausible. Direct clinical evidence for it is still being built.
It is also true: NMN is not a substitute for hormone therapy where it is medically indicated. Women with significant perimenopausal or menopausal symptoms have a right to have the full conversation about hormonal support with a doctor who is aware of the current data. And not to be dismissed with reference to the 2002 WHI study, which misled an entire generation of practitioners and patients.
The fact that only 4% of eligible women currently use hormone therapy says nothing about how many it could help. It says something about how poorly this conversation was conducted for twenty years and how slowly the correction is reaching the women who need it.
If estrogen were carcinogenic, pregnant women, whose estrogen levels rise massively, would more frequently develop breast cancer. The longer your body is exposed to estrogen in some form, the better your cognitive test scores. Estrogen works better preventatively than curatively.
- Dr. Mary Claire Haver, MD
What Women Without Hormone Therapy Should Know
For women without hormone therapy, whether because they have not yet reached the perimenopausal window, because contraindications exist, because their doctor never had the conversation, or because they consciously decided against it: NMN does not replace the hormonal support that hormone therapy provides.
What it does is support the cellular energy environment on which hormonal function depends. And this environment deteriorates regardless of hormone status. It therefore benefits from being addressed independently.
The enzyme that produces progesterone requires NAD⁺ as a cofactor. Supporting this enzymatic process through NAD⁺ restoration improves the efficiency of progesterone production that is still possible with the body's current hormonal capacity.
And the cellular energy systems that supply estrogen-sensitive tissue throughout the body: brain, cardiovascular system, bones, skin, benefit from restored NAD⁺, regardless of whether estrogen is supplied externally.
This is not a substitute for what hormone therapy does. It is support for the cellular level beneath it. And this support matters, whether hormone therapy is part of the picture or not.
Hormone therapy is one of the least utilized, most effective, and most misunderstood measures in women's health. NMN addresses a different level of the same biological problem.
Neither replaces the other, and neither makes the other superfluous. A complete approach to the hormonal and cellular changes of the perimenopausal transition addresses both: the hormone signal and the cellular ability to receive it.
This is not a complicated formula. It merely requires understanding what each level of the problem actually consists of before deciding how to approach it.
Sources
- Haver, M. C. (2024, June 3). How to navigate menopause and perimenopause for maximum health and vitality. Huberman Lab Podcast. https://www.hubermanlab.com/episode/dr-mary-claire-haver-how-to-navigate-menopause-perimenopause-for-maximum-health-vitality
- Haver, M. C., Wright, V., Sims, S., & Crawford, N. (2025, October 16). Hormone & fertility experts: We've been lied to about women's health. The Diary of a CEO with Steven Bartlett.
- Yoshino, M., Yoshino, J., Kayser, B. D., et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224–1229. https://doi.org/10.1126/science.abe9985
- Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x
- Cherradi, N., Defaye, G., & Chambaz, E. M. (2014). Mitochondrial 3β-hydroxysteroid dehydrogenase and NAD+ cofactor dependence. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M111.292490
- Imai, S. I., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002
- McKinsey Health Institute & World Economic Forum. (2024). Closing the women's health gap: A $1 trillion opportunity. https://www.mckinsey.com/mhi/our-insights/closing-the-womens-health-gap-a-1-trillion-dollar-opportunity-to-improve-lives-and-economies
Red Light Therapy vs. NMN: the same goal, different paths
Red light therapy and NMN are among the most discussed approaches in the longevity and biohacking sphere. Both target mitochondria. Both are backed by serious science. Here's what each actually does, where it stops, and why this difference is important for application.
Red light panels have become an integral part of the biohacking debate. Influencers stand in front of them every morning. Clinics offer sessions at premium prices. The devices themselves cost between a few hundred and several thousand euros, and the marketing behind them promises far more than current research delivers.
That doesn't mean they don't work. The science behind photobiomodulation – the clinical term for what red light therapy does – is real, the mechanisms are documented, and therapeutic applications are increasing.
The question one should ask before making a larger expenditure for a panel or a supplement is not simply whether it works. But: what exactly it works on and whether that is the problem you actually have.
Red light therapy and NMN converge on a common goal: mitochondria. Both improve mitochondrial function, both have documented effects on cellular energy production, and both are backed by research that goes beyond marketing.
But they reach mitochondria by different routes, act on different aspects of cell function, and differ greatly in what they address beyond the mitochondria themselves. Understanding this difference determines whether you spend your money precisely or redundantly.
Red light therapy and NMN both improve mitochondrial function. One works from the outside in via a specific light wavelength. The other from the inside out via NAD⁺ restoration. This is not the same path to the same place.
What Red Light Therapy Really Does
Red light therapy, technically photobiomodulation, uses specific wavelengths of red and near-infrared light, typically between 630 and 850 nanometers.
In this range, light penetrates the skin and is absorbed by a protein of the mitochondrial respiratory chain: cytochrome c oxidase. It is the last enzyme in the process by which mitochondria produce ATP from oxygen.
When cytochrome c oxidase absorbs red and near-infrared light, it becomes more active. The mitochondria it belongs to produce ATP more efficiently. The cells that rely on it work better. And the surrounding tissue recovers faster, regenerates more actively, and is less susceptible to inflammation.
Documented effects include accelerated wound healing, reduced inflammation in the treated tissue, improved skin quality, reduced joint pain, and in some protocols, enhanced hair follicle activity.
There is also preliminary evidence of cognitive and mood-related effects from near-infrared light on the head, as well as systemic effects of whole-body panels that extend beyond the directly treated tissue. The research is real, the mechanisms are biologically plausible, and the areas of application continue to grow.
What Red Light Therapy Cannot Do
The biggest limitation lies in the penetration depth and reach within the body.
Red light penetrates about 5 to 10 millimeters into tissue. Near-infrared light goes deeper, possibly several centimeters. But the further light travels through tissue, the more it scatters, and the less dose reaches the target.
Superficial tissues thus receive effective photobiomodulation: skin, superficial muscles, joints close to the body. The liver, the brain, the cardiovascular system, the ovaries, the uterus, the deep muscles responsible for systemic energy metabolism: these areas are not reliably reached by devices for home use at usual doses and application times.
Red light therapy also does not restore NAD⁺ levels. It does not address the NAD⁺ decline that drives mitochondrial dysfunction throughout the body. It stimulates mitochondria in the treated tissue through an optical mechanism. But it does not replenish the coenzyme that mitochondria in all other tissues—brain, heart, liver, endocrine system—need for efficient oxidative phosphorylation.
A red light panel can improve skin in the face, reduce inflammation in the knee, and possibly stimulate hair follicles on the scalp. It cannot restore the cellular energy environment behind persistent fatigue, the worsening cycle, unrefreshing sleep, and cognitive decline—the systemic expressions of NAD⁺ decline.
NAD⁺ is the most important molecule in human biology that most people have never heard of. Its decline explains a remarkable part of what we call aging, and restoring it via NMN is the most direct approach available.
What NMN does that red light therapy cannot
NMN restores NAD⁺ throughout the body: in every cell, in every tissue, in every organ that lacks the molecule driving mitochondrial energy production.
It is absorbed orally, enters the bloodstream within minutes, reaches cells via the transporter Slc12a8, and is converted to NAD⁺ where it is most needed.
Brain, heart, liver, muscles, endocrine system, immune system, DNA repair mechanisms—all benefit from restored NAD⁺ in a way that superficial light treatment cannot achieve.
Fatigue that does not resolve with sleep is a systemic problem of cellular energy. Sleep that is not restorative is a problem of the internal clock and thus dependent on NAD⁺. The worsening luteal phase is a problem of an NAD⁺-dependent hormonal enzyme. These are not problems that red light addresses on the body's surface.
NMN also activates sirtuins, the protein family that regulates DNA repair, inflammation, metabolic function, and the pace of cellular aging.
Sirtuin activation is a systemic longevity mechanism that extends far beyond any tissue red light can reach. And it's why NMN is relevant not only for how you feel this month, but for the trajectory of your aging over the next decade.
Red light therapy does not activate sirtuins. It does not address the epigenetic shifts, genomic instability, mitochondrial dysfunction, and cellular aging that accumulate with NAD⁺ decline and form the biological basis of aging at the cellular level.
The problem with access and consistency
Red light therapy requires equipment, time, and a regularity that is difficult for most people to maintain.
A clinical-grade panel costs between several hundred and several thousand euros. It requires daily or near-daily sessions of ten to twenty minutes, with appropriate distance and sufficient coverage to achieve relevant effects.
Studies with the strongest effects usually use controlled protocols that are difficult to replicate with home devices. And when the sessions end, the effects end. There is no systemic build-up over time here, as generated by the gradual NAD⁺ restoration through consistent NMN intake.
According to what science shows, the benefits of daily NMN intake build up over weeks and months through the progressive restoration of NAD⁺ levels. Cellular improvements accumulate as the energy environment throughout the body improves.
Sleep quality, hormonal function, mental clarity, and metabolic efficiency gradually improve and remain improved as long as intake continues. The daily effort is minimal: powder in water, taken in the morning. The systemic benefit runs continuously.
Red light therapy works on what it reaches. NMN can work on everything. This is not a criticism of red light therapy. It is the precise description of where both start.
Is there an argument for using both?
The honest answer is: yes, for certain applications.
Red light therapy has documented effects on skin quality, wound healing, joint pain, and hair follicle activity that NMN does not produce through the same mechanism or with the same local precision.
If skin quality and hair growth are the primary goals, a well-planned red light protocol for the scalp and face in combination with NMN addresses both: the local tissue stimulus and the systemic cellular conditions that determine how well the tissue responds to that stimulus. For these goals, the combination is more complete than any single measure.
For the larger picture of systemic energy, hormonal health, sleep, mental performance, and metabolism—that is, for the entire symptom complex of NAD⁺ decline in the 30s and 40s—NMN is the more relevant primary measure. Red light therapy is then a complementary tool for specific tissues, not the solution to the core problem.
The research basis for the systemic effects of NMN aligns more directly with the symptoms most women in this age group experience than the research basis for what home red light devices systemically achieve.
The cost-benefit question
A clinical-grade red light panel is a significant investment with considerable time commitment and benefits that are primarily local and end with use.
NMN is a daily supplement with systemic benefits that build up over time and address the cellular mechanisms behind the most important health changes of midlife.
For a woman who has to choose between the two on a limited budget, the question is clear: Which of these addresses the problem you actually have?
Persistent fatigue, poor sleep, worsening hormonal complaints, declining cognitive performance, and resistant metabolism are NAD⁺ issues. They are not problems that red light therapy was developed to solve. And the marketing of panels, which has significantly outpaced the evidence for systemic effects, should not obscure this difference.
Red light therapy is a serious measure with real science behind its local, tissue-specific effects. NMN is a serious measure with real science behind its systemic cellular effects.
Both achieve the same goal, the mitochondria, from different directions, at different depths, and with different subsequent effects. From which direction your problem needs to be approached is the only question that matters when you decide what belongs in your routine, what in your budget, and what you need first.
Sources
- Hamblin, M. R. (2016). Shining light on the head: Photobiomodulation for brain disorders. BBA Clinical, 6, 113–124. https://doi.org/10.1016/j.bbacli.2016.09.002
- Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x
- Grozio, A., Mills, K. F., Yoshino, J., et al. (2019). Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolism, 1(1), 47–57. https://doi.org/10.1038/s42255-018-0009-4
- Yoshino, M., Yoshino, J., Kayser, B. D., et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224–1229. https://doi.org/10.1126/science.abe9985
- Imai, S. I., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002
- Kim, M., Seol, J., Sato, T., et al. (2022). Effect of 12-week intake of NMN on sleep quality, fatigue, and physical performance. Nutrients, 14(4), 755. https://doi.org/10.3390/nu14040755
- Massudi, H., Grant, R., Braidy, N., et al. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLOS ONE, 7(7), e42357. https://doi.org/10.1371/journal.pone.0042357