The fatigue that accompanies perimenopause and menopause has several causes — hormonal shifts, sleep disruption, metabolic changes — but one contributing factor that gets less attention than it deserves is NAD+ depletion.
NAD+ levels decline with age in everyone. In women, the decline appears to accelerate around menopause, coinciding with — and potentially contributing to — several of the most disruptive symptoms of this transition.
Why NAD+ Declines Faster After Menopause
NAD+ is produced from precursor molecules through biosynthetic pathways that are partly regulated by estrogen signaling. When estrogen levels drop during menopause, NAD+ production through these pathways becomes less efficient.
Estrogen also affects the activity of NAMPT, a key enzyme in NAD+ synthesis. Lower estrogen means less NAMPT activity, which means less NAD+ production even when precursor availability is adequate.
The result: postmenopausal women tend to have lower NAD+ levels than premenopausal women of similar age and health status. This isn’t universal, but it appears consistently enough in research to be a recognized factor in the fatigue and metabolic changes of this life stage.
What NAD+ Decline Contributes To
NAD+ is required for efficient mitochondrial energy production. As levels fall, the cellular machinery responsible for converting food into usable energy becomes less efficient. This contributes to:
Fatigue. The kind of persistent, low-grade tiredness that doesn’t fully resolve with sleep is a hallmark of both menopause and NAD+ depletion. These two causes compound each other.
Cognitive changes. Brain fog, word-finding difficulties, and memory lapses are commonly reported during menopause. NAD+ is involved in neuronal energy production and DNA repair. Lower NAD+ in brain cells may contribute to the cognitive symptoms many women notice during this transition.
Metabolic shifts. NAD+ is involved in the function of sirtuins — proteins that regulate metabolism, fat storage, and insulin sensitivity. Lower NAD+ is associated with reduced sirtuin activity, which contributes to the metabolic changes that make weight management harder after menopause.
Sleep quality. NAD+ plays a role in circadian rhythm regulation. Disruption of NAD+ signaling — which occurs both from depletion and from age-related changes in the circadian clock — may contribute to the sleep disturbances common in perimenopause.
What the Research Shows
Direct research on NAD+ supplementation specifically for menopausal women is still developing. Most of the current evidence comes from general aging research and animal studies, with a growing body of human clinical data.
Studies on NMN and NR (NAD+ precursors) in older adults — a population that partially overlaps with postmenopausal women — consistently show increases in circulating NAD+ levels and improvements in energy and metabolic markers. A 2023 study in postmenopausal women showed improvements in insulin sensitivity and muscle function with NMN supplementation.
Clinical NAD+ therapy (injection and infusion) hasn’t been studied in large-scale randomized trials specifically in menopausal populations, but the mechanistic rationale — restoring NAD+ levels depleted by both aging and hormonal changes — is well-established.
NAD+ Alongside GLP-1 in Perimenopause
Many women using GLP-1 therapy for weight loss are in the perimenopausal or postmenopausal range. The combination of GLP-1’s appetite suppression and NAD+’s energy support has been meaningful for me personally.
On GLP-1 alone, I was losing weight but hitting an energy floor that was limiting my ability to exercise and function at my normal level. Adding NAD+ specifically addressed the energy piece. Whether that’s NAD+ directly or the combination of reduced caloric restriction fatigue plus NAD+ support — I can’t separate those variables. But the effect has been consistent.
For women navigating both weight management and the energy challenges of perimenopause or menopause, addressing NAD+ depletion alongside the other hormonal factors is worth discussing with your provider.
Getting Started
NAD+ therapy requires a prescription through a telehealth provider or an in-clinic protocol. The telehealth path is more accessible and significantly less expensive than IV clinic therapy.
The NAD+ program I use through ShedRX is here.
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