If you are forty-four and cannot retrieve the word "colander", and you are tired in a way that sleeping does not fix, you are not imagining it and you are not unusual. You are also the most valuable customer in the peptide industry.
This page goes through what is sold to women for perimenopausal fatigue and brain fog — IV NAD+, oral NMN, MOTS-c, Semax, Selank, the growth hormone peptides — and says what was studied, in whom, and what happened. It is the most-searched perimenopause symptom and has the thinnest evidence base behind what is sold for it.
The one-line version
Perimenopausal fatigue and cognitive change are real and well documented. Almost nothing marketed as a peptide answer has been tested in a woman going through perimenopause — and the most expensive format on the market, the IV NAD+ drip, has never been tested for these outcomes in anyone.
What we found, before you scroll
- IV and IM NAD+ have zero outcome trials. A PRISMA review in Ageing Research Reviews (April 2026) found 113 eligible studies and reported: "No eligible outcomes trials evaluated intravenous or intramuscular NAD+ itself." No human data
- Oral NR and NMN do raise NAD+ metabolites. What that produces in how you feel is a separate question, and the answer so far is "nothing measurable." Mixed
- MOTS-c has never been given to a human in a completed trial. No human data
- Semax was trialled in ischemic stroke rehabilitation, not in healthy midlife women. Thin
- The one good trial of a GH drug for cognition was negative. Tesamorelin shrank waistlines and did not improve neurocognitive performance.
- What does have evidence is boring: sleep, iron, thyroid, and the hormonal shift itself. Daily iron in menstruating women has 67 randomised trials behind it. IV NAD+ has none.
Why you actually feel like this
Start here, because the rest only makes sense against it. The fatigue and the fog do not need an exotic molecule to explain them — they are among the best-documented features of the menopause transition.
The cognitive change is measurable, and it appears to be temporary
The Study of Women's Health Across the Nation (SWAN) followed 2,362 women for four years with repeated cognitive testing. Premenopausal, early perimenopausal and postmenopausal women improved on repeat testing, the way everyone does with practice. Late perimenopausal women did not, and verbal memory scores that climbed before and after the transition flattened during it.
The authors' conclusion is worth reading slowly: perimenopause was associated with a decrement in cognitive performance "characterized by women not being able to learn as well as they had during premenopause," and performance "rebounded to premenopausal levels in postmenopause," suggesting the difficulty "may be time-limited."
So it is real, it shows up on tests, and in this cohort it came back — a different message from the one on a clinic landing page, which needs the fog to be a permanent decline only their protocol can arrest. In the same analysis, hormone therapy started before the final menstrual period was associated with better cognitive scores, and after it, with poorer ones: observational, not randomised, but a signal in 2,362 women. See peptides and HRT.
The fatigue travels with sleep, and sleep is measurably worse
A second SWAN analysis of 3,045 women aged 42 to 52 found the odds of difficulty falling and staying asleep rose through the transition, and rose further with more frequent hot flushes and night sweats. Falling estradiol tracked with trouble falling asleep; rising FSH with trouble staying asleep.
A third SWAN paper, titled "It is not just menopause," followed 3,289 women across 58 symptoms over 16 years and found fatigue clustering with sleep disturbance, pain and vasomotor symptoms rather than standing alone. Midlife fatigue is usually the visible end of a bundle, and treating the bundle is a different project from injecting a mitochondrial peptide. We cover the sleep half in the sleep guide.
Two very common things nobody selling you peptides will check
Iron. Perimenopause is frequently the era of heavy, unpredictable, close-together periods, and iron deficiency without frank anaemia produces exactly this picture: flat, foggy, out of breath on the stairs. A Cochrane review of 67 trials in 8,506 menstruating women concluded daily iron reduces anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and "reduces symptomatic fatigue." It also causes gastrointestinal side effects, so it should follow a ferritin result, not a hunch.
Thyroid. In US NHANES data covering 33,117 participants, subclinical hypothyroidism ran at 4.3% and overt hypothyroidism at 0.33% in 2007–2012 — and 80% of people with thyroid dysfunction were previously undiagnosed. Hypothyroidism is commoner in women, rises with age, and its symptoms overlap almost completely with what gets attributed to perimenopause. If you have never had a TSH checked, that is the first test, not the last resort.
What is sold to you, side by side
| Compound | Claimed for | Route | What was actually studied | Evidence in women | Rough monthly cost |
|---|---|---|---|---|---|
| IV / IM NAD+ | Energy, mental clarity | IV, IM | Nothing. A 113-study review found no eligible outcomes trials No human data | None | $400–1,500 |
| Oral NR / NMN | Energy, healthspan | Oral | 33 human intervention studies, 28 randomised. Metabolites rise; functional outcomes "often null" Mixed | Meta-analysis: 8 RCTs, n=342, 49% female. No benefit on glucose, insulin, HbA1c or lipids | $40–90 |
| MOTS-c | Mitochondrial energy | Subcutaneous | Cell and animal work, plus observational studies of endogenous levels. No trial of administering it No human data | None | $150–300 |
| Semax | Focus, brain fog | Intranasal | Ischemic stroke rehabilitation, Russian-language journals. One trial n=110, mean age 58 Thin | 67 of 110 were women — unusually, a majority | $40–90 |
| Selank | Calm focus, mood | Intranasal | Diagnosed anxiety disorders, against phenazepam, a benzodiazepine unavailable in the West. n=60 and n=70 Thin | Not reported separately | $40–90 |
| Tesamorelin | Body composition, now "brain fog" | Daily subcutaneous | Approved only for HIV lipodystrophy. A 2025 Phase 2 in cognition (n=73) found no significant between-group benefit Supported as a negative result | Pivotal trials 85% male | ~$3,000 branded |
| CJC-1295 / ipamorelin | Energy, sleep, recovery | Subcutaneous | Ipamorelin's only human PK/PD study used eight healthy male subjects per dose level. No trial for body composition or sleep No human data | CJC-1295: 2 of 33 papers human+female | $150–400 |
| BPC-157 | Gut, recovery, "systemic repair" | Oral, subcutaneous | ~230 papers, none indexed as clinical trials. The IV safety paper enrolled two people No human data | 5 of 230 papers human+female; none perimenopausal | $60–150 |
| Epitalon | Anti-ageing, cognition | Subcutaneous | Two human trials from one St Petersburg group; neither did cognitive testing. Telomere claims come from cell lines No human data | Participant sex not reported | $50–150 |
Costs are ranges observed across US clinic menus and vendor listings in 2026 — market observations, not figures from any study.
The IV NAD+ drip: the most expensive thing here, and the emptiest
This is the one to understand properly: marketed hardest, priced highest, aimed most precisely at a tired forty-seven-year-old woman.
In April 2026, Ageing Research Reviews published a PRISMA-guided systematic review of NAD+ supplementation covering January 2010 to October 2025. It identified 113 eligible studies: 33 human intervention studies (28 randomised) and 80 rodent studies. Its finding on the intravenous route, quoted exactly:
"No eligible outcomes trials evaluated intravenous or intramuscular NAD+ itself for anti-aging or wellness indications."
outcome trials of intravenous or intramuscular NAD+ for anti-ageing or wellness, out of 113 eligible studies in a 2026 systematic review. The format with the highest price has the least evidence behind it.
The review found one non-randomised IV NMN study contributing short-term safety data, and an IV NAD+ pharmacokinetic pilot with no eligible clinical outcomes, treated as context only. Somebody has measured what the molecule does in blood. Nobody has run a trial asking whether people who get it feel better than people who do not.
That is not a technicality. There is no controlled evidence that an NAD+ infusion improves fatigue, mental clarity, mood or sleep, in anyone, of any age or sex. Nobody has tested this. A drip costing $400 to $800 a session, sold in courses and carrying the ordinary infection risk of any IV line, is priced as though the question were settled. It has not been asked.
In fairness to the review's authors: the first author part-owns a management services organisation serving an aesthetics clinic that does not offer NAD+ infusions. That disclosure points away from their conclusion, not toward it.
Oral NR and NMN: the honest middle case
Oral nicotinamide riboside and nicotinamide mononucleotide are the most defensible things on this page, and they still probably will not do what you are hoping.
Across 33 human intervention studies, oral NR and NMN "consistently demonstrated biochemical target engagement" — they measurably raise NAD-related metabolites — and were "generally well tolerated over weeks to months." That is real, and it is the whole of the good news. The same review describes effects on "functional, metabolic, vascular, and other healthspan-relevant outcomes" as "heterogeneous and often null or endpoint-specific." A separate meta-analysis of NMN pooled 8 randomised trials, 342 adults, 49% female, at 250 to 2,000 mg a day for two to twelve weeks, and found no significant benefit on fasting glucose, insulin, HbA1c, HOMA-IR or lipids. Not a small benefit. No significant benefit.
Raising a biomarker is not the same as feeling better
This is the most useful idea on this page, and it goes well beyond NAD+. A supplement that reliably moves a number in your blood has proven it is absorbed and metabolised. It has not proven the number was the problem, or that moving it changes anything you would notice. "It raises NAD+ levels" is a fact about chemistry. "It will fix your afternoon crash" is a claim about you, and it has not been tested.
If you want to try it anyway: it is cheap, the short-term safety record looks clean, and you will be doing roughly what the trial participants did. Give it eight to twelve weeks, decide honestly whether anything changed, and stop if it did not.
MOTS-c: correlation sold as causation
MOTS-c is a genuine mitochondrial-derived peptide and the basic science is legitimate — the 2018 Cell Metabolism work from Changhan Lee's group at USC, showing it moves to the nucleus and regulates gene expression under metabolic stress, is a real finding in a real journal.
What happens next is a category error vendors have been allowed to make unchallenged. PubMed returns about 146 hits tagged "human," and almost all are observational: they measured how much MOTS-c people already had and correlated it with exercise capacity, diabetes status or age. Lower levels in less healthy people is not evidence that injecting more makes you healthier — the association can run the other way, with fitness driving the peptide. There is no completed trial of administering MOTS-c to a human being. Nobody has tested this.
One Phase 2 is now recruiting: NCT07505745, Hudson Biotech, 120 participants, primary completion estimated February 2027. Worth watching — and worth noticing what it studies. The title is "MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity." Not fatigue. Not cognition. Not menopause.
Semax and Selank: the right drugs studied in the wrong people
Unlike BPC-157 or epitalon, these two are real approved pharmaceuticals — in Russia. No FDA status, and ClinicalTrials.gov holds zero registered Semax studies.
Semax is sold to Western consumers as a nootropic for focus and clarity. The clinical literature is in ischemic stroke rehabilitation. The most-cited trial, published in Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova in 2018, enrolled 110 patients — 43 men and 67 women, mean age 58 — at different stages after a stroke and measured BDNF, motor performance and the Barthel index, which scores how independently someone can wash, dress and feed themselves. That is a study of recovery after brain injury, used to sell a nasal spray to a healthy forty-nine-year-old who loses her train of thought in meetings.
Credit where it is due, and note what it cost
That Semax trial — 67 women out of 110 — is one of the very few studies anywhere in this field where women were the majority. Elsewhere the picture is bleak: ipamorelin's foundational pharmacology came from eight healthy men per dose level, tesamorelin's pivotal trials were 85% male, BPC-157's human IV safety paper enrolled one man and one woman, and epitalon's two trials did not report participant sex at all. The best-represented study of women in the peptide literature is a Russian stroke trial. That should tell you how much of this was designed with you in mind.
Selank is marketed for calm focus and mood. Its trials are in patients with diagnosed anxiety disorders under ICD-10 F40–45, compared with or added to phenazepam, a benzodiazepine not available in the West; two trials, n=60 and n=70, from the same Russian group in the same journal. Nothing in that design tells you what an intranasal peptide does to low mood and mental fatigue in a perimenopausal woman with no anxiety diagnosis. Nobody has tested that; more in our libido and mood guide. Both peptides are typically studied without placebo control or blinding and have never been replicated outside Russia — not an accusation of fraud, a statement about how much weight the results can carry.
Growth hormone peptides for brain fog: there is a trial, and it was negative
Sermorelin, CJC-1295, ipamorelin and tesamorelin all work by pushing growth hormone, and all four are marketed for mental sharpness alongside body composition. When someone tells you GH secretagogues clear brain fog, this is the study to put in front of them.
In 2025, a Phase 2 randomised trial in the Journal of Infectious Diseases tested tesamorelin — the strongest molecule in this class, FDA-approved and properly manufactured — against standard of care for neurocognitive impairment in 73 people with HIV and abdominal obesity, over six months. The tesamorelin group showed a trend toward improvement (mean change 0.146, 95% CI −0.002 to 0.294, P = .060), the standard-of-care group did not, and the between-group difference was not significant (P = .673). IGF-1 rose, and the rise did not correlate with cognitive change. Waist circumference fell more with tesamorelin, by a median 2.7 cm.
The authors are appropriately careful — open-label, no placebo arm, underpowered — and conclude it "suggests no clear benefit." The best-resourced test of this idea, using the best drug in the class, in people selected for measurable impairment, did not find the effect. Everything sold as a cheaper version of that mechanism is on weaker ground, not stronger.
If you take oral estradiol, this category has a specific problem
Oral oestrogen, but not transdermal, blunts growth hormone's action in the liver. This is established endocrinology, not speculation: oral oestrogen induces SOCS-2, which inhibits GH's JAK/STAT signalling, lowering IGF-1 production and fat oxidation. IGF-1 generation testing confirms it, with transdermal reducing the response to a lesser degree.
The consequence: a woman on oral estradiol paying for sermorelin, CJC-1295, ipamorelin or tesamorelin is taking a drug that pharmacologically opposes the mechanism she is paying for. Route matters, and we have not found one clinic protocol or product label that discloses this. Full detail in peptides and HRT.
If you're going to buy, buy from someone who tests
ZestyRat publishes batch COAs and third-party purity results. Given that independent testing has found problems in roughly 30% of peptide vials on the market, this is the part that matters most.
The rest of the shelf, briefly
BPC-157 reaches this page indirectly, via gut healing and "systemic repair." Around 230 PubMed papers, none indexed as clinical trials; a 2025 University of Utah scoping review found only three human pilot studies and called it investigational. The paper circulated as the human IV safety study enrolled two people, and oral BPC-157, the form most commonly sold, has never been studied in humans. Epitalon, marketed for cognition, rests on two human trials from one St Petersburg group across forty years, never replicated, neither doing any cognitive testing.
One regulatory correction, since you will see this claim. In April 2026 the FDA moved BPC-157, TB-500, Semax, Epitalon and MOTS-c off Category 2, its list of substances that may present significant safety risks, and in July 2026 an advisory committee voted in favour of six of seven peptides put to it — against the FDA's own career scientists, who advised against all seven. Sites are now writing that these are "FDA approved" or "no longer banned." Both are false: Category 2 removal only means "no longer flagged as a significant safety risk," an advisory vote is advisory, and legality for compounding requires rulemaking that last time took over two years.
What we would chase first
This is a reordering, not a counsel of despair. The highest-yield moves are unglamorous and mostly cost less than one infusion.
- Get bloods, including ferritin and thyroid. Full blood count, ferritin, TSH, free T4. Eighty per cent of thyroid dysfunction in the NHANES sample was undiagnosed, and iron deficiency with heavy periods is common and correctable.
- Treat the sleep as its own problem, not a symptom. Fixing the night is upstream of fixing the day — our sleep guide covers what has evidence and what does not.
- Have the hormone therapy conversation properly. It has by far the most data in this population, and the timing question is real.
- Resistance training and protein — lean mass, strength and energy are linked, and the loss accelerates here. See muscle and bone.
- Then run one cheap experiment at a time. Oral NR or NMN for eight to twelve weeks is the most defensible thing on the shelf.
Before you buy anything, the purity problem
Independent testing by BioTools found problems in nearly 30% of peptide vials tested: mislabelled, underdosed, overdosed, or contaminated with toxins or bacteria. Co-founder Rina Dukor: "Among the thousands of tests we are doing, we do find either live or dead bacteria in a lot of the vials. That could lead to hospitalizations." That makes every dosing discussion on every peptide site partly hypothetical for anyone buying without third-party testing — and it is why batch COAs matter more, not less, on the cheaper route.
What this costs over a year
IV NAD+ at two sessions a month runs roughly $9,600 to $18,000 a year for an intervention with no outcome trials. Branded tesamorelin is around $37,500, for an indication it is not approved for, on the back of a negative cognition trial. Oral NMN is $480 to $1,080. A ferritin, TSH and free T4 panel is usually under $150 and often free through primary care; iron tablets cost a few dollars a month and have 67 randomised trials behind them.
If weight change is tangled into the fatigue, the one well-supported compound here is a GLP-1, with real perimenopause-specific data — see the weight guide, or the collagen page if skin and hair changed too.
Questions people actually ask
Does an IV NAD+ drip help with perimenopause fatigue?
Nobody has tested this. A 2026 PRISMA systematic review of 113 studies found no eligible outcomes trials of intravenous or intramuscular NAD+ for anti-ageing or wellness in anyone, of any age or sex. There is short-term safety and pharmacokinetic information, but no trial asking whether people who receive it feel better than people who do not. It is the most expensive format in the category and has the least evidence behind it.
Is oral NMN or NR worth trying instead?
It is the most defensible option here, with modest expectations. Across 33 human intervention studies, oral NR and NMN reliably raise NAD+ metabolites and are well tolerated. But effects on functional and metabolic outcomes are heterogeneous and often null, and a meta-analysis of 8 RCTs in 342 adults, 49% of them women, found no significant benefit on glucose, insulin, HbA1c or lipids.
Does MOTS-c help with energy?
Nobody has tested this. There is no completed trial of administering MOTS-c to humans. The studies described as human research are observational: they measured levels people already had and correlated them with fitness, age or diabetes status, which cannot tell you what injecting it does. One Phase 2 began recruiting in February 2026 (NCT07505745), studying insulin sensitivity in prediabetes — not fatigue or cognition.
Will Semax clear brain fog?
The Semax evidence base is ischemic stroke rehabilitation, not cognitive enhancement in healthy people. The most-cited trial enrolled 110 stroke patients, mean age 58, and measured BDNF, motor performance and the Barthel index. Those trials are Russian-language, often without placebo or blinding, and never replicated outside Russia. Nobody has tested Semax for brain fog in midlife women.
Do growth hormone peptides like sermorelin or ipamorelin help memory and focus?
The best test of that idea was negative. A 2025 Phase 2 trial gave tesamorelin, the strongest FDA-approved drug in this class, to 73 people with cognitive impairment for six months. Waist circumference fell, but the between-group difference in neurocognitive performance was not significant (P = .673). Ipamorelin and CJC-1295 have no human trials at all for these outcomes, in either sex.
What should I get tested before spending money on peptides?
A full blood count, ferritin, TSH and free T4, at minimum. Iron deficiency is common in perimenopause because periods often become heavy and unpredictable, and it produces exactly this symptom picture; a Cochrane review of 67 trials in 8,506 menstruating women found daily iron reduces symptomatic fatigue. Thyroid symptoms overlap almost completely with perimenopausal ones and, in US NHANES data, 80% of cases were undiagnosed.
Is perimenopausal brain fog permanent?
In the largest longitudinal study of this, it was not. SWAN followed 2,362 women for four years and found cognitive performance did decline during perimenopause, but rebounded to premenopausal levels afterwards. That does not make it less real while it is happening. It does mean you are not managing a permanent decline — the frame most clinic marketing depends on.
The bottom line
These are the most searched symptoms in the space and the least well served by what is sold for them. The IV NAD+ industry has no outcome trials. MOTS-c has never been administered to a human in a completed study. Semax was tested on stroke patients. The one good trial of a growth hormone drug for cognition came back negative. Not one compound on this page has a completed trial in perimenopausal women.
What is documented: the fatigue is real, it clusters with sleep disruption, cognitive performance measurably dips during the transition and tends to recover after it, and two common, easily checked conditions — low iron and an underactive thyroid — produce the same symptoms and are routinely missed. We would rather tell you that than sell you a drip.
hat than sell you a drip.Sources
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