Interest in NAD+ is particularly common among women in their 40s and 50s, often in connection with perimenopause and menopause. This stems from both a broader interest in healthy ageing and a smaller, but gradually growing, body of research regarding NAD+ metabolism, hormonal changes, and women's metabolic health. In this article, we discuss where this interest comes from, what current research on NAD+ and menopause actually shows, how the evidence differs between age groups, and which safety issues are particularly important for women.
Why is NAD+ a frequent topic in the context of women's health?
There are several biological reasons why NAD+ is attracting particular attention from middle-aged women, beyond general wellness and longevity trends.
One study involving 205 people — 91 men and 114 women aged 18 to 83 years — showed sex differences in the plasma NAD+/NADH ratio. In women, the median of this ratio was higher than in men, at 1.33 compared with 1.09, although this difference decreased with age [1].
This result suggests that sex-related differences in this metabolic marker may change over time. However, it comes from an observational study and does not prove that the drop in the NAD+/NADH ratio causes menopause symptoms or that supplementation could correct them.
NAD+ is also linked to pathways involved in hormone production, including estradiol metabolism, and both NAD+ and estradiol levels decrease with age [2].
This potential biological connection has contributed to the growing interest in research on NAD+ and the menopause as a more specific topic within the broader field of NAD+ and ageing research.
NAD+ and the menopause: what do the studies show?
The most direct human study data come from a small open-label pilot study that did not include a placebo group.
In the study, 40 women aged over 35 were administered a combination of 250 mg of nicotinamide riboside and 50 mg of pterostilbene daily for 7 days [2].
Among the 32 participants who reported menopausal symptoms at the start of the study, there was a reduction of at least 50% in the frequency and severity of hot flushes, bloating and sleep disturbances. The study also observed a change in the ratio of oestradiol to oestrone, two forms of oestrogen [2].
Seventy-five per cent of participants reported less frequent hot flushes, whilst 21% reported that their hot flushes had completely disappeared after 7 days [2].
These results are interesting, but the study has significant limitations. It was small, lasted only a week, was open-label, and did not include a placebo group.
Without a placebo group, it is difficult to separate the effects associated with the intervention itself from expectations, the placebo effect, natural fluctuations in symptoms, or changes that may have occurred during the study for other reasons.
The research team also included employees of the company that manufactures and sells the supplement under investigation, which represents a significant potential conflict of interest.
The study's authors themselves pointed out these limitations and noted that larger, independent, randomised, placebo-controlled trials are needed before the results can be considered conclusive [2].
The individual study provides additional information specific to postmenopausal women, although it was not designed to assess menopausal symptoms.
In a randomised, double-blind, placebo-controlled trial, overweight or obese postmenopausal women with prediabetes received 250 mg of NMN daily for 10 weeks [3].
The study showed a significant improvement in muscle insulin sensitivity in the NMN group [3].
This result does not confirm an effect on hot flushes, sleep disturbances, hormonal symptoms or other menopausal features. However, it shows that the NAD+ precursor produced a measurable metabolic effect in a precisely defined population of postmenopausal women.
Overall, the evidence regarding the menopause remains preliminary. The most direct findings concerning symptoms come from a single small, uncontrolled pilot study, while stronger controlled data currently relate to metabolic outcomes in post-menopausal women rather than menopausal symptoms themselves.
Age-related differences: the 40s, 50s and beyond
Women in their 40s are often in perimenopause, a transitional phase during which reproductive hormone levels can fluctuate significantly before menopause occurs.
Research focusing specifically on NAD+ supplementation during the perimenopausal period is still limited. The pilot study described previously included women aged over 35, but was not designed specifically for a clearly defined perimenopausal population [2].
Consequently, the available evidence does not allow us to determine whether perimenopausal women respond differently than younger women or postmenopausal women.
For women aged 50 and over, there is slightly more directly relevant research.
They include both a pilot study on menopausal symptoms [2] and a randomised trial of NMN in postmenopausal women with prediabetes [3].
This age group also aligns more closely with broader research regarding age-related NAD+ decline, which appears to intensify as the years go by [4].
This biological background may explain why NAD+ research focuses more frequently on middle-aged and older people. However, the age-related decline itself does not prove that supplementation yields clinical benefits.
Most general NR and NMN studies included both women and men, without consistently presenting the results separately by sex.
For this reason, a significant portion of the available information regarding tolerance, biomarkers, dose ranges, and general metabolic effects comes from mixed-sex populations rather than from studies specifically designed with women's health in mind.
Dosage and timing of administration in studies involving women
No female-specific dose of the NAD+ precursor has been established that would differ from the doses studied in mixed adult populations.
In a pilot study on menopause, 250 mg of NR combined with 50 mg of pterostilbene per day was used [2]. In a study involving postmenopausal women with prediabetes, 250 mg of NMN per day was used [3].
These doses fall within the lower range of the broader doses investigated in other clinical studies of NAD+ precursors in adults, some of which evaluated NR or NMN at doses reaching 1000–2000 mg per day.
However, using a specific dose in a clinical trial does not mean it is the optimal dose for women in general, nor specifically for menopause symptoms.
It was also not established that the time of day was of particular importance to women.
Current data from human studies does not show that taking it in the morning or evening leads to better outcomes in women, nor that women need a different timing schedule than men.
Available pharmacokinetic literature provides more information on repeated exposure and changes in NAD+ biomarkers than on the ideal time of administration.
Security issues of particular importance to women
Certain safety considerations are of particular importance when NAD+ is discussed in the context of women's health.
Pregnancy and breastfeeding remain the greatest evidence gaps.
No controlled human clinical trials have confirmed the safety of NAD+ precursors during pregnancy or breastfeeding.
The research discussed in this article mainly concerns middle-aged women, during or after the menopause, and should not be interpreted as evidence of safety during pregnancy.
Another unresolved issue is the combination of NAD+ precursors with hormone replacement therapy.
No dedicated clinical trials have been identified that specifically evaluate NR or NMN together with hormone replacement therapy.
This matters because hormone replacement therapy directly alters hormone exposure, whereas the pilot menopause study noted a change in the estradiol-to-estrone ratio following the use of NR combined with pterostilbene [2].
This observation does not prove the existence of a clinically significant interaction, but the lack of direct studies regarding such a combination means that the interaction profile remains insufficiently characterised.
The history of cancer, particularly breast cancer, is another important issue.
In one preclinical study, NR supplementation was associated with an increased number of brain metastases in an animal model of triple-negative breast cancer [5].
This result comes from an animal model and does not confirm a comparable effect in humans.
However, because NAD+ metabolism is closely linked to cancer cell biology, and many general NAD+ studies were not designed to assess cancer recurrence or metastasis, general adult safety data provides limited information for women with active cancer or a history of breast cancer.
Similar caution applies to women with a strong family history of breast cancer, although a family history alone does not mean that an increased risk associated with NAD+ supplementation has been demonstrated.
Overall, the evidence base regarding women's health remains narrow. The most directly relevant human data include a small pilot study on menopausal symptoms and a controlled metabolic study in postmenopausal women with pre-diabetes, whilst several important areas—including interactions with hormone replacement therapy, pregnancy, breastfeeding, long-term impacts on hormones, and cancer-related outcomes—remain insufficiently researched.
Limitations of current evidence
- The pilot study on menopausal symptoms was small-scale, lasted only 7 days, was open-label and did not include a placebo group [2].
- The menopause study involved researchers employed by the company that manufactures the supplement under investigation, which represents a significant potential conflict of interest [2].
- The symptom results therefore require confirmation in larger, independent, randomised, placebo-controlled trials.
- A randomised NMN trial in postmenopausal women focused on insulin sensitivity rather than menopausal symptoms [3].
- No dedicated clinical trials evaluating NAD+ precursors together with hormone replacement therapy have been identified.
- Most general NAD+ studies do not consistently present results separately for women and men.
- A significant proportion of the available safety and dosage data therefore comes from mixed-gender adult populations rather than from studies conducted exclusively in women.
- The reported sex difference in the plasma NAD+/NADH ratio comes from a single observational study and has not been widely replicated [1].
- Research focusing specifically on perimenopausal women is still limited.
- No female-specific dose of the NAD+ precursor has been established, nor has an optimal time of day for taking it.
- Data regarding safety during pregnancy and breastfeeding remain insufficient.
- The discussed risk of breast cancer comes from an animal model and has not been confirmed as a comparable risk in humans [5].
- The long-term impact of NAD+ precursor supplementation on hormone regulation in women remains insufficiently characterised.
Disclaimer
The article is purely educational and summarises scientific research. It does not constitute medical advice or an individual recommendation for or against NAD+ supplementation.
NAD+ and its precursors should not be presented as FDA- or EMA-approved treatments for menopause symptoms, hormonal disorders, metabolic diseases, cancer, fertility issues or other conditions concerning women's health, unless referring to a specific approved medicinal product and indication.
Available evidence regarding women's health remains limited and varies depending on age, menopausal status, baseline metabolic status, study design, the specific NAD+ precursor, dose and the outcome assessed.
The results of small pilot studies, studies involving mixed populations of women and men, or animal models should not be interpreted as evidence of clinical benefit or safety for women in general.
References
[1] Schwarzmann, L., Pliquett, R. U., Simm, A., & Bartling, B. (2021). Sex-related differences in human plasma NAD+/NADH levels depend on age. Bioscience Reports, 41(1), BSR20200340. https://doi.org/10.1042/BSR20200340
[2] Holmes, H. E., Srivastava, K., Scalici, J. M., Dhuguru, J., Shea, A. E., Migaud, M. E., & Dellinger, R. W. (2026). Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: An open-label, pilot clinical trial. Frontiers in Aging, 7, 1773667. https://doi.org/10.3389/fragi.2026.1773667
[3] Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S.-I., & Klein, S. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224–1229. https://doi.org/10.1126/science.abe9985
[4] Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., & Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127–1139. https://doi.org/10.1016/j.cmet.2016.05.006
[5] Maric, T., Bazhin, A., Khodakivskyi, P., Mikhaylov, G., Solodnikova, E., Yevtodiyenko, A., Giordano Attianese, G. M. P., Coukos, G., Irving, M., Joffraud, M., Cantó, C., & Goun, E. (2023). A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosensors and Bioelectronics, 222, 114826. https://doi.org/10.1016/j.bios.2022.114826