Interest in NAD+ is particularly common among women in their 40s and 50s, often in connection with the perimenopause and menopause period. This stems from both a broader interest in healthy aging and a smaller, but gradually growing, body of research on 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 relevant for women.
Why is NAD+ a frequent topic in the context of women's health?
There are several biological reasons why NAD+ attracts special attention from middle-aged women, beyond general wellness and longevity trends.
One study involving 205 participants—91 men and 114 women aged 18 to 83—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 to 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 decline 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 link has contributed to the growing interest in research on NAD+ and menopause as a more specific topic within the broader field of NAD+ and aging research.
NAD+ and menopause: what do the studies show?
The most direct human data comes from a small, open-label pilot study that did not include a placebo group.
In the study, 40 women over the age of 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 menopause-related symptoms at the start of the study, there was a reduction of at least 50% in the frequency and severity of hot flashes, bloating, and sleep disturbances. The study also observed a change in the ratio of estradiol to estrone, two forms of estrogen [2].
Seventy-five percent of the participants reported less frequent hot flashes, while 21% reported that their hot flashes had completely subsided 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 of the intervention itself from expectations, the placebo effect, natural fluctuations in symptoms, or changes that might have occurred during the study for other reasons.
The research team also included employees of the company that manufactures and sells the studied supplement, which represents a significant potential conflict of interest.
The study authors themselves pointed out these limitations and noted that larger, independent, randomized, placebo-controlled trials are needed before the results can be considered conclusive [2].
The individual study provides additional information specifically regarding postmenopausal women, although it was not designed to assess menopausal symptoms.
In a randomized, double-blind, placebo-controlled study, 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 flashes, sleep disturbances, hormonal symptoms, or other menopausal features. However, it shows that the NAD+ precursor produced a measurable metabolic effect in a specifically defined population of postmenopausal women.
Overall, the evidence regarding menopause remains preliminary. The most direct results regarding symptoms come from a single small, uncontrolled pilot study, while stronger controlled data currently relate to metabolic outcomes in postmenopausal women rather than menopause 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 over the age of 35, but it was not specifically designed for a clearly defined perimenopausal population [2].
As a result, the available evidence does not allow to determine whether perimenopausal women react differently than younger women or postmenopausal women.
For women aged 50 and older, there is somewhat more directly relevant research.
They include both a pilot study on menopausal symptoms [2] and a randomized NMN trial 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 with advancing years [4].
This biological background may explain why NAD+ research focuses more frequently on middle-aged and older individuals. However, the age-related decline itself does not prove that supplementation provides clinical benefits.
Most general NR and NMN studies included both women and men, without consistently presenting 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 designed specifically with women's health in mind.
Dosage and timing of administration in studies on women
No sex-specific dose of the NAD+ precursor has been established that differs from the doses studied in mixed adult populations.
In a pilot study on menopause, 250 mg of NR along with 50 mg of pterostilbene per day was used [2]. In a study on postmenopausal women with prediabetes, 250 mg of NMN per day was used [3].
These doses are in the lower range of the broader doses evaluated in other preclinical studies of NAD+ precursors in adults, some of which evaluated NR or NMN at doses reaching 1000–2000 mg per day.
However, the use of a specific dose in a clinical trial does not mean that it is the optimal dose for women in general, nor specifically for menopause symptoms.
It has also not been established that the time of day is of particular importance to women.
Current human study data do not show that taking it in the morning or evening leads to better outcomes in women, nor that women require 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
Some safety issues are of particular importance when NAD+ is discussed in the context of women's health.
Pregnancy and breastfeeding remain the biggest evidence gaps.
No controlled clinical trials in humans have confirmed the safety of NAD+ precursors during pregnancy or breastfeeding.
The studies discussed in this article focus primarily on middle-aged women, during or after 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 studies specifically evaluating NR or NMN together with hormone replacement therapy have been identified.
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 administration of NR along 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 characterized.
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 evaluate cancer recurrence or metastasis, general adult safety data provide 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 family history alone does not mean an increased risk associated with NAD+ supplementation has been demonstrated.
Generally, the evidence base regarding women's health remains narrow. The most directly relevant human study data include a small pilot study on menopausal symptoms and a controlled metabolic study in postmenopausal women with prediabetes, while several key areas—including interactions with hormone replacement therapy, pregnancy, breastfeeding, long-term impact on hormones, and cancer-related outcomes—remain insufficiently studied.
Limitations of current evidence
- The pilot study on menopause symptoms was small, lasted only 7 days, was open-label, and did not include a placebo group [2].
- In the study on menopause, researchers employed by the company manufacturing the investigated supplement participated, which constitutes a significant potential conflict of interest [2].
- The symptom results therefore require confirmation in larger, independent, randomized, placebo-controlled trials.
- A randomized 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 portion of the available safety and dosing 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 remains limited.
- No female-specific dose of the NAD+ precursor has been established, nor has the optimal time of day for taking it.
- Safety data regarding 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 characterized.
Disclaimer
The article is purely educational and summarizes 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 by age, menopausal status, baseline metabolic state, study design, specific NAD+ precursor, dosage, and evaluated outcome.
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