MENOPAUSE is a biological transition that generally takes place in women between 45 and 55 years of age and involves a substantial reduction in estrogen and progesterone levels. Reduced estrogen is associated with changes in skin physiology, including dryness, thinning, loss of elasticity, and increased wrinkle formation. As a result, skin aging often accelerates after menopause.
The stratum corneum (SC), the outermost layer of the skin, functions as a protective barrier that limits transepidermal water loss (TEWL) and is continuously renewed through desquamation, a process typically lasting 28-40 days and influenced by many genetic and environmental factors. Niacinamide, a vitamin B3 derivative, is commonly used in skincare to support skin barrier function and improve skin hydration, tone, and texture, yet its effects on post-menopausal (PoM) skin condition and on post-menopausal skin lipidome are not well characterized. To address this gap, Imfeld and colleagues used tape stripping to sample the SC and compare molecular and microbial differences between pre-menopausal (PreM) and PoM facial skin, while also evaluating the potential benefits of niacinamide in PoM subjects.
At baseline, skin hydration levels were comparable across all study groups. After placebo treatment with niacinamide being replaced with water, only modest improvements were observed, with hydration increasing by 6% in the premenopausal group and 11% in the post-menopausal group. In contrast, the niacinamide formulation produced a markedly greater effect, increasing hydration by 23% in nearly all participants. Baseline TEWL was slightly lower in the PoM group, though not significantly. Placebo treatment led to minor TEWL reductions, whereas niacinamide treatment resulted in a substantial 19% decrease in TEWL, observed in most participants.
Skin hydration and barrier measurements in pre-menopausal (PreM) and post-menopausal (PoM) skin at baseline and after treatment. Treatment indicates application of 5% niacinamide. Corneometer units measure skin hydration level. For corneometer readings, *** p < 0.0001, ** p < 0.001. For TEWL, ***p < 0.0001. d0, day 0; d28, day 28; TEWL, transepidermal water loss.
Imfeld et al., IFSCC magazine 2025, ifscc.org/magazines/volume-28-no-1
Niacinamide and its metabolites were detected at high levels only in post-menopausal (PoM) skin treated with the niacinamide product at Day 28 and strongly correlated with improved barrier function, showing a strong negative correlation with TEWL and a positive correlation with hydration in high responders.
Metabolomic analyses showed that niacinamide induced measurable metabolic changes in PoM skin, with multivariate and univariate analyses identifying treatment-associated metabolites despite generally subtle differences between pre- and post-menopausal skin. PoM skin exhibited higher levels of amino acids and histidine catabolism metabolites, along with reduced cytosine levels and decreased long-chain unsaturated fatty acids. Niacinamide partially normalized these age-related changes by reducing histidine pathway metabolites, lowering proline-related compounds, and fully restoring cytosine levels, while having limited effects on free fatty acids.
Lipidomics analysis supports comprehensive measurement of hundreds and thousands of individual lipid molecules from biological samples. In this study, lipidomic profiling of tape-strip samples was used to characterize skin surface lipids before and after treatment in PoM cohort, and PreM cohort without treatment, allowing both global lipid trends and molecular-level changes to be examined.
At baseline (pre-treatment), pre-menopausal (PreM) skin showed slightly lower total lipid levels compared to post-menopausal (PoM) skin. Because ceramides are key regulators of skin barrier function and hydration, subsequent analyses focused specifically on this lipid class.
Using lipidomics analysis, 297 distinct ceramide species were identified in at least 70% of samples, highlighting the analytical depth of this approach. Across all groups, total ceramide levels declined over the 28-day study period which could be explained by the seasonal effect as the study took place from August till November. However, this decrease was significantly less pronounced in the niacinamide-treated PoM group, which retained higher ceramide levels than placebo-treated PoM skin at study end.
Ceramide subclasses change upon niacinamide treatment compared to placebo (pmol lipid per µg protein). Sum of the molar amounts of lipid per protein (pmol lipid per µg protein) within each ceramide subclass of the PoM placebo group as compared to the PoM niacinamide-treated group after treatment. * p < 0.05.
Imfeld et al., IFSCC magazine 2025, ifscc.org/magazines/volume-28-no-1
Further mol% ceramide lipid subclass (i.e. the molar fraction of the classes of total ceramides) analysis revealed that post-menopause skin changes were associated with reduced non-hydroxy-sphingosines (NS), non-hydroxy-dihydrosphingosine (NdS), AS, EOS, and EOH ceramides and increased AH, AP, NP, and AdS compared with PreM skin. Niacinamide treatment partially reversed these shifts, increasing NS, NdS, AS, and EOS while reducing non-hydroxy-6-hydroxyshingosines (NH), AP, NP, and AdS relative to placebo.
Selected ceramide subclasses change upon niacinamide treatment compared to placebo in pre-menopausal and post-menopausal skin (% of molar amount). The molar ceramide amounts as fraction of the total ceramides is shown for PreM, PoM, and PoM treated groups. * p < 0.05.
Imfeld et al., IFSCC magazine 2025, ifscc.org/magazines/volume-28-no-1
Several ceramide classes and species showed positive correlations with skin hydration, particularly in PreM skin, whereas these associations were weaker in PoM skin. In contrast, sebum lipid classes showed no meaningful differences between groups and were largely unaffected by treatment.
This study demonstrates how lipidomics supports research on treatment-responsive molecular lipid changes. Niacinamide selectively preserved ceramide levels and remodeled ceramide subclass composition in post-menopausal skin, shifting the lipid profile toward a healthier, more pre-menopausal-like state associated with improved barrier function and hydration. These findings highlight lipidomics as a powerful tool for understanding skin biology and for evaluating targeted interventions that act through lipid-mediated mechanisms.
Lipotype Skin Lipidomics technology supports cosmetic scientists and dermatology professionals in developing and optimizing skincare products, such as moisturizers, by enabling precise measurement of how different formulations affect different types of skin. Through comprehensive lipid profiling, researchers get detailed data covering skin lipid composition and product-induced changes, helping drive the creation of more effective and innovative skincare solutions in health and disease, such as atopic dermatitis and eczema.
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