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Decision-ready map
• Check whether baseline and error tails differ by sex, pregnancy, anemia
• Validate near decision thresholds (e.g., SpO₂ cutoffs, NIRS rSO₂ alerts)
• Separate physiology shifts from artifact (motion, low perfusion, coupling)
• Use mismatch rule + confirmatory tests for borderline/discordant cases
• Log device model/site + sex + Hb (if available) for local audit
(1) What it is
Sex-based biological differences can change optical signatures used in wearable PPG/SpO₂, tissue spectroscopy (DRS/fluorescence/Raman), and NIRS/tissue oximetry. Mechanistically, sex-linked differences in hemoglobin concentration distributions, microvascular perfusion, and skin structure (layer thickness/collagen affecting scattering) alter absorption and path length assumptions that devices and algorithms rely on. Hormone-linked life stages such as pregnancy or menopause can further shift perfusion and blood volume. The clinical translation question is therefore: before treating an optical number as a decision gate, have you validated that baseline values and error distributions (especially near thresholds) behave similarly across sexes in your real workflow?
(2) Who it helps
This brief supports clinicians and governance leads who use optical outputs to titrate oxygen, trigger escalation, assess perfusion, or interpret NIRS rSO₂ targets. It is most relevant where decisions are threshold-driven (e.g., SpO₂ cutoffs, NIRS desaturation alarms) and where physiology differs by sex or life stage (anemia prevalence, pregnancy, hormone therapy).
(3) What evidence exists
Evidence exists at multiple levels. PPG studies show sex-dependent timing and morphology features, which implies that wearable-derived indices can shift by sex even with identical hardware (Dehghanojamahalleh & Kaya 2019). Large-cohort diffuse reflectance spectroscopy estimates show differences in absorption and reduced scattering coefficients across sex, age, and BMI—directly relevant to DRS inverse models (Jonasson et al. 2023). Microcirculation studies combining DRS and laser Doppler report lower red-blood-cell tissue fraction and total perfusion in females across baseline and workload conditions, affecting signal amplitude and quality (Samils et al. 2023). Quantitative time-resolved NIRS work reports lower baseline prefrontal oxygenated hemoglobin concentration in women while optical properties were similar, showing that baseline oxygenation can be sex-shifted even when scattering is not (Asahara & Matsukawa 2023). Fluorescence spectroscopy of skin shows sex-related differences in autofluorescence intensity, reinforcing that endogenous fluorophore signals are not sex-invariant (Morvová et al. 2018). Finally, WHO’s 2024 guideline formalizes sex- and pregnancy-specific hemoglobin cutoffs—meaning absorption priors differ by population (WHO 2024).
(4) Translation barriers
Clinical translation barriers are usually ‘hidden variables’. Many deployments record sex but not mediators like hemoglobin, pregnancy status, temperature, or vasopressor use, making subgroup differences hard to interpret and fix. Device heterogeneity (wavelengths, geometry, processing) means evidence is model-specific. Motion, low perfusion, or poor contact can dominate variance and can interact with anatomical differences, which can appear as sex effects unless quality controls are explicit. Finally, protocols often treat optical thresholds as hard gates; this is where small baseline shifts become different clinical actions.
(5) Equity/safety checks
Use sex as a biological variable without conflating it with gender identity. Collect only what is necessary for safety/quality improvement and protect privacy. Operationalize safety: define a mismatch rule (symptoms/signs override the number), require repeat/relocate measurement when quality is poor, and specify confirmatory pathways (e.g., ABG/co-oximetry for borderline SpO₂; alternative assessment when NIRS alarms). Audit discrepancies and adverse events stratified by sex and, where feasible, by mediators such as hemoglobin and pregnancy status.
(6) Decision questions
• Which decisions in our pathway are threshold-driven (alerts, escalation, discharge), and how sensitive are they to small shifts?
• Do baseline values or artifact rates differ by sex, pregnancy, or anemia for our device and measurement site?
• What is the mismatch protocol when clinical presentation conflicts with the reading?
• What confirmatory measures exist and when are they triggered?
• Are we logging device model/firmware, site, sex, and key mediators (Hb when available) for audit?
(7) Practical next steps
1) Map the high-stakes thresholds in your workflow (SpO₂ cutoffs, NIRS alarms, perfusion flags).
2) Run a local audit/pilot comparing optical outputs to reference standards (SaO₂/co-oximetry, lab Hb, imaging/clinical endpoints) and stratify by sex and life stage.
3) Update SOPs: mismatch rule, repeat/relocate guidance, and clear confirmatory triggers.
4) Train staff on quality indicators and conditions that increase error (motion, low perfusion, vasopressors).
5) Feed findings into procurement and governance: require vendor sex-stratified evidence and revalidation after updates.
(8) References
Dehghanojamahalleh S, Kaya M. Sex-Related Differences in Photoplethysmography Signals Measured From Finger and Toe. IEEE J Transl Eng Health Med. 2019;7:1900607.
https://doi.org/10.1109/JTEHM.2019.2938506
Charlton PH, Pilt K, Kyriacou PA. Establishing best practices in photoplethysmography signal acquisition and processing. Physiol Meas. 2022;43(5):050301.
https://doi.org/10.1088/1361-6579/ac6cc4
Jonasson H, Fredriksson I, Bergstrand S, et al. Absorption and reduced scattering coefficients in epidermis and dermis from a Swedish cohort study. J Biomed Opt. 2023;28(11):115001.
https://doi.org/10.1117/1.JBO.28.11.115001
Samils L, Henricson J, Strömberg T, Fredriksson I, Iredahl F. Workload and sex effects in comprehensive assessment of cutaneous microcirculation. Microvasc Res. 2023;148:104547.
https://doi.org/10.1016/j.mvr.2023.104547
Asahara R, Matsukawa K. Prefrontal oxygenation is quantified with time-resolved NIRS: effect of sex on baseline oxygenation and response during exercise. Am J Physiol Regul Integr Comp Physiol. 2023;325:R31–R44.
https://doi.org/10.1152/ajpregu.00048.2023
Morvová M Jr, Jeczko P, Šikurová L. Gender differences in the fluorescence of human skin in young healthy adults. Skin Res Technol. 2018;24(4):599–605.
https://doi.org/10.1111/srt.12471
Hung C-H, Chou T-C, Hsu C-K, Tseng S-H. Broadband absorption and reduced scattering spectra of in-vivo skin using δ-P1 approximation. Biomed Opt Express. 2015;6(2):443–456.
https://doi.org/10.1364/BOE.6.000443
Staritzbichler R, Hunold P, Estrela-Lopis I, et al. Raman spectroscopy on blood serum samples of patients with end-stage liver disease. PLoS One. 2021;16(9):e0256045.
https://doi.org/10.1371/journal.pone.0256045
WHO. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. 2024.
https://www.who.int/publications/i/item/9789240088542
NIH Office of Research on Women’s Health. Sex as a Biological Variable (SABV).
https://orwh.od.nih.gov/sex-as-biological-variable
FDA. Evaluation of Sex-Specific Data in Medical Device Clinical Studies (final guidance). March 2025.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-sex-specific-data-medical-device-clinical-studies-guidance-industry-and-food-and-drug