Why is there a difference in the hemoglobin levels of men women and children?

Answer 1

In their recent Blood correspondence, Murphy et al. postulate that the reason that men and woman have different red cell masses despite similar erythropoietin levels is due to physiologic modulation of the Fahraeus-Lindqvist effect by age, gender and red cell count 1. This hypothesis is based on the authors' observation that the difference between the venous and finger capillary hemoglobin concentrations was inversely proportional to the capillary hemoglobin level and parallel for both sexes. However, the mechanism for preferentially improved modulation of tissue oxygen delivery in women on this basis remains to be explained, particularly since the differences between the venous and finger capillary hemoglobin concentrations in men and women disappear with age even though erythropoietin production does not change with age 2. I would assert to the contrary that the explanation for differences in the red cell mass between men and women lies elsewhere and that the Fahraeus-Lindqvist effect is unlikely to be involved. First, Murphy et al. conflate the venous-capillary hemoglobin concentration difference with the so-called f-cell ratio, which is calculated by dividing the total body venous hematocrit, derived from direct measurement of the red cell mass and plasma volume, by the peripheral venous hematocrit. Importantly, unlike the authors' observed differences between the venous and capillary hemoglobin concentrations, the f-cell ratio is independent of the actual venous hematocrit and gender. Second, it is also highly unlikely that even a peripheral capillary hematocrit could serve as a surrogate for the directly measured total body hematocrit because of the wide variation in the hematocrit in various body tissues 3. Third, the hemoglobin level is a measure of something entirely different than the hematocrit and cannot be used as a substitute as the authors infer. Fourth, it is also formally possible that the authors' age-related data simply represent a regression towards the mean because as men age their hemoglobin level falls, while the female hemoglobin level does not change appreciably 4.Thus, contrary to the authors' data, the difference between the venous and capillary hemoglobin concentrations in men should have risen with age, not fallen, and the difference for the women should have remained constant unless anemia ensued. But by far the most important explanation for the difference in the hemoglobin level between normal men and women despite similar serum erythropoietin levels, is male androgen production, which the authors reject. However, when men were chemically castrated, their serum erythropoietin levels remained unchanged but their hemoglobin levels fell and when testosterone production was restored, the hemoglobin level recovered without a change in the serum erythropoietin level 5. As a corollary, when women were given testosterone, their hemoglobin levels increased. Thus, the difference between men and women with respect to hemoglobin and serum erythropoietin levels can be simply explained on a hormonal basis without having to invoke changes in tissue capillary blood flow, particularly when there is no evidence that peripheral capillary blood flow recapitulates that in the kidney where the bulk of erythropoietin is produced in the adult...