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