Inhibin B as a Serum Marker of Spermatogenesis: Correlation to Differences in Sperm Concentration and Follicle-Stimulating Hormone Levels. A Study of 349 Danish Men1
Tina Kold Jensen,
Anna-Maria Andersson,
Niels Henrik I. Hjollund,
Thomas Scheike,
Henrik Kolstad,
Aleksander Giwercman,
Tine Brink Henriksen,
Erik Ernst,
Jens Peter Bonde,
Jørn Olsen,
Allan McNeilly,
Nigel P. Groome and
Niels E. Skakkebæk
Department of Growth and Reproduction (T.K.J., A.-M.A., A.G.,
N.E.S.), Rigshospitalet, DK-2100 Copenhagen, Denmark; Department of
Occupational Medicine (N.H.I.H., H.K., J.P.B.), University of Aarhus;
Department of Biostatistics (T.S.), University of Copenhagen;
Department of Obstetrics and Gynaecology (T.B.H., E.E.), Aarhus
University Hospital; The Danish Epidemiology Sciences Centre (J.O.),
Aarhus University; Centre for Reproductive Biology (A.M.), Medical
Research Council, Edinburgh; and School of Biological and Molecular
Sciences (N.P.G.), Oxford Brookes University, Oxford
Address all correspondence and requests for reprints to: Tina Kold Jensen, Department of Growth and Reproduction, The National University Hospital, Rigshospitalet, sect. GR 5064, 9-Blegdamsvej, DK-2100 Copenhagen, Denmark.
Recent studies have focused on reproductive health of men inthe
general population. However, semen samples are difficultto obtain
within sampling frames that allow comparisons. Bloodsamples are easier
to obtain than ejaculates. Therefore, serumbiomarkers of
spermatogenesis are of major interest for populationstudies. FSH has
previously been used as a marker of spermatogenesis,although it is
also influenced by the hypothalamus. Serum inhibinB was recently
suggested as a possible, more direct serum markerof spermatogenesis in
men with testicular disorders. In a Danishnationwide collaborative
study, we found an unexpected differencein semen concentration between
two groups of men recruited fromtwo different centres. We, therefore,
analyzed reproductivehormones in blood, including inhibin B, to test
whether theobserved difference in semen concentration was reflected in
thereproductive hormones.
From 1992 to 1995, a total of 430 men, 20–35 yr old, wholived with a
partner and who had not previously attempted toachieve a pregnancy,
were recruited. The couples were enrolledinto the study in one of two
centres (centre A, n = 231; andcentre B, n = 199) when they
discontinued birth control. Atenrollment, they provided a semen sample
(n = 419), and a bloodsample was drawn (n = 349). The semen
analysis was performedin accordance with the WHO 1992 guidelines, and
interlaboratorydifferences were tested. Inhibin B was measured in an
enzymeimmunometric assay, which has previously been described. All
bloodsamples were analyzed in the same laboratory.
Median sperm concentration and the percentage of morphologically
normalspermatozoa were significantly higher among men from centreA
(56.0 mill/mL and 42.5%), compared with men from centre B(44.8
mill/mL and 39%). Men from centre B had a significantlyhigher median
FSH (3.42 IU/L) and a lower inhibin B (186 pg/mL)than men from centre
A (3.21 IU/L and 209 pg/mL). The differencespersisted after control
for potentially confounding variables.A significant correlation was
found between the cubic root-transformedserum FSH and inhibin B levels
(r = -0.61, P < 0.001), betweenthe cubic
root-transformed serum FSH and sperm concentration(r = -0.40,
P < 0.001), and between the cubic root-transformed
inhibinB and sperm concentration (r = 0.38, P
< 0.001). The predictivepower of detecting sperm counts below 20
mill/mL among men who’sinhibin B and FSH both were below 80 pg/mL and
above 10 IU/L,respectively, was 100%.
The unexpected significant difference in semen concentrationbetween
two groups of normal Danish men was probably causedby differences in
sampling procedures in the two centres wherethe men were recruited,
rather than geographical differences.However, similar differences in
serum levels of inhibin B andFSH between centres were found. These
findings suggest thata real difference in spermatogenic potential
between the twogroups of men existed. We suggest that serum inhibin B,
in futurepopulation studies on male reproductive health, may serve as
anew marker of spermatogenesis, in addition to sperm concentrationand
serum FSH.
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