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Secular Decline in Male Testosterone and Sex Hormone Binding Globulin Serum Levels in Danish Population Surveys

Department of Growth and Reproduction (A.-M.A., T.K.J., A.J., J.H.P., N.E.S.), Copenhagen University Hospital, Copenhagen DK-2100, Denmark; Department of Environmental Medicine (T.K.J.), University of Southern Denmark, Odense DK-5230, Denmark; Department of Biostatistics (J.H.P.), University of Copenhagen, DK-2400 Copenhagen, Denmark; and Research Centre for Prevention and Health (T.J.), Glostrup University Hospital, Glostrup DK-2600, Denmark

Address all correspondence and requests for reprints to: Anna-Maria Andersson, Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Sect. GR 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: anna{at}rh.dk.

Context: Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function.

Objective: The objective of the study was to examine whether an age-independent time trend in male serum testosterone levels exists.

Design and Setting: Testosterone and SHBG were analyzed in 5350 male serum samples from four large Danish population surveys conducted in 1982–1983, 1986–1987, 1991–1992, and 1999–2001. Free testosterone levels were calculated. The effects of age, year of birth, and time period on hormone levels were estimated in a general linear statistical model.

Main Outcome Measures: Testosterone, SHBG, and calculated free testosterone levels in Danish men in relation to age, study period, and year of birth were measured.

Results: Serum testosterone levels decreased and SHBG levels increased with increasing age. In addition to this expected age effect, significant secular trends in testosterone and SHBG serum levels were observed in age-matched men with lower levels in the more recently born/studied men. No significant age-independent effect was observed for free testosterone. Adjustment for a concurrent secular increase in body mass index reduced the observed cohort/period-related changes in testosterone, which no longer were significant. The observed cohort/period-related changes in SHBG levels remained significant after adjustment for body mass index.

Conclusions: The observed age-independent changes in SHBG and testosterone may be explained by an initial change in SHBG levels, which subsequently lead to adjustment of testosterone at a lower level to sustain free testosterone levels.