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Age or Factors Associated with Aging Attenuate Testosterone’s Concentration-Dependent Enhancement of the Regularity of Luteinizing Hormone Secretion in Healthy Men

Endocrine Research Unit (P.Y.L., P.D.R., J.D.V.) and Department of Internal Medicine (P.Y.T.), Mayo Clinic School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Endocrine Research Unit, Mayo Clinic School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

Background: Healthy older men have reduced testosterone (Te) production and frequent, small irregular LH pulses. Which is cause and which is effect are not known.

Rationale: In model systems, frequent and irregular LH pulses reflect attenuated feedback inhibition by Te.

Hypothesis: Factors associated with aging impair negative feedback by Te.

Subjects and Setting: Healthy men at an academic medical center were studied.

Methods: The study used quantification of the regularity of LH release patterns during blockade of gonadal steroidogenesis and graded transdermal Te addback in 18 healthy men aged 18–65 yr.

Results: In the cohort as a whole, stepwise Te repletion repressed LH concentrations (P = 0.001) and enhanced the quantifiable orderliness of LH release patterns (P < 0.001). By regression analysis, age attenuated the capability of increasing Te concentrations to regularize LH secretion patterns (P = 0.019). However, after a fixed GnRH stimulus, the effect of Te on LH regularity was invariant of the age factor (P = 0.16), thus pointing to a hypothalamic locus of impaired Te feedback.

Summary: Aging disrupts the capability of systemic Te concentrations to maintain orderly LH secretion under endogenous, but not exogenous, GnRH drive.

Conclusions: Age or factors associated with increased age reduce negative feedback by any given total Te concentration on hypothalamopituitary GnRH-LH outflow, thus contributing to disorderly LH secretion.

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