Effects of Aging and Illness on the Pituitary Testicular Axis in Men: Qualitative as Well as Quantitative Changes in Luteinizing Hormone∗

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Abstract
Decreased testicular function occurs as a concomitant of aging in men and is accentuated by the presence of systemic illness. Previous studies identified an intrinsic Leydig cell defect, as reflected by high LH to testosterone ratios and impaired hCG responsiveness in older men. This study questioned whether a qualitative change in LH secretion, as reflected by secretion of LH with an altered ratio of biological to immunological LH (B⁄I) activity, might occur during aging. To examine this possibility, we measured the levels of plasma LH by RIA and rat interstitial cell testosterone bioassay in 67 men, ranging from 20⁄80 yr of age. Mean LH levels measured by immunoassay were similar in healthy men older than 40 yr [11.4 ± 1.0 (= SE) mlU–ml; n = 22] and those younger than 40 yr(9.4 ± 0.6; n ± 18; P < 0.01). Mean bioactive LH levels were also similar (30.0 ± 4.8 vs. 36.7 ± 3.3). LH B⁄I ratios, however, were significantly lower in older men (2.52 ± 0.33) compared to those in younger (4.10 ± 0.34; P < 0.01) men. Regression analysis confirmed the expected inverse relationship of B⁄I ratio with age (r = –0.47; P < 0.01) and plasma testosterone with age (r = −0.35; P < 0.05). Systemic illness independently lowered B⁄I LH ratios. Systemically ill men over 40 yr of age had lower ratios (1.05 ± 0.08; n = 27) than age-matched healthy men (2.52 ± 0.33; n = 22; P < 0.01). The significant changes in B⁄I ratio among subgroups reflected modest changes in LH immunoactivity and larger alterations in LH bioactivity in certain subgroups. These findings indicate that the qualitative nature of LH secreted by the pituitary, as reflected by altered LH B⁄I ratios, may vary as a function of aging and illness in men.