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Luteinizing Hormone and Different Genetic Variants, as Indicators of Frailty in Healthy Elderly Men

Department of Internal Medicine III, Erasmus University Rotterdam (A.W.v.d.B., H.A.P.P., F.H.d.J., S.W.J.L.), 3015 GD Rotterdam; and the Julius Center for Patient Oriented Research, Utrecht University Hospital (A.W.v.d.B., D.E.G.), Utrecht, The Netherlands; and the Departments of Physiology (I.T.H.) and Biotechnology (K.S.L.P.), University of Turku, Turku, Finland

Address all correspondence and requests for reprints to: Dr. Anne-wieke W. van den Beld, Department of Internal Medicine III, Room D433, University Hospital Dijkzigt, 40 Dr. Molenwaterplein, 3015 GD Rotterdam, The Netherlands. E-mail address: lamberts{at}inw3.azr.nl

We investigated the possible clinical correlates between the serum LH concentration and characteristics of frailty and determined the presence and concentration of a genetic LH variant in an independently living population of elderly men. After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (aged 73–94 yr) were randomly selected from a population-based sample. Total testosterone (T), sex hormone-binding globulin (SHBG), and leptin were determined by RIA. Non-SHBG-bound T was calculated. LH and the presence of the genetic LH variant were measured using immunofluorometric assays. The characteristics of frailty were leg extensor strength using dynamometry, bone mineral density of total body and proximal femur, and body composition, including lean mass and fat mass, measured by dual energy x-ray absorptiometry. Disability was further assessed by the Modified Health Assessment Questionnaire and by a measure of physical performance.

LH significantly increased with age and inversely correlated with T and non-SHBG-bound T. LH was inversely related to muscle strength and lean mass, and both relations were independent of T. LH was positively related to self-reported disability (Modified Health Assessment Questionnaire); 12.5% of the study population was heterozygous for the LH variant allele. T levels and the degree of frailty were not different in the wild-type LH group compared with the heterozygote LH variant group. A significant positive relation between LH and fat mass as well as leptin was only present in the heterozygote LH variant group.

In conclusion, serum LH levels increases with age in independently living elderly men and correlates inversely with a variety of indicators of frailty. The observed relation between LH and frailty, independent of T, suggests that LH reflects serum androgen activity in a different way than T, possibly reflecting more closely the combined feedback effect of estrogen and androgen. A difference in biological response between the two LH forms is suggested, as a difference exists in the relation between LH and fat mass, respectively, and leptin in the heterozygote LH variant subjects vs. the wild-type LH subjects.

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