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Luteinizing hormone and different genetic variants, as indicators of frailty in healthy elderly men
A van den Beld1, I T Huhtaniemi, K S Pettersson
1Department of Internal Medicine III, Erasmus University Rotterdam, The Netherlands. lamberts@inw3.azr.nl
Insights
Serum Luteinizing Hormone (LH) increases with age in elderly men and correlates with frailty indicators, independent of testosterone. A genetic LH variant may influence fat mass and leptin relationships.
Area of Science:
- Endocrinology
- Gerontology
- Genetics
Background:
- Serum Luteinizing Hormone (LH) levels and their relationship with aging and frailty in men are not fully understood.
- A genetic variant of LH may influence its biological activity and clinical correlates.
Purpose of the Study:
- To investigate the association between serum LH concentration and frailty characteristics in elderly men.
- To determine the prevalence and impact of a genetic LH variant on frailty and hormonal profiles.
Main Methods:
- Cross-sectional study of 403 healthy elderly men (73-94 years).
- Measurements included serum LH, testosterone (T), sex hormone-binding globulin (SHBG), leptin, leg strength, bone density, body composition (DXA), and disability assessments.
- Genetic analysis for an LH variant was performed.
Main Results:
- Serum LH increased with age and inversely correlated with T, non-SHBG-bound T, muscle strength, and lean mass, independent of T.
- Higher LH was associated with increased self-reported disability.
- 12.5% of men were heterozygous for the LH variant; no differences in T or frailty were observed between variant and wild-type groups.
- A positive relationship between LH, fat mass, and leptin was found only in heterozygote LH variant carriers.
Conclusions:
- Serum LH increases with age in elderly men and is inversely related to frailty indicators, suggesting it reflects androgen activity differently than T.
- The LH variant may alter biological responses, influencing the relationship between LH, fat mass, and leptin.
Abstract:
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.