Hypothalamic-Pituitary-Gonadal Axis in Aging Men and Women: Increasing Total Testosterone in Aging Men

Abstract

Background: Aging is associated with variations in hypothalamic-pituitary-gonadal (HPG) axis hormones. However, it is not clear how aging changes these hormones. This study examined the natural alterations in the HPG axis in aging men and women in China. Methods: Data were obtained from our cross-sectional study (SPECT-China) in 16 areas of three provinces in East China between February and June 2014. There were 6,825 subjects selected, including 2,908 men and 3,917 women aged 25-93 years who had no diseases affecting HPG hormones and did not take exogenous supplements. Total testosterone (TT), estradiol (E2), free testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured. Results: In men, the ranges of the 10-90th percentiles for each hormone were as follows: TT, 9.9-23.4 nmol/l; SHBG, 20.6-79.54 nmol/l; E2, 34.84-187 pmol/l. TT values were higher in men aged 25-30 years than in those aged 31-35 years and began to increase progressively at the age of 41-50 years until men reached their eighties. The unadjusted annual age trend (β) was 0.079 nmol/l/year (p < 0.001). A linear regression analysis, after full adjustment for demographic variables, metabolic factors, other hormones, lifestyle and co-morbidities, showed that higher TT levels were still associated with aging (p < 0.05). However, the ratio of TT to LH decreased with age (β = -0.272/year, p < 0.001). E2 and SHBG increased with age (β = 1.774 pmol/l/year and 1.118 nmol/l/year, respectively, p < 0.001). In women, the 10-90th percentile range of E2 was 32.79-565.8 pmol/l. E2 began to decrease at the age of 46-50 years, declined sharply at the age of 51-55 years (β = -5.73 pmol/l/year, p < 0.001) and then stabilized at a low concentration after the age of 55 years. The 10-90th percentile ranges of LH and FSH in men were 2.4-9.2 and 3.4-15.5 IU/l, and in women they were 3-36.6 and 4-89.28 IU/l, respectively. FSH increased by 7.11% per annum in men and by 12.76% per annum in women, but LH increased by only approximately 4.00% per annum in both sexes. Conclusions: The influence of aging on the HPG axis is sex dependent. The pattern of age-related TT was different in Chinese Han men when compared with previous studies in Western populations. TT values increased in aging men, so it is not suitable to estimate the life quality of older Chinese men just based on TT.

Testosterone: Relationships with Metabolic Disorders in Men—An Observational Study from SPECT-China

“…It is interesting that we found TT increased with aging in men in our study, which was elaborately discussed in our previous paper [ 34 ]. T is the major androgen in males and 95% of T is secreted by Leydig cells, most of which adhere with the sex hormone-binding globulin (SHBG).…”

“…Recently, Kelsey et al [ 40 ] analyzed a dataset obtained from 13 studies ( n = 10,097; age range 3–101 years) regardless of ethnicity and found no evidence to support a progressive decline in T in middle-aged and older men. In our population, age-related increases of SHBG and declining clearance by the kidneys could partially explain the pattern of changes in TT with age in Chinese men [ 34 ]. Moreover, we found that the LH levels in Chinese men were positively associated with TT, which suggests that the testicular responsiveness to LH in Chinese men was not decreased to the same degree as in other populations [ 34 ].…”

“…In our population, age-related increases of SHBG and declining clearance by the kidneys could partially explain the pattern of changes in TT with age in Chinese men [ 34 ]. Moreover, we found that the LH levels in Chinese men were positively associated with TT, which suggests that the testicular responsiveness to LH in Chinese men was not decreased to the same degree as in other populations [ 34 ].…”

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study

“…The values of total T measured by the IMMULITE 2000 platform are not reliable when they are at low concentrations, as observed in women. 35 The phases of the menstrual cycle and age of menopause for the women were not available. In addition, the effect of pregnancy on TN formation was considered.…”

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men

“…In a recent cross-sectional study of 2,908 men in China, there was no decrease in total testosterone with age, although sex hormone-binding globulin (SHBG) and serum LH both increased with age, suggesting a degree of compensation for testicular insensitivity and the possibility of a decline in free testosterone levels [4]. Similarly, Kelsey et al [5] did not find any evidence of a further reduction in total testosterone beyond the age of 40 years, although there was increased variability in total testosterone at older ages.…”