Health-related physical fitness and quality of life in men with congenital hypogonadotropic hypogonadism.

Congenital hypogonadotropic hypogonadism is a rare disorder characterised by impaired testosterone secretion since birth, and represents a valuable model for studying the effects of testosterone replacement therapy (TRT) in humans. This cross-sectional study aimed to investigate all health-related physical fitness (HRPF) components and quality of life in a series of eight men with hypogonadotropic hypogonadism under regular TRT. The study group was compared to a control group of 16 healthy subjects paired for age, body mass index and physical activity. Body composition, aerobic capacity, muscular strength and endurance, and joint flexibility were evaluated in two different 7-day interval time points, based on the pharmacokinetics of testosterone in the hypogonadal group. Quality of life was assessed by the WHOQOL-brief questionnaire. Both groups had similar performances in all HRPF components evaluated, independently of plasma testosterone levels (p > .05). Quality of life was also similar in the four domains analysed (p > .05). The results of this pilot study suggest that regular testosterone replacement was efficient in providing HRPF and quality of life in a series of congenitally hypogonadal men to levels like those observed in healthy men. In addition, acute fluctuations in plasma testosterone did not correlate with changes in muscle strength and endurance.

Health-related physical fitness in middle-aged men with and without metabolic syndrome.

AIM: Objective of the study was to compare health-related physical fitness (HRPF) between men with and without metabolic syndrome (MS) and to evaluate the risk of being unfit associated with MS. METHODS: The study included 79 middle-aged civil servant men (46.2 ± 8.4 years) who underwent a physical annual evaluation to access HRPF as follows: BMI; cardiorespiratory fitness by Ebbeling test (VO(2max)), flexibility by sit-and-reach test (SRT), muscular strength by handgrip test (HDT) and vertical jump test (VJT) and muscular endurance by push-up test (PUT). MS was defined by the ATP III (2009) criteria. Comparisons were performed with the Mann-Whitney test and univariate General Linear Model was used for age-adjusted analysis. Odds ratio (OR-95% CI) was calculated to evaluate the odds of the MS group to be unfit and the odds of having MS according to the HRPF levels. RESULTS: Nineteen volunteers (24.1%) with MS were identified. After age adjustment, VO(2max) and BMI were significantly different in the MS group than in the non-MS group: 39.7 vs. 44.8 mL.kg-1.min⁻¹ and 29.4 vs. 25.7 kg/m² (P<0.05) and PUT tended to be lower in men with MS (16 vs. 21 repetition; P=0.06). Blood pressure ≥ 130/85 mmHg was the most prevalent MS criterion, associated with lower VO(max) (40.3 vs. 45.6 mL.kg⁻¹.min⁻¹) and SRT (22.2 vs. 28 cm), and higher BMI (28.9 vs. 25.3 kg/m²) (P<0.05). The OR of being unfit for VO2max and BMI in the MS group were 6.5 (1.9-22.6) and 5.7 (1.2-26.8). The odds of having MS increased by 23% (3-45%) for each BMI unit increase, irrespectively to age. CONCLUSION: MS group showed lower VO(2max), PUT, higher BMI and a greater risk of being unfit compared to the non-MS one. The proportion of MS was 3.4-fold higher within those with lower VO(2max). Small reductions on BMI may produce significant decrease on MS prevalence.

Mutational analysis of the genes encoding RFamide-related peptide-3, the human orthologue of gonadotrophin-inhibitory hormone, and its receptor (GPR147) in patients with gonadotrophin-releasing hormone-dependent pubertal disorders.

RFamide-related peptide-3 (RFRP-3), the orthologue of avian gonadotrophin-inhibitory hormone, and its receptor GPR147 have been recently identified in the human hypothalamus, and their roles in the regulation of reproductive axis has been studied. The present study aimed to investigate whether the presence of variants in the genes encoding human RFRP-3 (NPVF gene) and its receptor, GPR147 (NPFFR1 gene), is associated with the occurrence of gonadotrophin-releasing hormone-dependent pubertal disorders. Seventy-eight patients with idiopathic central precocious puberty (CPP) and 51 with normosmic isolated hypogonadotrophic hypogonadism (nIHH) were investigated. Fifty healthy subjects comprised the control group. The coding sequences of the NPVF and NPFFR1 genes were amplified and sequenced. Odds ratios (OR) were used to estimate the likelihood of CPP or nIHH in the presence of the described polymorphisms. All such polymorphisms have already been registered in the National Center for Biotechnology Information database. A three-nucleotide in frame deletion was identified in the NPVF gene (p.I71_K72), with a smaller proportion in the CPP (5%) compared to the nIHH (15%) group (P = 0.06). This results in the deletion of the isoleucine at position 71, adjacent to lysine at an endoproteolytic cleavage site of the precursor peptide. This polymorphism was associated with a lower risk of CPP (OR = 0.33; 95% confidence interval = 0.08-0.88); interestingly, only two men with nIHH were homozygotes for this variant. A total of five missense polymorphisms were found in the NPFFR1 gene, which encodes GPR147, with similar frequencies among groups and no association with pubertal timing. Our data suggest that RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out and deserves further investigation.

Effects of metformin and short-term lifestyle modification on the improvement of male hypogonadism associated with metabolic syndrome.

AIM: The metabolic syndrome is associated with male hypogonadism, but specific studies about the mechanisms and treatment of the testosterone deficit are scanty. The aim of this study was to evaluate the effects of metformin combined with diet and physical activity on the testicular function of men with metabolic syndrome. METHODS: Thirty-five men (40.4 ± 13.3 years old) with metabolic syndrome were evaluated before and after a four-month period of therapy with metformin 850 mg twice daily, associated with a balanced normocaloric diet and subtle improvement in physical activity. The subjects were divided in two groups: 21 males with normal plasma testosterone levels (≥ 300 ng/dL) and 14 males with low plasma testosterone levels (< 300 ng/dL). RESULTS: There was a significant decrease in fasting insulin levels and HOMA-IR after treatment (P = 0.01 and P = 0.06), which was more pronounced in the hypogonadic group (for the effect of absence or presence of hypogonadism, P = 0.04). The mean total and free testosterone levels increased significantly after treatment in both groups, similarly. The increase in FSH levels was more pronounced in the hypogonadic group than in the eugonadic group. CONCLUSION: In this series of males with metabolic syndrome, treatment with metformin associated with healthy dietary modifications and a mild physical activity increment resulted in significant improvement of insulin sensitivity and increase in total and free testosterone levels, regardless of the presence of hypogonadism.