Dataset Information

Testosterone's short-term positive effect on luteinizing-hormone secretory-burst mass and its negative effect on secretory-burst frequency are attenuated in middle-aged men.

ABSTRACT:

Background

Testosterone (T) production declines and LH pulses become smaller and more frequent in middle-aged men. The mechanisms underlying these changes are not known.

Rationale

Small frequent LH pulses in middle-aged men could reflect impaired feedback by systemic T.

Hypothesis

Middle age disrupts negative feedback by T on selected facets of LH secretion.

Subjects and setting

Healthy men were studied at an academic medical center.

Methods

The protocol comprised blockade of gonadal steroidogenesis and graded transdermal addback of T doses of 0, 2.5, 5, or 7.5 mg/d designed to span the castrate to physiological range of T concentrations in each of 23 healthy men ages 19-71 yr (interquartile range, 28-53 yr). We quantified 12-h basal and pulsatile LH secretion (92 time series) using a mathematically justified deconvolution method.

Results

Stepwise T supplementation from the hypogonadal through the eugonadal range repressed mean (12-h) LH concentrations (P = 0.001). By regression analysis, age attenuated the capabilities of increasing T concentrations to 1) increase LH secretory-burst mass (P < 0.0001); and 2) decrease LH secretory-burst frequency (P = 0.025). Age did not alter T's feedback on basal LH secretion, interpulse regularity, the waveform of LH secretory bursts, or the slow half-life of LH.

Conclusion

Middle age impairs both the positive and negative actions of systemic T on pulsatile LH secretion in healthy men, thus potentially explaining earlier inconsistencies in feedback studies based upon single-sample mean LH concentrations. Longitudinal studies will be required to elucidate the precise age dependence of inferred dual feedback failure.

SUBMITTER: Liu PY

PROVIDER: S-EPMC2758726 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Testosterone's short-term positive effect on luteinizing-hormone secretory-burst mass and its negative effect on secretory-burst frequency are attenuated in middle-aged men.

Liu Peter Y PY Takahashi Paul Y PY Roebuck Pamela D PD Bailey Joy N JN Keenan Daniel M DM Veldhuis Johannes D JD

The Journal of clinical endocrinology and metabolism 20090707 10

<h4>Background</h4>Testosterone (T) production declines and LH pulses become smaller and more frequent in middle-aged men. The mechanisms underlying these changes are not known.<h4>Rationale</h4>Small frequent LH pulses in middle-aged men could reflect impaired feedback by systemic T.<h4>Hypothesis</h4>Middle age disrupts negative feedback by T on selected facets of LH secretion.<h4>Subjects and setting</h4>Healthy men were studied at an academic medical center.<h4>Methods</h4>The protocol compr ...[more]

PMID: 19584190

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Project description:BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.

Project description:INTRODUCTION:Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis. AIM:The aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels. METHODS:Basal morning plasma levels of testosterone, LH, and sex hormone-binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-Åsberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis-coupled genes were included. MAIN OUTCOME MEASURES:Testosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis-coupled CpG sites with testosterone and LH levels. RESULTS:LH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis-coupled genes and plasma testosterone or LH levels after multiple testing corrections. CONCLUSIONS:Subtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men. Chatzittofis A, Boström AE, Öberg KG, et al. Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder. Sex Med 2020;8:243-250.

Dataset Information

Testosterone's short-term positive effect on luteinizing-hormone secretory-burst mass and its negative effect on secretory-burst frequency are attenuated in middle-aged men.

Background

Rationale

Hypothesis

Subjects and setting

Methods

Results

Conclusion

Publications

Testosterone's short-term positive effect on luteinizing-hormone secretory-burst mass and its negative effect on secretory-burst frequency are attenuated in middle-aged men.

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