Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone

LʼAbbate, Antonio; Wu, Frederick C. W.; O’Neill, Terence W; Pye, Stephen R.; Ahern, Tomás; Laurent, Michaël; Huhtaniemi, Ilpo; Lean, Michael E. J.; Keevil, Brian; Rastrelli, Giulia; Forti, Gianni; Bártfai, György; Casanueva, Felipe F.; Kula, Krzysztof; Punab, Margus; Giwercman, Aleksander; Claessens, Frank; Decallonne, Brigitte; Vanderschueren, Dirk

doi:10.1210/jc.2015-4106

Cited by 139 publications

(100 citation statements)

References 45 publications

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“…More recently, the CHAMP study showed a decline of serum total T around 2% per year 81 ( Table 3). The EMAS results have confirmed, in the last years, the data concerning the progressive decline in aging men of serum total T, free T, and E 2 82 , as well as those concerning the rise of SHBG with aging 83 (Table 3). The CHAMP recently replicated these results except for a surprising increase of E 2 81 (Table 3).…”

Section: Risk Increasesupporting

confidence: 74%

“…4,8,82,83,89,90 However, according to a more recent analysis, total serum T levels seem to be quite stable until the age of 70 years, after that there would be a progressive, significant decline, while the bioavailable serum T seems to decline more linearly with aging. 79 In line with other studies, 3,8,89,90 in the Tromsø study the investigation of hormonal changes with aging resulted in the finding of lower serum T levels and higher gonadotropins levels in older men 60 (Table 3), even though the measurement of gonadotropins in aging men is scarcely helpful in predicting the future development of hypogonadism 91 (Table 3).…”

Section: Consequences Of Hormonal Changes Related To Male Agingmentioning

confidence: 99%

“…47 In particular, in the EMAS study lower serum free T levels have been more strongly associated with severe sexual dysfunction (such as increased erectile dysfunction and lower masturbation frequency). 83,92 Less data are available on sexual function in the BLSA and MrOS studies 97 (Table 3). Overweight and obesity are strongly associated to the decline of both total serum T and SHBG in several studies such as the MMAS, 37 and diabetes 107 (Table 3).…”

Section: Main Outcomes Of Cohort Studiesmentioning

confidence: 99%

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Aging and sex hormones in males

2016

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Several large cohort studies have disclosed the trajectories of sex steroids changes overtime in men and their clinical significance. In men the slow, physiological decline of serum testosterone (T) with advancing age overlaps with the clinical condition of overt, pathological hypogonadism. In addition, the increasing number of comorbidities, together with the high prevalence of chronic diseases, all further contribute to the decrease of serum T concentrations in the aging male. For all these reasons both the diagnosis of late-onset hypogonadism (LOH) in men and the decision about starting or not T replacement treatment remain challenging. At present, the biochemical finding of T deficiency alone is not sufficient for diagnosing hypogonadism in older men. Coupling hypogonadal symptoms with documented low serum T represents the best strategy to refine the diagnosis of hypogonadism in older men and to avoid unnecessary treatments.

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Section: Risk Increasesupporting

confidence: 74%

Section: Consequences Of Hormonal Changes Related To Male Agingmentioning

confidence: 99%

Section: Main Outcomes Of Cohort Studiesmentioning

confidence: 99%

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Aging and sex hormones in males

2016

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“…• A TT level <8 nmol/L or a free testosterone (FT) level <0.180 nmol/L usually requires therapy 4,6,21 • A TT level >12 nmol/L or a FT >0.225 nmol/L does not require therapy 4,6,21 • Levels between 8-12 nmol/L may require a trial of testosterone therapy (minimum six months), based on symptoms 4,6,21 • A FT level <0.225 nmol/L provides supportive evidence for TT 22 Furthermore:…”

Section: Box 2 Thresholds For Testosterone Therapy (Tt)mentioning

confidence: 99%

BSSM guidelines on testosterone deficiency: a summary

Hackett

Kirby

2018

Trends Urol & Men's Health

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“…Furthermore, longitudinal studies have clearly documented the decline in testosterone with aging [1,52]. Testosterone levels decrease steadily and continuously during aging, resulting in late-onset hypogonadism (LOH).…”

Section: Androgen-deprivation Therapy Late-onset Hypogonadism (Loh) mentioning

confidence: 99%

The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

Takayama

2017

Endocr J

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Abstract. Hormonal alterations with aging contribute to the pathogenesis of several diseases. Androgens mediate their effects predominantly through binding to the androgen receptor (AR), a member of the ligand-dependent nuclear receptor superfamily. By androgen treatment, AR is recruited to specific genomic loci dependent on tissue specific pioneer factors to regulate target gene expression. Recent studies have revealed the epigenetic modulation by AR-associated histone modifiers and the roles of non-coding RNAs in AR signaling. Androgens are male sex hormone to induce differentiation of the male reproductive system required for the establishment of adult sexual function. As shown by several reports using AR knockout mouse models, androgens also have anabolic functions in several tissues such as bone, muscle and central nervous systems. Notably, AR has a central role in prostate cancer progression. Prostate cancer is the most frequently diagnosed cancer in men. Androgen-deprivation therapy for cancer patients and decline of serum androgen with aging promote several diseases associated with aging and quality of life of older men such as osteoporosis, sarcopenia and dementia. Thus, androgen replacement therapy for treating late onset hypogonadism (LOH) or new epigenetic regulators have the potential to overcome the symptoms caused by the low androgen, although adverse effects for cardiovascular diseases have been reported. Given the increasing longevity and consequent rise of age-related diseases and prostate cancer patients, a more understanding of the AR actions in male health remains a high research priority.

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Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone

Abstract: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms; therefore, cFT levels should be assessed in men with suspected hypogonadal symptoms.

Cited by 139 publications

References 45 publications

Aging and sex hormones in males

Aging and sex hormones in males

BSSM guidelines on testosterone deficiency: a summary

The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

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