Male Hypogonadism: A Review

Marcelli, Marco; Mediwala, Sanjay

doi:10.1136/jim-2019-001233

Cited by 14 publications

(18 citation statements)

References 268 publications

(448 reference statements)

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Section: Discussionsupporting

confidence: 69%

“…On the other hand, the majority of firefighters in this cohort were overweight or obese and obesity is the chronic condition associated with the most significant decline in testosterone levels in men. 21,36,37 In our study, as in the general population, a significantly higher BMI was found in Presenting the quartiles, analysis improves external validity of the data, by better reflecting the overall distribution of TT levels among all men of the study population. 6 In contrast, the categorization analysis has the advantage of increasing intragroup specificity by clustering men based on a similar hormonal and/or clinical profile, providing a further description of a multifactorial, complex biological phenomenon.…”

Section: Discussionsupporting

confidence: 59%

“…Nevertheless, our study population was composed mainly of young and middle‐aged firefighters; thus, aging was an improbable independent factor impacting serum testosterone levels. On the other hand, the majority of firefighters in this cohort were overweight or obese and obesity is the chronic condition associated with the most significant decline in testosterone levels in men 21,36,37 . In our study, as in the general population, a significantly higher BMI was found in both the low‐TT and borderline‐low TT groups.…”

Section: Discussionsupporting

confidence: 46%

“…In the low testosterone group, other factors stimulating hypertrophy may override this adjustment-such factors may include aging, obesity, hypertension, and diabetes which are known to promote myocardial hypertrophy. Borderline testosterone levels may occur in the absence of clinically significant symptoms of testosterone deficiency, 7,37 and it is possibly related to deleterious effects on the heart. This suggests a potential condition of preclinical or subclinical testosterone insufficiency that may prove to be an important window for detecting, and possibly managing, mild homeostatic derangements, similar to what happens in pre-diabetes.…”

Section: Lvwt (Cm)mentioning

confidence: 99%

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Borderline‐low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis

et al. 2020

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Background Low endogenous testosterone has been associated with increased cardiovascular risk in men. Objectives To determine the prevalence of low serum testosterone level (TT) in a cohort of male US career firefighters and to examine its relation with left ventricular wall thickness (LVWT). Materials and Methods We conducted a cross‐sectional study among 341 career firefighters, (age: 37.5 ± 10.3 years; BMI: 28.9 ± 4.5 kg/m2), who underwent an occupational medical screening examination. TT quartiles were determined, and LVWT distribution among them was plotted. Then, TT values were categorized as low (<264 ng/dL), borderline (264‐399 ng/dL), reference range (400‐916 ng/dL), and high (>916 ng/dL). To further investigate the association of mildly decreased TT on LVWT, we divided the borderline group into borderline‐low (264‐319 ng/dL) and borderline‐high (320‐399 ng/dL) ranges. LVWT values were classified as low LVWT when <0.6 cm. A multivariate model was used to compare LVWT, age, BMI, systolic blood pressure (SBP), and HbA1c among groups by TT values. Results The prevalence of low TT was 10.6% and of borderline was 26.4%, while 58.7% had levels in the reference range. The low‐TT group was older and had higher BMI and SBP as compared to the reference group (P < .01). LVWT values were different among groups (P = .04) and significantly lower in firefighters with borderline‐low TT as compared to the reference group (P < .05). This finding also occurred within obese firefighters (P = .03). The borderline‐low group had a higher adjusted risk for a low LVWT as compared to the reference group [OR: 4.11 (95% CI: 1.79‐9.43)]. Discussion Our findings highlight the possible relationship between a mild reduction in testosterone levels (borderline) and lower LVWT. Conclusions A high prevalence of subnormal TT levels (low and borderline: 37%) was observed in this relatively homogeneous cohort of career firefighters. Mildly decreased TT levels and lower LVWT might represent a preclinical condition and a window of opportunity for cardiovascular preventive interventions in firefighters.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 59%

Section: Discussionsupporting

confidence: 46%

Section: Lvwt (Cm)mentioning

confidence: 99%

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Borderline‐low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis

et al. 2020

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“…The diagnosis of hypogonadism was based on the presence of unequivocal low testosterone level, presence of classical hypogonadal symptoms and low/normal serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In accordance to the Clinical Reference Laboratory of the Center for Disease Control program, biochemical diagnosis of hypogonadism was done in serum testosterone levels lower than 264 ng/dL in patients with hypogonadal symptoms [7,8]. In the present study, patients with hypogonadotropic hypogonadism had normal prolactin levels, normal pituitary and target hormone levels and normal pituitary magnetic resonance imaging.…”

Section: Methodsmentioning

confidence: 72%

Treatment of male hypogonadism partially reverses oxidative stress in patients with hypogonadism

et al. 2020

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There are some studies regarding the presence/absence of oxidative stress in patients with hypogonadism with limited number of parameters. We aimed to investigate the effects of male hypogonadism and its treatment on oxidative stress parameters. Thirteen male patients with hypogonadotropic hypogonadism and 20 healthy subjects were involved in the study. Patients with hypogonadism were evaluated before and after six months of therapy. Markers indicating lipid and protein oxidation, total oxidant status (TOS) and total anti-oxidant capacity (TAC) were evaluated. Control subjects had significantly higher serum testosterone levels in comparison to hypogonadal patients before the treatment period. After the treatment of hypogonadism serum testosterone levels increased significantly. Myeloperoxidase (MPO) activity, levels of advanced oxidation protein products (AOPP), total lipid hydroperoxide and protein carbonyl compounds (PCC) were similar between the control subjects and the patient group before treatment. Pyrrolized protein and TOS were significantly lower and thiol levels and TAC were significantly higher in the control subjects than in patients with hypogonadism. Treatment of hypogonadism resulted in a significant decrease in AOPP levels while a significant increase was determined in TAC. No significant change was found in MPO activity. In conclusion, patients with hypogonadism have an increased status of oxidative stress which is at least partially improved after appropriate therapy.

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Population Pharmacokinetic Modeling and Simulations to Evaluate a Potential Dose Regimen of Testosterone Undecanoate in Hypogonadal Males

Pastuszak

Bush²,

Curd³

et al. 2021

The Journal of Clinical Pharma

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Intramuscular testosterone undecanoate is indicated as testosterone replacement in adult males with a deficiency in or absence of endogenous testosterone (hypogonadism). Intramuscular testosterone undecanoate 750 mg is approved to be administered at initiation and at 4 weeks, followed by a maintenance dose every 10 weeks. However, a more frequent maintenance regimen may improve symptom management of low testosterone at the end of each dosing interval. The current objective was to develop a population pharmacokinetic (PK) model for intramuscular testosterone undecanoate 750 mg and to perform PK simulations to assess the impact of an 8‐week maintenance regimen on testosterone exposure. A 1‐compartment model with first‐order absorption and first‐order elimination best described the PK of testosterone undecanoate. The model included time‐dependent suppression and gradual recovery of endogenous testosterone production during testosterone undecanoate administration. Significant covariates included body weight and sex hormone–binding globulin level. With the final PK model, simulations were performed to evaluate the impact of an 8‐week vs a 10‐week maintenance regimen on testosterone exposure. The 8‐week testosterone undecanoate regimen had a predicted 11% increase in average concentration and last observed concentration during a dosing interval before a subsequent dose and a 5% increase in maximum concentration. This translated into an ≈10% increase in the percentage of patients predicted to have a last observed concentration during a dosing interval before a subsequent dose >300 ng/dL, minimal change in the percentage of patients with average concentration in the normal range, and a low likelihood of maximum concentration >2500 ng/dL. These simulations suggest that more frequent administration of intramuscular testosterone undecanoate may be beneficial in some patients. Further clinical evaluation of an 8‐week dose regimen is warranted.

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Male Hypogonadism: A Review

Abstract: This article contains a systematic review of the main developments that have occurred in the area of male hypogonadism between the publication of the Endocrine Society Guidelines of 2010 and 2018 and after 2018.

Cited by 14 publications

References 268 publications

Borderline‐low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis

Borderline‐low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis

Treatment of male hypogonadism partially reverses oxidative stress in patients with hypogonadism

Population Pharmacokinetic Modeling and Simulations to Evaluate a Potential Dose Regimen of Testosterone Undecanoate in Hypogonadal Males

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