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Purpose: To evaluate total testosterone distribution in male idiopathic infertility., Methods: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL)., Results: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020)., Conclusion: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile., (© 2024. The Author(s).) more...

Background: It is widely demonstrated that obesity and hypogonadism are bi-directionally correlated, since the hypogonadism prevalence is higher in obese population, while weight loss increases testosterone serum levels. Several approaches are available to contrast weight excess, from simple dietary regimens to more complex surgical procedures. Ketogenic diets (KD) fit in this context and their application is growing year after year, aiming to improve the metabolic and weight patterns in obese patients. However, KD influence on testosterone levels is still poorly investigated., Objectives: To systematically evaluate the potential effect of KD on testosterone levels., Methods: A systematic literature search was performed until April 2022 including studies investigating testosterone levels before and after KD. Secondary endpoints were body weight, estradiol and sex-hormone binding globulin serum levels. Any kind of KD was considered eligible, and no specific criteria for study populations were provided., Results: Seven studies (including eight trials) were included in the analysis for a total of 230 patients, five using normocaloric KD and three very low calories KD (VLCKD). Only three studies enrolled overweight/obese men. A significant total testosterone increase was recorded after any kind of KD considering 111 patients (2.86 [0.95, 4.77], p = 0.003). This increase was more evident considering VLCKD compared to normocaloric KD (6.75 [3.31, 10.20], p < 0.001, versus 0.98 [0.08, 1.88], p = 0.030). Meta-regression analyses highlighted significant correlations between the post-KD testosterone raise with patients' age (R-squared 36.4, p < 0.001) and weight loss (R-squared 73.6, p < 0.001)., Conclusions: Comprehensively, KD improved testosterone levels depending on both patients' age and KD-induced weight loss. However, the lack of information in included studies on hormones of the hypothalamic-pituitary-gonadal axis prevents an exhaustive comprehension about mechanisms connecting ketosis and testosterone homeostasis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

Background: Hypogonadism is a common comorbidity in human immunodeficiency virus (HIV)-infected men, although the real prevalence is difficult to be estimated. Moreover, in HIV settings, the efficacy of exogenous testosterone (Te) administration at improving body composition remains unclear., Aim of the Study: This review has a double aim. First, to estimate the prevalence of pituitary-testis axis abnormality in HIV-infected patients compared to uninfected subjects. Second, to evaluate the effect of androgen administration on body composition in HIV-infected men., Materials and Methods: A systematic review of the literature and meta-analysis was carried out. Two separated literature searches were performed, the first to evaluate the prevalence of Te deficiency in HIV-infected men and the second one to evaluate effects of androgen administration on body composition., Results: The overall prevalence of Te deficiency in HIV-infected men was calculated from 41 studies, showing a 26% prevalence, which was even higher when free T (fT) levels, more than total T, were considered. Indeed, TT serum levels were similar between HIV patients and controls, although higher SHBG and lower fT were detected in HIV populations. When HIV-infected men were treated with exogenous Te, a significant increase in body weight, lean body mass and fat free mass was detected., Conclusion: The systematic review confirms the high prevalence of Te deficiency in HIV-infected men, particularly when fT has been considered. Moreover, chronic androgen supplementation improves body composition, affecting the lean mass compartment. However, considering the general frailty of HIV patients, a tailored indication for Te therapy should be advocated. more...

Testicular volume (TV) is proposed to be a positive predictor of male fertility status, because of the relation known between the TV and the seminiferous tubule content. Independently of the measurement methodology, the role of TV and testicular ultrasound (US) assessments is still debated in andrological clinical practice. In this retrospective cohort study, we evaluated TV and testis US role in the diagnostic workup of andrological patients. All consecutive outpatients undergoing single-operator testis US (Modena, Italy) from March 2012 to March 2018 were enrolled, matching sonographic, hormonal, and seminal data. A total of 302 men were referred and evaluated for gynecomastia, suspected hypogonadism, couple infertility (CI), or sexual dysfunction. In the hypogonadal group, TV was lower compared to that in other groups (P < 0.001), and a significant, direct correlation between TV and testosterone level was observed in nonandrogen-treated patients (R = 0.911, P < 0.001), suggesting that testicular size could be related to the testosterone-secreting compartment. In the CI group, normozoospermic patients showed higher TV compared to men with impaired semen quality (P = 0.003) and azoospermia (P = 0.003). However, TV was not able to discriminate between patients presenting normal and altered semen quality. On the contrary, testis US inhomogeneity was more frequent in patients with impaired sperm quality (55.0%; P = 0.007) and azoospermia (40.0%; P = 0.012), compared to patients with normozoospermia (5%), identifying thereby the sonographic pattern as an informative parameter of the fertility status. Therefore, in the CI workup, US evaluation seems to be more informative than the TV assessment alone., Competing Interests: None more...

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male. more...