Aging and sex hormones in males

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

Long-Term Use of Temozolomide as Safe and Effective Therapy for an Aggressive Corticotroph Adenoma in a Very Old Patient

Background: Temozolomide (TMZ) is safe and effective in the treatment of aggressive pituitary adenomas (PAs). However, the optimal duration of TMZ therapy is still unknown. Moreover, data about administration of TMZ in elderly (≥65 years) people to treat aggressive PAs are scarce. We report the case of the oldest female patient undergoing the longest TMZ protocol described so far to treat an aggressive, initially silent corticotroph PA. Case report: The patient initially underwent partial surgical removal of the PA. Subsequent treatment with cabergoline was applied, but it was unsuccessful in controlling the growth of the residual tumor. Pasireotide and external radiation also showed to be ineffective; therefore, treatment with TMZ was started at the standard dose of 200 mg/m2/day for 5 days every 4 weeks for a total of 47 cycles. At the time of treatment's beginning, the patient was 83 years old. Radiological follow-up documented a progressive, remarkable reduction of the adenoma and the last imaging, after 39 cycles of TMZ, showed an intrasellar lesion with large areas of cystic degeneration. The patient also developed adrenal deficiency managed with glucocorticoid replacement. No major side effects were observed throughout the treatment, with exception of nausea, well controlled with anti-emetic medication. TMZ therapy was discontinued after 47 cycles; hormonal and imaging follow-up investigations documented sustained functional and dimensional response. Conclusions: Our case supports the long-term use of TMZ, confirming its safety and efficacy also for elderly patients

Psychological, rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men.

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED)1,2. In HIV- infected men ED seems to be less related to serum Testosterone (T)2-4, ED and sexual dysfunction mainly depending from other factors1,2. However, data on other components of sexual dysfunction in HIV are scanty2. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using different validate questionnaire in HIV-infected men with normal serum T who are mainly homosexual (70%). METHODOLOGY: Prospective, cross-sectional, observational study on 225 eugonadal, HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used for the evaluation of sexual function. Moreover, the sexual desire was further evaluated using a direct question during the visit. Statistical analysis: comparison of continue variables among groups was performed using Kruskal-Wallis test and Dunnet test for post-hoc analyses. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36 years) with average duration of HIV- infection and of HAART treatment of 187.62±101.71 and 156.38+89.81 months, respectively. Table 1 summarizes the score obtained in each item evaluated by questionnaires.The SIEDY scores obtained at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (appendix: 7.64+4.39 vs 4.35+3-14, p<0.001) (scale 3: 2.72+4.39 vs 2.07+1.86, p=0.015). Conversely, scale 1 (2.76+2.16 vs 2.46+2.10, p=0.448) and 2 (0.53+1.02 vs 0.61+1.47, p=0.503) of SIEDY did not differ between patients with or without ED. This suggests that the psychological basis of ED was predominant in HIV-infected men. However, when patients were grouped according to the severity of ED at IIEF-15 all SIEDY items did not differ among the 3 groups (p>0.05). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001). Similarly, the score at SIEDY appendix was significantly different among the ED degree found at IIEF-15 (p<0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p<0.001, p=0.001, and p<0.001, respectively), confirming the reliability of these tools. Sexual desire was evaluated using IIEF-15 appropriate domain and during the interview through direct question performed by the clinician. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the item of IIEF-15 on sexual desire (p<0.001). CONCLUSIONS: The psychological component of ED impacts in a significant manner on ED in men with HIV. Despite the high prevalence of comorbidities in these patients the organic component does not affect erectile function. Similarly, the relational component seems to play a not significant role probably because of the high percentage of men not in a stable relationship. All the three validated questionnaires well describe the degree of erectile dysfunction, with a good correlation index, suggesting that they are all reliable and accurate for the diagnosis of ED in this peculiar population. REFERENCES 1Zona S et al. Erectile dysfunction is more common in young to middle-aged HIV-infected men than in HIV-uninfected men. J Sex Med. 2012 Jul;9(7):1923-30. 2Santi D et al. Male sexual dysfunction and HIV--a clinical perspective. Nat Rev Urol. 2014 Feb;11(2):99-109. 3Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 4Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30

Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay

Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged < 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p < 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p < 0.0001) or cFT (9.5% vs 7%, p < 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency.Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged < 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p < 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p < 0.0001) or cFT (9.5% vs 7%, p < 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency

IL SODIO SIERICO È INVERSAMENTE CORRELATO ALLA FRAILTY E ALLA DENSITÀ MINERALE OSSEA (BMD) NEI PAZIENTI CON INFEZIONE DA HUMAN IMMUNODEFICIENCY VIRUS (HIV)

L'iponatriemia si associa alla frailty nei pazienti con infezione da HI

Serum sodium is inversely related to frailty and bone mineral density (BMD) in human immunodeficiency virus (HIV)-infected patients

Background HIV-infected patients are predisposed to an increased risk of hyponatremia. In healthy population, low sodium is associated with impaired health status and reduced BMD, but less is known about this association in HIV-infection. Aim To investigate the relationship between serum sodium, frailty and BMD in a large cohort of HIV-infected patients. Methodology A retrospective, observational, cohort study on adult HIV-infected patients (age R18 years), attending the Multidisciplinary Metabolic Clinic of Modena, was carried out including all sodium examinations performed at the Modena lab from 2007 to 2017 available in a large database. Laboratory ranges of normality for sodium (136\u2013146mEq/l) were used to subdivide records in hyponatremic (HypoNa), hypernatremic (HyperNa) and normonatremic (NormoNa) groups. BMD was measured at total body, lumbar spine (L1\u2013L4) and total hip using a Hologic QDR-2000 densitometer (DXA). Frailty was calculated through 38-item multimorbidity frailty index. Statistical analysis Parameters were not normally distributed and Kruskal-Wallis test, followed by Dunn\u2019s test, was used to compare continuous variables. Correlations were performed using linear regression models. Results 8101 records (5454 from males and 2647 from females) of serum sodium (mean 139.4G3.1 mEq/l) evaluated in HIV-infected patients (mean age 49.0G7.9 years) were considered. 617 (7.6%), HypoNa, 44 (0.5%) HyperNa and 7440 (91.8%) NormoNa were found. Frailty score was inversely related to serum sodium (rZK0.174, R2Z0.03, P!0.0001), even after the exclusion of HyperNa group (RZK0.191, R2Z0.036, P!0.0001). Frailty was significantly higher in HypoNa than NormoNa (P!0.001). Considering results at DXA examination, BMD was normal in 30.3% and reduced in 69.7% (54.8% osteopenia, 14.9% osteoporosis). Total body BMD, but not femoral nor lumbar, directly correlated with serum sodium (RZ0.049, P!0.001) and it was significantly lower in HypoNa compared to NormoNa (PZ0.029). Conclusions This study shows that serum sodium is inversely related to frailty, suggesting its potential role as reliable and cheap marker in the HIV-infection follow-up. Furthermore, we demonstrate a direct correlation between sodium and body BMD in HIV-infected patients, similarly to general population. DOI: 10.1530/endoabs.56.P74

Testosterone (T) is poorly related to erectile dysfunction (ED) in young/middle aged human immunodeficiency virus (HIV)-infected men.

BACKGROUND: HIV-infection is strongly associated to ED in men. Preliminary data suggests that ED is poorly associated with serum T in HIV+ men. AIM: To investigate in HIV-infected men the relationship between sexual function as assessed by the validated International Index of Erectile Function (IIEF-15) and T deficiency using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS). METHODOLOGY: Prospective, cross-sectional, observational study on HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Clinic of Infectious Diseases. IIEF-15 and IIEF-5 questionnaires were used to define ED, while LC-MS/MS was used for hormonal assays. RESULTS: 233 consecutive HIV-infected patients were enrolled (mean age 45.29±5.33years). Eight patients (3.4%) had total T <300ng/dL, while 142 patients (61.5%) had ED (score ≤25). Age, hormonal data and duration of HIV-infection and HAART did not differ among groups of patients according to the degree of ED. The direct comparison of each ED cluster showed that months of infection were significantly higher in men with severe ED compared to mild ED (p=0.037). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001), as expected. Moreover, the IIEF-15 score was inversely related to months of infection (-0.147, p=0.026), but not to months of HAART therapy (-0.121, p=0.071). CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the relationship between erectile function and serum T, assessed by LC-MS/MS in HIV-infected men. In our cohort, a) IIEF-5 is reliable as IIEF-15 for ED diagnosis, b) ED is not associated with serum T, c) erectile function is not influenced by T and HAART, but only by HIV-infection duration. In conclusion, several specific factors, such as the duration of HIV infection, are involved in erectile function in HIV-infected men and should be carefully considered in this setting, while hormonal status seems to be less importan

Determinants of sexual function in men living with HIV younger than 50 years old: Focus on organic, relational, and psychological issues

Background: Sexual dysfunctions, particularly erectile dysfunction, are common in men living with HIV, whose organic and psychological components remain to be clarified. The aim of the study is to investigate the impact of risk factors of sexual dysfunctions, including organic, relational, and psychological determinants of erectile function, in men living with HIV younger than 50 years old. Methods: A cross-sectional, observational study was conducted in men living with HIV&nbsp;&lt;&nbsp;50 years. The questionnaire International Index of Erectile Function-15 was used to assess the prevalence and degree of erectile dysfunction. The structured interview of erectile dysfunction was used to explore the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction. Total testosterone, estradiol, and dihydrotestosterone were measured by liquid chromatography-tandem-mass spectrometry; free testosterone was calculated by the Vermeulen equation. Results: A total of 313 consecutive men living with HIV were prospectively enrolled (median age 47.0 years; median HIV-infection duration 16.2 years). 187 patients (59.7%) had erectile dysfunction, with a higher prevalence of non-heterosexual (138 out of 187, 73.8%) than heterosexual patients (p&nbsp;=&nbsp;0.003). Patients with erectile dysfunction showed a worse score of structured interview of erectile dysfunction scale 3 compared to patients without erectile dysfunction (p&nbsp;=&nbsp;0.025); the International Index of Erectile Function-15 was inversely related to structured interview of erectile dysfunction scale 3 (p&nbsp;=&nbsp;0.042). No difference was found for sex steroids (total testosterone, estradiol, free testosterone, and dihydrotestosterone) between men living with HIV with and without erectile dysfunction. In the multivariate analysis sexual orientation, and lack of stable relationships were major determinants for erectile dysfunction. Only 35 of 187 patients with erectile dysfunction (18.7%) reported the use of erectile dysfunction medications. Conclusions: Within the multidimensional network of erectile dysfunction in men living with HIV, the psychological component is predominant, highlighting the contribution of peculiar factors related to HIV distress (e.g., fear of virus transmission, stigma) rather than gonadal status and other classical risk factors. In contrast to the high prevalence, only a few patients reported the use of erectile dysfunction medications suggesting a general under-management of such issues