Importance of Sexual Function Assessment in Multidimensional Evaluation of AGHD Patients: Results from the MAGHD Study.

Background: Adult growth hormone deficiency (AGHD) is a debilitating clinical condition leading to decreased quality of life (QoL). The impact of reduced muscle mass, weakening and loss of vitality on QoL have been well characterized in AGHD. The impact of AGHD on sexual function, a recognized factor able to modify well-being, has never been investigated. Aim: To investigate the prevalence of sexual dysfunction in AGHD patients referring to a single endocrinological center and grouped according to their his- tory of r-hGH therapy.Methods: The Management of Adult Growth Hormone Deficiency (MAGHD) Study is a pro- spective, real-life trial aiming to improve management of AGHD patients through a smartphone app (MAGHD App)and a wearable device. The 83 AGHD enrolled patients (31 Females, 52 Males, mean age 56.27 + 14.68 years) were divided in 3 groups (G) according to r-hGH therapy: on long-term r-hGH therapy (G1, n=32), previously treated with r-hGH (G2, n=20), never treated (G3, n=31). Within the first phase of the study, a large database was created collecting clinical, biochemical and psychological data. In addition to QLS-H and QoL-AGHDA routinely used to as- sess QoL, IIEF-15 and FSFI were employed to evaluate sexual function in males and females, respectively. The nonparametric Kruskal-Wallis test was used for compar- ison among 3 groups.Results: Here only baseline data of the MAGHD Study are presented.According to IIEF-15 results, the prevalence of erectile dysfunction (ED) in male AGHD cohort was 60%. Erectile function (EF) score was signifi- cantly higher in G1 compared to both G2 and G3 (p < 0.05) with an ED prevalence of 35% in G1, 75% in G2 and 75% in G3. Even excluding patients with serum testosterone lower than 2 ng/ml and older than 65 years, ED prevalence did not change significantly in the 3 groups. Moreover, EF do- main was inversely and directly correlated to age (R20.130, β-0.360) and IGF1 levels (R20.156, β0.395), respectively. The prevalence of female sexual dysfunction according to FSFI was 89.3%. Even though desire, arousal, lubrication and overall scores were significantly higher (better results) in G1 compared to G2 and G3 (p < 0.05), no correlation resulted between FSFI domains and IGF1 levels. Instead an inverse correlation resulted between desire domain and age.Conclusions: This study, performed in a real-life clinical setting, demonstrates a high prevalence of sexual dysfunc- tion in AGHD patients and that r-hGH treatment seems to be associated to better sexual outcomes. These results suggest that the evaluation of sexual function should be in- tegrated in the global assessment of AGHD patients since sexual activity is a fundamental domain able to influence both well-being and QoL

Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay

Purpose Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. Methods Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height(2) (ALMI) < 7.26 kg/m(2) or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. Results Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. Conclusions T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions

Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer?

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50\u200akb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case-control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single-nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC

Premature Decline of Serum Total Testosterone in HIV-Infected Men in the HAART-Era

BackgroundTestosterone (T) deficiency remains a poorly understood issue in men with Human Immunodeficiency Virus (HIV). We investigated the gonadal status in HIV-infected men in order to characterize T deficiency and to identify predictive factors for low serum T.Methodology/Principal FindingsWe performed a cross-sectional, observational study on 1325 consecutive HIV male outpatients, most of them having lipodystrophy. Serum total T<300 ng/dL was used as the threshold for biochemical T deficiency. Morning serum total T, luteinizing hormone (LH), estradiol, HIV parameters, and body composition parameters by CT-scan and Dual-Energy-X-ray-Absorptiometry were measured in each case. Sexual behavior was evaluated in a subset of 247 patients. T deficiency was found in 212 subjects, especially in the age range 40\u201359, but was frequent even in younger patients. T deficiency occurred mainly in association with low/normal serum LH. Adiposity was higher in subjects with T deficiency (p<0.0001) and both visceral adipose tissue and body mass index were the main negative predictors of serum total T. Osteoporosis and erectile dysfunction were present in a similar percentage in men with or without T deficiency.Conclusions/SignificancePremature decline of serum T is common (16%) among young/middle-aged HIV-infected men and is associated with inappropriately low/normal LH and increased visceral fat. T deficiency occurs at a young age and may be considered an element of the process of premature or accelerated aging known to be associated with HIV infection. The role of HIV and/or HIV infection treatments, as well as the role of the general health state on the gonadal axis, remains, in fact, to be elucidated. Due to the low specificity of signs and symptoms of hypogonadism in the context of HIV, caution is needed in the diagnosis of hypogonadism in HIV-infected men with biochemical low serum T levels

Sexual dysfunction: a neglected and overlooked issue in adult GH deficiency: the management of AGHD study.

Context: Although sexuality influences well-being and quality of life (QoL), studies on sexual dysfunction (SD) in adult growth hormone deficiency (AGHD) patients are lacking. Objective: To investigate the prevalence of SD in AGHD patients grouped according to recombinant human growth hormone (r-hGH) therapy. Design: Prospective, cross-over, 24 months, monocentric study. Setting: Real-life clinical setting in a tertiary, endocrinological center. Patients: 83 AGHD patients (31 women, 52 men, mean age 56.3 \ub1 14.7 years) were enrolled according to stringent criteria. Interventions: Patients already on long-term r-hGH therapy (Group 1, n = 32) vs untreated (Group 2, n = 51). Main outcome measures: Serum hormones, QoL Satisfaction in Hypopituitarism (QLS-H) and QoL Assessment of GHD in Adults (QoL-AGHDA) questionnaires for QoL, Index for Erectile Function-15 (IIEF-15) in men, and Female Sexual Function Index (FSFI) in women for SD. Results: The overall prevalence of SD was 71.2% (60% men, 89% women). All IIEF-15 scores were lower (P = 0.001) and erectile dysfunction was more prevalent in Group 2 (75%) than Group 1 (35%). IGF-1 was correlated to scores of all IIEF-15 domains, particularly with that of erectile function (EF) (R2=0.123, P = 0.019). EF domain score correlated with QLS-H (P &lt; 0.005) and QoL-AGHDA (P = 0.001). Despite the high prevalence of female SD also in untreated AGHD women, FSFI scores did not correlate with IGF-1 levels and QoL scores. Conclusions: SD is highly prevalent in AGHD patients, especially in those untreated. SD represents an overlooked and neglected issue in AGHD, regardless the contribution of sexual life on QoL. The evaluation of sexual function should be integrated in the global assessment of AGHD patient