Testosterone supplementation and bone parameters: a systematic review and meta-analysis study.

BACKGROUND: The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate. METHODS: All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered. RESULTS: Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive effect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone < 12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a significant reduction of bone resorption markers in observational but not in controlled studies. CONCLUSION: TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic effect of T and estrogens on bone metabolism to take place.

Long-term high-dose L-arginine supplementation in patients with vasculogenic erectile dysfunction: a multicentre, double-blind, randomized, placebo-controlled clinical trial.

PURPOSE: The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of L-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild-moderate and severe vasculogenic ED. METHODS: The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU). RESULTS: L-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of patients with mild-moderate (p < 0.0001) and severe (p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p < 0.0001) and in patients with mild-moderate (p < 0.0001), but not severe vasculogenic ED. At study completion, 74% of patients improved ED degree category, although only 24% of patients, mainly belonging to the baseline category of mild ED, reached IIEF-6 scores compatible with absence of ED; moreover, 20% of patients, exclusively belonging to the baseline category of mild-moderate vasculogenic ED, reached PSV values compatible with absence of ED. CONCLUSION: The results of the current study demonstrated that supplementation with relatively high doses of L-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild-moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that L-ARG might be an alternative treatment in mild-moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds.

Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing's syndrome.

INTRODUCTION: Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women. Currently, it is unclear if patients with subclinical Cushing's syndrome (SCS) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given. OBJECTIVE: This pilot randomized study was aimed at evaluating the effects of 12-month im administration of clodronate (100 mg every week) on vertebral and femoral bone mineral density (BMD), bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas. METHODS: Forty-six women (age, 43.1+/-7.7 yr) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were randomized to receive clodronate plus supplement of Calcium (500 mg daily) and Vitamin D3 (800 mg daily) (group 1, no.=23) or supplements only (group 2, no.=23). Both groups were similar in terms of age, body mass index, cortisol levels, BMD values, and bone turnover markers. All of the women were re-evaluated after 12 months. RESULTS: After 12 months of treatment, in group 1, a significant increase in lumbar BMD occurred (p=0.04), while bone turnover markers decreased by about one third (p<0.05). In group 2, bone turnover markers did not change and BMD values slightly decreased (p=ns). The differences in bone turnover markers and in lumbar BMD between the two groups were significant (p<0.05, all). No new vertebral fracture occurred in group 1, while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures. An improvement in subjective back pain, assessed by visual analogue scale pain score was observed in group 1 (from 4.3+/-2.7 to 2.9+/-2.0; p<0.05) but not in group 2 (from 4.4+/-3.1 to 4.2+/-3.4; p=ns). No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study. CONCLUSIONS: Intramuscular administration of clodronate effectively increased lumbar BMD values, preserved bone mass at the femoral neck, stabilized vertebral fracture index, and decreased subjective back pain in pre-menopausal women with SCS. Since the untreated group continued to lose bone, antiresorptive treatment should be considered in patients with SCS, according to the prevision of surgical treatment, prevalent fractures, BMD values, age, concomitant morbidities, and desire for pregnancy.

Hypothalamus-pituitary-adrenal axis in central diabetes insipidus: ACTH and cortisol responsiveness to CRH administration.

A strong relationship has been found between arginine-vasopressin (AVP) and hypothalamus-pituitary-adrenal axis in humans. The aim of the current study was to evaluate baseline and CRH-stimulated ACTH and F levels in patients with central diabetes insipidus (CDI), before and after replacement therapy with desamino-D-AVP (DDAVP). Twenty-five patients with CDI, and 25 sex- and age- and BMI-matched healthy subjects entered the study. A standard CRH test (measurement of plasma ACTH and serum F before and every 15 min for 2 h after the administration of 100 microg of human CRH) was performed in all subjects. In patients with CDI, CRH test were repeated after 1 week of DDAVP at standard doses. At study entry, ACTH and F levels were significantly higher in patients with CDI than in controls either at baseline (ACTH: 45.5+/-4.8 vs 18.5+/-3.3 ng/l, p<0.05; F: 375.1+/-55.7 vs 146.6+/-19.4 microg/l, p<0.05) or after CRH test considered as a peak (ACTH: 90.8+/-14.4 vs 42.5+/-7.4 ng/l, p<0.05; F: 501.6+/-65.7 vs 226.3+/- 25.6 microg/l, p<0.05) and AUC (ACTH: 3997.0+/-571.7 vs 2136.0+/-365.8 ng/l/120 min, p<0.05; F: 31,489.0+/-4299.4 vs 14,854.5+/-1541.5 microg/l/120 min, p<0.05). In patients with CDI, 1 week of replacement with DDAVP brought down ACTH (peak: 56.9+/-9.3 ng/l; AUC: 2390.7+/-480.7 ng/l/120 min) and F (peak: 310.3+/-39.5 microg/l; AUC: 17,555.5+/-2008.7 microg/l/120 min) responses to CRH to normal but did not significantly modify baseline hormone levels (ACTH: 29.6+/-3.6 ng/l; F: 239.0+/-32.3 microg/l). In conclusion, CDI is associated to increased baseline ACTH and F levels and increased responsiveness of ACTH and F to CRH administration. In addition, replacement treatment with DDAVP normalized CRH-induced but not baseline ACTH and F secretion.