ABSTRACT
OBJECTIVE: To determine the long-term incidence of glucose disorders in treated HIV infection, associations with traditional and HIV-specific risk factors. METHODS: Observational cohort of 104 men with treated HIV infection and without diabetes, aged 43â±â8 years at baseline, with (meanâ±âSD) 11.8â±â3.5 years follow-up. Ascertainment of glucose status by fasting glucose or, in a subset (nâ=â33), a 75âg oral glucose tolerance test by 10-12 years follow-up. A subset underwent sequential body composition measures (nâ=â58) to determine changes in total body and central abdominal adiposity. RESULTS: The cumulative incidence of glucose disorders was 48.1% (prediabetes 35.6%, diabetes 12.5%), with an incidence rate of 34.5/1000 years of patient follow-up (PYFU) (prediabetes: 24.3/1000 PYFU; diabetes: 10.2/1000 PYFU). Incident glucose disorders were independently associated with higher age (44.9â±â8.4 vs. 41.1â±â7.5 years, Pâ=â0.027), baseline C-peptide (2.9â±â1.3 vs. 2.4â±â1.1âng/ml, Pâ=â0.019) and baseline 2-h glucose (135â±â41 vs. 95â±â25âmg/dl, Pâ<â0.001). A prior AIDS-defining illness was independently associated with higher follow-up fasting glucose (108â±â38 vs. 94â±â16âmg/dl, Pâ=â0.007). Abdominal fat gain over 2-4 years was associated with a 3.16-fold increased risk of incident glucose disorders (95% CI 1.30-7.68, Pâ=â0.011). In a subgroup who underwent further oral glucose tolerance testing, 60% had a glucose disorder, the majority not detected by fasting glucose. CONCLUSION: Men with long-term treated HIV infection have high rates of incident glucose disorders associated with modest abdominal fat gain. Directed measures to prevent diabetes in this population are warranted.
Subject(s)
Diabetes Mellitus/epidemiology , HIV Infections/complications , Prediabetic State/epidemiology , Adult , HIV Infections/drug therapy , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.
Subject(s)
Ejaculation/drug effects , Nitric Oxide/physiology , Phosphodiesterase Inhibitors/therapeutic use , Sexual Dysfunction, Physiological/drug therapy , Ejaculation/physiology , Humans , Male , Sexual Dysfunction, Physiological/enzymology , Treatment OutcomeSubject(s)
Erectile Dysfunction/therapy , Phosphodiesterase Inhibitors/therapeutic use , Administration, Oral , Drug Therapy, Combination , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Humans , Life Style , Male , Patient Education as Topic , Penile Prosthesis , Phosphodiesterase Inhibitors/pharmacokinetics , Psychotherapy/methods , Referral and Consultation , Risk Factors , Testosterone/therapeutic use , Treatment Failure , VacuumABSTRACT
Premature ejaculation (PE) is a common male sexual disorder. Recent normative data suggest that men with an intravaginal ejaculatory latency time (IELT) of less than 1 minute have "definite" PE, while men with IELTs between 1 and 1.5 minutes have "probable" PE. Although there is insufficient empirical evidence to identify the etiology of PE, there is limited correlational evidence to suggest that men with PE have high levels of sexual anxiety and inherited altered sensitivity of central 5-HT (serotonin) receptors. Pharmacological modulation of the ejaculatory threshold using off-label daily or on-demand selective serotonin re-uptake inhibitors (SSRIs) offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, consequential improvements in sexual desire and other sexual domains and is well tolerated. Investigational drugs such as the ejaculo-selective serotonin transport inhibitors (ESSTIs) such as dapoxetine and UK-390,957 represent a major development in sexual medicine. These drugs offer patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control, and sexual satisfaction with minimal adverse effects.
