An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study.

OBJECTIVES: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr. METHODS: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >or= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. RESULTS: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >or= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >or= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p=0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. CONCLUSIONS: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.

Through the eyes of women: the partners' perspective on tadalafil.

OBJECTIVES: To evaluate patient and female partner responses on the efficacy of, and overall satisfaction with, tadalafil to treat erectile dysfunction using sexual encounter profile (SEP) diaries. METHODS: Data were pooled from four double-blind, placebo-controlled, 12-week trials that included 746 couples. Patients were randomized to placebo or tadalafil 10 or 20 mg. Efficacy was evaluated by the mean per-patient/per-partner percentage of "yes" responses to patient SEP questions 1, 2, and 5 and partner SEP questions 1 to 3 (erection achievement, penetration, and overall satisfaction with the sexual experience, respectively) for tadalafil versus placebo. For each SEP question, the number of postbaseline intercourse attempts when each couple agreed on the outcome was tabulated and divided by the total number of postbaseline attempts to calculate the mean percentage of agreement by couple. The overall satisfaction with successful postbaseline intercourse attempts was determined. RESULTS: Tadalafil significantly improved the responses for the patient and partner-evaluated SEP questions (P <0.001, both doses versus placebo). Partners tended to report greater overall satisfaction than patients at baseline and postbaseline. The mean percentage of agreement by couple was approximately 98% for erection achievement and penetration and 85% for overall satisfaction. For successful intercourse attempts, patients and partners treated with tadalafil reported more overall satisfaction than those treated with placebo (P <0.05, tadalafil versus placebo comparisons). CONCLUSIONS: Partners reported significantly improved overall sexual satisfaction and corroborated the man's report of improved erections and penetration ability with tadalafil 10 mg or 20 mg. Men reported improved erection achievement, penetration, and overall satisfaction with the sexual experience after taking tadalafil.

Chemically resolved imaging of biological cells and thin films by infrared scanning near-field optical microscopy.

The infrared (IR) absorption of a biological system can potentially report on fundamentally important microchemical properties. For example, molecular IR profiles are known to change during increases in metabolic flux, protein phosphorylation, or proteolytic cleavage. However, practical implementation of intracellular IR imaging has been problematic because the diffraction limit of conventional infrared microscopy results in low spatial resolution. We have overcome this limitation by using an IR spectroscopic version of scanning near-field optical microscopy (SNOM), in conjunction with a tunable free-electron laser source. The results presented here clearly reveal different chemical constituents in thin films and biological cells. The space distribution of specific chemical species was obtained by taking SNOM images at IR wavelengths (lambda) corresponding to stretch absorption bands of common biochemical bonds, such as the amide bond. In our SNOM implementation, this chemical sensitivity is combined with a lateral resolution of 0.1 micro m ( approximately lambda/70), well below the diffraction limit of standard infrared microscopy. The potential applications of this approach touch virtually every aspect of the life sciences and medical research, as well as problems in materials science, chemistry, physics, and environmental research.