Evidence that changed

All three major PDE5 inhibitors improve erectile function versus placebo with broadly similar efficacy in meta-analyses. Differences in onset, duration, food interactions, and side-effect profiles often matter more than marginal efficacy differences for most patients.

Headache, flushing, dyspepsia, and nasal congestion are common and usually dose-related. Visual disturbances and back pain occur with agent-specific frequency; non-arteritic anterior ischemic optic neuropathy is rare. Counsel on timing, alcohol, and when to stop and seek care.

On-demand dapoxetine and daily or on-demand SSRIs lengthen intravaginal ejaculatory latency and improve control in men with lifelong or acquired premature ejaculation. Behavioral therapy and topical anesthetics are adjunctive options depending on preference and side-effect tolerance.

Optimize dosing timing, adherence, and comorbidity management before labeling true non-response. Switching PDE5 agents, adding lifestyle and vascular risk-factor control, vacuum devices, intracavernosal therapy, or referral for specialized evaluation are evidence-supported pathways when oral therapy fails.

Testosterone improves sexual desire and some erectile function endpoints in men with confirmed hypogonadism, but effects are smaller than PDE5 inhibitors for vascular erectile dysfunction. Treat documented deficiency when indicated; do not rely on testosterone alone for moderate-to-severe ED without evaluating PDE5 therapy.

Erectile dysfunction often precedes symptomatic cardiovascular disease and shares endothelial dysfunction pathways with atherosclerosis. Men presenting with ED warrant cardiovascular risk assessment and conventional prevention strategies independent of PDE5 therapy decisions.

Combined PDE5 inhibition and nitric oxide donor therapy can produce profound synergistic vasodilation and symptomatic hypotension. Nitrates and PDE5 inhibitors should not be used together; allow appropriate washout intervals when switching between agents in acute coronary care.

In stable cardiovascular disease, PDE5 inhibitors do not appear to increase major adverse cardiac events when used appropriately and nitrate co-administration is avoided. Sexual activity itself carries modest cardiovascular demand; individualized assessment remains important after recent events.

Both daily low-dose and on-demand tadalafil improve erectile function. Daily dosing may improve spontaneity and lower urinary symptom scores in men with comorbid LUTS, while on-demand dosing minimizes drug exposure for men with infrequent sexual activity.

PDE5 inhibitors substantially improve erectile function versus placebo across broad ED populations, with landmark trials showing clinically meaningful IIEF improvements. On-demand dosing before sexual activity is standard; response rates are high though not universal.

Growth hormone replacement is evidence-supported for adults with confirmed GH deficiency from pituitary disease, improving body composition and quality of life. Use in healthy aging or performance enhancement lacks safety and efficacy evidence.

DHEA raises circulating androgens and estrogens modestly but lacks robust outcome trial evidence for cardiovascular, cognitive, or mortality benefit in healthy aging adults without documented deficiency.