Research · PMID 37589949 · Landmark study
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism.
The Journal of clinical endocrinology and metabolism · January 2024 · Karol M Pencina, Thomas G Travison, Glenn R Cunningham, A Michael Lincoff, Steven E Nissen, et al.
What this study found
In middle-aged and older men with hypogonadism and low libido, TRT for 2 years improved sexual activity, hypogonadal symptoms, and sexual desire, but not erectile function.
Why this trial matters
TRAVERSE sexual function substudy
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Core study
Does testosterone therapy improve depression or low mood in hypogonadal men?
Some randomized trials and meta-analyses show modest improvements in depressive symptoms among men with low testosterone, but effects are heterogeneous and not a substitute for standard psychiatric evaluation when major depression is present.
Open evidence analysisCore study
Does testosterone therapy improve erectile function in hypogonadal men?
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.
Open evidence analysisSupporting literature
How effective are PDE5 inhibitors for erectile dysfunction?
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.
Open evidence analysisSupporting literature
Is daily low-dose tadalafil better than on-demand dosing for erectile dysfunction?
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.
Open evidence analysisSupporting literature
Are PDE5 inhibitors safe for cardiovascular disease in men with erectile dysfunction?
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.
Open evidence analysisSupporting literature
Why are PDE5 inhibitors contraindicated with nitrates?
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.
Open evidence analysisSupporting literature
Is erectile dysfunction a marker of future cardiovascular disease?
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.
Open evidence analysisSupporting literature
What options exist for men who do not respond to PDE5 inhibitors?
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.
Open evidence analysisSupporting literature
What treatments are effective for premature ejaculation?
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.
Open evidence analysisSupporting literature
What are the common side effects of PDE5 inhibitors?
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.
Open evidence analysisSupporting literature
Do sildenafil, tadalafil, and vardenafil differ in effectiveness for erectile dysfunction?
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.
Open evidence analysis