Can statins (HMG-CoA reductase inhibitors) cause side effects such as drowsiness, fatigue, and erectile dysfunction?

Statins and Side Effects: Drowsiness, Fatigue, and Erectile Dysfunction

Statins can cause fatigue as a recognized side effect, but drowsiness is not well-documented; the relationship with erectile dysfunction is complex and controversial, with evidence suggesting statins may actually improve erectile function rather than cause it.

Fatigue

Fatigue is an established statin-associated side effect that warrants clinical attention. 1

• The 2013 ACC/AHA guidelines explicitly recommend measuring hepatic function during statin therapy if symptoms suggesting hepatotoxicity arise, specifically listing "unusual fatigue or weakness" as a concerning symptom 1
• The 2018 ACC/AHA cholesterol guidelines similarly recognize fatigue as part of the clinical presentation requiring evaluation, particularly when assessing for statin-associated muscle symptoms (SAMS) 1
• FDA labeling for atorvastatin lists "fatigue" as a postmarketing adverse reaction reported during post-approval use 2
• Pravastatin clinical trials showed fatigue occurring in 8.4% of statin-treated patients versus 7.8% in placebo groups in long-term controlled trials 3
• A 2022 BMJ guideline on lipid-lowering therapy notes that ezetimibe can cause "headache, and fatigue" as adverse reactions, with similar mild and transient effects 1

Clinical approach to fatigue: When patients on statins report unusual fatigue or weakness, evaluate for hepatotoxicity (check ALT/AST if not recently done) and assess for muscle symptoms that might indicate myopathy 1. If severe muscle symptoms or fatigue develop unexpectedly, promptly discontinue the statin and evaluate CK and creatinine 1.

Drowsiness

Drowsiness is not recognized as a documented statin side effect in major guidelines or FDA labeling. 1, 2, 3

• Neither the 2013 nor 2018 ACC/AHA cholesterol guidelines mention drowsiness or somnolence as statin-associated side effects 1
• FDA labeling for atorvastatin lists "dizziness" but not drowsiness or somnolence in postmarketing reports 2
• Pravastatin trials reported dizziness in 7.3% of statin users versus 6.6% in placebo groups, but drowsiness was not documented 3
• The 2012 European cardiovascular prevention guidelines do not list drowsiness among statin adverse effects 1

If a patient reports drowsiness on statins, consider alternative explanations such as other medications, sleep disorders, or unrelated medical conditions rather than attributing it to statin therapy 1.

Erectile Dysfunction

The evidence indicates statins likely improve rather than cause erectile dysfunction, though this remains an area of ongoing debate. 1, 4, 5, 6

Evidence Supporting Improvement of ED:

• A 2014 meta-analysis of randomized controlled trials showed statins were associated with a significant increase in IIEF-5 scores (mean difference: 3.27; 95% CI: 1.51 to 5.02; P < 0.01), indicating improvement in erectile function 5
• The 2012 Princeton III Consensus on ED and cardiovascular disease reported that "several reports of improvements in erectile function among men using statins with and without PDE5 inhibitors" exist 1
• A 2018 systematic review and meta-analysis of 69,448 men found statin use was not associated with increased risk of new-onset erectile dysfunction (risk ratio 0.96; 95% CI: 0.84-1.10; P = .58) 6
• A 2012 review concluded that statins improve quality of erection by reducing endothelial dysfunction, a key factor in ED pathophysiology 4

Contradictory Evidence:

• The Princeton III Consensus noted that Solomon et al. reported new-onset ED in 22% of 93 high-risk men after 6 months of statin use, though this finding is inconsistent with other evidence 1
• A 2014 review listed erectile dysfunction among potential statin-induced side effects, noting that statins may reduce testosterone levels 7
• Research acknowledges that statin therapy may reduce testosterone levels and potentially aggravate ED symptoms, representing a "double-edged role" 5

Clinical Implications:

For patients with cardiovascular disease or risk factors who develop ED, statins should not be discontinued based on concerns about causing ED, as the cardiovascular benefits far outweigh theoretical risks. 1, 4, 5, 6

• Patients with dyslipidemia are at increased risk of developing ED independent of statin use, and statins exert a protective vascular effect 4
• Statins may have synergistic effects with PDE5 inhibitors (sildenafil, tadalafil, vardenafil) for ED treatment 4
• The 2012 Princeton Consensus emphasizes that management of ED should always be considered secondary to maintaining cardiovascular function, and treatment for ED should not negatively affect cardiovascular health 1

Common Pitfalls to Avoid:

• Do not attribute every symptom to statins: Fatigue and muscle symptoms are common in the general adult population at baseline; obtain a comprehensive history before initiating statins to establish baseline symptoms 1
• Do not unnecessarily discontinue statins: The cardiovascular benefits of statins substantially outweigh the risks of side effects for the vast majority of patients 1
• Distinguish between different muscle-related symptoms: Myalgia without CK elevation is more common (1-10%) than myositis or rhabdomyolysis, which are rare 1
• Consider drug interactions: Fatigue and muscle symptoms are more likely with concomitant use of CYP3A4 inhibitors, fibrates (especially gemfibrozil), or in patients with multiple comorbidities 1