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Statins and erectile dysfunction

Systematic review [1]
Drug monitoring systems
Prospective cohort study
Statins can improve erectile function
Comment

A patient-led story, following a query from a patient. Do statins cause erectile dysfunction? At face value this seems highly improbable, given the huge number of men given statins over the last decade or so, and the increasing attention given to adverse events. But we know that there has been some association between statins and erectile dysfunction, so a quick literature survey seemed in order, following up on a systematic review from 2002 [1].


Systematic review [1]

The review process involved searching eight electronic databases for any reports linking erectile dysfunction or impotence in men with the use of cholesterol lowering drugs. National regulatory adverse drug reaction registers were also examined.

The review reported that:


Drug monitoring systems

In Spain and France [3], 75 cases of impotence associated with statins were identified. All had a temporal sequence. About 90% of men recovered potency on statin withdrawal, and in some cases impotence appeared again on re-challenge. All statins were implicated.

In Holland [4] eight men were identified with decreased libido shortly after starting statins, and in two in whom testosterone was measured there was a large decrease in serum testosterone while on statins, with recovery of testosterone levels on stopping statin.

In 2003/4, the WHO Uppsala Monitoring Centre had 144 reports of decreased libido, and 498 reports of impotence.


Prospective cohort study

Eighty men were recruited and completed an international index of erectile function questionnaire (IIEF) before starting statins [5]. Their mean age was 61 years, and they had high rates of smoking, ischaemic heart disease, and diabetes, and most were receiving antiplatelet therapy.

Before starting statins, the median IIEF score was 21 out of a maximum of 25, and 43% of men had scores above 21, indicating no erectile dysfunction. After starting statins, the median IIEF score fell to 6.5 (Figure 1) and the percentage without erectile dysfunction fell to 21% (Figure 2). Over half of men had a fall in 5 or more points on IIEF with statins, and 22% experienced new onset erectile dysfunction.



Figure 1: Change in IIEF before and after statins in cohort study







Figure 2: Percentage of men with adequate erectile function score before and after statins in cohort study






Statins can improve erectile function

Erectile dysfunction is more common in men with cardiovascular risk factors, and some small studies indicate that statins can help. One was a small, but randomised and double blind comparison of atorvastatin and placebo in 12 men with erectile dysfunction and who were taking sildenafil [6]. After six weeks of statin, but not placebo therapy, the IIEF score increased with sildenafil, and all men on atorvastatin had improved confidence in obtaining and keeping an erection.


Comment

We know that men with erectile dysfunction tend to have increased cardiovascular risk factors, including raised cholesterol. There are also studies showing that reducing cardiovascular risk factors, like losing weight, can improve erectile function. There is tentative evidence that cholesterol reduction with statins can also help erectile function.

That statins may also be the cause of erectile dysfunction is another matter, but the evidence does seem to be growing. To yellow card reporting in different countries can be added the prospective cohort study. Yet randomised trial results show no increase in erectile dysfunction rates with statins, and these were large trials, like 4S, conducted over a long period of time. In clinical practice, men may be different.

What is going on? The number of cases is small compared to the very widespread prescribing of lipid lowering drugs, especially statins. It is made more complicated by the average age of men reporting erectile dysfunction, mainly in their 50s when erectile dysfunction may occur anyway, and because many men using statins may be on therapy for other conditions. Though in most men testosterone metabolism in not affected by statin therapy, we have clear interference with testosterone biosynthesis in some of the affected men, and clear re-challenge evidence of the problem in others.

It looks as if this is a real problem for a small number of men. It is far too early to speculate on mechanisms, but testosterone synthesis needs cholesterol, and perhaps we should not be surprised that we may not all be average in the way our bodies work.

The good news is that the problem is reversible on stopping statins, and that drug switching helped in a number of cases. That just leaves the little problem of what to tell men when statins are needed.

References:

  1. K Rizvi et al. Do lipid-lowering drugs cause erectile dysfunction? A systematic review. Family Practice 2002 19: 95-98.
  2. E Bruckert et al. Men treated with hypolipidaemic drugs complain more frequently of erectile dysfunction. Journal of Clinical Pharmacology and Therapy 1996 21: 89-94.
  3. A Carvajal et al. HMG CoA reductase inhibitors and impotence: two case series from the Spanish and French drug monitoring systems. Drug Safety 2006 29: 143-149.
  4. L de Graaf et al. Is decreased libido associated with the use of HMG-CoA-reductase inhibitors? British Journal of Clinical Pharmacology 2004 58: 326-328.
  5. H Solomon et al. Erectile dysfunction and statin treatment in high cardiovascular risk patients. International Journal of Clinical Practice 2006 60: 141-145.
  6. HC Herrman et al. Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial. Journal of Sexual Medicine 2006. Epub ahead of print. DOI: 10.1111/j.1743-6109.2005.00156.x

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