Dr. Ron’s Research Review – April 23, 2014

© 2014

This week’s research review focuses on statins, testosterone and erectile dysfunction.

Testosterone Reduction

In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l. In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l. Overall statins lowered testosterone by -0.44 nmol/l. A typical normal male testosterone level range given is 260 -1080 ng/dl as (which corresponds to about 8.8 - 36.7 nmol/l). (Schooling, Au Yeung et al. 2013)

Erectile Dysfunction

Patients with dyslipidemia are at increased risk of developing erectile dysfunction (ED); hence, statins exert a protective effect. At the same time, they reduce endothelial dysfunction, a key factor in the onset of ED. (La Vignera, Condorelli et al. 2012)

A systematic review by Rizvi showed that a substantial number of cases of ED associated with statin usage have been reported to regulatory agencies. (Rizvi, Hampson et al. 2002)

A recent study found increased ED with atorvastatin, and no effect with Rosuvastatin. (Nurkalem, Yildirimturk et al. 2014)

A recent article published in JAMA is entitled: "Healthy men should not take statins." (Redberg and Katz 2012) (Beckman 2012)

Dr. Ron


Articles

Use of statins in healthy men

         (Beckman 2012) Download

To the Editor: The Viewpoint by Drs Redberg and Katz advocated against the use of statins in otherwise healthy middle- aged men with elevated total cholesterol. I believe the authors misrepresent the data in a number of the studies cited in support of their points.

Statins and erectile dysfunction: a critical summary of current evidence

         (La Vignera, Condorelli et al. 2012) Download

Recently, it was reported that the administration of statins (lipid-lowering drugs) is associated with reduced levels of testosterone, and this evidence has opened a debate on the consequences these widely used drugs might have on the quality of erection. This is a very important clinical problem because patients with dyslipidemia are at increased risk of developing erectile dysfunction (ED); hence, statins exert a protective effect. At the same time, the administration of these drugs reduce endothelial dysfunction, a key etiopathogenetic factor in the onset of ED. Moreover, statins are universally considered a key element of secondary prevention for vascular events; therefore, several points are opened. In this critical summary, we attempt to evaluate the effects of statins on ED and to understand the mechanisms through which statins improve the quality of erection and the possible synergism with V phosphodiesterase inhibitors, drugs largely used for the treatment of ED.

The effect of rosuvastatin and atorvastatin on erectile dysfunction in hypercholesterolemic patients

         (Nurkalem, Yildirimturk et al. 2014) Download

OBJECTIVE: The aim of this study was to evaluate effect of different statin types on erectile dysfunction in hypercholesterolemic patients. METHODS: Ninety male hypercholesterolemic patients (mean age 50.4+/-7.9 years) who are otherwise healthy were included into the study prospectively. None of patients had any cardiovascular risk factors except hypercholesterolemia. Patients were divided into two different groups. One of the groups have received atorvastatin while the other groups was given rosuvastatin. All patients were followed for 6 months and IIEF score and blood samples were re-evaluated. RESULTS: Patients were in similar ages in both groups. There were also no statistical differences in terms of blood glucose levels, total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG) and mean IIEF score in both groups at the beginning. After 6 months, no IIEF score changes has been observed in Group-1 after the medication however, IIEF score was significantly lower in Group-2 (p=0.019). There was no difference in IIEF scores between 2 groups after statin therapy. CONCLUSIONS: It has been suggested that statins may cause ED secondary to inhibition of testosterone synthesis. Rosuvastatin showed no effect on ED while we observed an increased ED with atorvastatin, however there were no difference between both groups. Our study reveals that different statin types may have different effect on ED.

Healthy men should not take statins

         (Redberg and Katz 2012) Download

Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature CHD be treated with a statin? —No.

Do lipid-lowering drugs cause erectile dysfunction? A systematic review

         (Rizvi, Hampson et al. 2002) Download

BACKGROUND: Erectile dysfunction (ED) is common although under-reported by patients. Along with the better known causes of ED, drug-induced impotence needs to be considered as a cause of this symptom. Lipid-lowering drugs have been prescribed increasingly. Their relationship to ED is controversial. OBJECTIVES: Our aim was to clarify the relationship between lipid-lowering therapy and ED. A secondary aim was to assess the value of the systematic review procedure in the area of adverse drug reactions. METHODS: A systematic review was carried out using computerized biomedical databases and Internet sources. Terms denoting ED were linked with terms referring to lipid-lowering drugs. Information was also sought from regulatory agencies. RESULTS: A significant literature was identified, much from obscure sources, which included case reports, review articles, and information from clinical trials and from regulatory agencies. Information from all of these sources identified fibrates as a source of ED. A substantial number of cases of ED associated with statin usage have been reported to regulatory agencies. Case reports and clinical trial evidence supported the suggestion that statins can also cause ED. Some information on possible mechanisms was obtained, but the mechanism remains uncertain. CONCLUSIONS: The systematic review procedure was applied successfully to collect evidence suggesting that both statins and fibrates may cause ED. More numerous reports to regulatory agencies complemented more detailed information from case reports to provide a new perspective on a common area of prescribing.

The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials

         (Schooling, Au Yeung et al. 2013) Download

BACKGROUND: Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone. METHODS: A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. RESULTS: Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13). CONCLUSIONS: Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.


References

Beckman, J. A. (2012). "Use of statins in healthy men." JAMA 308(7): 666; author reply 666-7. [PMID: 22893156]

La Vignera, S., R. A. Condorelli, et al. (2012). "Statins and erectile dysfunction: a critical summary of current evidence." J Androl 33(4): 552-8. [PMID: 22052777]

Nurkalem, Z., O. Yildirimturk, et al. (2014). "The effect of rosuvastatin and atorvastatin on erectile dysfunction in hypercholesterolemic patients." Kardiol Pol. [PMID: 24142756]

Redberg, R. F. and M. H. Katz (2012). "Healthy men should not take statins." JAMA 307(14): 1491-2. [PMID: 22496261]

Rizvi, K., J. P. Hampson, et al. (2002). "Do lipid-lowering drugs cause erectile dysfunction? A systematic review." Fam Pract 19(1): 95-8. [PMID: 11818357]

Schooling, C. M., S. L. Au Yeung, et al. (2013). "The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials." BMC Med 11: 57. [PMID: 23448151]