Effect of Atorvastatin on SHBG levels in Men

[Youthful55guy]

In several recent forum posts, we've discussed the possibility that the use of the statin Atorvastatin may lower testosterone production in men and/or SHBG production. I conducted a search of the medical literature using PubMed and did not find much in the way of published research. I conclude that the effect on testosterone is mostly conjecture and not supported by clinical data. The little data that does exist does not support the theory.


I searched the literature using these terms: (((atorvastatin) OR Lipitor)) AND ((((((sex) AND hormone) AND binding) AND globulin)) OR SHBG). I found 7 articles, 4 of which were of women with polycystic ovaries and not applicable. The remaining 3 papers were wither of men or analyzed the data for men and women separately.

I conclude from these 3 studies that Atorvastatin may have a very small effect on SHBG production in men, but the effect is probably not clinically relevant. It is interesting that these studies (an internet chatter) point to the reduction of cholesterol, which is a distant upstream precursor for testicular androgen syntheses, as a potentially reducing circulating testosterone levels in men treated with Atorvastatin. However, there is no direct proof that testosterone production is actually effects, only that Total (but not Free) T is directionally lower in Atorvastatin treated patients. I propose that this may be a measurement artifact.I offer up a different theory based on my own observations. Testosterone production may not be affected at all by treatment with Atorvastatin. However, Atorvastatin may have a small effect on reduction of SHBG levels, which means that there is a shift in testosterone toward free T, which is more susceptible to liver metabolism and excretion. Thus, decreasing the level of measured (not produced) Total testosterone.

Here's a summary of the 3 articles that I was able to find in the literature. Two of the articles are available Open Access for you to read. The third one I accessed through my work.

Study 1
Interesting study in 355 men with Type 2 Diabetes showing a non-significant reduction of SHBG with use of Atorvastatin (n=81) compared to untreated (n=186) men with Type 2 Diabetes (35.3 vs 27.6 nmol/L, p=0.022). There was also a significant (==0.006) reduction in Total Testosterone but not Bioavailable or Free Testosterone or Estradiol compared to no treatment. A limitation of the study was that there were varying doses and not all doses were known for all men.An analysis of a sub-population of study participants where Atorvastatin doses were known shows a dose-response effect in lowering of SHBG with use of Atorvastatin, which became significant at doses ³20 mg. Mean levels of SHBG in the non-treated (n=186), 10 mg (n=38), and ³20 (n=14) mg groups were 35.3, 30.1, 21.7 nmol/L, respectively. The 10 mg group was directionally but no significantly reduced compared to the non-treated group (p=0.322). The ³20 mg was statistically reduced (==0.043), though the number of participants was small.

Stanworth, R.D., Kapoor, D., Channer, K.S., and Jones, T.H. (2009). Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care 32, 541-546. PMID 19114614 (https://www.ncbi.nlm.nih.gov/pubmed/19114614). Full text Open Access.

Study 2
A larger study of men with coronary heart disease did not find a correlation between Atorvastatin use and either Total Testosterone (p=0.27), Free Testosterone (p=0.42), or SHBG levels (p=0.31). In this study basal and 12 week post-treatment follow up levels were measured and statistically compared for a group of 83 men treated with 10-20 mg/day and 77 men treated with 40-80 mg/day.

Kocum, T.H., Ozcan, T.I., Gen, R., Tekin, A., Erol, T., Akcay, B., and Doven, O. (2009). Does atorvastatin affect androgen levels in men in the era of very-low LDL targeting therapy? Exp Clin Endocrinol Diabetes 117, 60-63. PMID 18523929 (https://www.ncbi.nlm.nih.gov/pubmed/18523929). Not Open Access.

Study 3
A third study also did not find any reduction in either Total Testosterone or SHBG in 16 men after 3 months of treatment with 20 mg/day Atorvastatin. Full text Open Access.

Santini, S.A., Carrozza, C., Lulli, P., Zuppi, C., CarloTonolo, G., and Musumeci, S. (2003). Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia. J Atheroscler Thromb 10, 160-164. PMID 14564085 (https://www.ncbi.nlm.nih.gov/pubmed/14564085)

[Quester]

Nice work.
This is something that, unfortunately, will likely have strong relevance to this community. I wonder if the conjecture (false) is based upon the fact that cholesterol is necessary for steroidogenesis? Which makes me wonder if it is also false conjecture that testosterone replacement decreases the use of cholesterol in steroidogenisis leading to higher cholesterol levels? My dad takes Lipitor (atorvastin), I am happy to know it will be an option if I need it one day.
Thanks

[Youthful55guy]

Nice work.
This is something that, unfortunately, will likely have strong relevance to this community. I wonder if the conjecture (false) is based upon the fact that cholesterol is necessary for steroidogenesis? Which makes me wonder if it is also false conjecture that testosterone replacement decreases the use of cholesterol in steroidogenisis leading to higher cholesterol levels? My dad takes Lipitor (atorvastin), I am happy to know it will be an option if I need it one day.
Thanks

Granted I'm an N of 1, but my cholesterol did go up pretty much the same time as I started TRT. Given I have a long history of testing prior to TRT where my total cholesterol was under 200, I don't think having it go up into the 230 to 260 range shortly after starting TRT was not a coincidence. I took a couple of years for my doc to convince me to try Atorvastatin (10 mg daily). There were no side-effects that I could discern and my cholesterol came back down under 200 and has remained there for several years.


So, the damming up of cholesterol may be a real phenomena, but the research pretty conclusively shows that lowering of cholesterol does not have a clinically significant effect on the synthesis of downstream steroid hormones, or at least not testosterone . I believe the little data that shows a reduction in total testosterone may be more due to a weak effect on lowering SHBG.