Is lipid lowering treatment aiming for very low LDL levels safe in terms of the synthesis of steroid hormones?

Med Hypotheses. 2007;69(1):104-12. doi: 10.1016/j.mehy.2006.10.058. Epub 2007 Jan 17.


Today atherosclerotic diseases are among the most important causes of death in the world. Epidemiological, clinical, genetic, experimental and pathological studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is the major atherogenic lipoprotein and has been defined as the primary target of lipid lowering treatment by NCEP. Although the level of LDL, the primary target in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to below 70 mg/dl for the group defined as very high risk group by the ATP (Adult Treatment Panel) guide that has been updated following the new clinical studies. As we already know, cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids, besides being a structural component of the cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid hormones are primarily synthesized using the LDL-cholesterol in the circulation. In addition to this, there is 'de novo' cholesterol synthesis in both the adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway, which under normal circumstances has little contribution as compared to the first two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is quite limited. However, since statins both decrease circulatory LDL and inhibit de novo cholesterol synthesis, they are likely to affect the synthesis of steroid hormones.

MeSH terms

  • Clinical Trials as Topic
  • Endocrine System Diseases / blood*
  • Endocrine System Diseases / chemically induced*
  • Evidence-Based Medicine
  • Gonadal Steroid Hormones / biosynthesis*
  • Humans
  • Hyperlipidemias / blood*
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / adverse effects*
  • Lipoproteins, LDL / blood*
  • Risk Assessment / methods
  • Risk Factors


  • Gonadal Steroid Hormones
  • Hypolipidemic Agents
  • Lipoproteins, LDL