Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.

Abstract

1. Adrenal and gonadal steroids are derived from cholesterol, which may be derived from plasma lipoproteins or de novo synthesis. 2. Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme in cholesterol synthesis, may therefore affect steroidogenesis when used as lipid‐lowering agents in hypercholesterolaemia. 3. We have assessed gonadal and adrenal function in subjects with heterozygous familial hypercholesterolaemia (FH) before and after 12 weeks treatment with pravastatin, an HMG CoA reductase inhibitor, or cholestyramine as a control in maximal recommended doses. 4. No changes in measured plasma cortisol responses to tetracosactrin injection were seen in 11 patients on cholestyramine or 12 on pravastatin. 5. No changes were seen in testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17 alpha‐hydroxyprogesterone. 6. Gonadotrophin levels were unaffected in 10 male subjects on cholestyramine and 7 on pravastatin. 7. Measurements on a subset of subjects continuing to 24 weeks treatment also showed no changes. 8. No adverse effect on adrenal or gonadal function could be demonstrated in patients with familial hypercholesterolaemia on maximal recommended doses of pravastatin.

Effects of Evolocumab on Vitamin E and Steroid Hormone Levels

“…24,27,29,30,[37][38][39][40]45,[52][53][54] Studies that included female patients found no change in ovarian steroidogenesis. 26,38,40,54 Our study confirms these findings and extends them to patients with very low levels of LDL-C. This is the first publication describing vitamin E and steroid hormone levels in patients treated with monoclonal antibodies to PCSK9.…”

“…35,36 The impact of statins on adrenal function has been studied in multiple populations with a wide variety of statins. 23,[25][26][27][28][29]31,32,[37][38][39][40][41][42][43][44][45] None of these studies showed clinically relevant impairment of adrenal function, secondary to statin therapy. Patients with heterozygous or homozygous familial hypercholesterolemia could also theoretically be at increased risk of adrenal dysfunction because of their reduced capacity to use LDL receptor-mediated cholesterol uptake.…”

“…46 In addition, studies involving both heterozygous and homozygous patients with familial hypercholesterolemia did not find any evidence of impaired adrenal function as a consequence of statin therapy. 26,28 Animal studies have also showed that LDL-C or LDL receptor activity are not required for steroid hormone production 47 and that absence of receptor-mediated endocytosis of cholesterol from LDL particles does not alter the cholesterol balance in extrahepatic organs, further showing that the role of cholesterol derived from LDL particles is minimal in the production of steroid hormones. 48 The adrenal safety of pharmacologically lowering LDL-C to levels <1.0 mmol/L (40 mg/dL) has not been studied in detail previously because currently available lipid-lowering therapy is unable to achieve such low levels in a significant proportion of patients.…”

“…[23][24][25][26][27][28][29][30][31][32] Some of this concern was based on studies in isolated patients with abetalipoproteinemia and homozygous hypobetaliproteinemia showing mildly raised ACTH levels, normal cortisol levels, and a blunted response to prolonged ACTH stimulation. 33,34 Further studies of abetalipoproteinemic patients have not always confirmed these early observations, although the endocrine evaluations undertaken have varied substantially.…”

Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia

“…These findings are consistent with the data from studies evaluating the effect of long-term statin therapy on gonadal and adrenal steroid production in adults. 32,33 The hypothalamic feedback factors (LH and FSH) for the gonadal hormones were difficult to evaluate because of the great variability and large proportion of nondetectable plasma levels. However, Tanner stage, testicular volume, and menstrual cycle length exhibited the normal pattern, and simvastatin (40 mg) did not appear to …”