Does statin therapy influence steroid hormone synthesis?

Statins reduce cholesterol and isoprenoid de novo biosynthesis as well as receptor mediated uptake of cholesterol for steroidogenesis. The present randomized placebo-controlled trial investigated whether pravastatin (40 mg/day) reduces the plasma concentrations of steroid hormones as well as of gonadotropins. Patients (n = 22; 15 males, 7 females) were treated with pravastatin (40 mg/day) or placebo. Levels of total and LDL cholesterol, the steroid hormones estradiol, testosterone, cortisol and dehydroepiandrosterone sulphate (DHEAS) as well as FSH and LH were studied. Pravastatin led to a significant reduction of total cholesterol and LDL cholesterol. There was no significant change in estradiol, testosterone, cortisol or DHEAS plasma concentrations. There was no compensatory change in FSH or LH. It is concluded that pravastatin does not alter steroid hormones or gonadotropins in a clinically applicable dose, which significantly reduces total and LDL cholesterol.     

Who should receive hormone replacement therapy?

Coronary heart disease is the leading cause of death in women in the United States and increases dramatically in postmenopausal women. The following review summarizes the known benefits and risks of hormone replacement therapy and gives recommendations for use of hormone replacement in women. Estrogen may play a role in preventing the development of atherosclerosis in women by raising levels of HDL cholesterol, lowering levels of LDL cholesterol and lipoprotein (a), lowering levels of fibrinogen and plasminogen activator inhibitor-1, dilating coronary arteries, preventing the oxidation of LDL cholesterol, decreasing the proliferation and migration of smooth muscle cells, and decreasing the production of inflammatory cell activators. These anti-atherogenic effects of estrogen may translate into clinical benefits. A meta-analysis of 31 studies yielded a 44% reduction in the risk of coronary heart disease in women taking estrogen alone. Unopposed estrogen is associated with an increased risk of endometrial cancer; therefore, progestin is added to estrogen in women with an intact uterus. Less is known about the effect of the combination of estrogen and a progestin on the risk of coronary heart disease. Estrogen is also beneficial in the prevention of osteoporosis; however, long-term use of estrogen alone and estrogen in combination with progestin may increase the risk for breast cancer. Mathematical modeling predicted that women with no risk for cardiovascular disease, cancer, or osteoporosis may gain 0.9 years of life with the use of estrogen alone; women with risk factors for cardiovascular disease can expect to gain 1.5 years of life; and women with coronary heart disease at the age of 50 can expect to gain 2.1 years of life. The current American College of Physicians recommendations for hormone replacement are as follows: (1) All women should be considered; (2) women with a hysterectomy should receive estrogen alone; (3) women at risk for, or with, coronary heart disease are most likely to benefit from estrogen; with an intact uterus, progestin must be added; (4) risks of estrogen may outweigh benefits in women at increased risk for breast cancer. Definitive guidelines for the treatment of women must await the results of randomized clinical trials in the ongoing Women's Health Initiative. These will not be available for several years, and until then any recommendations for women will have to be judged from estimates of risk rather than of benefit from reduction of risk. The decision whether to initiate estrogen replacement in postmenopausal women is one that still needs to be made on an individual patient basis.Supported by NHLBI grant HL 02626. Dr. Welty is the 1995 recipient of the Alpha Phi Foundation Award.     

Can a healthy endothelium influence the cardiovascular effects of hormone replacement therapy?

Emerging clinical and observational evidences suggest that estrogen confers physiologic benefits that are receptor mediated and depend on the integrity and functional status of the endothelium within the coronary vasculature. In postmenopausal women, estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) regimens can enhance the lipoprotein panel; blunt the expression of numerous cytokines, chemokines, and other proinflammatory mediators of endothelial injury and vascular smooth muscle cell proliferation; up-regulate endothelial nitric oxide synthase activity and nitric oxide production; and augment fibrinolysis potential and vasodilator capacity (diminish arterial resistance). Advancing age and atherosclerotic injury to the vessel wall tend to deplete estrogen receptors, compromise endothelial function, promote thrombus formation, and thus potentially diminish the efficacy of ERT and HRT. Therefore, optimizing the clinical benefits of these regimens in postmenopausal women depends largely on promoting a healthy endothelium through life-style modifications that diminish coronary risk.     

Shouldn't adults with growth hormone deficiency be offered growth hormone replacement therapy?

Growth hormone as therapy for adults with growth hormone deficiency has not been universally accepted by endocrinologists who treat adult patients. The following are addressed in this commentary: the evidence on safety and efficacy in the literature supporting the idea that growth hormone should be offered as replacement therapy to adults who are growth hormone deficient; common concerns of the average prescribing endocrinologist, including the purported association between insulin-like growth factor-I and malignant neoplasms and quality-of-life issues with long-term therapy; and controversial subjects, such as differences in dosing for adults versus children and diagnostic issues. This analysis should encourage reluctant practitioners to at least consider growth hormone replacement therapy for patients with definite growth hormone deficiency--that is, patients with symptomatic panhypopituitarism.     

What is the cardioprotective role of hormone replacement therapy?

A very large body of literature has yielded strong biologic and mechanistic plausibility for the consistent observational findings that estrogen is cardioprotective. Recently completed randomized, controlled trials have been interpreted as challenging the doctrine that hormone replacement is cardioprotective for postmenopausal women. However, other than the Estrogen in the Prevention of Atherosclerosis Trial, none of the currently completed (and no ongoing) randomized, controlled trials have appropriately tested the hypothesis generated from observational data that estrogen replacement is cardioprotective. This mainly results from the fact that randomized, controlled trials have not tested the same pattern and type of hormone use in the same population of women observed in the epidemiologic studies. On the other hand, recently completed randomized, controlled trials provide important but limited information concerning the clinical use of a specific regimen of hormone replacement for the prevention of cardiovascular disease in a particular population of postmenopausal women. Observations made from epidemiologic studies will have to be appropriately tested in randomized, controlled trials before any real conclusions can be drawn as to whether hormone replacement is cardioprotective.     

Anterior pituitary hormone replacement therapy—a clinical review

This clinical review summarizes current approaches to diagnosis and treatment of anterior pituitary hormone deficiency. The diagnostic value of endocrine function tests and replacement strategies for hydrocortisone, thyroxine, sex steroids, and growth hormone replacement are reviewed. Female androgen deficiency syndrome and the current role of DHEA and testosterone replacement in women are also discussed.     

Does antioxidant therapy influence every aspect of quality of life?

To present problems that might severely impact the conclusions drawn by the authors of an article on antioxidant treatment in chronic pancreatitis (World J Gastroenterol 2010; 16: 4066-4071). We analyzed and discussed this paper by Shah et al, and found that promising as it is, this study has some methodological shortcomings, such as: cross-sectional nature of the study, lack of initial evaluations of quality of life and regular follow-ups to determine the dynamics and real directions of changes in quality of life. We therefore concluded that the results of the study by Shah et al are biased and, although very promising, should not be considered as scientifically relevant.     

Does intensive medical therapy influence the outcome in unstable angina?

Three hundred and forty-six patients of all ages and both sexes were admitted to coronary care with documented unstable angina. Management was conservative, without the routine use of beta-blockers or calcium antagonists. Mortality was 3.2%, and the nonfatal myocardial infarction rate was 10.1% during the first 28 days. After one year, coronary mortality was 10.5% with a nonfatal infarction rate of 13.1%. Twenty-six patients were subjected to coronary artery bypass surgery, eleven during the first 28 days and fifteen subsequently. No patient underwent coronary angioplasty. The factors influencing immediate and long-term prognosis in these patients were studied. Persistence of pain in hospital, previous chronic angina, and age had an adverse effect on outcome. A total of 143 patients complained of persistent pain lasting for 24 hours or more. The use of beta blockers or calcium antagonists in patients with persistent pain exceeding five days did not appear to influence outcome. The current widespread adherence to "intensive medical treatment," including the routine use of beta blockers and calcium antagonists, is questioned.