Polyphenols of Antibacterial Potential - May They Help in Resolving Some Present Hurdles in Medicine?

The phenomenon of antibiotic resistance has been recognized as one of the greatest threats to humanity. Therefore, there is an enormous need to introduce new antibiotics to the medical practice that will effectively eradicate the resistant bacterial strains threatening human health and life. One solution currently being considered as an alternative to antibiotics involves secondary metabolites of plants that can be used in modern antibacterial therapy. Polyphenols represent a broad and diversified group of plant-derived aromatic compounds. Their antibacterial potential has been recognized via specific mechanisms of action, e.g., by inhibition of bacterial biofilm formation, through synergistic effects with the action of currently used antibiotics, and by inhibition of the activity of bacterial virulence factors.

A Neutral Effect of Metformin Treatment on Macroprolactin Content in Women with Macroprolactinemia.

Background: Metformin decreases serum levels of monomeric prolactin. No previous study has investigated the effect of metformin on macroprolactin content in patients with macroprolactinemia. Methods: We studied three age-, sex- and weight-matched groups of patients: 15 women with monomeric prolactin, 12 women with macroprolactin, as well as 15 women with normal prolactin levels. Because of coexisting 2 diabetes or prediabetes all patients were treated with metformin (1.7-3 g daily). Plasma lipids, glucose homeostasis markers, as well as serum levels of prolactin and macroprolactin were assessed at baseline and after 4 months of metformin treatment. Results: As expected, metformin reduced plasma glucose and triglycerides, as well as improved insulin sensitivity in all treatment groups. Moreover, the drug reduced post-polyethylene glycol prolactin levels and tended to reduce pre-polyethylene glycol prolactin levels in women with monomeric prolactin but not in women with macroprolactinemia and women with normal prolactin levels. Conclusion: The obtained results indicate that metformin has a negligible effect on macroprolactin levels.

The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study.

Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high-dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy.

Obesity, ultrasound indexes of fat depots and lipid goal attainment in patients with high and very high cardiovascular risk: A novel approach towards better risk reduction.

AIM: Our aim was to assess the attainment of primary (low density lipoprotein cholesterol; LDL-C) and secondary (non-high density lipoprotein cholesterol; non-HDL-C) lipid therapeutic goals in relation to obesity, clinical measures of adiposity and ultrasound indexes of fat depots, including the novel index of periarterial adipose tissue (PAT): carotid artery extra media thickness (EMT). METHODS AND RESULTS: High and very high cardiovascular (CV) risk patients (n = 420; F/M: 34/66%; age: 61.2 ± 7 years) with prior statin treatment (≥ 18 months) were enrolled into this cross-sectional study. All patients had a detailed assessment with several anthropometric measures and ultrasound indexes of fat depots indexed to BMI: abdominal (Intra-abdominal Fat Thickness; IAT and Pre-peritoneal Fat Thickness; PreFT), paracardial (Epicardial Fat Thickness; EFT and Pericardial Fat Thickness; PFT) and the new index corresponding to PAT (carotid EMT). Lipid goals attainment in the study group was as follows: 34% (LDL-C goal), 39% (non-HDL-C goal) and 35% (both LDL and non-HDL-C goals). Among ultrasound indexes, patients with both lipid goals attainment revealed significantly lower carotid EMT/BMI (LDL-C goal: 25.2 ± 4.2 vs 27.5 ± 4.1, p < 0.01 and non-HDL-C goal: 26.1 ± 4 vs 27.7 ± 4.2, p < 0.01) and IAT/BMI (LDL-C goal: 2.35 ± 0.66 vs 2.51 ± 0.71, p = 0.02 and non-HDL-C goal: p = ns) compared to individuals without goals achievement. Moreover, lipid goals attainment was associated with both measures: carotid EMT/BMI (LDL-C goal: r = -0.2, p < 0.05 and non-HDL-C goal: r = -0.2, p < 0.05) and IAT/BMI (LDL-C goal: r = -0.2, p < 0.05 and non-HDL-C goal: r = -0.2, p < 0.05). Multivariable regression analysis showed also independent association between carotid EMT/BMI and both goals achievement: LDL-C (p = 0.01) and non-HDL-C goal (p = 0.01). Other fat depots indexes (EFT, PFT and PreFT) failed to provide additional data. CONCLUSION: Contrary to overall obesity and most clinical measures of adiposity, carotid EMT and abdominal IAT, but not other ultrasound indexes of fat depots revealed associations independent from BMI with lipid goal attainment and may help identify patients requiring more aggressive lipid management.

The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study.

BACKGROUND: One of the most frequent adverse effects of interferon-α therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with interferon-induced thyroiditis. METHODS: The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto's thyroiditis (n=12). Fasting plasma glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. RESULTS: Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto's thyroiditis, as well as correlated with its impact on insulin sensitivity. CONCLUSIONS: Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism.

The Effect of Simvastatin on Plasma Steroid Hormone Levels in Metformin-Treated Women with Non-Classic Congenital Adrenal Hyperplasia.

Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the presence of hyperandrogenism. Recently both simvastatin and metformin were found to reduce plasma steroid hormone levels in this disorder. This study included 8 women with NC-CAH and diabetes or impaired glucose tolerance, as well as 12 matched women with similar glucose metabolism abnormalities but normal adrenal function. Both groups of women, receiving metformin for at least 6 months, were then treated with simvastatin (20 mg daily) for the following 12 weeks. Compared to patients with normal adrenal function, metformin-treated women with NC-CAH showed increased plasma levels of 17-hydroxyprogesterone, total testosterone, free testosterone, androstenedione and DHEA-S. Simvastatin reduced total and LDL cholesterol levels in both patients with NC-CAH and normal adrenal function. Moreover, in the former group of women, statin therapy decreased plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and tended to reduce 17-hydroxyprogesterone. Our results suggest that metformin-statin combination therapy may be useful in the management of symptomatic women with NC-CAH.

The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis.

The study included 38 non-lactating l-thyroxine-treated women with postpartum thyroiditis (PPT) and 21 matched healthy postpartum women. Women with vitamin D deficiency were treated with oral vitamin D (4000 IU daily), whereas women with vitamin D insufficiency and women with normal 25-hydroxy vitamin levels were either treated with vitamin D (2000 IU daily) or left untreated. Serum hormone levels and thyroid antibody titers were measured at the beginning of the study and 3 months later. 25-hydroxy vitamin D levels were lower in women with PPT than in healthy women. Thyroid peroxidase and thyroglobulin antibody titers inversely correlated with vitamin D status. Apart from increasing serum levels of 25-hydroxy vitamin D and decreasing serum levels of parathyroid hormone, vitamin D reduced titers of thyroid peroxidase antibodies and this effect was stronger in women with vitamin D deficiency. The study's results suggest that vitamin D supplementation may bring benefits to l-thyroxine-treated women with PPT.

The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance.

No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone.

Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto's Thyroiditis and Glucose Metabolism Abnormalities.

Metformin was found to reduce serum thyrotropin levels in patients with hypothyroidism. This effect was less pronounced if patients were additionally treated with bromocriptine. The study included 39 premenopausal women with autoimmune thyroiditis and thyrotropin levels exceeding 3.0 mU/L. All patients had been treated for at least 6 months with bromocriptine (5.0-7.5 mg daily) or cabergoline (0.5-1.0 mg weekly). Because of coexisting type 2 diabetes or impaired glucose tolerance, they were then given metformin (1.7-2.55 g daily). Glucose homeostasis markers, thyroid antibody titers, as well as serum levels of thyrotropin, total and free thyroid hormones and prolactin were determined before and after 6 months of metformin treatment. At baseline, cabergoline-treated patients were less insulin resistant as well as tended to have lower levels of prolactin than bromocriptine-treated patients. Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline. However, only in bromocriptine-treated patients, metformin decreased serum thyrotropin and this effect reached the level of significance in a subgroup of patients with subclinical hypothyroidism. Neither in cabergoline- nor in bromocriptine-treated patients, metformin affected thyroid hormone levels and thyroid antibody titers. Our results indicate that the effect of metformin on hypothalamic-pituitary-adrenal axis activity is partially determined by endogenous dopaminergic tone, thyrotrope activity and insulin sensitivity.

The association between macroprolactin levels and vitamin D status in premenopausal women with macroprolactinemia: a pilot study.

BACKGROUND: Macroprolactinemia is a frequent cause of misdiagnosis and mismanagement of patients with elevated prolactin levels. Its pathogenesis and clinical significance are still controversial. METHODS: The aim of this study was to investigate the relationship between elevated macroprolactin content and vitamin D status. The study population included 20 premenopausal women with isolated macroprolactinemia, 10 of whom were later treated with vitamin D (2 000 IU daily). Serum prolactin, macroprolactin, 25-hydroxyvitamin D and PTH levels were assessed at baseline and after 4 months of treatment. RESULTS: Compared with the control age- and weight-women with normal prolactin levels (n=11), patients with macroprolactinemia were characterized by lower levels of 25-hydroxyvitamin D and slightly higher levels of PTH. Vitamin D administered to patients with macroprolactinemia increased 25-hydroxyvitamin, reduced total prolactin and macroprolactin, as well tended to reduce PTH. The effect of vitamin D on total prolactin and macroprolactin correlated with their baseline values and baseline 25-hydroxyvitamin D levels. CONCLUSIONS: The results of our study suggest the association between vitamin D status and elevated macroprolactin levels in premenopausal women.

Different effects of atorvastatin on metabolic and cardiovascular risk factors in hypercholesterolemic women with normal thyroid function and subclinical hypothyroidism.

BACKGROUND: The presence of hypothyroidism seems to be associated with increased cardiovascular risk. No previous study compared circulating levels of plasma lipids and other cardiovascular risk factors in statin-treated patients with different thyroid function states. METHODS: We studied 15 women with untreated subclinical hypothyroidism (group A), 16 women with treated hypothyroidism (group B) and 17 women with normal thyroid function (group C) who, because of coexistent hypercholesterolemia, were treated with atorvastatin. Plasma lipids, glucose homeostasis markers and plasma levels of cardiovascular risk factors were assessed before and after 12 weeks of therapy. 46 patients completed the study. RESULTS: Baseline lipid levels were similar in all groups of patients. Plasma levels of high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were higher in group A than in groups B and C. Although the effect on total and LDL cholesterol was observed in all treatment groups, it was less pronounced in patients with untreated hypothyroidism. Similarly, the effect of atorvastatin on hsCRP, homocysteine, fibrinogen and uric acid was stronger in groups B and C than in group A. CONCLUSIONS: Our results suggest that the effect of atorvastatin on plasma lipids and circulating levels of other cardiovascular risk factors partially depends on thyroid function.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism.

The effect of atorvastatin and atorvastatin-ezetimibe combination therapy on androgen production in hyperandrogenic women with elevated cholesterol levels.

Statins decreased serum androgen levels in hyperandrogenemic women with polycystic ovary syndrome. No previous study has investigated whether this effect is dose-dependent and observed in patients simultaneously treated with other hypolipidemic agents. The study included 23 premenopausal women with elevated total testosterone levels coexisting with hypercholesterolemia, unsuccessfully treated for at least 6 months with atorvastatin (20 mg daily). These patients were then treated with either an increased dose of atorvastatin (40 mg daily, n=11) or atorvastatin (20 mg daily) plus ezetimibe (10 mg daily) (n=12). Plasma lipids, glucose homeostasis markers and serum levels of androgens, sex hormone-binding globulin and gonadotropins were assessed at baseline and after 3 months of treatment. Although both treatments decreased plasma levels of total and LDL-cholesterol levels, only high-dose atorvastatin reduced serum levels of total testosterone, free testosterone and androstendione. The effect of high-dose atorvastatin on serum androgen levels did not differ between insulin-resistant and insulin-sensitive subjects. The obtained results suggest that atorvastatin reduces serum androgen levels in a dose-dependent manner and that its administration in a higher dose is associated with a more pronounced effect on serum androgens than combination therapy with low-dose atorvastatin and ezetimibe.

The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia.

Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the clinical features of hyperandrogenism. This study included 19 women with recently diagnosed and previously untreated type 2 diabetes, 8 of whom suffered from NC-CAH, treated with metformin (2.55-3.0 g daily). Glucose homeostasis markers, plasma lipids, as well as plasma levels of 17-hydroxyprogesterone, androgens and gonadotropins were assessed at baseline and after 6 months of therapy. In both groups of patients, metformin reduced fasting plasma glucose, insulin resistance, triglycerides and glycated hemoglobin. Moreover, in patients with NC-CAH, but not in women with normal adrenal function, metformin decreased plasma levels of 17-hydroxyprogesterone, total and free testosterone, androstenedione and dehydroepiandrosterone sulphate. The obtained results suggest that metformin partially normalizes androgen production in symptomatic patients with NC-CAH.

Porcine endogenous retrovirus (PERV) infection of HEK-293 cell line alters expression of human endogenous retrovirus (HERV-W) sequences.

The risk of infections of human recipients after xenotransplantations is now mainly represented by porcine endogenous retroviruses (PERVs) as these particles are part of the porcine genome. As in all vertebrates, human genome harbours its own numerous genetic sequences of retroviral origin; it is estimated that they comprise about 8 % of the human genome. Because some of them play an important role in human physiology, it is valuable to estimate whether the presence of PERVs in human cells influences homeostasis of the human endogenous retrovirus (HERV) expression pattern. The aim of the study was to evaluate whether the expression profile of HERV-W genes changes after infection of cells by porcine endogenous retroviruses. In the experimental settings, human embryonic kidney cell line (HEK-293) was infected by PERV particles and cultivated up to 22th passage after infection. HERV-W gag, pol and env, as well as env from locus 7q21.2 gene expression was monitored by means of realtime reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot techniques. We found that the expression level of HERV-W genes differs in PERV-infected HEK-293 cell cultures in comparison with that from non-infected cultures. Relative HERV-W gene expression also differed significantly between particular passages (P < 0.05). Moreover, we have noticed a high correlation between the HERV-W Env(7q21.2) mRNA and protein level (Spearman rank r = 0.65; P < 0.05) during the course of the experiment. As previously hypothesized, human genomic sequences of retroviral origin may be changed by the presence of porcine endogenous retroviruses.

The emering role of helminths in treatment of the inflammatory bowel disorders.

The problem of immune-mediated diseases, such as inflammatory bowel disorders (IBDs), still remains a significant clinical and therapeutic problem. Therefore, the tendency to search for safer and more effective methods of reducing their incidence and increasing the efficiency of therapy of this group of diseases is understandable. Recently, attention has been drawn to the potential therapeutic influence of intestinal helminths on the inflammatory process induced by the immune response, as well as the observed significant potential of these organisms for modulating the host immune response, which is beneficial both for the dwelling parasite and the host with an IBD. It has been proven that the effects of certain intestinal helminths on the host immune system are complex and omni-directional. They involve the modulation of TLRs expression, causing proliferation and activation of TH2 lymphocytes, leading to proliferation of regulatory T cells (TREG), and production of immunomodulatory proteins, such as cystatins and glycoprotein ES-62. In the developing countries of Africa, South America and Asia, where the level of personal and environmental hygiene is relatively low, the incidence of autoimmune diseases is also significantly lower. Limited exposure to common bacterial and parasitic pathogens in populations of very highly developed countries has probably contributed to depletion of immunological memory and the development of hypersensitivity mechanisms. Thus, reasonable suggestions have been made that the host-parasite biocenotic relationship between humans and nematodes of the gastrointestinal tract can be considered as a mutualism, rather than a typical parasitism, and may in the future be used as an alternative therapeutic model for IBD patients.

Potentiation of Endocrine Adverse Effects of Lithium by Enalapril and Verapamil.

Lithium, which is widely used in the management of patients with bipolar disorder, may alter the function of some endocrine organs, particularly the thyroid and parathyroid glands, as well as it may reduce the sensitivity of the kidneys to vasopressin. In most lithium-treated patients, endocrine abnormalities are limited to one endocrine organ and are observed only after long-term lithium therapy. The patient reported in this study developed hypothyroidism, hyperparathyroidism and nephrogenic diabetes insipidus. However, the last two disorders were induced by a small increase in plasma lithium levels as a result of the treatment with enalapril and verapamil. This case shows that patients at high risk of thyroid, parathyroid or renal disorders receiving lithium should not be treated with drugs known to interfere with plasma lithium levels.

Relapse of asthma after surgical treatment of Cushing's syndrome.

Endogenous overproduction of glucocorticoids may mask the clinical course of some inflammatory/ autoimmune disorders. In the present paper, we report a man with a history of asthma, which spontaneously remitted after 20 years of duration. Several years later, he was diagnosed with Cushing's syndrome of pituitary origin and underwent transsphenoidal microsurgery of an ACTH-producing pituitary adenoma. Shortly after tumour removal, he developed a severe asthmatic attack requiring hospitalisation and intensive treatment. We conclude that patients with Cushing's syndrome and coexisting inflammatory/autoimmune disorders should be closely supervised after normalisation of cortisol production for exacerbation of the associated disease and would eventually benefit from glucocorticoid treatment.

Highly organized nanostructures for brain drug delivery--new hope or just a fad?

The blood-brain barrier significantly impedes treatment of central nervous system disorders by preventing drug entry into the brain. Several strategies have been developed to overcome this problem, but progress has been hampered due to a lack of efficacious drug delivery systems (DDS). Now, owing to DDS, therapeutic compounds can be transported to the site of action and accumulate there. This modern approach allows one to decrease the required dose of drug and, therefore, minimize toxicity and side effects. Also, treatment efficiency is increased. Highly organized nanostructures made of biological, polymeric or carbon-based materials are promising carriers in drug delivery to the brain, due to their unique and easily tailorable properties. The drug can be either attached to or entrapped in a carrier. To achieve greater site specificity and selectivity, DDS can be also modified with suitable ligands, providing identification of the molecular site of action. This review illustrates recent advances in using highly-organized structures: dendrimers, fullerenes, liposomes, micelles, nanogels, nanoparticles and nanotubes for this purpose. We also discuss advantages and limitations of each system.

The effect of simvastatin treatment on plasma steroid levels in females with non-classic congenital adrenal hyperplasia.

Non-classic congenital adrenal hyperplasia (NC-CAH) is one of the most frequent genetic disorders and its presence often results in androgen excess. 4 females with coexisting symptomatic NC-CAH and isolated hypercholesterolemia and 11 sex- and weight-matched control subjects with elevated cholesterol but normal steroid levels, participating in our study, were treated with simvastatin (20 mg daily). Throughout the whole period of simvastatin treatment, plasma levels of 17-hydroxyprogesterone, testosterone, androstendione and dehydroepiandrosterone sulfate in patients with NC-CAH remained lower compared with baseline, but increased in 2 patients after withdrawal of this drug. No changes in plasma steroids were observed in simvastatin-treated control subjects. Our findings suggest that simvastatin treatment may bring some benefits to symptomatic female patients with NC-CAH.