Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine. To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits associated with the use of SGAs during pregnancy and lactation is limited, although the direction of dose adjustments during pregnancy depends on the drug and the enzyme that is responsible for its metabolism. In general, data on sex differences were mostly obtained by posthoc analysis and, therefore, the conclusions that can be drawn are limited. For a better understanding of the basic mechanisms of sex differences, future studies with a primary focus on this topic are required. Data that are more specific will help determine the extent to which these differences will have implications for clinical management.
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PMID:Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles? 1680 51

In this review we investigate whether sex differences exist for side effects of second-generation antipsychotics. Results are based on a MEDLINE search for the years 1974 through 2005. Even if pharmacokinetics differ between females and males, significantly higher plasma levels for women have been demonstrated only for olanzapine and clozapine. Hyperprolactinaemia is mainly induced by treatment with risperidone and amisulpride, and there is evidence for more pronounced prolactin levels in females. Most studies reviewed indicate that clozapine and olanzapine are associated with more body weight gain, once more especially in female patients. Furthermore, the few published studies indicate that metabolic syndrome is more frequent in females and there are likely no gender-specific differences between the new antipsychotic medications concerning frequency and degree of acute or chronic movement disturbance. The risk of QT prolongation with torsades de pointes arrhythmia is again higher in females. In conclusion, there is some evidence of sex differences in the side effects of second-generation antipsychotics. For better understanding of the basic mechanisms in sex differences, future studies with a primary focus on this topic are required. More specific data will help to determine how these differences shall affect clinical management.
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PMID:[Differences between men and women in side effects of second-generation antipsychotics]. 1687 2

Endocrine disease frequently interrupts sexual function, and sexual dysfunction may signal serious endocrine disease. Diabetic autonomic neuropathy and endothelial dysfunction impair erectile function, and phosphodiesterase inhibition produces only moderate benefit. The effect of diabetes on women's sexual function is complex: the most consistent finding is a correlation between sexual dysfunction and depression. Reductions in testosterone level in men are associated with low sexual desire and reduced nocturnal erections and ejaculate volume, all of which improve with testosterone supplementation. The age-dependent decline in testosterone production in men is not associated with precise sexual symptoms, and supplementation has not been shown to produce sexual benefit. In women, sexual dysfunction has not been associated with serum testosterone, but this may be confounded by limitations of assays at low concentrations and by the greater importance of intracellular production of testosterone in women than in men. Testosterone supplementation after menopause does improve some aspects of sexual function in women, but long-term outcome data are needed. More research on the sexual effects of abnormal adrenal and thyroid function, hyperprolactinaemia, and metabolic syndrome should also be prioritised. We have good data on local management of the genital consequences of oestrogen lack, but need to better understand the potential role of systemic oestrogen supplementation from menopause onwards in sexually symptomatic women.
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PMID:Sexual dysfunction in men and women with endocrine disorders. 1744 19

Epilepsy in women is relatively often linked with reproductive disorders which include polycystic ovarian syndrome, hypothalamic amenorrhea and functional hyperprolactinaemia. These disorders have a significant share in a high incidence of infertility and premature menopause while the polycystic ovarian syndrome, also manifested by the metabolic syndrome, places the affected patients at risk of later consequences such as type 2 diabetes mellitus, cardiovascular diseases including arterial hypertension, gynaecological neoplasias (the breast and the endometrium), and in the case of pregnancy, a higher incidence of pregnancy induced hypertension. Apart from epilepsy as such, also antiepileptic treatment may have negative impact on the female's reproductive functions. In many cases, adverse effects of treatment complicate the patient's life more than the attacks alone. Medication induced weight gain might be responsible for different endocrine diseases (menstruation disorders, polycystic ovarian syndrome, hyperandrogenism). The article analyses the influence of side effects of the different antiepileptic drugs on the development of metabolic and endocrine anomalies. The role of antiepileptic drugs in the development of reproductive and endocrine disorders was first described by Isojarvim in 1993. A high incidence of polycystic ovarian syndrome and/or hyperandrogenism (43%) was observed in women taking valproat, which was clearly higher than in women taking other antiepileptics. Results reported in literature are rather controversial. The article gives an overview of current knowledge with respect to the influence of epilepsy and antiepileptics on the incidence ofpolycystic ovarian syndrome, which is considerably higher in women with epilepsy (10-25%) than in the unaffected population (4-7%), and of the related metabolic syndrome. The article concludes with recommendations for clinical practice in the treatment of epilepsy in women in reproductive age.
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PMID:[Epilepsy and disorders of reproduction]. 1747 15

The earlier the onset of schizophrenia, the more severe the disease. Atypical antipsychotics are the first-line treatment of choice in children as in adults. Nonetheless, most of these drugs have not been approved for use in patients younger than 15 years. In children and adolescents, the atypical antipsychotics have fewer adverse effects than first-generation antipsychotics do, but are nonetheless not tolerated as well as in adults. Among the notable adverse effects are weight gain, sedation, and hyperprolactinemia. The most recent data suggest the need for prevention and attentive monitoring of the components of the metabolic syndrome (elevation of blood pressure, waist circumference, HDL cholesterol, blood glucose, and triglycerides).
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PMID:[Drug treatment of early-onset schizophrenia]. 1835 7

While there are many effective antipsychotics available to clinicians for treating schizophrenia or bipolar mania, the onset of antipsychotic-associated prolactin-related and metabolic adverse effects can diminish the effectiveness of treatment. Increased levels of prolactin (hyperprolactinemia) associated with some antipsychotics raises the risk of sexual side effects. The increased appetite and/or sedation (reduced activity levels) induced by other antipsychotics can lead to weight gain, dyslipidemia, and high blood pressure and, if unchecked, ultimately to cardiovascular disease, diabetes, and metabolic syndrome. Clinicians should take steps to help their patients avoid unnecessary risks associated with antipsychotic use. These steps include monitoring risk factors for developing these illnesses by taking careful patient histories and baseline measurements of patients' weight and blood chemistry. Patients should be made aware of potential metabolic and prolactin-related side effects, and periodic checks should also be made to watch for changes in weight, body mass index, waist size, blood pressure, fasting glucose, or lipid levels that could be harmful and may increase risk for cardiovascular disease.
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PMID:Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. 1848 6

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne, and pattern alopecia. It is a heterogeneous syndrome of hyperandrogenic anovulation that is typically due to intrinsic ovarian dysfunction, which is often aggravated by insulin-resistant hyperinsulinemia with its risks of diabetes mellitus and metabolic syndrome and their complications. Because there are many pitfalls to androgen assays, evaluation for hyperandrogenemia is suggested in women with moderate or severe hirsutism or hirsutism equivalents, menstrual irregularity, acanthosis nigricans, or intractable obesity. An endocrinologic work-up is necessary to rule out other hyperandrogenic disorders that require specific therapy (e.g., virilizing tumors, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, and Cushing's syndrome). Ultrasonography helps in the differential diagnosis and may demonstrate the polycystic ovaries that have recently been vetted as an alternative to oligo-anovulation as a diagnostic criterion. Management of PCOS is determined by symptomatology. For those women not desiring pregnancy, the most common therapies are oral contraceptive pills, antiandrogens (contraindicated in the absence of adequate contraception), and insulin-lowering treatments (which have little effect on hirsutism).
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PMID:What every physician should know about polycystic ovary syndrome. 1884 13

Schizophrenia affects about 1% of the world's population. Those with schizophrenia are at elevated risk of a variety of physical health conditions, including diabetes, coronary heart disease, hypertension and osteoporosis. Osteoporosis secondary to antipsychotic-induced hyperprolactinaemia (i.e. raised prolactin levels) has received little attention, when compared with reports on metabolic syndrome for instance. A recent study established that schizophrenia and prolactin-raising antipsychotic medication is directly associated with hip fractures. This is important and concerning as osteoporotic fractures are associated with much morbidity and mortality. This paper reviews the literature on antipsychotic-induced hyperprolactinaemia and its subsequent effects on bone mineral density.
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PMID:Antipsychotic-induced hyperprolactinaemia in patients with schizophrenia: considerations in relation to bone mineral density. 1982 78

People with schizophrenia have an increased prevalence of overweight/obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, which increases the risk for cardiovascular diseases and mortality. Part of this increased risk is attributable to the use of antipsychotic medications, especially second-generation antipsychotics. Antipsychotic drugs differ in their potential to induce weight gain, with clozapine and olanzapine exhibiting the highest weight gain liability; evidence for differing effects of antipsychotics on glucose and lipid metabolism is less convincing. Individuals with schizophrenia may develop hyperprolactinemia, with or without clinical symptoms, after starting antipsychotic medications. This effect is particularly frequent with first-generation antipsychotics and with the second-generation antipsychotic risperidone and paliperidone. Psychiatrists should be aware of metabolic and endocrine side effects of antipsychotics and should make every effort to prevent or minimize them to improve the patients' compliance and quality of life.
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PMID:Management of schizophrenia with obesity, metabolic, and endocrinological disorders. 1994 83

The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome are reviewed in light of the recent expert guidelines, including risk assessment and treatments, such as monoamine transport inhibitors, anticonvulsants and cannabinoid receptor antagonists, as well as lifestyle changes.
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PMID:Adverse endocrine and metabolic effects of psychotropic drugs: selective clinical review. 1995 39


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