Urinary 6-sulfatoxymelatonin excretion and aging: New results and a critical review of the literature

The apparent age-related decline in melatonin production has been thought to continue in a secular manner across the lifespan. While it is clear that melatonin levels in children and adolescents are elevated compared to older individuals, the question of whether there is a sudden or gradual change has not been adequately addressed. In this study, we report the excretion of the melatonin metabolite, 6-sulfatoxymelatonin in 253 subjects aged between 21 and 82 yr. The correlation with age was significant (r = -0.24; P < 0.05). When the data was analysed by ANOVA using 5-yr age spans, there was a significant effect of age, but post hoc analysis indicated that after 25 yr of age there was no significant decline in excretion of the metabolite. Thus, although the oldest subjects excreted 36% less melatonin metabolite than the youngest, the decrease occurred at a very early age. In the second part of the study, we re-evaluated the data from seven previous studies that measured plasma melatonin levels or metabolite excretion across a wide range of ages and 11 studies comparing young versus older subjects. Statistical analysis by ANOVA again suggested that the changes in melatonin occurring with age were essentially complete before 30 yr of age. The youngest subjects produced at the most twice the amount of melatonin as the oldest subjects. Finally, we evaluated the mean plasma melatonin levels in 144 groups of normal subjects reported in 137 separate publications with respect to age. Again, whereas there was a significant correlation with age, ANOVA showed that there was no difference between groups after 35 yr of age, and the oldest groups had levels that were only 43% of the youngest groups. We conclude that melatonin production is lower in older people, but that the change occurs very early in life, around 20-30 yr of age.     

Increase in H-Y antigen-positive lymphocytes in hirsute women: effects of cyproterone acetate and estradiol treatment

To investigate a possible relationship between lymphocyte H-Y antigen expression and plasma androgen concentrations in hirsute women, 27 hirsute women were studied. A significant increase in the percentage of H-Y-positive lymphocytes was found in both hirsute women with idiopathic hirsutism [13.4 +/- 2.9% (+/- SD); n = 15] and hirsute women with the polycystic ovary syndrome (13.0 +/- 2.8%; n = 12) compared to that in normal women (10.0 +/- 1.9%; n = 30; P less than 0.0005). Plasma testosterone and androstenedione concentrations, % H-Y+ lymphocytes, and hirsutism scores diminished during oral cyproterone acetate (50 mg/day) and percutaneous estradiol (3 mg/day) treatment. Significant correlations between % H-Y+ lymphocytes and hirsutism scores (P less than 0.001), % H-Y+ lymphocytes and plasma T concentrations (P less than 0.01) were found. We conclude that 1) women can produce H-Y antigen in the same way as men; 2) hirsutism is associated with an increase in H-Y antigen; and 3) the antiandrogen cyproterone acetate reduces H-Y antigen expression on lymphocytes.     

Secretion of melatonin and 6-sulfatoxymelatonin urinary excretion in functional dyspepsia

AIM:To evaluate blood concentration of melatonin and urinary excretion of its metabolite,6-sulfatoxymelatonin(6-OHMS),in functional dyspepsia(FD).METHODS:Ninety individuals were enrolled in the study:30 in each study group:patients with postprandial distress syndrome(PDS),epigastric pain syndrome(EPS),and controls.Blood samples were drawn at 02:00 and 09:00 h and 24-h urine collection was performed.Serum melatonin and urinary 6-OHMS concentrations were measured by enzyme-linked immunosorbent assay.RESULTS:S...     

The influence of combined cyproterone acetate-ethinyl oestradiol therapy on serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women.

Serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women suffering from either idiopathic hirsutism or the polycystic ovary syndrome were determined before and during treatment with cyproterone acetate combined with ethinyl oestradiol. During this treatment the hirsutism decreased markedly. In untreated hirsute women serum dehydroepiandrosterone levels do not differ from those in normal women and do not change during therapy; androstenedione levels are higher than normal and decrease markedly during treatment, and the testosterone levels are elevated compared to normals, with a considerable overlap, and show only a tendency to decrease. There is no correlation between dehydroepiandrosterone and androstenedione levels or between androstenedione and testosterone levels in the serum of untreated hirsute women. After 12-14 months of cyproterone acetate-ethinyl oestradiol therapy a linear correlation is found between dehydroepiandrosterone and androstenedione levels. This can be explained by the relatively higher contribution of the peripheral conversion of dehydroepiandrosterone to androstenedione to the occurrence of lower androstenedione levels. The linear correlation between androstenedione and testosterone after treatment, also found in normal women, indicates the restoration of the role of androstenedione as the major peripheral precursor of testosterone.     

Urinary free cortisol excretion pattern in morbid obese women.

The urinary excretion of free cortisol in a group of 10 control and 20 morbidly obese women was measured in all bladder voidings during 24 h. The data from obese women were measured under Hospital basal controlled conditions and after 3 days of very low calorie diet (VLCD, 1.9 MJ/d). The hourly cortisol excretion pattern was determined for each woman, and means of each group were computed in order to obtain a 24 h excretion pattern. In controls, the highest excretion rate was in the morning (8-9 h) and the lowest at 21-22 h. Inbasal conditions, the obese showed a similar but flatter pattern; the highest peak was also in the morning (9-10 h), but the lowest rate was between 21 and 24 h. The VLCD diet flattened the pattern even more, in away that no clear peak was observed from the early morning until the afternoon; however, the nadir coincided with that found in basal conditions. These patterns resulted in significant differences between VLCD, basal diet and control. The amount of free cortisol excreted was 93.0 +/- 6.9 nmol/ day in controls, 70.1 +/- 4.7 nmol/day in obese under basal conditions and 62.6 +/- 3.0 nmol/day when subjected to VLCD. The results presented are consistent with a lower overall cortisol secretion in the morbid obese women, which also show a narrower margin of variation in cortisol secretion than non-obese controls. The data also show the significant influence of dietary energy on the pattern of cortisol excretion in obese women.     

The effect of cyproterone acetate on the pituitary-adrenal axis in hirsute women.

The functioning of the hypothalamo-pituitary-adrenal axis was assessed in 10 adult women with idiopathic hirsutism treated for 2 weeks with the anti-androgen cyproterone acetate in a dose of 50 mg b. d. daily and in 4 patients treated for at least 3 months. Basal plasma ACTH and cortisol levels and the cortisol response to 8 h ACTH infusion were comparable before and during short-term treatment. The plasma ACTH and cortisol responses to insulin induced hypoglycaemia before and during anti-androgen therapy also were of the same order of magnitude. In the 4 patients treated for at least 3 months also no suppressive effect of the anti-androgen on basal plasma cortisol levels was observed. From these data the conclusion seems warranted that short-term cyproterone acetate treatment in the given dose not significantly influences pituitary-adrenal function in adult women with idiopathic hirsutism.     

Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis

The objective was to analyse whether the activity of the cytochrome P450 isoenzyme CYP3A4 is altered by disease activity of rheumatoid arthritis (RA). Urinary 6 beta-hydroxycortisol excretion, expressed as a fraction of the urinary creatinine output, was measured in 21 patients with RA treated with three different disease-modifying anti- rheumatic drugs (DMARDs) over 24 weeks. There were no correlations between urinary 6 beta-hydroxycortisol/creatinine (6 beta-OHC/Creat) ratio and measurements of disease activity such as plasma viscosity, Ritchie articular index and early morning stiffness. In addition, the three DMARDs sulphasalazine, sodium aurothiomalate and D-penicillamine, smoking and the intake of various CYP3A4 substrates had no consistent detectable effect on the 6 beta-OHC/Creat ratio. There is no evidence that the dosage of drugs metabolized by the CYP3A4 isoenzyme needs to be adjusted for disease activity in RA.      

Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy

PURPOSE: Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged >or=55 years and its relation with the subsequent response to melatonin therapy. METHODS: We studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between 10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of controlled-release melatonin, of which 372 provided complete datasets. Clinical response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as an improvement of 10 mm or more on the visual analog scales. RESULTS: Mean (+/- SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 +/- 8.3 microg per night) than in volunteers of the same age (18.1 +/- 12.7 microg per night, P <0.05) and in younger volunteers (24.2 +/- 11.9 microg per night, P <0.05). About 30% of patients (112/372) excreted 相似文献   

Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women

Melatonin's potential preventive effect against cardiovascular disease (CVD) remains hypothetical. No study has evaluated the relationships between endogenous melatonin and the established blood biomarkers related to CVD. The objective of the present study is to examine the association between the endogenous melatonin level and various established blood biomarkers of risk of CVD, including white blood cell (WBC) count and plasma concentrations of lipids, homocysteine, uric acid (UA), and high-sensitivity C-reactive protein (hs-CRP). This cross-sectional study included 181 Japanese women who attended a health checkup program provided by a general hospital between March 2005 and March 2006. All study subjects responded to a self-administered questionnaire and were measured for weight, height, and blood pressure. Venous fasting blood and first-void morning urine were obtained from all subjects. Statistically significant inverse correlations were observed between urinary 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin in urine, and WBC count, UA, and hs-CRP after controlling for age, body mass index, menopausal status, smoking status, diet, sleeping habits, and exercise (r = -0.19, -0.21, and -0.24, respectively). There were no significant correlations between urinary aMT6s and plasma lipids and homocysteine. These data suggested that the urinary aMT6s level was inversely associated with established independent risk factors for CVD, such as WBC, UA, and hs-CRP. Endogenous melatonin may have implications for the risk of CVD.     

A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women

OBJECTIVES: To compare the relative effectiveness of two newer antiandrogens (flutamide and finasteride) with cyproterone acetate (CPA), at both low and high doses in the treatment of moderate to severe acne in hyperandrogenic women. SUBJECTS AND DESIGN: Forty-eight hyperandrogenic women were prospectively randomized to the following treatments for 1 year: CPA 2 mg with 35 micro g ethinylestradiol; CPA 50 mg with 25 micro g ethinylestradiol (reverse sequential regimen); flutamide 250 mg daily; and finasteride 5 mg daily. Assessment of Cook scores was the primary end-point of the trial. Blood for androgens was obtained at baseline in these women and 30 ovulatory age-matched controls. RESULTS: Serum androgens were elevated in all 48 women and was similar in each of the four treatment groups. Cook scores were significantly and equally decreased (59-71%) with flutamide and both low and high doses of CPA (P < 0.01). The decrease with finasteride (-36 +/- 2%) was statistically significant but lower than that obtained with the other agents. All treatments were well tolerated. CONCLUSIONS: In hyperandrogenic women with moderate to severe acne, low doses of certain antiandrogens appear to be effective. Low and high doses of CPA with ethinylestradiol were equally effective and were comparable to the effects of a low dose of flutamide. Finasteride was less beneficial.     

Urinary tract infections in women: diagnosis and treatment

Acute urinary tract infection is a major health problem among women, accounting for considerable morbidity and health care costs. We review recent developments in the diagnosis and treatment of these infections. In acute lower urinary tract infection, empiric short-course therapy (single-dose or 3-day therapy) with one of several antibiotics is recommended in the absence of complicating factors. When complicating factors are present, the antibiotic susceptibility profile of the infecting organism should be determined and therapy with an appropriate agent should be provided for 7 days. Ampicillin and related drugs are probably inferior to trimethoprim-sulfamethoxazole in the treatment of occult renal infection. In acute pyelonephritis, most patients require hospitalization and treatment with intravenous antibiotics until they can take oral medications. In uncomplicated cases, a single broad-spectrum intravenous agent can be used initially, followed by an oral agent selected on the basis of antibiotic-susceptibility testing results. Patients with uncomplicated acute pyelonephritis who are less ill can be managed with oral therapy as outpatients, again with reference to the results of antibiotic-susceptibility testing. Complicated acute pyelonephritis requires more aggressive diagnostic and therapeutic measures. Therapy for uncomplicated acute pyelonephritis should be given for 14 days. The role of post-therapy cultures in the management of urinary tract infection is not well defined, but cultures probably can be safely omitted in most cases of uncomplicated acute cystitis.     

Urinary copper excretion in rheumatoid arthritis.

The pattern of urinary copper excretion in relation to urine osmolality (as shown by series of aliquots of urine) was studied in rheumatoid patients and in control groups. Rheumatoid patients showed an abnormal copper excretion pattern compared with nonrheumatoid subjects. This was not a direct function of the raised serum copper in rheumatoid disease. Measurements based on 24-hour series of aliquots of urine (as distinct from total pooled 24-hour collections) have been shown to be a useful and sensitive method for studying copper excretion patterns.     

Associations between urinary 6-sulfatoxymelatonin excretion and diabetic vascular complications or arteriosclerosis in patients with type 2 diabetes

Aims/IntroductionThere are limited reports on the association between melatonin levels and vascular complications in patients with type 2 diabetes. The aim of this study was to determine the association between urinary 6‐sulfatoxymelatonin, which is a urinary metabolite of melatonin, and diabetic vascular complications or arteriosclerosis in patients with type 2 diabetes.Materials and MethodsThis retrospective study included patients (167 patients with type 2 diabetes and 27 patients without diabetes adjusted for age and sex) admitted to the hospital who underwent measurement of urinary 6‐sulfatoxymelatonin. The urinary 6‐sulfatoxymelatonin/creatinine ratio (6‐SMT) was calculated.ResultsThe natural logarithmically scaled 6‐SMT level (Ln 6‐SMT) was significantly lower in type 2 diabetes patients (1.9 ± 1.1) compared with patients without diabetes (2.8 ± 1.0, P < 0.001). Multivariate linear regression analysis identified duration of diabetes, smoking status, urinary albumin‐to‐creatinine ratio, retinopathy and coronary heart disease as factors that could influence Ln 6‐SMT levels in type 2 diabetes patients (R ² = 0.232, P < 0.001). Ln 6‐SMT was associated with decreased odds of diabetic retinopathy, even after adjustment for various confounding factors (odds ratio 0.559, 95% confidence interval 0.369–0.846, P = 0.006). Similarly, Ln 6‐SMT was associated with decreased odds of coronary heart disease (odds ratio 0.442, P = 0.030).ConclusionsOur results showed the presence of low levels of Ln 6‐SMT in type 2 diabetes patients relative to patients without diabetes. Furthermore, Ln 6‐SMT is an independent risk factor of diabetic retinopathy and coronary heart diseases. These findings suggest that 6‐SMT could be a useful biomarker for the prediction of micro‐ and macrovasculopathies in patients with type 2 diabetes.     

Urinary excretion of vasoactive factors are correlated to sodium excretion.

BACKGROUND: The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in humans. PROCEDURE: Excretion rates of sodium, nitrates/nitrites (NOx), cGMP, and endothelin-1 (ET-1) were measured before and after ingestion of a mixed electrolyte solution (8 oz Gatorade) while undergoing a routine cardiovascular evaluation in a sample of 51 normotensive young adults. RESULTS: Significant correlations were detected for changes in excretion between all four variables, r ranged from 0.50 to 0.86 (P < .001). Correlations were higher in African Americans than white Americans. CONCLUSIONS: The association of renal ET-1 and NO activity with sodium excretion supports the hypothesis that these factors play a role in the physiologic response to acute changes in sodium intake, particularly in African Americans.