Melatonin receptor 1b polymorphisms in women with Systemic Lupus Erythematosus.

AIM: The pineal hormone melatonin could exert an important influence on the immune system and autoimmunity. Its effect on the immunocompetent cells might be mediated at least partially through specific melatonin receptors. However, the role of melatonin - melatonin receptor 1B (MTNR1B) interrelations in human autoimmune diseases is still unknown. Therefore, the present study aimed to investigate the possible influence of the MTNR1B gene polymorphisms for the development and clinical expression of systemic lupus erythematosus (SLE). METHODS: 109 female SLE patients and 101 healthy women were genotyped for the MTNR1B rs1562444, rs10830962 and rs10830963 polymorphisms. RESULTS: No genotype distribution differences were found between patients and controls. The presence of MTNR1B rs10830963 C/C genotype was related to increased prevalence of leucopenia compared to genotypes C/G and G/G after Bonferroni correction for multiple comparisons [36.5% vs. 14.5%, p=0.014]. Moreover, the rs10830963 G/G carriers had lower number of lupus criteria in comparison to patients with C/C genotype. CONCLUSIONS: The present data suggested that MTNR1B polymorphisms could influence the clinical features in lupus patients, and especially the susceptibility to leucopenia.

Anti-Müllerian hormone and inhibin B levels reflect altered Sertoli cell function in men with metabolic syndrome.

The aim of the present study was to investigate the Sertoli cell markers inhibin B and anti-Müllerian hormone (AMH) in men with metabolic syndrome (MS). Twenty patients with MS according to the criteria of the International Diabetes Federation and 20 non obese age-matched men were investigated. The levels of testosterone, sex hormone binding globulin (SHBG), gonadotropins, inhibin B and AMH were measured in all of them. In obese patients with MS total testosterone (15.74 ± 6.95 versus 27.84 ± 12.80 nmol l(-1), P = 0.001), SHBG (21.71 ± 11.08 versus 38.80 ± 17.51 nmol l(-1), P = 0.001) and free testosterone (430.35 ± 237.40 versus 613.85 ± 303.65 pmol l(-1), P = 0.040) were significantly lower than in the controls. Interestingly, the inhibin B (103.64 ± 56.77 versus 149.88 ± 68.31 pg ml(-1), P = 0.025) and AMH levels (30.84 ± 13.14 versus 43.14 ± 9.66 pmol l(-1), P = 0.002) were also significantly lower in MS group in comparison to the other participants. The lowest levels of AMH were found in patients with MS and carbohydrate disturbances. The decreased concentrations of testosterone, inhibin B and AMH in patients with MS could reflect an impaired Leydig and Sertoli cell function. Further studies in men with obesity, insulin resistance and diabetes type 2 could reveal more information about the interrelations between the metabolic disturbances and reproductive function in men.

Anti-Müllerian hormone in women with polycystic ovary syndrome before and after therapy with metformin.

Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2 550 mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42 pmol/l) were significantly elevated in comparison with the controls (21.58±3.41 pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30 pmol/l to 38.25±6.89 pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.

Timing of pubertal maturation according to the age at first conscious ejaculation.

The first conscious ejaculation (ejacularche) is an important event in the somatic and psychic development of boys. The aim of this study was to reveal the age at first ejaculation in Bulgarian boys and to observe the secular trend of this marker for puberty. A total of 1582 (901 from urban and 681 from rural origin respectively) gave a positive answer admitting the age in years at the first ejaculation. The mean age ± standard deviation (SD) of ejacularche was 13.27 ± 1.08 years, and the median was 13.0. It was found a significant difference between the urban (13.34 ± 1.07) and rural (13.18 ± 1.08) inhabitants in relation to the age of their remembered first ejaculation (P = 0.003). A secular trend in appearance of ejacularche was revealed when our results were compared with those from the previous studies in Bulgaria. We can suggest that in the presence of testicular volume ≥6 ml asking about ejaculation is reasonable and not superfluous. Self-reported spontaneous ejaculation can be used as an index of male pubertal timing.

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria.

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.

Disturbances in gonadal axis in women with anorexia nervosa.

UNLABELLED: Anorexia nervosa negatively affects multiple body systems including the reproductive system. AIM: To assess the disturbances in the hypothalamic-pituitary-gonadal axis (HPG) and the relationship between the gonadotropins and body weight, duration of the disease and amenorrhea we studied 40 female anorexic patients (aged 14-31 years) with a body mass index (BMI) 15.14+/-1.80 kg/m(2) and a degree of weight loss 28.67+/-8.74%. Fifteen healthy, age-matched women with normal weight served as controls. METHODS: We investigated the disturbances in the gonadotropin levels before and after stimulation with gonadotropin-releasing hormone (GnRH) 100 microg i.v. One week later 100 mg of clomiphene citrate (CC) was administered orally for 5 days. RESULTS: Basal levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly lower in the patients. The responses of LH to GnRH were diminished, but those of FSH were exaggerated. However, after clomiphene citrate administration, LH increased 5.4 times whereas FSH increased 1.7 times. The basal levels of LH were significantly correlated with body weight (r=+0.373, p<0.05), BMI (r=+0.385, p<0.01) and percentage of the weight loss (r=-0.356, p<0.05). FSH levels were positively correlated with the duration of the disease (r=+0.481, p<0.01) and amenorrhea (r=+0.540, p<0.01). CONCLUSIONS: Our study demonstrates dissociation in the secretion of gonadotropins after hypothalamic stimulation in anorexic patients. It also reveals the relationship between alterations in the hormones of the HPG axis, not only with the changes in body weight, but also with the duration of the disease.

Low testosterone levels and unimpaired melatonin secretion in young males with metabolic syndrome.

The interrelations between testosterone, insulin and melatonin levels in males with metabolic syndrome (MS) are still not clarified, especially in young age groups. The aim of the present study was to compare the testosterone serum levels in young men with MS to those in healthy controls, and to determine the possible changes in their melatonin rhythm, as well as the relation between melatonin, insulin and lipid profile. Fasting insulin and testosterone concentrations were measured in 10 healthy nonobese and 10 MS patients. Blood samples for melatonin, insulin and luteinizing hormone (LH) were collected at 19.00, 03.00 and 11.00 hours. A significant difference was found between the testosterone levels in controls and patients. Luteinizing hormone levels in both groups were similar, however, higher night LH levels in MS patients were observed. No changes in the melatonin concentrations of the two groups were found. In conclusion, total testosterone levels were significantly lower in young men with MS compared with healthy age-matched controls. Mild hypoandrogenia in hyperinsulinaemic patients was not related with changes in their melatonin levels. No alterations in the endogenous melatonin rhythm of the MS patients were found.

The influence of hyperthyroidism on the hypothalamic-pituitary-gonadal axis.

We have investigated the function of the hypothalamic-pituitary-gonadal (H-P-G)-axis in patients with severe, untreated Graves' disease. We studied 7 male and 6 female healthy volunteers, and 7 male and 7 female patients with Graves' disease. Hormone profiles were developed by blood sampling every 10 min for an 8 hour period. In women this was done in the early follicular phase of menstrual cycle. LH-, FSH-, and PRL levels were measured using immunoradiometric assays and testosterone (T), estradiol (E2), sex-hormone binding globulin (SHBG), and progesterone (P) were measured with standard assays. The pulsatility of LH, FSH and PRL was calculated using the programmes Pulsar, Cluster and Desade. The temporal relationship of plasma LH, FSH, and PRL pulses was also investigated using specific concordance analysis. Data were evaluated by means of non-parametric statistics. LH-secretion was increased in all hyperthyroid patients, while FSH-secretion was increased in hyperthyroid men only. Pulsatile characteristics of LH- and FSH-secretion (frequency, peak shape) in patients were not different from controls. No change in PRL-secretion was shown. Significant copulsatility occurred between LH and FSH, and LH and PRL. This was more pronounced in hyperthyroid than in healthy study subjects. Plasma levels of steroid hormones and sex-hormone-binding globulin were significantly (p<0.005) increased in hyperthyroid men. Free Androgen Index was significantly (p<0.005) decreased in hyperthyroid males. No other auto immune diseases were noticed. Our results indicate that the function of the H-P-G axis is not impaired in hyperthyroid patients, but gonadotropin levels are increased. Hyperthyroid men show relative primary gonadal insufficiency that may be due to exaggerated SHBG levels. The copulsatility of LH and FSH, and of LH and PRL was confirmed both in patients and controls.

Two male patients with ring Y: definition of an interval in Yq contributing to Turner syndrome.

Turner syndrome is thought to result from the haploinsufficiency of genes on the sex chromosomes, but these genes have not been identified yet. We describe two males with deleted ring Y chromosomes, one (TS) with full Turner syndrome and one (DM) without. TS has short stature, skeletal anomalies, lymphogenic obstruction, cardiovascular abnormalities, and miscellaneous features including pigmented naevi, antimongoloid slanting of the palpebral fissures, and widely spaced nipples. In contrast, DM has short stature but no other specific Turner stigmata except high arched palate and a few pigmented naevi. Since little chromosomal mosaicism was detected, the different segments of the Y chromosome retained by these two males identify the location of one or more "anti-Turner" genes. Most of the Yp pseudoautosomal region and Yq were deleted from both patients during the formation of the ring chromosome, while the Y specific portion of Yp and the centromere were retained. The major difference detected was an interval of proximal Yq present in DM and deleted in TS. None of the previously identified genes, DFFRY, DBY, UTY, or TB4Y, lies entirely within this interval, although DFFRY was truncated by DM's breakpoint. These data suggest that one or more additional "anti-Turner" gene(s) remains to be identified in the region of Yq proximal to DFFRY.

Sex differences and similarities of hormonal alterations in patients with anorexia nervosa.

The aim of the present study was to gain better insight into hormonal disturbances in male patients with anorexia nervosa. It included six men with anorexia nervosa aged 13-26 years, with a mean body weight of 42.83 +/- 8.03 kg, a body mass index of 15.08 +/- 1.26 and an average degree of weight loss 29.98 +/- 4.73%. The results were compared with those of 15 healthy age-matched males and 40 women with anorexia nervosa. Prolactin, growth hormone and the gonadal and thyroid axis were studied in detail. The gonadotropin basal levels and their responses to gonadotropin-releasing hormone in male patients were lower, but not significantly, in comparison with healthy men. The basal levels and the responses of luteinizing hormone in anorexic women were significantly lower in comparison with female controls, but the decreased basal level of follicle-stimulating hormone showed an exaggerated response to gonadotropin-releasing hormone. In male anorexics the testosterone levels (7.1 +/- 10.9 nmol l-1) were significantly lower. The changes in the thyroid axis and in prolactin secretion were almost the same in male and female patients. The data of this study suggest that endocrine disturbances in males are similar to those in females with anorexia nervosa, but differences exist mainly in relation to the gonadal axis.

Factors related to sex hormone binding globulin concentrations in women with anorexia nervosa.

The published reports concerning serum levels of sex hormone binding globulin (SHBG) in women with anorexia nervosa are few in number and controversial. Indeed, very little is known of the factors influencing SHBG concentrations in these patients. In an attempt to clarify this problem we evaluated serum levels of SHBG, estradiol, testosterone, luteinizing hormone, follicle stimulating hormone, triiodothyronine, thyroxine, their free fractions and insulin in 19 women with anorexia nervosa. Plasma glucose levels, total protein, triglycerides and cholesterol were also studied. Seven healthy women with normal weight and regular menstrual cycles served as controls. The serum concentrations of SHBG in patients with anorexia nervosa (165.27 +/- 63.5 nmol/l) were significantly higher (p < 0.01) than those in the control group (96.21 +/- 38.04 nmol/l), but the levels of estradiol, testosterone, free triiodothyronine and the ratio of testosterone to SHBG were significantly lower. An inverse correlation between SHBG and body weight (r = -0.761) was found in the patients. The alterations in SHBG concentrations were not associated with the changes in testosterone, gonadotropins, thyroid hormones and biochemical parameters. These findings suggest that body weight is one of the more important factors influencing the SHBG concentrations in women with anorexia nervosa.

Increased prolactin secretion and thyrotrophin response to thyrotrophin releasing hormone in Klinefelter's syndrome.

The reports published thus far on prolactin and thyrotrophin secretion in patients with Klinefelter's syndrome are controversial. The aim of the present study was to investigate the interrelation between prolactin on one hand, and hormones of the hypothalamic-pituitary-gonadal axis and thyrotrophin, on the other, in males with Klinefelter's syndrome. Fifteen patients with Klinefelter's syndrome, aged between 17 and 43 years, and 15 healthy males, aged 22-35 years, were studied. Mean +/- SD basal serum prolactin levels were 529.6 +/- 174.6 mU l-1 in the patients, and 270.1 +/- 113.0 mU l-1 in the control group (P < 0.001). Following 200 micrograms thyrotrophin releasing hormone, an enhanced prolactin response was seen in the males with Klinefelter's syndrome. There was no evidence of any of the well-known causes of hyperprolactinaemia. The response of thyrotrophin to thyrotrophin releasing hormone was more pronounced in Klinefelter patients in comparison with controls. Presumably, in Klinefelter's syndrome both alterations--of prolactin and thyrotrophin secretion--may be caused by decrease of testosterone levels or they could reflect a disturbance in neuroendocrine regulation with some neurotransmitter imbalance.

Elevated basal levels and exaggerated responses to thyrotrophin-releasing hormone of prolactin and thyrotrophin in Turner-Noonan-Syndrome.

Basal levels of prolactin (Prl), FSH, LH, testosterone, estradiol, total thyroxine (T4), total triiodothyronine (T3) and thyrotrophin (TSH) were determined in four males with Turner-Noonan-Syndrome. The responsiveness of gonadotrophins to LH-RH (100 micrograms i.v.) and of Prl and TSH (200 micrograms i.v.) was studied. High basal levels and exaggerated responses to TRH of Prl were found in all patients. However no evidence of any of the well known causes of hyperprolactinaemia could be detected in them. The four men were with normal levels of T4 and T3 and showed exaggerated TSH responses to TRH. It is suggested that the alterations in Prl and TSH release are reflections of a congenital disorder in Turner-Noonan-Syndrome not yet well studied.