Acne vulgaris is associated with intensive pubertal development and altitude of residence--a cross-sectional population-based study on 6,200 boys.

UNLABELLED: Acne vulgaris is a chronic inflammatory disease with a complex pathogenesis that affects predominantly adolescents. The aim of the study was to investigate the interrelations between the presence of acne and several variables associated with somatic growth, pubertal maturation, and environmental conditions (altitude and regions of residence). A population sample of 6,200 clinically healthy boys (0-19 years) was examined and the presence of acne was determined. Height, weight, testicular volumes, penile length and circumference, as well as pubic hair were also measured. The prevalence of moderate and severe acne in the whole group was 7.74 %, while in the age group 12-19 years, it was 19.31 %. Twelve-15-year-old boys with acne were taller and heavier than the ones without. They also had increased penile length and circumference as well as larger testicular volumes. Somatometric and pubertal characteristics of 17-19-year-old boys with and without acne were similar. The prevalence of the disease did not differ between the rural and urban inhabitants. However, the acne frequency decreased with the increasing of the altitude where the boys lived. CONCLUSIONS: Our results showed that the development of acne vulgaris in male adolescents was associated with an intensive growth and pubertal maturation, while obesity per se did not play an important role. Of particular interest was the association between the prevalence of acne and the altitude of residence.

Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects mainly females. Therefore, interrelations between the reproductive and immune system have been assumed. Considering the complex influence of hormones and receptors, we aimed to investigate the influence of androgens and androgen receptor (AR) polymorphism in women with SLE. One hundred and sixteen patients and 44 healthy women were investigated. Testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulphate (DHEAS) concentrations and AR (CAG)n polymorphism were determined. SLE patients had significantly lower levels of total and free testosterone and DHEAS in comparison with the controls. No differences in the CAG repeat length between the groups were established. Women with two alleles carrying more than 22 CAG repeats had significantly higher levels of SHBG (101.51 ± 61.81 vs. 69.22 ± 45.93 nmol/l, p = 0.015) and DHEAS (3.11 ± 2.65 vs. 2.11 ± 3.06 µmol/l, p = 0.007) and a tendency to higher testosterone concentrations (2.35 ± 2.10 vs. 1.71 ± 1.70 nmol/l, p = 0.056) in comparison with other women. The CAG repeat length in the relatively longer (CAG)n allele was inversely related to the Systemic Lupus International Collaborating Clinics/ACR index (r = -0.258, p = 0.009). In conclusion, the androgen receptor (CAG)n polymorphism is not related to the development of SLE, but it could modulate the severity of the lupus chronic damages as well as the androgen levels in women.

Prevalence of micropenis among boys from different regions of Bulgaria.

AIMS: Micropenis is a normally formed penis whose length is more than 2.5 SD below the mean penile length for age. However, the definition of this disorder depends on penile length norms. METHODS: Penile length, circumference and anthropometric values of 310 boys under one year of age from five regions in Bulgaria were investigated. RESULTS: The mean penile length for all boys was 3.55 +/- 0.46 cm, thus micropenis could be defined as a penile length below 2.40 cm. However, regional differences were observed in penile length and circumference. According to regional mean values and the appropriate definition of micropenis, only two of the children had micropenis. CONCLUSIONS: In a prospective study of Bulgarian boys we established wide regional variations of normal penile length. Consequently, the diagnostic and therapeutic approach to micropenis should consider the mono-ethnic inter-regional differences.

Are dehydroepiandrosterone sulphate and lipids associated with erectile dysfunction?

OBJECTIVE: Considering the results of the Massachusetts Male Aging Study (1994) we undertook the current investigation in an attempt to clarify the role of dehydroepiandrosterone sulphate (DHEAS), testosterone and lipids on age related deterioration of erectile function. METHODS: Forty males (13 under 40 years of age and 27 over 40) with erectile dysfunction were investigated. Seventeen healthy subjects (8 under 40 and 9 over 40 years) volunteered as controls. Serum levels of DHEAS, testosterone, total cholesterol, high-density lipoprotein cholesterol (HDL-ch), low-density lipoprotein cholesterol (LDL-ch) and triglycerides were assessed in blood samples. RESULTS: Plasma levels of DHEAS in patients over 40 years of age (4.17 +/- 2.76 micromol/l) were significantly lower in comparison with the younger group of patients (10.49 +/- 3.87 micromol/l), P < 0.001. There was no statistically significant difference in the DHEAS levels between patients and controls in the same age group. DHEAS in the patients showed an inverse correlation with age (r = -0.705, P < 0.001) and a positive correlation with testosterone (r = +0.402, P < 0.01). The same was found in the controls. The HDL-ch results were in the reference range. The total cholesterol levels (5.35 +/- 0.74 mmol/l) and LDL-ch levels (3.58 +/- 0.76 mmol/l) of the patients with erectile dysfunction in the group under 40 years were significantly higher in comparison with the controls (4.21 +/- 0.69 and 2.46 +/- 0.74 mmol/l, respectively, P <0.01). CONCLUSION: The data indicates that the decline in DHEAS is an age-related process rather than a causative factor of erectile dysfunction; total cholesterol and mainly LDL-ch may contribute to erectile dysfunction, especially in younger men.

Influence of the body weight on the onset and progression of puberty in boys.

BACKGROUND: Unlike in girls, the data on the relationship between pubertal development and body weight in boys are controversial. METHODS: We measured the height, body weight, body mass index (BMI), pubic hair stages, testicular volume, penis length and circumference of 4030 boys, aged between 7 and 19 years. According to their body weight, the investigated children and adolescents were divided in four groups at each age: underweight boys (BMI <12th percentile), boys with normal weight (12th-84.99th percentile), overweight boys (85th-94.99th percentile) and boys with obesity (BMI ≥95th percentile), and their data were compared. RESULTS: The onset of puberty occurred when the boys' weight gained 40.33±9.03 kg (median 39.00) and BMI was 18.62±3.12 kg/m2 (median 17.80), whereas the late stage was reached at weight of 62.44±10.39 kg (median 61.00) and BMI 21.47±2.84 kg/m2 (median 21.20). Earlier maturing boys were heavier than their coevals, whereas underweight boys developed puberty later. CONCLUSIONS: The onset and progression of puberty in boys are in a significant positive relationship with weight and BMI. Moreover, in the overweight boys pubertal development begins and comes to the late stage earlier in comparison with normal weight children, whereas in those who are underweight a delay at every stage of the development is observed.

A Novel SRY Gene Mutation p.F109L in a 46,XY Female with Complete Gonadal Dysgenesis.

46,XY complete gonadal dysgenesis (CGD) is a disorder of sexual development that can result from different mutations in genes associated with sex determination. Patients are phenotypically females, and the disease is often diagnosed in late adolescence because of delayed puberty. Here, we present the clinical and molecular data of a 46,XY female CGD patient with gonadoblastoma with dysgerminoma and incidentally found inherited thrombophilia. The clinical significance of the described de novo SRY gene mutation c.325T>C (p.F109L) is discussed. This case report supports the critical role of the HGM domain in the SRY gene and the need of a multidisciplinary approach for CGD patients.

Does an Association between the Idiopathic Left-Sided Varicocele and Eye Colour Exist?

The possible interrelation between male reproductive disorders and iris pigmentation is poorly understood. We have found a link between eye colour and the existence of adolescent varicocele. Therefore, we aimed to extend our investigation on the relationship between the eye colour and varicocele in adult men. 231 andrology outpatients from Caucasian origin were included in the study. The presence of varicocele, sperm disturbances, and the iris pigment of the patients were investigated. Left-sided varicocele was found in 93 adults. In the group of light-eyed men the prevalence of varicocele was significantly lower than among the dark-eyed men (15% versus 59.5%, P < 0.001). No associations were found between the eye colour and disturbances in semen parameters in males with varicocele (P = 0.419) and in those without varicocele (P = 0.586). The present results in adult men suggest that the prevalence of varicocele could be associated with the iris pigment. A possible genetic linkage between the eye colour and the susceptibility to some disorders like varicocele could not be excluded. However, the iris pigmentation seems not to have a direct relationship with the sperm disturbances.

Decreased daily melatonin levels in women with systemic lupus erythematosus - a short report.

BACKGROUND: The neuroendocrine system is known to influence immunity, but the precise interactions between different hormones and autoimmune disorders remain obscure. AIMS: The present study aimed to investigate the role of daily serum melatonin concentrations in the development of systemic lupus erythematosus (SLE) in women. STUDY DESIGN: Case-control study. METHODS: One-hundred and eleven SLE female patients and 46 healthy women were included in the study. Daily serum melatonin levels were investigated in all participants. RESULTS: SLE patients showed significantly lower daily melatonin levels in comparison to healthy women during the short photoperiod (17.75±7.13 pg/mL [16.05] vs. 21.63±6.60 pg/mL [20.10], p=0.012). Hormone concentrations were inversely related to the SLE activity index (SLEDAI) (r= -0.268, p=0.004), but they did not correlate to any particular American College Rheumatology (ACR) criterion (p>0.05 for all). CONCLUSION: Daily melatonin levels were decreased in women with systemic lupus erythematosus and correlated inversely to the activity of the autoimmune disease. Further studies are needed to clarify the importance of the pineal and extrapineal melatonin secretion in patients with systemic lupus erythematosus as well as the interrelations between hormones and autoimmunity.

Growth and development of male external genitalia: a cross-sectional study of 6200 males aged 0 to 19 years.

OBJECTIVE: To provide estimates of normal variations in penile measurements and testicular volumes, and to establish reference ranges for clinical use. DESIGN: Cross-sectional, population-based study. SETTING: Schools, kindergartens, and child care centers in different parts of Bulgaria. PARTICIPANTS: A population of 6200 clinically healthy white males aged 0 to 19 years. INTERVENTIONS: The study physician chose schools, kindergartens, and child care centers randomly and examined children at random until he reached the required number. Each of the 20 age groups (age range, 0-19 years) had an equal number of males (ie, 310). MAIN OUTCOME MEASURES: The mean (SD) values and fifth, 50th, and 95th percentiles of height (Siber Hegner anthropometer), weight (beam balance), testicular volume (Prader orchidometer), penile length (rigid tape), and penile circumference (measuring tape) from birth to 19 years of age. RESULTS: Testes did not show any increase in size until the onset of puberty at age 11 years, whereas penile growth was gradual after birth. However, both penile and testicular development demonstrated peak growth from 12 to 16 years of age, which coincided with the maximal male pubertal growth spurt. Data indicate an earlier pubertal development for this study population than that for a similar population several decades ago. Significant differences between urban and rural populations regarding penile length were also noticed. CONCLUSIONS: Our study provides the contemporary reference range values for height, weight, testicular volume, and penile length and circumference of males aged 0 to 19 years. Our data show that, even by the end of 20th century, there is still some acceleration of male pubertal development. For the first time are reported somatic differences in genitalia within a population between urban and rural representatives.

Adolescent varicocele: who is at risk?

OBJECTIVES: Varicocele results from the abnormal dilation of the veins of the pampiniform plexus and is the most common identifiable cause of male infertility. It can develop during puberty and thus affect the testicular growth and function. The aim of this study was to determine the prevalence and the risk factors for the development of the varicocele among Bulgarian boys. METHODS: In a prospective study, 6200 boys from 5 regions of the country aged 0 to 19 years were evaluated for varicocele. All were clinically healthy. Height, weight, testicular volumes, penile length, and penile circumference were also examined. RESULTS: Varicocele was found in 4.1% of all investigated boys, whereas in the age group 10 to 19 years, it was 7.9%. After adjustment for age, the negative factors associated with the development of the disorder were height, penile length, and penile circumference, whereas the weight and BMI had a protective role. The prevalence of varicocele demonstrated clear regional differences, and it was found significantly more often among dark-eyed boys. The incidence of the disease increased rapidly during midpuberty. CONCLUSIONS: The incidence of varicocele is related to some somatometric parameters and with the accelerated pubertal development. Longitudinal studies are needed to clarify better the relations between the adolescent varicocele and puberty.

Prevalence of cryptorchidism among Bulgarian boys.

BACKGROUND: Cryptorchidism is the most common congenital defect of the male urogenital system. It may be an important cause for male infertility. The data about its prevalence in South-eastern European countries and especially for the Balkan region are still incomplete. OBJECTIVE: The aim of the present study was to establish the prevalence of the abnormality in the Bulgarian population living in the different areas of the country. METHODS: In a population-based cross-sectional study in Bulgaria 6200 Caucasian boys (aged under 1 year to 19 years) from five regions of the country were included. One physician examined all children in order to reduce the inter-observer error. RESULTS: The prevalence of cryptorchidism was 1.52% for the total group. It was 3.2% for boys under one year of age, 2.1% for those between one and ten years and dropped significantly in older boys (0.6%). No regional or seasonal trends were established. CONCLUSIONS: Our study suggests a relatively higher prevalence of cryptorchidism in Bulgaria for children younger than one year of age, while the overall prevalence is comparable to those reported for other countries. The prevalence of cryptorchidism did not differ significantly from the prevalence reported thirty years ago.

Melatonin secretion and non-specific immune responses are differentially expressed in corticotropin-dependent and corticotropin-independent Cushing's syndrome.

BACKGROUND: This study was done to clarify the relation between melatonin secretion and the hypothalamic-pituitary-adrenal axis. MATERIAL/METHODS: In this clinical study using a follow-up approach, we investigated the circadian melatonin secretion and immune parameters of patients with corticotropin-dependent (Cushing's disease) and corticotropin-independent Cushing's syndrome. Plasma hormone concentrations, interleukin 1-beta (IL-1beta) and total immunoglobulin E (IgE) were determined before surgical treatment and during remission of the syndrome 1 year later. RESULTS: Patients with Cushing's disease showed mean nocturnal and diurnal melatonin plasma values similar to those of healthy controls. Only the midday level of patients (taken at 12:00) was significantly higher in comparison to controls (35.44+/-19.5 pg/mL vs 17.14+/-3.58 pg/mL; P<0.05). In contrast, patients with corticotropin-independent Cushing's syndrome had significantly lower mean nocturnal and significantly higher mean diurnal melatonin levels (52.8+/-17.7 pg/mL and 59.2+/-28.7 pg/mL, respectively; P<0.05 and P<0.05) as compared with corresponding values for controls (101.4+/-43.1 pg/mL and 28.9+/-11.7 pg/mL, respectively). In the last group of patients, significantly higher mean IL1beta and plasma IgE concentrations (3.30+/-1.72 pg/mL and 527.8+/-474.0 IU/mL, respectively) were observed compared with controls (1.43+/-0.95 pg/mL and 35.7+/-32.1 IU/mL, respectively) (P<0.05). Remission of the hypercortisolism in these patients resulted in restoration of circadian melatonin secretion and significant reductions in plasma IL1beta and total IgE levels. CONCLUSIONS: Our results demonstrate a specific mode of melatonin secretion and different nonspecific immune responses in the 2 investigated forms of hypercortisolism, specifically, corticotropin-dependent and corticotropin-independent Cushing's syndrome.

Testosterone replacement therapy in male hypogonadism is not associated with increase of endothelin-1 levels.

Differences in endothelin-1 (ET-1) blood plasma levels were established between healthy men and women. Little is known about vascular effects of testosterone and the interactions between sex hormones and endothelin. In order to study the relationship between ET-1 and testosterone in more detail, we have investigated 33 male patients with various forms of hypogonadism (13 with hypergonadotropic hypogonadism and 20 with hypogonadotropic hypogonadism). Fourteen age-matched healthy males served as controls. The basal ET-1 levels in patients with hypogonadism (0.96 +/- 0.12 fmol/mL) (mean +/- SEM) were significantly higher in comparison with the controls (0.44 +/- 0.04 fmol/mL), p < 0.01. Fifteen individuals of these patients were studied during the therapy with testosterone depot 250 mg i.m. The ET-1 levels decreased in this group from 0.99 +/- 0.22 to 0.78 +/- 0.14 fmol/mL at the third and to 0.76 +/- 0.25 fmol/mL at the sixth month of the medication, respectively. The differences were not significant compared with the initial levels, but the concentrations at the sixth month of the treatment were not statistically different in comparison with the ET-1 levels of the controls. There was no significant difference in lipid data between patients before and during testosterone medication, except for the high-density lipoprotein cholesterol, which decreased at the third month of the treatment. Our results show that plasma ET-1 levels in males with hypogonadism are elevated with a tendency to decrease after testosterone administration. The optimum testosterone is not associated with enhanced cardiovascular risk as far as ET-1 plasma levels and lipids are concerned.

Relationship of adolescent gynecomastia with varicocele and somatometric parameters: a cross-sectional study in 6200 healthy boys.

PURPOSE: To evaluate the relationship of gynecomastia with varicocele and somatometric parameters in otherwise clinically healthy boys. METHODS: The relationship between gynecomastia and somatometric parameters was examined with 6200 clinically healthy boys aged 0-19 years of different socioeconomic backgrounds in various schools, kindergartens, and childcare centers. Multivariable logistic regression analysis was used to model the prevalence of gynecomastia (>or=1cm) in relation to height, weight, testicular volume, penile length and circumference, age, pubic hair Tanner stage, and residential status. RESULTS: Pubic hair Tanner stages 3 and 4 had the highest incidence of gynecomastia. Gynecomastia was found only in boys more than 10 years old and its prevalence in the age group of 10-19 years (n = 3082) was 3.93 %. In boys 10-13 years old, gynecomastia was positively correlated with varicocele, the adjusted odds ratio (OR) was 2.1 (95% confidence interval [CI] = 1.1-4.1). For the age at which gynecomastia was most prevalent (group aged 12-14 years), the adjusted OR of gynecomastia occurring in boys with varicocele, using the Cochran-Mantel-Hasenzel method of adjusting for age was 1.9 (95% CI = 1.1-3.4). Gynecomastia was negatively correlated with body mass index (BMI). In addition, it was weakly correlated with testicular volume, positively in age group 10-13 years and negatively in those 14-19 years. However no relationship was found between gynecomastia and penis size, urban/rural status, and sea level of residence. CONCLUSIONS: Adolescent gynecomastia is a mid-puberty event. It is significantly associated with varicocele and somatometric parameters including BMI and testicular volume.

Adolescent varicocele: association with somatometric parameters.

INTRODUCTION: The developmental changes that occur as a result of puberty have been hypothesized to be important causes of varicocele. Various somatometric parameters were known to affect the occurrence of varicocele during the growth period. We conducted this study in order to examine these relationships and to determine the incidence of varicocele in adolescent males. PATIENTS AND METHODS: We evaluated 1,200 healthy males aged 0-19 years for varicocele and correlated it with the following somatometric parameters: age, height, body mass index (BMI), pubic hair distribution, penile length and testicular volume. RESULTS: Adolescent varicocele was found in 5.6% of the participants. The 13- to 19-year age-group had the highest incidence of varicocele (10.5%). Logistic regression analysis showed that the incidence was positively correlated with age, height and penile length (odds ratio 1.61, 1.04 and 1.37, respectively) and negatively correlated with left testicular volume, BMI and pubic hair distribution (odds ratio 0.87, 0.87 and 0.47, respectively). CONCLUSION: Varicocele was more prevalent in tall boys with a lower BMI, who had quickly progressed through puberty. Our observations suggest that varicocele is associated with various somatometric parameters.

Inhibin B is a better marker of spermatogenesis than other hormones in the evaluation of male factor infertility.

OBJECTIVE: To assess the role of inhibin B in the evaluation of male factor infertility. DESIGN: Prospective study. SETTING: Reproductive endocrinology clinic. PATIENT(S): Seventy-five patients with infertility problems (mean age 31.2 +/- 7.5 years) and 12 controls (32.1 +/- 8.8 years) with proven fertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization guidelines. Testicular volume was assessed with the Prader's orchidometer. Serum levels of inhibin B (pg/mL), LH (mIU/mL), FSH (mIU/mL), prolactin (micro IU/mL), and testosterone (nmol/L) were assessed. RESULT(S): The mean +/- SEM inhibin B and testosterone levels were significantly lower in the patients than in the controls (inhibin B: 116.4 +/- 11.7 vs. 181.2 +/- 20.9, P=.008; testosterone: 13.6 +/- 0.9 vs. 25.1 +/- 2.9, P=.008). In general, sperm count and testicular volume in the patients were significantly and positively correlated with inhibin B (sperm count: r = 0.476, P<.0001; testicular volume, right: r = 0.57, P=.0001; left: r = 0.53, P=.0001); the inhibin B-FSH index was negatively correlated with FSH. Inhibin B was more strongly correlated with testicular volume and semen parameters than FSH. Inhibin B in the patients was negatively correlated with FSH (r = -0.723, P=.0001) and LH (r = -0.52, P=.0001) and was positively correlated with testosterone (r = 0.4, P=.0013). CONCLUSION(S): Inhibin B measurement is a better marker of fertility status than FSH and LH. Concentration of inhibin B in patients with infertility may provide useful information on spermatogenesis and possibly serve as a more direct marker of spermatogenesis than FSH.

Altered melatonin secretion in hypogonadal men: clinical evidence.

The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary-gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release.

Significance of inhibin in reproductive pathophysiology and current clinical applications.

The human reproductive process is regulated by complex mechanisms that involve many organs, including the brain, gonads and endocrine system. It has been more than 70 years since the name 'inhibin' was used to describe a substance produced in the gonads that negatively regulates pituitary secretion. Inhibin B controls FSH secretion via a negative feedback mechanism. It is a glycoprotein hormone secreted by the Sertoli cells of the testis and granulosa and theca cells of the ovary. Serum inhibin B concentrations are positively related to testicular volume and sperm counts. Current understanding of inhibin physiology and pathology in the human suggests that inhibin B may be of importance as a marker of Sertoli cell function in men with infertility and as a prognostic indicator in women undergoing ovulation induction therapy. Inhibin concentrations are elevated in patients with granulosa cell tumours and in post-menopausal women with mucinous ovarian cancers. Immunoreactivity against the inhibin alpha-subunit was identified in all cases of adrenal cortical adenoma and carcinoma, and levels are suppressed in the malignant prostate disease. This article discusses the structure, regulation and clinical use of inhibin and other related substances.