The role of sex hormone replacement therapy on self-perceived competence in adolescents with delayed puberty.

The objective of the present study was to determine the role of sex steroids in the development of self-perceived competence during adolescence. The Harter Self-Perception Scale was administered to 56 adolescents with delayed puberty who were receiving depo-testosterone (males) or conjugated estrogens (females) administered in 3-month blocks alternating with placebo. Treatment was given at three dose levels approximating early, middle, and late pubertal replacement levels. Hormone treatments had a significant positive effect for both males and females in one subscale domain--perceived job competence. Significant positive hormone effects were also obtained for perceptions of romantic appeal and close friendship in females and perception of athletic abilities in males. It can be inferred from the results of this study that the hormonal changes associated with sexual maturation have targeted influences on specific domains of self-perceived competence and that there are clear gender differences.

Children with organic growth hormone deficiency have elevated cortisol responses to stimuli.

The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPA) function in children with GH deficiency. Ninety-four patients were evaluated for GH deficiency and cortisol (F) deficiency using clinical criteria and L-dopa and insulin-induced hypoglycemia stimulation tests. They were assigned to three diagnostic groups: organic GH deficient (OGHD), idiopathic GH deficient (IGHD), and not GH-deficient (NGHD). Time series, cross-sectional, regression analysis revealed statistically significantly elevated F [>828 nmol/L (30 microg/dL)] in the OGHD group vs. the NGHD group. The value for F in the IGHD group was not different from the NGHD group. This finding suggests that dysregulation of the HPA axis is present in most children with OGH deficiency and significantly less often in children with IGH deficiency or without GH deficiency. Anatomical disruption of the control pathways for the HPA axis or stress may cause the dysregulation.

Age of puberty: data from the United States of America.

In an attempt to determine whether the secular trend toward an earlier onset of puberty has continued over recent decades in the United States of America, published reports concerning the age of attainment of pubertal events have been reviewed. Such reports are very limited and vary in both design and inclusive ages of study subjects. Among females, two recent large cross-sectional studies indicate that fifty percent of females in the United States attain Tanner breast stage 2 at 9.5 to 9.7 years of age. This is younger than previously thought, although adequate earlier studies of girls in the United States are not available for comparison. These two studies also indicate that about 14% of girls attain Tanner stage 2 while 8 years of age; one study extends earlier reporting that about 6% exhibit onset of breast development while 7 years of age. There is no evidence that the age of menarche or the attainment of adult (Tanner 5) breast development has decreased over the past 30 years. The data also suggest an earlier onset of Tanner stage 2 pubic hair but no change in attainment of stage 5. Among males, pubic hair may be appearing at younger ages, but data are inadequate or too inconsistent to allow firm interpretation. The lack of standardization of genital criteria of pubertal onset in the male makes any conclusions regarding secular trends impossible. In summary, earlier secular trends over recent decades related to better health, improved nutrition or socio-economic status, or any putative influence by endocrine disrupters cannot be verified.

Dysregulation of the hypothalamic-pituitary-adrenal axis in short children with and without growth hormone deficiency.

The effects of L-dopamine (LD) administration and insulin-induced hypoglycemia in adrenocorticotropin (ACTH) and cortisol secretion were studied in 14 short boys. LD caused moderate changes in both hormones. The four boys with isolated, idiopathic growth hormone (GH) deficiency (IGD) demonstrated a greater cortisol increase in response to hypoglycemia than the 10 boys with normal GH secretion. In at least some short children with IGD, abnormal regulation of the hypothalamic-pituitary-adrenal axis may be present.

Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an unusual polyposis syndrome that has enjoyed a rich and somewhat confusing history. Mucocutaneous pigmentation and diffuse gastrointestinal hamartomas are the hallmark features of this autosomal dominant inherited condition. Peutz-Jeghers syndrome is now also recognized as a cancer predisposition syndrome. In this review, we highlight the historical aspects of PJS polyposis with special emphasis on its extraintestinal manifestations, particularly genital tract tumors. A PJS management scheme for clinicians is included.

Self-assessment of physical sexual maturation in boys and girls with delayed puberty.

We studied 49 boys and girls with delayed physical sexual maturation during treatment with sex steroids. We found significant agreements, but also some disagreements between physicians' and subjects' Tanner sexual maturity ratings. We found neither effects of treatment with sex steroids nor gender differences, comparing ratings between physicians and patients.

Body composition development of adolescent white females: the Penn State Young Women's Health Study.

OBJECTIVE: To obtain simultaneous and longitudinal measures of height, weight, total body bone mineral content, total body bone mineral density, percentage of body fat, lean body mass, and body mass index in healthy white females between the ages of 11 and 18 years. DESIGN: A longitudinal, observational study. SETTING: University medical center in a small city. STUDY PARTICIPANTS: At initiation in 1990, 112 premenarchal, healthy girls were enrolled. Results presented in this report are based on measurements made on the 82 participants who remained in the study in 1996 and for whom we had comprehensive measurements. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry was used to obtain measurements of total body bone mineral content, total body bone mineral density, percentage of body fat, and lean body mass every 6 months for the first 4 years of the study and yearly thereafter. RESULTS: The mean age for peak velocity and peak accumulation for each measurement was as follows: height, 11 1/2 and 17 1/2 years, respectively; weight, 11 1/2 and 17 1/2 years; body mass index, 11 1/2 and 17 1/2 years; percentage of body fat, 11 1/2 and 13 1/2 years; lean body mass, 12 and 17 1/2 years; total body bone mineral content, 13 1/2 and 17 1/2 years; and total body bone mineral density, 13 1/2 and 17 1/2 years. CONCLUSIONS: Among a healthy population of white females, the age of peak velocities for height, weight, body fat, and lean body mass occur at 11 1/2 to 12 years. Thus, peak soft-tissue velocities precede hard-tissue velocities by about 2 years, with peak accumulation of all tissue components being reached, on average, by age 17 1/2 years.

The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty.

OBJECTIVE: The objective of this clinical study was to determine the effects of sex steroids on behavior and mood in adolescents with hypogonadism. STUDY DESIGN: The experimental design consisted of a randomized, double-blind, placebo-controlled, crossover trial lasting for 21 months. The study group consisted of 39 boys and 16 girls recruited from a pediatric endocrine clinic for delayed puberty. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks, alternating with placebo, at 3 dose levels approximating early, middle, and late pubertal amounts. The Child Behavior Checklist, Youth Self Report, Differential Emotion Scale, and Daily Mood Diary were administered after each placebo and treatment period to ascertain the effect of sex steroids on self- and parent-reported behavior problems and moods. RESULTS: The data demonstrated only one significant treatment effect, namely, an increase in withdrawn behavior problems during administration of low-dose estrogen in girls. There were no consistent sex differences. CONCLUSION: These results demonstrate that administered testosterone or estrogen has minimal effects on behavior problems or mood in adolescents.

Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents.

The purpose of this study was to investigate the effects of administration of sex steroids on self-reported sexual responses and behaviors in hypogonadal adolescents. We used a randomized, double blind, placebo-controlled, cross-over, clinical trial as the experimental design. The subjects were 39 boys and 16 girls with delayed puberty. We treated girls with oral conjugated estrogen and boys with testosterone enanthate in 3 dose levels intended to simulate early, middle, and late pubertal levels. We administered a modification of the Udry sexual behavior questionnaire after each 3-month placebo and treatment period to detect the effect of sex steroids on self-reported sexual behaviors and responses. We employed a strict intent to treat statistical analytical model. The data showed significant effects of the administration of testosterone to boys causing increases in nocturnal emission and touching behaviors at the mid- and high doses. No other treatment effects on sexual behaviors or responses were seen in boys. For girls, there was a significant increase in necking caused by the administration of estrogen only at the late pubertal dose. No other treatment effects on sexual behaviors or responses were seen in girls. We noted some gender differences for thinking about sex, sexual "turn-on," and the nature of sexual behavior. The administration of physiological doses of sex steroids to boys or girls with delayed puberty have few effects on sexual behaviors and responses.

Collaboration between specialties: a US and European experience.

Inter-departmental experiences in endocrinology at the Pennsylvania State University College of Medicine, Hershey, Pennsylvania, and the National University Hospital, Copenhagen, Denmark are described. These co-operative units maximize specialty resources for patient care, teaching and research, and constitute an organizational format now appearing in inter-disciplinary centres of excellence. Many perceived threats to academic-based endeavours may be aided by greater collaboration between traditional specialty groupings, particularly the primary care oriented departments of medicine and paediatrics.

Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents.

A randomized, double-blinded, placebo-controlled cross-over clinical trial was used to determine the role of sex steroids on the development of aggressive behaviors in 35 boys and 14 girls. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks alternating with placebo at three dose levels approximating early, middle and late pubertal amounts. The Olweus Multifaceted Aggression Inventory was administered after each placebo and treatment period to ascertain the effect of sex steroids on self-reported aggressive behaviors. We employed a strict intent-to-treat analytical model. The data demonstrated significant hormone effects on physical aggressive behaviors and aggressive impulses, but not in verbal aggressive behaviors nor aggressive inhibitions in both boys and girls. These results are the first to causally relate the administration of physiological doses of sex steroids to changes in aggressive behaviors in adolescents.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

Environmental effects on human reproduction: the basis for new efforts in eastern Europe.

Increasing data are becoming available to implicate toxic environmental effects on the reproductive process in animals and man. Political changes in Central and Eastern Europe have provided new opportunities to study reproductive health in an area where environmental effects may be marked. Eastern European health has been affected by environmental transgressions, but other factors, including life style, have played a role in recent changes in life expectancy in the region. While a few programs worldwide are actively pursuing the implications of environmental toxins on reproduction, human data remain sparse. Further research in this field on a global basis is needed. A new center in Copenhagen has begun to pursue such activities, additionally supported by wider World Health Organization (WHO) programs to promote greater communication between eastern and western scientists working in reproductive health.

Hypothalamic-pituitary-gonadal axis function in pubertal male and female siblings with glucocorticoid-treated nonsalt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia.

We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female siblings spontaneously developed thelarche and menarche at 10 and 12 yr, respectively, and manifested irregular menses, hirsutism, and polycystic ovaries at 17 yr. The 16-yr-old male sibling spontaneously developed secondary sex characteristics at age 11 yr and exhibited Tanner IV-V pubic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnodular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min) and gonadal steroid levels (every 2 h) under ACTH adrenal suppression revealed the following. In the male sibling, there were overall normal Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, normal peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the female sibling, there were normal follicular phase range LH (10-28 mIU/mL) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitude of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH (62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E2) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal delta 5-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day for 3 days) after prolonged adrenal suppression by dexamethasone resulted in suppression of dehydroepiandrosterone (DHEA) and E2 in the female and DHEA and T in the male. Gonadal stimulation via hCG administration (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E2 response in the female (200 pmol/L; control, 295-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas delta 5-17-hydroxypregnenolone and DHEA levels rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonadal hormone secretion in these siblings indicate the absence of increased LH secretion, in contrast to the markedly increased ACTH secretion resulting from adrenal 3 beta HSD deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)