Treatment of constitutional delay in growth and puberty (CDGP).
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Oxandrolone in low dose for constitutional delay of growth and puberty in boys.
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Management of constitutional delay of growth and puberty.
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Effects of donor age on urinary chemosignals that influence the timing of first oestrus in young female house mice, Mus domesticus.
The effects of donor age on the effectiveness of puberty-influencing urinary chemosignals in wild house mice was tested in a series of 3 experiments. The chemosignal from male mice that accelerates puberty was present in the urine from about the time of puberty and throughout the normal lifespan, but declined about 1 year of age. Oestrous females released a substance in their urine that accelerates puberty in young females. This substance remained effective from first oestrus until over 1 year of age, although older females were in oestrus less frequently than younger mice. Females that are pregnant or lactating released a puberty-accelerating substance in their urine regardless of age. Production and release of the puberty-delaying chemosignal by grouped females was initiated before puberty and continued throughout the lifespan of the mouse.
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Endocrine manipulation of constitutional delay in growth and puberty.
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[Constitutional delay of growth and puberty].
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Adolescent medicine: attitudes and skills of pediatric and medical residents.
Adolescents receive care from different specialists whose training may affect the quality of care. To measure possible effects, all 80 level 1 and 3 pediatric and medical residents at one institution completed a questionnaire that asked if they planned to care for adolescents and determined their attitudes and skills for 30 relevant tasks. The mean age chosen for transfer of care from a pediatrician to an internist was 18.7 years by the pediatric residents and 16.6 years by the medical residents (P = .00001). Skill in obtaining histories; staging puberty; screening for scoliosis; performing pelvic examinations; diagnosing delayed puberty, psychiatric disorders, or learning disabilities; immunizing; and treating knee and hip pain more often were thought to be important by pediatric residents (88% to 100%) than by medical residents (40% to 75%) (P less than .02). More than 70% of PL-3 but fewer than 50% of ML-3 residents rated themselves skilled for these tasks (P less than .05). Fewer than 60% of each resident group rated themselves skilled in contraception. Both groups rated themselves underskilled in adolescent history-taking; counseling; evaluation of psychopathology; and treatment of dysmenorrhea and hypertension. In both groups, the decision to care for an adolescent was negatively influenced by the presence of a psychosocial disorder. In conclusion, both pediatric and medical residents plan to care for adolescents, and both recognize deficiencies in their training. Pediatric residents, however, are more confident of their skills in adolescent care than are medical residents.
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Psychological aspects of developmental endocrinopathies in adolescence.
Ninety-six adolescents referred to a pediatric endocrinology clinic were divided into eight groups according to degree of sexual maturity and height. Each adolescent was assessed by a psychiatric interview, a self-concept questionnaire, a human figure drawing test and a cognitive screening battery. The results showed a definite deleterious effect of growth retardation, but not sexual maturity, on self-concept. Sex of the adolescent did not affect the results. Cognitively there was no difference between groups. The psychological impact of short stature should be taken into consideration in the decision to utilize pharmacological or delay of puberty.
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Immunization against growth hormone releasing factor or chronic feed restriction initiated at 3.5 months of age reduces ovarian response to pulsatile administration of gonadotropin-releasing hormone at 6 months of age and delays onset of puberty in heifers.
A severe or moderate suppression of serum insulin-like growth factor I (IGF-I) was induced in heifers, beginning at 104 days of age, by active immunization against growth hormone-releasing factor (GRFi) or by chronic feed restriction (RES), respectively. We hypothesized that reduced serum IGF-I results in decreased serum estradiol-17 beta (E2), which in turn delays onset of puberty. The objectives of this experiment were to determine 1) whether GRFi and RES would alter follicular development and delay onset of puberty through similar mechanisms, and 2) whether GnRH would enhance follicular growth in control, GRFi, and RES heifers at 6 mo of age. Changes in IGF-I, somatotropin, LH, FSH, and E2 were evaluated. Serum IGF-I was greater in control than in RES heifers, and was greater in both these groups than in GRFi heifers by 169 days of age. Basal LH decreased in control and RES but not in GRFi heifers from 136 to 157 days of age. During the same period, a decrease in mean FSH was detected in control but not in GRFi and RES heifers. RES decreased mean serum E2 from 148 to 183 days of age. At 6 mo of age, pulsatile administration of GnRH (5 micrograms every 2 h for 42-46 h) increased serum LH and FSH similarly across treatments but had no effect on the number of follicles > or = 8 mm in GRFi and RES heifers relative to saline treatment. Serum E2 and IGF-I in follicular fluid from follicles > or = 8 mm were increased in all GnRH-treated heifers; however, concentrations of both hormones were lower in GRFi than in control or RES heifers. The main effect of treatments on serum IGF-I was reflected in follicles < or = 7 mm; follicular fluid IGF-I was greater in control than in RES heifers and was greater in both these groups than in GRFi heifers. Serum E2 was lower in RES than in control and GRFi heifers from 253 to 281 days of age. Because of an interaction, E2 was lower in GRFi-GnRH than in control-GnRH heifers but similar in GRFi-saline and control-saline heifers. By 393 days of age, 0% of RES and 32% of GRFi heifers had reached puberty compared to 71% of control heifers. These data support our hypothesis that decreased serum IGF-I results in decreased serum E2. GRFi appears to delay puberty in heifers because decreased serum IGF-I impairs the ovary's ability to synthesize preovulatory concentrations of E2, thereby delaying stimulation of an LH surge. In contrast, RES may delay puberty by delaying follicular development at two stages: a) decreased IGF-I in follicles < or = 7 mm may delay predominant follicular growth, and b) decreased LH may delay maturation of the preovulatory follicle.
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Somatostatin analog treatment slows growth and the tempo of reproductive maturation in female rhesus monkeys.
The present study tested the hypothesis that a reduction in serum GH during adolescence would result in slower growth and delayed puberty. Skeletal growth and maturation as well as indices of reproductive development were studied in juvenile female rhesus monkeys receiving a constant sc infusion of a somatostatin analog, Sandostatin, at a dose of approximately 4.50 micrograms/kg BW.day (Ssa; n = 6) and in untreated females (Con; n = 6) from 18 months of age through the luteal phase of the second ovulation. Although age at menarche was similar in Con and Ssa females, first ovulation was delayed significantly in Ssa females, such that the interval between menarche and first ovulation was significantly longer in Ssa females. Serum concentrations of GH, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 were reduced in Ssa females, particularly after menarche. Although changes in body weight were similar between Ssa and Con females, growth in height was significantly greater in Con females. Furthermore, peak growth velocity in height occurred at a significantly later age in SSa females, but at a similar degree of skeletal maturity. Serum insulin and glucose levels in response to iv glucose were similar in the two groups; however, fasting levels of serum glucose decreased significantly in both groups with advancing age, but the decrease was greater in Con. During the luteal phase of the first 2 ovulatory cycles, there were diminished serum progesterone in 16.7% (2 of 12) of the Con and 41.7% (5 of 12) of the Ssa females. Serum estradiol was significantly lower throughout the first 2 ovulatory cycles in Ssa females, whereas serum LH and IGF-I were similar to those in Con females. Multiple regression analyses revealed that age at menarche was best predicted from the amount of growth in height before menarche, whereas those females who had higher serum IGF-binding protein-3 levels before menarche had an earlier growth spurt, and those who grew faster had a shorter interval between menarche and first ovulation. These data indicate that treatment with a long-acting somatostatin analog, which produces a relative deficiency in the GH axis, slows growth and delays the tempo of puberty. The data suggest that this delay may be due to a reduction in gonadal sensitivity to LH.
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Lung function in white children aged 4 to 19 years: I--Spirometry.
OBJECTIVE: A study was performed to produce reference standards for spirometric lung function in white children and to calculate standard deviation scores adjusted for gender and pubertal stage. METHODS: A cross sectional study was made of 772 white children aged 4.6 to 18.8 years (455 male) tested on an OHIO 840 spirometer and assessed anthropometrically and pubertally. RESULTS: Before puberty there was a linear increase in all lung function measurements with height. During puberty a sudden increase occurred, but subsequently the relationship was again linear. No simple single equation described this pattern. Advanced puberty in younger children conferred a respiratory advantage, whilst delayed puberty resulted in the converse. Girls had poorer volumes per unit height, but young girls had superior airflow/unit lung volume. In both sexes lung volumes and flows bore a constant relationship to external thoracic dimensions. CONCLUSIONS: Puberty has a dramatic effect on lung function. Regression equations for predicted values of lung function measurements and for calculation of standard deviation scores are given (with pubertal correction factors) for each gender.
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Metabolic interfaces between growth and reproduction. IV. Chronic pulsatile administration of growth hormone and the timing of puberty in the female sheep.
Puberty in the female lamb is accompanied by an increased frequency of LH pulses, and during normal development this is preceded by a decline in GH. Conversely, in the growth-retarded lamb, when LH levels are depressed by low nutrition, GH secretion is elevated. Based upon this inverse relationship, we tested the hypothesis that GH may act as a metabolic signal from the brain to inhibit the secretion of LH, and that the decline in GH times puberty. Our approach was to extend high circulating GH levels far beyond the early postnatal period, in a physiological pattern and level, in an attempt to block the pubertal LH rise. To evaluate the pattern of LH as a continuous variable under conditions of constant estradiol negative feedback, the gonadotropin was measured in blood samples collected by jugular venipuncture twice weekly; the lambs were ovariectomized and treated chronically with estradiol (Silastic capsule) beginning at 3 weeks of age. Nine lambs served as untreated controls, and 7 were infused iv with pituitary-derived bovine GH (bGH) between 5 and 28 weeks of age. A programmable backpack infusion pump delivered bGH as hourly pulses, with a total dose of 18 micrograms/kg.24 h, to maintain a physiological pattern and level of GH. At various ages, blood samples were collected at 12-min intervals for 6 h to monitor patterns and levels of peripheral LH and GH. Circulating GH in untreated and treated lambs averaged 7.7 +/- 1.5 ng/ml over a 6-h period at 4 weeks of age and declined to 1.1 +/- 0.2 ng/ml by 19 weeks in the untreated lambs; in contrast, bGH-infused lambs averaged 10.4 +/- 0.9 ng/ml at 19 weeks. Although body weights did not differ, back fat depth and quantity of perirenal fat were reduced in bGH-treated females compared to that in controls. Moreover, insulin-like growth factor-I levels were higher in bGH-treated compared with control lambs, and the bGH-treated lambs exhibited glucose intolerance, thus confirming that infused bGH was biologically active. Neuroendocrine sexual maturity, however, was not different in bGH-treated and control lambs, and it occurred at 21-22 weeks of age. The results do not support our hypothesis that decreasing GH secretion is a requirement for puberty in the sheep. Moreover, unlike in children with delayed puberty, exogenous bGH did not advance normal puberty in the lamb.(ABSTRACT TRUNCATED AT 400 WORDS)
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Disorders of Pubertal Development: Too Early, Too Much, Too Late, or Too Little.
Major disturbances of pubertal development and variations of normal puberty are discussed. The authors highlight four kinds of pubertal disorders: "too early" (precocious puberty), "too much" (gynecomastia, macroorchidism, and hyperandrogenism), "too late" (delayed puberty), and "too little" (hypogonadism).
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[Menstrual function in adolescent girls in Tbilisi].
700 adolescent girls aged 10-17 were examined in the schools of Tbilisi (2004-2005). The average age of menarche was ascertained to 12.4 y, which does not differ from the corresponding data obtained in 1984 (12.5 y). Premature puberty and menarche was detected in one patient (0.25%), delayed puberty and menarche in 0.75%. The frequency of menstrual rhythm disorders was equal to 38.3%. Authentic increase of frequency of menstrual disorders in I phase of puberty rather than in II phase (49.4%, 20.7%, p<0.001) was detected. Oligomenorrhea was most frequent disorder of menstrual cycle (32.9%). Dysfunctional uterine bleeding was observed in 1.25% of adolescents, algomenorrhea in 18.5%. In cases of combination of menstrual cycle disturbances with clinical symptoms of androgenization, it is possible to consider presence of endocrine-reproductive disorders. High frequency of menstrual disorders, possible occurrence of endocrine and reproductive disorders and low rate of attendance for medical help (2.4%), indicates at importance of their early revealing, for timely treatment and avoiding complications.
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The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty.
UNLABELLED: Short-term oxandrolone treatment is used to stimulate growth in boys with constitutional delay of growth and puberty (CDGP). Oxandrolone stimulates growth, but a beneficial effect on final height has not been established. In our study, we report the effect of long-term treatment (30-57 months) with oxandrolone in 18 boys with CDGP, compared with nine puberty-matched, untreated controls (group 1). The oxandrolone-treated boys were divided into two groups: four boys who received oxandrolone before onset of puberty (group 2), and 14 boys who started oxandrolone therapy during Tanner stage 2 (group 3). Height standard deviation scores for calender age (HSDSCA) between the three groups of patients at Tanner stage 2 (G2) were not different: -2.86 (SD 0.56) in the controls and -2.60 (SD 0.52) in group 2 and -2.81 (SD 0.59) in group 3. Age at G2 was 15.1 (SD 1.4) years (controls), 14.6 (SD 0.5) years (group 2) and 14.0 (SD 0.9) years (group 3). Height velocity in the time span from G2 to G5 was more pronounced in the oxandrolone-treated boys: 7.7 (SD 0.5) cm/year in group 2 and 7.7 (SD 1.4) cm/year in group 3 versus 5.1 (SD 0.9) cm/year in the controls. Height gain was significantly increased in the oxandrolone treated groups: 25.8 (SD 3.8) in group 2 and 25.2 (SD 3.7) in group 3 versus 19.8 (SD 4.9) in the controls (P < 0.05). Final height did not differ significantly among the three groups: 168.5 (SD 7.0) cm in the controls and 173.0 (SD 4.0) cm in group 2 and 167.8 (SD 5.3) cm in group 3. HSDSCA increased during puberty in all three groups. At final height, HSDSCA (calculated at age = 20 years) was -2.01 (SD 1.05), -1.34 (SD 0.59) and -2.12 (SD 0.79) respectively in groups 1, 2 and 3. An effect of oxandrolone on HSDSCA was not found. Target height was neither reached by the controls nor by the treated groups. Tempo of pubertal development was not different in the three groups, and delta BA/delta CA did not alter after start of oxandrolone treatment in groups 2 and 3. CONCLUSION: Boys with CDGP may benefit from oxandrolone treatment in terms of increased height gain. Starting treatment before the onset of puberty may be favourable.
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Different frequencies of diabetic complications in insulin-treated patients with diabetes of comparable duration, in relation to age at onset of diabetes.
Diabetic complications such as retinopathy and nephropathy affect the quality of life of diabetic patients. The aim of this study was to find out whether there are differences in the development of these complications associated with the age at onset of diabetes and the different effects of diabetes onset before, during or after puberty. Therefore, we tested the hypothesis whether onset of insulin dependent diabetes in puberty was connected with an increased risk of developing diabetic microangiopathy. We found a significantly increased risk in patients with diabetes onset in puberty up to a diabetes duration of 20 years if compared with diabetes onset before but not with that after puberty. It seems that diabetes onset before puberty delays the development of early diabetic complications and that changes of the hormonal status during puberty may be responsible for an earlier development of retinopathy. After about 20 years of diabetes there are no significant differences between the groups. Our results emphasize the necessity of early ophthalmological diagnosis and adequate metabolic control, especially in patients with diabetes onset during or after puberty, in order to prevent or delay the development of diabetic complications.
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Crohn's disease post-cardiac transplantation presenting with severe growth failure and delayed onset of puberty.
We report a 15 yr-old girl who 10 yr post-cardiac transplantation presented with severe growth failure and delayed onset of puberty. She was found to have pan-enteric Crohn's disease and has done remarkably well on principally nutritional therapy with a significant growth spurt and the onset of menarche. The development of bowel disease whilst on immunosuppression is rare and the literature is reviewed.
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Effect of prepuberal chronic morphine administration on the onset of puberty in pituitary-grafted female rats.
The effect of morphine on the onset of puberty was studied in female Wistar rats bearing pituitary grafts implanted at 21 days of age, or sham operated (SO). Morphine was given sc, daily, from day 22 until the occurrence of vaginal opening (VO), taken as an index of puberty. Two doses of morphine (2 or 8 mg kg-1 day-1) were used and control animals received saline of the same volume. Morphine (both doses) induced delayed puberty in SO rats, as indicated by age at VO: mean +/- SEM, 36.90 +/- 0.75 and 36.33 +/- 1.08 days vs 33.06 +/- 0.69 days for 2 and 8 mg vs control group. Pituitary graft induced precocious puberty and this effect was reversed by the highest dose of morphine (29.47 +/- 0.84 vs 32.80 +/- 0.59 days for saline vs 8 mg morphine, grafted rats). These data show that chronic administration of morphine during the prepuberal period delayed the onset of puberty and reversed the precocious puberty induced by pituitary graft in the female rat.
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