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The change of fundamental voice frequency in continuous speech in female puberty was analysed in 47 girls by comparison of 2000 consecutive electroglottographic cycles in a reading situation. The results were compared with serum concentrations of androgens (dihydroepiandrosterone, delta-4-androstenedione, testosterone, and sex hormone binding globulin), oestrogens (oestradiol, oestrone, and oestronesulphate), and somatic puberty (weight, height, mamma stages, and pubic hair stages). Fundamental frequency in continuous speech was related only to oestrone r = -0.34, (P less than 0.05). But the tone range in continuous speech and the lowest tone in the phonetogram were found to be significantly correlated with many of the pubertal and hormone parameters. All these correlations could be explained by a common age-dependency. By multiple regression analysis different sets of variables for prediction of speaking fundamental frequency were found before and after menarche.

Serum calcium, magnesium proteins, phosphate, and immunoparathyroid hormone were measured in 338 normal children and adolescents aged between 7 and 20 years and in 123 normal adults aged between 21 and 50 years. Protein corrected serum calcium and magnesium remained stable throughout the study. Despite hyperphosphataemia protein corrected calcium exceeded the concentrations of normal adults. Serum phosphate and the Ca X P product greatly exceeded adult values and fell rather slowly towards adult levels after the pubertal growth spurt. Serum immunoparathyroid hormone tended to exceed normal adult values and was judged high for the level of serum calcium. Similarities between mineral metabolism in childhood an adolescence and in acromegaly were striking. On this basis in the light of studies demonstrating stimulatory actions of gonadal hormones on growth hormone and of growth hormone on the secretion of parathyroid hormone and 1,25-dihydroxyvitamin D3, a unifying concept is developed. This concept places growth hormone in the unique position of being the main driver and co-ordinator during childhood and adolescence of bone growth an mineralisation on the one hand, and of blood mineral homeostasis on the other. Gonadal hormones probably express some of their actions through stimulation of growth hormone secretion and others by different mechanisms. According to this concept growth hormone is maintaining th Ca X P product at a suitable high level as long as growth hormone and gonadal hormones deliver bone matrix for mineralisation at a high rate.

Twenty boys were followed during their puberty for about 2 years with examinations every third month. At each examination we determined serum concentrations of 25OHD3, 1,25(OH)2D3, 24,25(OH)2D3, 25.26(OH)2D3, alkaline phosphatase (AP) and testosterone together with bone mineral content (BMC) at the distal forearm. Highly significant increases in both BMC (P less than 0.001), serum AP (P less than 0.001), and peak height velocity (PHV) followed the increase in serum testosterone. The boys were grouped according to time of maximal increase in BMC, AP, and PHV. The serum levels of the vitamin D metabolites were related to these points. No significant changes in any of the serum vitamin D metabolites were found. Thus vitamin D metabolism does not seem to be significantly influenced during the period of life when both the linear growth and bone mineralization is maximal.

The concentrations of haemoglobin and of serum testosterone were measured in 215 normal children and adolescents aged 7--20 years, and in 8 boys with constitutional delayed puberty. From the age of 14 years onward haemoglobin and testosterone rose in normal boys and differed significantly from the stable levels observed in prepubertal children and pubertal girls. In the entire series of normal boys (n = 118, age 7--20 years) concentrations of haemoglobin and testosterone were found to be closely correlated (r = 0.73, p less than 0.001). These results provide further evidence for a major role of testosterone in the control of erythropoiesis. Therefore, this correlation suggests the use of serum testosterone determination for the proper selection of haemoglobin reference ranges in boys. The respective reference ranges of haemoglobin corresponding to testosterone levels at 0 and 30 nmol/l were 120.5--148.5 and 143.5--171.5 g/l (95% confidence limits). Boys with delayed puberty were found to have significantly reduced median values of haemoglobin and testosterone for their chronological age, and 6 of the 8 boys investigated were truly anaemic on this background. Nevertheless, their haemoglobin concentration did appear appropriate as judged from their testosterone levels. This observation supports the idea that the selection of the relevant reference range for haemoglobin in boys should depend on the state of physical development as expressed by serum testosterone.

The bone mineral content of the distal forearm (BMC) using single-photon absorptiometry and total body bone mineral (TBBM) using dual-photon absorptiometry were determined in 19 normal boys at different pubertal stages. A highly significant correlation between BMC and TBBM was seen (r = 0.78, P less than 0.001) with a standard error of estimate (SEE) of 13%. Subgroups of early and late pubertal stages did not show any significant differences in the regression lines indicating an identical relationship between BMC and TBBM at various stages of pubertal development although great changes in bone mineral content take place. Due to high accuracy and reproducibility of both methods, which are non-invasive and harmless, measurement of BMC is suitable to estimate changes in total mineral content of the body. This may be of importance in various diseases with disturbance in growth and bone metabolism.

Height velocity, bone mineral content (BMC), serum concentrations of alkaline phosphatase (AP), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (A-dione) were determined as a part of a longitudinal study of calcium metabolism in normal male puberty. The time of maximal increase (Tm) in concentrations was calculated for 20 boys from a curve-fitting analysis program. Highly significant correlations were found between Tm testosterone and Tm BMC (r = 0.73, p less than 0.001); Tm AP and Tm BMC (r = 0.68, p less than 0.001). The mean difference in time between Tm testosterone and Tm BMC was 4.7 months and between Tm AP and Tm testosterone 0.7 month. Our data indicate a very close relationship between testosterone, osteoblastic activity, and mineralization in normal male puberty, whereas the adrenal androgens do not seem to have a major influence on the mineralization at the male puberty growth spurt phase.

Bone mineral content and total serum alkaline phosphatase were measured simultaneously in 230 normal children and adolescents aged 7-20 years. The bone mineral content showed almost no variation from the age of 7 to 13 in boys a,d 7 to 11 in girls. Thereafter a sharp increase was seen in both sexes with a highly significant sex difference between the mean values. Bone mineral content showed a fairly high correlation with age, height, weight, and surface area in boys. Before the time of the growth spurt, however, these variables were poorly correlated or not correlated at all. Concentrations of total serum alkaline phosphatase increased up to the age of 14 in boys and 11 in girls. Thereafter a rapid fall was seen in both sexes, the mean levels being significantly higher in boys. The fall approximated adult levels in boys by the age of 20 and in girls by 18. A significant negative correlation between bone mineral content and serum alkaline phosphatase was seen both in boys (r=0.71, p less than 0.001) and in girls (r=0.79, p less than 0.001).

The bone mineral content (BMC) and body height were measured in 301 normal children and adolescents aged 7--20 years, and in 8 boys with constitutional delayed puberty aged 14--17 years. Serum testosterone was measured in the last group as well as in a subpopulation of the normal children and adolescents. The growth spurt, which coincided with a steep increase of serum testosterone in boys, indicated a great change in skeletal growth and mineralisation in both sexes. After the growth spurt, linear growth slowed down considerably while bone mineralisation rose steeply. When low levels of serum testosterone were maintained, as in delayed puberty, these combined changes of skeletal growth and mineralisation did not occur. It is suggested that gonadal hormones are the true initiators of the short-lived growth spurt as well as of prolonged acceleration of bone mineralisation.

The variation of fundamental voice frequency measured by the average of 2000 consecutive electroglottographic cycles in a reading situation has been examined in relation to pubertal development and androgens. Fundamental frequency among other parameters was related to height (r -0.82), pubic hair stage (r -0.87), testis volume (r -0.78), total testosterone (r -0.73) and serum hormone binding globulin (r 0.75). Single observations of fundamental frequency show a clear grouping of results under and over 200 Hz. Fundamental frequency of more than 200 Hz and serum testosterone of more than 10 nmol/l probably represent values for a boy in puberty. There seem to be comparable relations with other androgens and with serum hormone binding globulin.

Bioassayable somatomedin-A (SM-A) and serum concentrations of testosterone (T) and dehydroepiandrosterone (DHEA) were determined longitudinally in 26 normal boys during puberty. The mean trend of SM-A increased in relation to age, pubic hair development and peak height velocity (PHV) and significant correlations were observed with testicular volume, height velocity and T (all P less than 0.001) but not with DHEA. In relation to growth SM-A increased mainly during 12 to 6 months prior to PHV but no further increase was seen in the 6 months thereafter. Thus pubertal growth and development have to be taken into account in the evaluation of changes in bioassayable SM-A concentrations in boys.

We determined the serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25-(OH)2D], 24,25-(OH)2D, and 25,26-(OH)2D every third month in a 2-yr longitudinal study of 20 normal pubertal boys. Seasonal fluctuations and highly significant correlations with the hours of sunshine were found for 25-hydroxyvitamin D, 24,25-(OH)2D and 25,26-(OH)2D, whereas the serum concentrations of 1,25-(OH)2D were not related to sunshine duration. The boys were grouped according to the time at which the maximal increase in serum testosterone occurred, and the serum vitamin D metabolite levels were examined in relation to this point. No significant changes in the serum levels of the vitamin D metabolites were found. When compiling the data according to clinical evaluation of puberty estimated by pubic hair stages (PH1 to PH4), no significant changes in the serum levels of vitamin D metabolites were found. The present data indicate that the marked increase in serum testosterone in male puberty has no significant influence on circulating vitamin D metabolite levels.

Calcium homoeostasis and bone mineralization have been the subject of many studies, but few have dealt with these aspects specifically in puberty. The main observations in our own studies - together with those in other recent reports - are summarized below. According to the aims of the present survey (Chapter 1) the results are grouped as follows: BLOOD MINERAL HOMOEOSTASIS AND ALKALINE PHOSPHATASE. The serum concentrations of calcium, total or ionized, remain remarkably constant throughout puberty, which probably reflects the important functions of the calcium ion. Serum phosphate, however, remain high in childhood, increase slightly with acceleration of growth and pubertal development and the levels then decrease toward adult values. Consequently, the pattern of the product of serum calcium and phosphate, essential for mineralization, follows that of phosphate. Serum magnesium does not change during puberty. The serum concentrations of alkaline phosphatase increase with acceleration in linear growth and pubertal development which has to be taken into consideration, in evaluation of changes in serum AP. Changes in osteoblastic activity, as expressed by AP (and BGP), are closely associated with changes in testosterone secretion with almost simultaneous increases in serum levels of both variables. It is further concluded that longitudinal study designs may add to the understanding of the growth process and rate of changes, whereas cross-sectional data are relevant to establish proper reference ranges. BONE MINERAL CONTENT. The use of photon absorptiometry in determining BMC is a precise, easy, atraumatic and reproducible method. It is shown that forearm BMC has a highly significant correlation to total body bone mineral also in the pubertal period of rapid growth. It should be noted that single measurements of BMC are of little diagnostic value in the presence of wide biological variation. A spurt in mineralization corresponding to that of height in puberty has been known since the development of the BMC technique. It is evident from our data that BMC and indices of body size are only significantly related after the start of the growth spurt. Significant increases of 25% in the BMC have been found in the year prior to PHV progressing with each PH stage. The mean time of maximal increase in forearm BMC occurred some 5 months later than that of testosterone and AP, and changes in these three variables are closely interrelated. The change in the serum concentrations of the two major adrenal androgens did not appear to be related to BMC.(ABSTRACT TRUNCATED AT 400 WORDS)

In a longitudinal study of male puberty, 18 boys were examined every 3 months for at least 2 years. Serum bone Gla protein (BGP), a biochemical marker of bone formation, was determined and related to changes in serum testosterone (T), serum alkaline phosphatase (AP), serum calcitonin, and bone mineral content (BMC). The data demonstrate a steep increase in serum T during puberty (P less than 0.001), with an almost concomitant increase in serum BGP (P less than 0.001) and serum AP (P less than 0.001). Ten months after the maximal increase in serum T, the increase in BMC reached its maximum, whereas there was no significant change in the serum calcitonin. The data demonstrate that the steep increase in serum T during puberty, directly or indirectly, produces acute stimulation of bone formation (estimated from BGP and AP) followed by a highly significant increase in the integrated measurement of bone apposition (BMC).

In a longitudinal study of male puberty 20 boys were examined every three months for at least two years. Haemoglobin concentration was determined and related to changes in serum testosterone concentrations. The data show a steep increase in serum testosterone during puberty (p less than 0.001) followed with a five months delay, by a significant increase in haemoglobin concentration (p less than 0.001). It is concluded that the steep increase in serum testosterone during puberty produces an acute stimulation of erythropoietin leading to an increase in erythrocyte production and thereby to a detectable increase in haemoglobin concentration a few months thereafter. The present study supports the idea that the selection of the relevant reference range for haemoglobin in boys should depend on the state of physical developments as expressed by serum testosterone.

With the purpose of studying calcium metabolism at the growth spurt phase in puberty, bone mineral content (BMC) of the forearm, and serum concentrations of total alkaline phosphatase, phosphate, and calcium were determined in 36 boys every three months for about 2 years. BMC increased 35% throughout the study age period of 10.6 to 14.6 years, with a maximal rate between 12.8 and 13.8 years. In relation to growth velocity BMC rose steepest during the 12 months around peak height velocity (PHV) (p less than 0.001) and showed a progressive increase from 3 months before the first pubic hair stage (PH2) to PH4 (p less than 0.001). Serum alkaline phosphatase increased by a total of 55% throughout the age period with a diminished rate of increase from 13.5 to 14 years, around the PHV, and from PH3 to PH4.