Puberty in girls: correlation of serum levels of gonadotropins, prolactin, androgens, estrogens, and progestins with physical changes.

Twenty-seven girls aged 8 to 18 were studied in a longitudinal prospective fashion. Serum samples were collected at 6 month intervals up to 4 years and radioassayed for hormones of pituitary, ovarian, and adrenal origin. A progressive elevation of luteinizing hormone (LH), follicle-stimulating hormone/FSH), estradiol (E2), dehydroepiandrosterone (DHA), and androstenedione (delta4) occurred during puberty and continued until menarche. The onset of puberty occurred concomitantly with an elevation of estrone (E1) dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and 17-hydroxyprogesterone (17-OH-P). Prolactin (Prol) and progesterone (Prog) concentrations did not change during puberty until after menarche. After menarche, levels of LH and FSH were comparable with menstruating adult females. Concentrations of E2 and Prog were lower during the second half of the cycle among most regularly menstruating subjects than expected during the luteal phase. LH and Prog levels indirectly suggest that ovulation occurs in a few girls within months after menarche.     

DISSOCIATION OF ADRENARCHE AND GONADARCHE IN DIABETES MELLITUS

Serum concentrations of testosterone and dehydroepiandrosterone sulphate (DHAS) have been measured in 10 stable insulin-dependent diabetic (IDD) males (chronological age (CA) range 13.0-17.5 years). Their results have been compared with those of a control population of 69 non-diabetic males who presented with mild constitutional growth delay and whose skeletal maturity and pubertal development were similar to the diabetic subjects. Within bone ages (BA) 11.0-14.5 years no significant difference was observed between the serum testosterone concentrations of the diabetic patients and controls: diabetic males, 8.2 (0.3-25) nmol/l (median and range); controls, 7.0 (less than 0.3-23) nmol/l. In contrast, within BA 11.0-14.5 years, the diabetic males had significantly lower serum DHAS concentrations: diabetic males, 1.1 (0.7-4.2) mumol/l; controls, 3.7 (0.7-5.6) mumol/l (P less than 0.001). The serum DHAS concentrations of the diabetic males were also significantly lower than the controls when matched separately for pubic hair and genital development, testicular volume and serum testosterone, (in each comparison P less than 0.02). Serum DHAS concentrations of the diabetic males did not correlate significantly with CA, BA, BA delay (CA-BA), age of onset of diabetes, duration of diabetes, or glycosylated haemoglobin (GHb), but significant correlation was observed between BA delay and duration of diabetes, r = 0.65, P less than 0.05. We conclude that gonadarche appears to proceed despite delayed adrenarche in IDD males. This study presents further evidence in favour of adrenarche and gonadarche being independent physiological events. The causes and clinical significance of low serum DHAS concentrations in adolescent diabetic males remain to be established.     

SERUM PREGNENOLONE, PROGESTERONE, 17α-HYDROXYPROGESTERONE, ANDROSTENEDIONE, TESTOSTERONE, 5α-DIHYDROTESTOSTERONE AND ANDROSTERONE DURING PUBERTY IN BOYS

We have determined the concentrations of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosler-one and androsterone in serum samples collected from a total of seventy-nine boys who were 8–18 years of age at the time the first blood samples were drawn. Additional samples were drawn from sixty-six and forty-four of these boys after 1 and 2 year intervals, respectively. The first increases in serum steroid concentrations were those of androstenedione and androsterone, thus supporting the hypothesis that an early activation of the adrenal cortex is the first hormonal change in puberty. This increase in serum androstenedione occurred 2 years earlier than the first significant increase in serum testosterone, which took place by 13 5 years, after the first signs of external genital development, but in concert with the onset of pubic hair growth. The serum concentrations of 5α-dihydrotestosterone were closely related to those of testosterone, but the relative increases were smaller, the consequence of which is a decrease in the ratio of 5α-dihydrotestosterone: testosterone throughout puberty. The main increase in serum androsterone tends to take place after that of 5α-dihydrotestosterone and testosterone. In comparison with the four androgens, the serum concentrations of their C₂₁ precursors correlated rather poorly with the physical signs of advancing puberty. As in the case of androstenedione, the concentrations of pregnenolone and 17α-hydroxyprogesterone were relatively high in the youngest age groups, which probably also reflects an early adrenal activation. In contrast to testosterone, the major increases in precursor steroids occur at a relatively late stage of puberty. It seems likely therefore that a major qualitative shift in the testicular secretion of steroids occurs during puberty in boys.     

Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children.

To evaluate the relationship between the secretion of gonadotropins and adrenal androgens, patients with gonadal agenesis were evaluated by (a) administering human luteinizing hormone (hLH) for 5 days with or without estrogen pretreatment to agonadal patients who had prepubertal LH levels; (b) correlating circulating gonadotropin levels with adrenal androgens in 45 patients; and (c) comparing adrenal androgens with gonadotropins after long-term administration of estrogen or androgens. Results are as follows: (a) No alteration in serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), estrone (E1), testosterone (T), or in excretion of urinary 17-ketosteroid (17 KS) occurred after the administration of hLH. (b) No clearcut relationship between endogenous level of LH or FSH and DHA OR DHAS was demonstrated although a coincident increase of all hormones with age occurred. (c) Administration of estrogen to patients with gonadal agenesis did not affect their levels of DHA and DHAS although those patients given androgen developed higher DHAS, but not DHA, levels. Hence, increasing gonadotropin concentrations would not appear to be a primary etiologic factor in the maturation of the adrenal.     

Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens

An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n = 15), early control (n = 20), late (age, 29-40 yr) first pregnancy (n = 9), and late control (n = 20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17 beta-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DHA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship between serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Serum androgen bioactivity in adolescence: a longitudinal study of boys with constitutional delay of puberty

We have examined the relationship between serum androgen bioactivity, as measured with a recombinant cell bioassay, and progression of puberty in 14 boys with constitutional delay of puberty. Six boys were followed up without treatment (control group), and eight boys received low-dose (1 mg/kg) testosterone enanthate im for 0-6 months together with an aromatase inhibitor, letrozole, 2.5 mg orally once a day for 0-12 months (treatment group). In the control group, serum androgen bioactivity increased during the course of puberty (P < 0.001). During 0-12 months of the study, the boys in the treatment group had higher androgen bioactivity levels (P < 0.05) and faster rate of pubic hair growth than the control boys (P < 0.05). Overall, the average serum androgen bioactivity during 12 months of follow-up correlated strongly with the concomitant changes in Tanner genital (r(S) = 0.89; n = 13; P < 0.005) and pubic hair stages (r(S) = 0.79; n = 13; P < 0.01). In conclusion, our results suggest that circulating androgen bioactivity mediates the tempo of pubertal maturation and that the combination of testosterone and letrozole given to boys with constitutional delay of puberty accelerates puberty.     

The effect of serum prolactin on plasma adrenal androgens and the production and metabolic clearance rate of dehydroepiandrosterone sulfate in normal and hyperprolactinemic subjects

Hyperprolactinemic patients may have increases in plasma dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS). We examined the effect of lowering serum PRL with bromocriptine or pituitary surgery on the serum concentrations of adrenal androgens and on the production rate (PR) and MCR of DHAS in eight hyperprolactinemic women (HP). We also examined the effect of bromocriptine therapy on adrenal androgens in five normal men. Serum DHAS was elevated in HP compared to normal women (mean +/- SEM, 254 +/- 28 vs. 182 +/- 13 microgram/dl; P less than 0.04). Serum DHA and androstenedione (delta 4) in HP were not significantly different from normal. Serum PRL fell from 160 +/- 16 to 37 +/- 9 ng/ml during or after treatment. Mean 24-h serum DHAS fell from 198 +/- 30 to 106 +/- 17 micrograms/dl (P less than 0.001) with treatment, without a change in the mean 24-h serum cortisol concentration (6.2 +/- 0.4 vs. 6.6 +/- 0.4 micrograms/dl). Thus, the DHAS to cortisol (DHAS/F) ratio fell significantly (32 +/- 5 to 17 +/- 4; P less than 0.001). This was also true of the DHAS/F ratio during ACTH stimulation (8 +/- 1 to 6 +/- 1; P less than 0.02). Similar changes were found in basal and ACTH-stimulated DHA/F ratios, whereas the basal and ACTH-stimulated delta 4/F ratios did not change significantly with treatment. Treatment lowered the PR of DHAS from 27 +/- 5 to 17 +/- 3 mg/24 h (P less than 0.03) and increased the DHAS MCR from 16 +/- 2 to 21 +/- 3 liters/24 h (P less than 0.01). Bromocriptine treatment of normal men lowered serum PRL from 15 +/- 2 to less than 2.5 ng/ml. There were no significant changes in the basal and ACTH-stimulated serum DHAS/F, DHA/F, or delta 4/F ratios or DHAS PR and MCR during bromocriptine therapy. The failure of bromocriptine to significantly alter these steroids in normal men suggests that bromocriptine was not directly responsible for the changes in HP treated with this drug. A mechanism for the increased PR of DHAS in HP was sought by examining the serum concentrations of the steroid biosynthetic intermediates relevant to DHAS production. Lowering serum PRL was associated with a decrease in basal and ACTH-stimulated 17-hydroxypregnenolone/17-hydroxyprogesterone and DHA/delta 4 ratios, suggesting an increase in 3 beta-hydroxysteroid dehydrogenase/delta 4,5-isomerase activity. However, increased gonadal secretion of the delta 4-steroids may have occurred with the fall in serum PRL.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.     

Effect of short dexamethasone suppression on plasma steroids in prepubertal and pubertal girls

In 40 girls aged from 2 to 14 years, subdivided into groups according to age and pubertal development, and in 6 adult female volunteers, plasma cortisol (F), pregnenolone (delta 5), dehydroepiandrosterone (DHA) progesterone (P), 17-hydroxyprogesterone (17P), androstenedione (A), testosterone (T) and estradiol (E2) were measured before and after short dexamethasone (DXM) suppression. The results confirmed the capacity of DXM to inhibit plasma steroids in all age groups, except T in 2-9 year old and P1 Tanner's stage girls. The percentage suppression of each given steroid was constant over the age groups from 6-9 years to P4-5 Tanner's stage, while lower suppression was found in 17P, P and DHA in 2-5 year old girls and in 17P, DHA and E2 in adult women. These results emphasize the fundamental role of ACTH as the overall stimulating factor of adrenal steroidogenesis but do not negate the possibility of another factor responsible for the development of the adrenal androgen secreting cells throughout prepuberty and puberty.     

Plasma LH and FSH response to LRH and plasma testosterone levels in boys with irregular puberty.

Nineteen boys with irregular puberty (IP), defined as a discrepancy of two or more pubertal stages between the criteria for genitalia and that for pubic hair, were subjected to a standard LRH test (50 microng/m2, iv) and the response of gonadotrophins as well as the basal levels of plasma testosterone, LH and FSH were compared to those of boys with normal, regular puberty. When the results were plotted against the pubertal stage for genitalia (Pg), it was found that in the boys with IP the basal plasma testosterone levels were lower and the response of plasma LH to LRH stimulation lesser than in the controls. However, when these parameters were plotted against the pubertal stage for pubic hair (Ph) it was found, that in the boys with IP the plasma testosterone levels were significantly higher and the response of both LH and FSH stimulation greater than in the control group. It was concluded that irregular puberty in boys may be regarded as a normal variation. The delayed development of sexual hair and penile length, and retarded pubertal growth spurt and bone age maturation seen in these boys, with normal testicular development, may be explained by a temporary reduced peripheral sensitivity to androgens and a compensatory effort by the pituitary, manifested in increased secretion of LH and testosterone, relatively to their pubertal stage for pubic hair.     

Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women

To investigate the basis of the hirsutism and elevated plasma dehydroepiandrosterone (DHA) and/or DHA sulfate (DHAS) in hyperprolactinemic women, we measured androgen binding parameters and an extensive profile of plasma androgens in normal (NL) and hyperprolactinemic women (HYPRL). ACTH tests and dexamethasone (dex) suppression tests were performed in subgroups. Free testosterone levels were higher in HYPRL (13.1 +/- 23.3 vs. 7.18 +/- 0.72 pg/ml; P less than 0.025), although total testosterone was comparable. This disparity was related to plasma testosterone-estradiol-binding globulin (TEBG) levels being one third lower in HYPRL (mean +/- SE, 27.4 +/- 4.0 nM) than in NL (41.2 +/- 3.7 nM; P less than 0.0125). Less striking elevations of plasma DHAS, androstenedione, and 11-deoxycortisol were found in HYPRL. Plasma total dihydrotestosterone [17 beta-hydroxy-5 alpha-androstan-3-one (tDHT)] was nearly 30% lower in HYPRL (11.2 +/- 2.6 ng/dl) than in NL (15.6 +/- 1.3 ng/dl; P less than 0.025), whereas free DHT was normal. Ratios of tDHT to precursors were lower in HYPRL (P less than 0.005). After ACTH stimulation, hyperresponsiveness of 17-hydroxyprogesterone and androstenedione were observed. Apparent adrenal enzyme efficiencies, judged from post-ACTH product to precursor ratios, were normal in HYPRL with one exception: the ratio of tDHT to total testosterone at 4 h was lower (P less than 0.05). Dex suppression normalized androgens and obliterated the abnormal tDHT to precursor ratios. These findings suggest an ACTH dependency of the abnormalities. In summary, we find that about 40% of HYPRL have an androgenic abnormality, and the most characteristic abnormality is an elevated free testosterone level (abnormal in 43%). Depressed TEBG and high DHAS levels were found with lesser frequency (19-21%). The plasma tDHT concentration was low, both in absolute terms and relative to its precursors. Dex suppressibility of the hyperandrogenemia was also observed. We postulate that PRL may exert multiple effects on steroid secretion and metabolism. Possibilities include the inhibition of the TEBG level.     

Concentration patterns of plasma dehydroepiandrosterone, delta 5-androstenediol and their sulphates, testosterone and cortisol in normal healthy women and in women with anorexia nervosa

Plasma levels of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), delta 5-androstenediol (delta 5-DIOL), delta 5-androstenediol sulphate (delta 5-DIOL-S) and testosterone were determined every 2 h from 10.00 to 20.00 h in 8 normal women and 10 with anorexia nervosa. Plasma levels of cortisol. DHA and delta 5-DIOL were significantly (P less than 0.001) higher while DHAS levels were significantly (P less than 0.001) lower in the anorexic women. The levels of delta 5-DIOL-S and testosterone were similar in both groups of women. In the normal women there were significant (P less than 0.001) diurnal fluctuations in the levels of cortisol, DHA and DHAS with high levels in the morning and a nadir in the evening; however, there were significant P less than 0.001) 'reverse' diurnal fluctuations in the levels of delta 5-DIOL, delta 5-DIOL-S and testosterone with low levels in the morning and elevated levels in the evening. In the anorexia nervosa women there was a loss of the diurnal variation in the levels of cortisol, DHA and DHAS and delta 5-DIOL-S; the diurnal variations of delta 5-DIOL and testosterone levels in the anorexic women were similar to those in the normal women. In general, these findings support the suggestion of a disturbance in the mechanisms regulating hypothalamic-pituitary-adrenal function resulting from a primary hypothalamic defect and/or abnormal alterations in steroid metabolism associated with the malnutrition in anorexia nervosa.     

Adrenarche

Between 6 and 8 years of age, while cortisol concentrations and production rates remain constant, urinary excretion and circulating concentrations of DHA, DHAS, and other adrenal androgens increase progressively. These hormonal changes, which constitute the adrenarche, are accompanied by the appearance of axillary and pubic hair and a transient acceleration of linear growth and bone maturation. Increased adrenarchal concentrations of adrenal androgens may also contribute to the observed developmental decrease in concentration of SHBG and increase in bioavailable testosterone that occur in preadolescent boys. It is not known if extraadrenal factors, intraadrenal factors, or a combination of both are responsible for the occurrence of adrenarche. However, known hormones, such as ACTH, prolactin, gonadotropins, and estrogens, do not appear to cause the adrenarche. During adolescence, ACTH and cortisol concentrations remain constant, but concentrations of adrenal androgens continue to increase. The existence of a relationship between adrenarche and puberty has been suggested, partly because increased concentrations of adrenal androgens in undertreated congenital adrenal hyperplasia have been associated with cases of true precocious puberty in boys. However, there is evidence against a causal relationship, including the observation that children with treated primary adrenal insufficiency have been found to enter puberty normally. Adrenarche may cause a transient acceleration of growth and serve as a permissive factor in male puberty but does not appear to be necessary for the initiation of puberty.     

Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche.

Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.     

Reduced adrenal androgens in patients with myotonic dystrophy

Endocrine disturbances associated with myotonic dystrophy (MD) include testicular atrophy, hyperinsulinemic glucose intolerance, thyroid abnormalities, and low or low normal urinary 17-ketosteroid (17-KS) excretion. Since the major circulating precursors of urinary 17-KS are dehydroepiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA), a decrease in adrenal androgen production has been suggested. This possibility was studied in 19 MD patients and 19 age- and sex-matched normal subjects. Each patient had a 24-h urine collection for 17-KS and cortisol determinations, a 4-h iv infusion of 25 micrograms tetracosactrin with serial measurements of serum DHAS, DHA, and cortisol, and an insulin-induced hypoglycemia test. Sixteen patients had 0800 and 2400 h serum collections for cortisol estimations. Serum DHAS [1.0 +/- 0.5 (+/- SD) vs. 3.9 +/- 1.9 mumol/liter; P less than 0.0005] and DHA (5.9 +/- 2.7 vs. 11.0 +/- 7.1 nmol/liter; P less than 0.005) levels were significantly lower in MD patients than in normal subjects; cortisol levels were higher (540 +/- 222 vs. 394 +/- 128 nmol/liter; P less than 0.01), almost certainly a reflection of stress. A normal diurnal cortisol rhythm was found in all 16 subjects. Cortisol responses to insulin-induced hypoglycemia were normal, increasing from 345 +/- 243 nmol/liter to a maximum of 831 +/- 282 nmol/liter. Urinary 17-KS excretion was low or low normal, while urinary cortisol levels were normal in 18 and mildly elevated in 1 patient. There was a significant correlation between 17-KS and DHAS levels (r = 0.46; P less than 0.05). DHAS, DHA, and cortisol responses to tetracosactrin infusion were similar in patients and normal subjects. It is concluded that 1) in MD patients, serum DHAS and DHA concentrations are significantly lower than those in normal subjects, explaining the frequent reports of low or low normal 17-KS excretion; 2) the reduced DHAS and DHA concentrations are most likely due to decreased production rather than increased clearance; and 3) glucocorticoid production is normal.     

Somatomedin A in male puberty. Variation with age, maturity, growth and androgens

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.     

A genetic component to the variation of dehydroepiandrosterone sulfate

Previous studies have shown wide variation in the normal range of serum concentrations of adrenal androgens, including dehydroepiandrosterone (DHA), and DHA sulfate (DHAS). Much of this variability has been shown to be due to the marked variation of the concentrations of these hormones with age. In a search for other sources of this variation, we examined the distribution of DHAS levels in 178 individuals drawn from 26 families. DHAS was chosen because of its relatively high serum concentration, long half-life, and lack of pulsatile variation. As expected, we observed a large age effect, such that it accounted for 68% of the overall variability. In addition, however, when age was factored out by appropriate polynomial regression, there was a significant genetic component to the residual variation, with a heritability of 65%. Thus there appeared to be a significant genetic determination to DHAS serum levels. The results are in accord with previous studies suggesting a genetic component to the variation in testosterone and sex hormone globulin concentrations, and the known correlation of DHAS and testosterone levels. Thus there appears to be significant genetic control of androgen concentrations in humans.     

Adrenocortical function in hyperprolactinemic women.

To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production.     

Plasma levels of 17-OH-progesterone and testosterone in patients with varicoceles

In order to study Leydig cell function in patients with varicoceles, we determined plasma levels of the most important testicular steroids, 17-OH-progesterone (17-OH-P) and testosterone (T) in the basal condition and after hCG stimulation. There was a significant inverse linear correlation between age, plasma testosterone, and 17-OH-P (n = 65, r = 0.316, P = 0.01, n = 48, r = 0.532, P = 0.01). This was in contrast to the absence of such correlations in normal men in the same age range. Following hCG stimulation in 16 patients the 17-OH-P/T ratio was significantly increased with respect to normal controls. No correlation was been observed between sperm count and age in varicocele patients. Analysis of variance of 17-OH-P plasma levels between the patients with a sperm count less than 10 million/ml and that of more than 10 million/ml did not reveal any significant difference. These results suggest that the deleterious effects of varicocele on seminiferous tubules and Leydig cells are unrelated. Moreover the increased 17-OH-P/T ratio after hCG stimulation suggests that some enzymatic impairment involving the last steps of testosterone biosynthesis exists in patients with varicoceles. This is evident in middle aged varicocele patients with a premature decrease of plasma levels of testosterone.     

PLASMA ANDROGENS IN WOMEN WITH HYPERPROLACTINAEMIC AMENORRHOES

Cortisol, androstenedione, testosterone, dehydroepiandrosterone sulphate (DHAS) and free dehydroepiandrosterone (DHA) were measured in plasma of ten women affected by amenorrhoea with hyperprolactinaemia and eleven women affected by secondary hypothalamic amenorrhoea; twelve normal women at the second day of the menstrual cycle were used as controls. All subjects were hospitalized and 17-ketosteroids, 170H-corticosteroids and total dehydroepiandrosterone were also measured in urine. Plasma DHAS was increased in all subjects affected by amenorrhoea with hyperprolactinaemia, while plasma DHA and urinary DHA were significantly increased in this group in comparison to other groups. Plasma cortisol, androstenedione and testosterone and urinary 17-oxosteroids and 170H-corticosteroids were not significantly different in the three groups. In subjects affected by amenorrhoea with hyperprolactinaemia treated with bromocriptine a clear decrease of DHAS correlating with a decrease of plasma prolactin was observed. Since in women DHAS seems to be almost exclusively secreted by the adrenal gland and most of the circulating DHA is derived from adrenal secretion, these data suggest that human prolactin can stimulate DHAS production by the adrenal cortex.