Steroid Excretion Patterns Research Articles

Diagnosis of the adrenogenital syndrome caused by 11beta-hydroxylase deficiency using gas chromatographic-mass spectrometric analysis of the urinary steroid profile

In 5-7% of all cases of congenital adrenogenital hyperplasia (AGH) there is 11 beta-hydroxylase deficiency (11 beta-HM). Its clinical picture is characterised by hyperandrogenism and, in some cases, arterial hypertension. The diagnosis of the enzyme deficiency depends on a reliable method of analysing the hormone in plasma and urine. As little is known and data often contradictory about the pattern of urinary steroid excretion in 11 beta-HM, these steroid metabolites were measured by a highly specific method. The pattern of urinary excretion of steroids was determined by gas chromatography and mass spectrometry (GC/MS) in 16 children and adults (11 males, 5 females: mean age 9(8)/12 [2/12-20(3)/12] years) with 11 beta-HM. In all patients there was greatly increased excretion of tetrahydrated (TH) and hexahydrated (HH) metabolites of 11-desoxycortisol (S) and desoxycorticosterone (DOC). The excretion of THS and THDOC was extremely increased in all patients. The metabolites 5 alpha-THS as well as 20 alpha- and 20 beta-isomers of HHS, not normal found in healthy persons, were present in 15 patients (94%), while the 20 alpha- and 20 beta-isomers of 5 alpha-HHS were demonstrated in 14 (88%). For the first time, 20 alpha- and 20 beta-isomers of 5 alpha-HHS were shown to be typical urinary steroid metabolites in 11-HM. The excretion of cortisol metabolites is typically decreased in 11 beta-HM. No corticosterone metabolites were found. The urinary steroid excretion pattern, measured by GC/MS, is a noninvasive, highly specific and nonselective method in the differential diagnosis of abnormal steroid metabolism.

Prediction of 1-year survival after resection of lung tumours from the preoperative steroid excretion pattern.

Abstract A prospective study of 50 patients with lung cancer who were treated by surgical resection of their tumour has shown that most of those who died within 1 year after resection had abnormalities in preoperative steroid excretion whereas most of those who are alive had normal steroid excretion. Of the 21 patients who died within 1 year, 5 died in hospital, mainly as a result of surgical complications, and were found to have an abnormally low androsterone to aetiocholanone ratio and a high total 17-oxosteroid excretion. Those who were discharged alive and well from hospital but who died within 1 year as a result of metastasis to other organs had a low androsterone level in relation to aetiocholanolone and to total 17-hydroxycorticosteroids. Thus, it has been possible to identify by their preoperative steroid excretion 12 out of 14 patients who died within 1 year although they had had a successful resection.

Diurnal patterns of urinary steroid excretion in wild chimpanzees.

Urinary testosterone and cortisol concentrations were quantified in a large number of samples (>500) collected from wild male chimpanzees (n=11) over the course of 1 year. For both steroids, urinary concentrations were higher and more variable in the morning than in the afternoon. Urinary creatinine levels showed no such diurnal pattern. These patterns are consistent with studies of steroid excretion in humans and gorillas. This study emphasizes the importance of considering time of day as a confounding variable in field studies of primate endocrine function. It also suggests that if a small number of samples are to be used to characterize an individual's basal steroid levels, afternoon samples may be preferable because they show less intra-individual variability.

Characterization of reproductive cycles and adrenal activity in the black‐footed ferret (Mustela nigripes) by fecal hormone analysis

AbstractThe reproductive cycle of the black‐footed ferret (Mustela nigripes) was characterized by enzyme immunoassay (EIA) analysis of ovarian fecal steroids (estradiol, progestins) in 29 females over two consecutive breeding seasons. Estrous status was determined by measuring the vulva size and examining the percentage of superficial cells in vaginal lavages. Mean fecal estradiol concentrations were correlated with vulval area (r = 0.370, P < 0.0001) and the percentage of superficial cells (r = 0.380, P < 0.0001). Ovulation resulted in a rise in fecal progestin concentrations 5 days after breeding that differed (P < 0.05) between pregnant (n = 14) and pseudopregnant (n = 12) females during the late luteal phase (days 12–40), with concentrations remaining higher in pregnant animals. Gestation length was 41.3 ± 0.7 days with 3.6 ± 0.4 kits produced per female. Litter size correlated significantly (P < 0.05) with fecal estradiol, but not progestins during the 12 to 40 days after breeding. Females failing to breed (n = 3) remained in estrus for 31 ± 6.2 days before ovulation induction with human chorionic gonadotropin. Adrenal activity in male (n = 4) and female (n = 6) black‐footed ferrets was monitored by quantifying fecal corticoid metabolites after a series of manipulations (physical restraint, intramuscular saline, intramuscular gel adrenocorticotropic hormone (ACTH), intramuscular liquid ACTH). A significant (P < 0.0001) increase in fecal corticoids above the pre‐treatment baseline occurred 20 to 44 hours after restraint (five of 10 animals), saline (six of nine), gel ACTH (seven of 10), and liquid ACTH (nine of 10) treatments. Immunoreactivity of high‐performance liquid chromatography–separated fecal elutes was compared using antibodies against cortisol and corticosterone. The cortisol EIA demonstrated immunoreactivity that co‐eluted with 3H‐cortisol, whereas a corticosterone radioimmunoassay detected a metabolite peak that co‐eluted with 3H‐corticosterone in addition to a slightly less polar and one considerably more polar peak. Despite recognizing different metabolites, both assays produced similar temporal profiles of corticoid excretion after manipulation. This study provides new information on the black‐footed ferret regarding differences in fecal steroid excretion patterns between pregnancy and pseudopregnancy and the potential application of fecal corticoid metabolite monitoring for evaluating responses to stressors associated with practices used in breeding management. Zoo Biol 20:517–536, 2001. © 2002 Wiley‐Liss, Inc.

Patterns of Urinary and Fecal Steroid Excretion during the Ovarian Cycle and Pregnancy in the African Elephant (Loxodonta africana)

The aims of the present study were to (i) determine the relative abundance of the 5α-reduced progestins 5α-pregnane-3-ol-20-one (5α-P-3OH) and 5α-dihydroprogesterone (5α-DHP) and progesterone (P4) in African elephant feces and to establish improved fecal progestin assays for monitoring ovarian function; and (ii) describe longitudinal profiles of urinary and fecal progestin and estrogen metabolites during pregnancy. Matched urine and fecal samples were collected weekly from six adult females throughout 18 nonfertile cycles and two complete pregnancies (89 and 93 weeks duration). Fecal samples were lyophilized and extracted with 80% methanol in water and immunoreactive 5α-P-3OH, 5α-DHP, and P4 and (for pregnant females only) estrone (E1) and estradiol (E2) determined by enzyme immunoassay. Urine samples were hydrolyzed, ether-extracted, and assayed for 5α-P-3OH, E1, and E2. HPLC cochromatography of fecal extracts with various radioactive progestin tracers confirmed the presence of large amounts of both 5-reduced progestins (5α-P-3OH>5α-DHP) but not of P4. 5-Reduced progestins (but not P4) were excreted in a cyclic pattern and levels were significantly correlated with urinary 5α-P-3OH. Fecal 5α-P-3OH showed the more pronounced and consistent luteal-phase elevation and a better correspondence to urine with respect to timing of the luteal-phase rise. Fecal and urinary 5-reduced progestins increased gradually during early pregnancy to maximum values around week 40–45. Levels gradually declined during the second half of pregnancy, reaching baseline values 2 days before parturition. Urinary estrogens did not show any cyclic pattern during the preconception period and levels remained low during the first 30 weeks of gestation. Thereafter, there was a rapid 10- to 20-fold increase to maximum values at mid-pregnancy, followed by a gradual decline to birth. There was no mid-pregnancy elevation in fecal estrogens, but there was a modest increase in E1 during the second half of gestation.

Assessment of female reproductive status in captive-housed Hanuman langurs (Presbytis entellus) by measurement of urinary and fecal steroid excretion patterns.

The study reports on the use of urinary and fecal hormone measurements for monitoring female reproductive status in captive-housed Hanuman langurs (Presbytis entellus). Matched urine and fecal samples collected throughout 7 complete menstrual cycles of two females, and during part of one pregnancy in a third female were analyzed. Estrone conjugates (E1C) and immunoreactive pregnanediol glucuronide (PdG) in urine and immunoreactive estradiol (E2), progesterone (P4), pregnanediol (Pd) and 20α-hydroxyprogesterone (20αOHP) in feces were measured by enzymeimmunoassay. E1C and PdG in urine were excreted in a cyclic pattern with E1C levels increasing 3- to 4-fold during the follicular phase to reach preovulatory peak values 2 days before a defined rise in PdG concentrations. Cycle lengths ranged between 20 and 34 days comprising a variable follicular phase of 7-21 days and a more consistent luteal phase of 12-14 days. High pressure liquid chromatography (HPLC) analysis of fecal extracts confirmed the presence of all fecal hormones measured, but indicated large amounts of additional immunoreactivity in the three progestin assays. The patterns of excretion of fecal E2 and all three fecal progestins corresponded well with those of steroid metabolites in urine in showing a clear and well defined follicular phase E2 rise followed by a luteal phase progestin increase. Measurement of 20αOHP immunoreactivity revealed the most stable baseline and the highest follicular/luteal phase differential. Levels of all hormones were clearly elevated during pregnancy although urinary E1C and PdG showed a more pronounced increase compared to fecal metabolites. The results indicate that urinary and fecal hormone analysis can be applied to noninvasive monitoring of reproductive status in the Hanuman langur. © 1995 Wiley-Liss, Inc.

Excretion of estrone, estradiol, and progesterone in the urine and feces of the female cotton-top tamarin (Saguinus oedipus oedipus).

The excretion of three gonadal steroids was studied in the urine and feces of female cotton-top tamarins (Saguinus oedipus oedipus). Each steroid, 14C-estrone, 14C-estradiol, and 14C-progesterone, was injected into a separate female cotton-top tamarin. Urine and feces were collected at 8 hr intervals for 5 days on the three tamarins. Samples were analyzed to determine the proportion of free and conjugated steroids. Steroid excretion patterns were determined by sequential ether extraction, enzyme hydrolysis, and chromatography. Labeled estrone was excreted in a slow and continuous manner into the urine (57%) and feces (43%) with 90% of the steroid conjugated. The nonconjugated form had an elution profile identical to 3H estrone, but the conjugated portion was not completely hydrolyzed by enzyme. Labeled estradiol was excreted primarily in the urine (87%) and was released rapidly. Over 90% of the injected 14C-estradiol was excreted in urine as a conjugate, of which 41% was converted to an estrone conjugate and the remaining 59% was excreted as a polar estradiol conjugate. Labeled progesterone was excreted primarily in the feces (95%), 61% of which was free steroid. Four to six individual peaks of radioactivity were found when using celite chromatography and high performance liquid chromatography (HPLC), indicating that progesterone is metabolized into several urinary and fecal metabolites. One of these peaks matched 3H-progesterone and others may be pregnanediols, pregnanetriols, and 17-hydroxyprogesterone. These steroidal excretion patterns help explain the atypical hormonal patterns seen during the tamarin ovarian cycle.

Detection of 3β-hydroxysteroid dehydrogenase deficiency in a newborn by means of urinary steroid analysis

A urinary steroid excretion pattern of a 3-wk-old newborn, suffering from 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency, has been produced, employing capillary gas chromatography and subsequent mass spectrometric identification of the various excreted steroids. The diagnosis could be established, apart from the clinical symptoms, on the basis of a grossly elevated excretion of 16-OH-DHEA and 16-OH-pregnenolone, combined with mass spectrometric identification of the following steroids: 17-OH-pregnanolone, pregnanetriol, pregnenediol, pregnenetriol and 17-OH-pregnenolone.

Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.

Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.

Urinary steroid evaluations to monitor ovarian function in exotic ungulates: III. Estrone sulfate and pregnanediol‐3‐glucuronide excretion in the Indian rhinoceros (Rhinoceros unicornis)

AbstractA study was undertaken to identify urinary estrogen and progesterone metabolites in the female Indian rhinoceros (Rhinoceros unicornis). Measurements of these metabolites were then used to monitor ovarian function and establish normal levels and patterns of steroid excretion during the estrous cycle and pregnancy. Urine samples were analyzed for estrone sulfate and pregnanediol‐3‐glucuronide (PDG) by direct radioimmunoassays. Both hormones produced discrete profiles reflecting ovarian activity in nonconceptive cycles. The estrous cycle was observed to be 48 days (range 39–64) with a mean follicular phase of 14.8 days (range 13–19), followed by a mean luteal phase of 19 days (range 17–21). Of the single gestation monitored, PDG levels rose above luteal phase levels by the third month after breeding and remained elevated throughout gestation. The combined estrogen and progesterone metabolite profiles present a complete evaluation of ovarian steriod production in the mature female Indian rhinoceros.

Modulation of oestrogen excretion profiles by adjuvant chemotherapy in pre- and postmenopausal breast cancer

Modulation of steroid status by conventional chemotherapy was studied in 31 breast cancer patients receiving CMF and in 31 age-matched breast cancer patients without any therapy, taken as controls. This was achieved through the study of oestrogen excretion profiles using previously identified parameters and referring not only to classical but also to the “other”, namely catechol and unusual, oestrogen metabolites. After CMF treatment the premenopausal patients exhibit a modified excretion pattern, mainly concerning a marked and significant reduction of classical oestrogens, as shown by pattern indices. Because there is evidence that oestriol metabolism is not markedly affected by CMF treatment, such a significant decrease in classical oestrogens must be attributed to the secretory function, presumably ovarian ab origine. To the contrary, after treatment, pattern indices show significantly higher median values in postmenopausal patients. Mean oestriol ratio values also display a significant increase, thus supporting the hypothesis that conventional cytotoxic drugs may act by enhancing oestrogen metabolic rates. In fact, the postmenopausal treated subgroup proved to have significantly higher excretion levels of most of the oestrogens considered to date. Surprisingly, E1 + E1-S fractions were strongly reduced in this subgroup and this leads to the suggestion of an increased steroid metabolic rate by CMF treatment. However, comparing 9 breast cancer patients, when having had both short-term and non-short-term CMF treatment, the effects on steroid excretion patterns appear to arise at an early stage.

Prenatal diagnosis and variable presentation of recessive X-linked ichthyosis

Three infants with X-linked ichthyosis have been observed following pregnancies in which placental sulphatase deficiency (PSD) was suggested prenatally by low oestrogen excretion and an abnormal urinary steroid excretion pattern. This was confirmed in two cases by the absence of placental enzyme activity. In one case labour was spontaneous but all deliveries required Caesarean section. At 8 months the first infant showed an eczema in an atopic distribution but when seen at 5 years had typical X-linked ichthyosis. The skin of the second child peeled extensively at the age of 2 days but was not troublesome for 2 years, when ichthyosis vulgaris was diagnosed on clinical grounds. This pattern has persisted for 3 years. The third infant showed a mildly scaly skin in the neonatal period but at 3 months the features and distribution of X-linked ichthyosis were apparent. X-linked ichthyosis may have a variable presentation which is not always apparent at birth.

Capillary gas chromatography as a tool for characterization of urinary steroid excretion in patients with congenital adrenal hyperplasia

Urinary steroid excretion was studied by capillary gas chromatography in 23 patients with congenital adrenal hyperplasia. In 5 patients the estimated excretion rates of pregnanetriol were in or below the normal range and 7 patients presented Supranormal excretion rates of tetrahydro-cortisone and/or other glucocorticoid metabolites. Deficiency of 21-hydroxylase was nevertheless demonstrated in each patient by an increased ratio of excreted precursors vs products of 21-hydroxylase e.g. of pregnanetriol/tetrahydro-cortisone. Due to this relative deficiency of glucocorticoids the patients' steroid excretion was further characterized by a predominance of 5α-hydrogenated C 19O 3, metabolites (11-keto-androsterone, 11-hydroxy-androsterone) over their 5β-hydrogenated homologues (11-keto-etiocholanolone, 11-hydroxy-etiocholanolone). An apparent preponderance in the excretion of pregnenetriol over that of pregnanetriol was found in 4 patients, but the presence of pregnenetriol was not confirmed by mass spectrometry following prepurification of the urine samples by thin-layer chromatography indicating interference of an unidentified steroid metabolite with the initial gas Chromatographic analysis. The simultaneous determination of steroids serving as precursors or products of 21-hydroxylase by capillary gas chromatography helps to establish the diagnosis of 21-hydroxylase deficiency and to characterize the pattern of steroid excretion in this syndrome even in patients where the estimation of single urinary steroids may lead to erroneous conclusions.

Fecal steroid excretion and degradation and breast cancer stage

Evaluation of excretion and degradation of fecal steroids in 74 women with breast cancer in relation to stage, tumor size, and histopathologic nodal status revealed significant differences in relation to stage of disease and tumor size. The level of total fecal steroids (mean ± SD in mg/g dry wt) in patients with Stage I disease was 40 + 20, Stage II = 56 ± 32, and Stage III = 75 ± 57 ( P = 0.006). Secondary fecal steroids in women with Stage I disease were 26 ± 16, Stage II = 40 ± 27, and Stage III = 57 ± 34 ( P = 0.003). Fecal steroid excretion and degradation was significantly higher in women with larger tumors, whereas nodal status did not contribute to observed differences indicating that dissemination of disease did not influence the results. These differences were noted to be independent of obesity since similar patterns of fecal steroid excretion were noted within the subgroups of both lean and obese women. Increased levels of total fecal steroids and secondary compounds apparently contribute to tumor promotion and may reflect a potential for excess estrogen synthesis since intestinal bacteria have the ability to synthesize estradiol, estrone, and 3,17-methoxyestradiol from secondary steroids present in the colon.

Endocrinology of pregnancy in the orang-utan (Pongo pygmaeus) and its evolutionary significance

Urinary concentrations of estrone, estradiol-17Β, estriol, pregnanediol-3α-glucuronide, and chorionic gonadotrophin (CG) were measured by radio-immunoassy through five pregnancies in four multiparous orang-utans. The excretion of all three estrogen metabolites increased substantially during pregnancy. Although estrone was the major metabolite during early pregnancy, estriol excretion increased considerably, to reach 10 times the concentration of estrone at term. Estradiol-17Β was of comparatively minor importance. Maximum CG excretion occurred during the first trimester and low but constant levels were present in urine throughout the remainder of pregnancy. An early peak of pregnanediol-3α-glucuronide excretion coincided with the CG peak and then rose steadily to reach a plateau 8 weeks prepartum which was maintained until term. Urinary excretion of all five hormones decreased rapidly immediately following parturition. These data suggest that the pattern of urinary steroid and CG excretion during pregnancy in the orang-utan closely resembles that in the other great apes and women.

The diagnosis of 21-hydroxylase deficiency in a prematurely born infant on the basis of the urinary steroid excretion pattern

The urine of a 6-day-old prematurely born female infant (birth weight 1060 g) suspected of having a 21-OH deficiency showed no steroid abnormalities on capillary GLC analysis. Using GC-MS tetrahydrocortisone (THE) and also 3α, 17α-dihydroxy-5β-pregnane-20-one (17-OH-Polone) were absent, but two androstanetriolone peaks were observed. In the urine collected on day 9 THE was absent, but a large amount of 3α, 11β-dihydroxy-5α-androstane-17-one (11-HA) was found by GC-MS to be contaminated by a small amount of 17-OH-Polone. The next urine specimen collected on the 22nd day while the child received cortisol therapeutically showed the characteristic steroid profile for the diagnosis 21-OH deficiency, large peaks of 17-OH-Polone, pregnanetriol (P 3) and 11-keto-pregnanetriol (11-keto-P 3). Over the next few weeks two other compounds were found to have been excreted in relatively large amounts, 3ξ, 16ξ, 17ξ, 20ξ-pregnanetetrol (16-OH-P 3) and surprisingly also a 21-hydroxylated compound, namely 3β, 20α, 21-trihydroxy-5-pregnene. These same two compounds were also found in the urine of another infant with suspected 21-OH deficiency. The urinary steroid excretion patterns characteristic for 21-OH deficiency are dependent on the maturity and age of .the infant. In the prematurely born infant androstanetriolones appear in the urine before 17-OH-Polone. The occurrence of these different steroid excretion patterns is tentatively explained.

DIFFERENTIATION OF PSEUDOHYPOALDOSTERONISM (PHA) AND ADRENAL BIOSYNTHETIC DEFECTS

Adrenal salt-wasting diseases in the neonatal period and early infancy can be confirmed by the pattern of steroids excreted in urine. The presence or absence of cortisol, aldosterone and corticosterone metabolites, plus certain precursors, is established in a single analysis of steroids using gas chromatography with capillary columns and mass spectrometry.In infants (n=5) with the Type II biosynthetic defect of aldosterone, the excretion of corticosterone and 18-hydroxycorticosterone metabolites were elevated. In PHA (n=8), both 18-hydroxycorticosterone and aldosterone metabolites were found at high concentrations in urine. When salt loss was controlled by replacement therapy or sodium supplements respectively, and plasma renin activity (pRA) were normalised, the excretion rates of the metabolites were lower but the ratios of excretion for 18-hydroxycorticosterone to aldosterone metabolites were greater than 30 to 1 in the biosynthetic defect but nearer unity in PHA. The interpretation of the overall pattern of steroid excretion also requires consideration of the changes in the nature of steroid metabolites in newborns through infancy, since conjugates of tetrahydro-metabolites replace hydroxylated and free compounds. These studies are complementary to determinations of pRA and plasma steroid concentrations in defining the diagnosis of infantile salt wasting disease.

Simple computer program for a low-cost desk-top calculator applied to the evaluation of gas-liquid chromatographic analyses of 17-ketosteroids and pregnanes

A simple computer program consisting of 445 steps for a low-cost desk-top calculator (Hewlett-Packard 97) to be applied in chromatographic analyses of 17-ketosteroids and pregnanes from human urine samples is described. This program permits the calculation of peak factors following the chromatographic separation of an external standard mixture containing up to ten different fractions, the subsequent printout of the constants and their transcription to magnetic data cards for later retrieval when making calculations for unknown samples. After manual input of sample constants (such as total and aliquot volumes, recovery as determined by addition of a radioactive tracer steroid, internal standard) and peak factors via the data card, the individual peak heights of the samples are automatically converted to milligrams of steroid in 24-h urine and each is stored separately. All fractions can be recalled later and printed out in the order of detection or can be transformed into several diagnostically valuable parameters such as the total sum of 17-ketosteroids and pregnanes excreted, the group sums of androgens, of 11-substituted steroids and of pregnanes, the individual percentages of both the fractions and the group sums, and the ratios of aetiocholanolone-androsterone and of pregnanetriol-pregnanediol. Finally, an extension subprogram can automatically generate a plot to illustrate the steroid excretion pattern in a comprehensive fashion.

Metabolism of fetal and neonatal adrenal steroids

There are marked differences between metabolism of steroids by the human fetus, neonatal infant and adult. These have been assessed by examination of the steroid excretion patterns in the fetus using analysis of pregnancy urine from patients with placental sulphatase deficiency and amniotic fluid from normal pregnancy, and in the neonate by analysis of urine collected during the first days of life. Metabolites of corticosterone and aldosterone have also been measured in infants with hyper-secretion of these hormones. The major differences in the perinatal period in comparison with adulthood are: (1) 3β-hydroxy-5-ene steroids are excreted in much greater absolute and relative amounts; (2) all the 3β-hydroxy-5-ene steroids contain additional hydroxyl groups in the 16α, 18 or 21 positions; (3) of the metabolites of cortisol and corticosterone, 60% contain additional hydroxyl groups in the 1β- or 6α-position, compared with 2–5% in adults; (4) more than 90% of the corticosteroid metabolites contain an 11-oxo group; (5) 21-dehydroxylation of corticosterone metabolites by gut bacteria is absent. Aldosterone metabolism does not differ greatly at different stages of life. The patterns of steroid conjugation are also similar with predominantly glucuronide conjugation of corticosteroids and sulphation of 3β-hydroxy-5-ene steroids. However, a significant proportion of the more polar corticosteroid metabolites are excreted by infants as free compounds. Adrenal steroid output decreases dramatically post partum. Other changes include a relative increase of 15- and 18-hydroxylation of 3β-hydroxy-5-ene steroids and an apparent decrease of 21-hydroxylation, the latter possibly due to utilisation for miner-alocorticoid biosynthesis. Following progressive changes, the adult pattern of steroid metabolism is reached at about 1 year of age.

Relationship Between Steroid Excretion Patterns and Breast Cancer Incidence in Israeli Women of Various Origins2

A nationwide study of the steroid excretion patterns in postmenopausal Israeli migrant women demonstrated differences between high- and low-risk groups for breast cancer in the following variables: age at first parturition, number of pregnancies, number of live births, height, and weight. The direction of the differnces was in line with those observed for breast cancer patients. The groups also differed in the exretion of estriol, 17-ketosteroids, and allotetrahydrocortisol. Multiple regression analysis revealed that the exretion of estriol was significantly lower in population groups in whom breast cancer incidence was high. Possibly this trend--which has also been observed in adolescent and premenopausal women--reflected environmental influences on peripheral estrogen metabolism.