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Comparison of plasma steroid and gonadotrophin profiles in spontaneous cycles in which conception did and did not occur.

Luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and progesterone were measured in plasma from blood samples obtained daily throughout 23 menstrual cycles in a total of 18 normal women. Eight of these women were trying to conceive at the time of investigation and five succeeded. The subjects were divided into those who were not exposed to pregnancy (Group I), those who became pregnant (Group II) and those who were trying to become pregnant but failed to do so (Group III). The mean profiles of each of the four hormones were similar for the three groups studied. Statistical comparisons (using 't' tests) between Groups II and III showed that FSH concentrations were significantly lower (P less than 0.01) in the late follicular phase (Days -7 to -3 before the LH peak) in Group III. Similarly, progresterone concentrations were significantly lower (P less than 0.05) during the early luteal phase (Days +3 to +7 after the LH peak) in Group III.

Estradiol↗

Effect of stress on the profile of plasma steroids in baboons (Papio hamadryas).

Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20alpha-dihydroprogesterone, oestone, oestradiol) or competitive protein binding (cortisol) techniques. The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20alpha-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration greater than 24 h) of oestradiol and oestrone concentrations during the follicular phase. It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females and inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.

17-alpha-Hydroxypregnenolone↗

Expression profiles of sex steroid receptors in desmoid tumors.

Desmoid tumors are benign fibrous neoplasms which arise from the fibrous tissue of intra- and extra- abdominal sites, but their clinical management is sometimes difficult because of extensive infiltration into the surrounding tissues. Desmoid tumors commonly occur in women, especially after childbirth. Recently, both clinical and experimental findings indicate the possible roles of sex steroids in the development and progression of desmoid tumors but detailed information is still ambiguous. In this study, we first examined immunoreactivity of sex steroid receptors in desmoid tumors (27 cases) by immunohistochemistry and compared the findings with those in reactive self-limiting lesions associated with fibrosis (8 cases). Estrogen receptor (ER) alpha and ERbeta immunoreactivities were detected in 7.4% (2/27) and 7.4% (2/27) of desmoid tumors, respectively. One desmoid tumor expressed both ERalpha and ERbeta. Progesterone receptor (PR)-A and PR-B were detected in 25.9% (7/27) and 33.3% (9/27), respectively, and androgen receptor (AR) in 52.9% (14/27). In reactive lesions with fibrosis, only AR was detected in 37.5% (3/8). Sex steroid receptor mRNAs was further examined by reverse transcription and polymerase chain reaction (RT-PCR) analysis using fresh frozen tissues, demonstrating the expression of PR (PR-A and/or PR-B) and AR mRNAs in eight desmoid tumors examined and all cases of reactive fibrosis. These results indicate that sex steroid hormones might play an important role in the pathogenesis of desmoid tumors and could lead to the introduction of novel hormone therapeutic approaches in managing patients with recurrent desmoid tumors.

Adolescent↗

The effect of early postnatal treatment with a gonadotropin-releasing hormone agonist on the developmental profiles of testicular steroid hormones in the intact male pig.

Three studies examined the effects of early postnatal treatment with a GnRH agonist on plasma concentrations of testosterone, dehydroepian-drosterone sulfate, 16-androstene steroids in fat and salivary glands, androstenone in fat and plasma, and testicular development of intact male pigs. The first study involved 45 7-d-old pigs assigned to three treatment groups: 1) boars administered 100 microg/kg of Lupron depot, 2) boars administered 200 microg/kg of Lupron depot, and 3) control boars receiving a saline carrier. The second study involved 20 7-d-old pigs assigned to two treatments: daily injection of 200 microL of 0.5 mg/mL Lupron from d 7 to 35 and controls treated with saline. The third study involved a total of 100 animals assigned to 10 groups of 10 based on their age at slaughter. These groups were subdivided into one of two treatments: 1) boars injected with 200 microL of 0.5 mg/mL of Lupron from d 3 to 35 and 2) control boars injected with saline. Testicular steroid hormone concentrations in plasma decreased (P < 0.01) within 7 d of GnRH agonist treatment. Following cessation of treatment, steroid levels increased to control levels and remained constant until the final rise at 5 mo. Plasma testosterone levels in the 100 microg/kg depot treatment group were higher (P < 0.05) than that of the 200 microg/kg and control group at 164 d of age. There were no differences between treatments (P > 0.05) in testicular steroid hormone levels at the end of study 2 or 3. There were no differences (P > 0.05) in concentrations of 16-androstene steroids in salivary glands between any of the treatment groups at market weight in studies 1 and 2. Fat androstenone levels measured in the third study ranged between 0.6 microg/g and 4.2 microg/g at 7 to 28 d of age. Treatment with GnRH agonist decreased plasma steroid levels and testicular development; however, by d 60 testicular size and weight were at control levels and remained similar until 180 d of age. The results of these studies indicate that daily administration of a GnRH agonist significantly decreased testicular development and steroidogenesis only during treatment, but testis growth and steroidogenesis had returned to control levels by 60 d of age in male pigs. Suppression of the early postnatal rise in testicular steroid hormones did not affect growth performance or steroid hormone levels at 5 to 6 mo of age.

Adipose Tissue↗

Urinary profile of endogenous steroids in postmenopausal women with stress urinary incontinence.

OBJECTIVE: To predict the role of estrogen in prevention of and therapy for stress urinary incontinence by comparing the urinary levels of estrogens and androgens and, to indirectly evaluate metabolism of estrogens and androgens by comparing the concentration ratios of precursor metabolites with those in controls (normal subjects). STUDY DESIGN: Urine samples collected for 24 hours were obtained from postmenopausal women with stress urinary incontinence (n = 20) and from age-matched, postmenopausal, normal female subjects (n = 14). The urinary levels of 20 estrogens and 25 androgens were analyzed by gas chromatography/mass spectrometry. RESULTS: The urinary levels of androgens were significantly higher in patients with stress urinary incontinence than normal subjects, and the urinary levels of estrogens were somewhat higher in patients than normal subjects. However, there were no significant differences between the groups, nor were there significant differences in the metabolism of estrogens and androgens between two groups. CONCLUSION: The urinary levels of endogenous steroids were rather higher in patients with stress urinary incontinence than in normal subjects, so it appears that estrogen should not play a significant role in prevention of and therapy for stress urinary incontinence.

Age Factors↗

Use of Mahalonobis generalized distance in interpreting low-resolution gas-chromatographic profiles of urinary steroids.

We used low-resolution gas-chromatography of urinary steroid metabolites, as their trimethylsilyl ethers, in conjunction with the Mahalonobis generalized distance to assess the analyses in terms of a multivariate normal distribution in two populations of women: 18-50 years old and older. We compare the use of this method of interpretation, presenting several cases to illustrate the use of this approach in a routine clinical chemistry laboratory. The improved accuracy of classification as abnormals and to the ability to identify an analysis result as abnormal, even when values for all the analyses fall within the univariate 95% regions of each constituent.

Adolescent↗

[In-vitro studies on the effect of D-norgestrel and norethisterone acetate on the formation of sex steroids in the human ovary].

In vitro incubations with slices of four normal human ovaries and 4-(14)C-pregnenolone as precursor were carried out to study the possibility of a direct influence of D-norgestrel and norethisterone acetate on the metabolism of pregnenolone. In agreement with our previous studies the in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, estrone and estradiol represents the characteristic profile of steroids of the ovaries from the corpus luteum phase. The in vitro-synthesis of 17 alpha-hydroxypregnenolone, DHA, androstenediol (basic metabolites) and androstenedione represents the characteristic profile of steroids of the ovaries from the follicle phase. The addition of D-norgestrel and norethisterone acetate to the incubation medium influences these steroid profiles in the same way. The metabolites of these characteristic profiles were inhibited by the progestogens, whereas the basic metabolites increased. In previous studies the same influence was found by addition of chlormadinone acetate. The influence of these progestagens on the two different profiles of steroids indicate that D-norgestrel and norethisterone acetate exert an inhibitory effect on the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase system and the aromatase system of the human ovary. These results suggest that these progestogens act directly upon ovarian function, an action which may be assumed to be operative in their contraceptive effect.

17-alpha-Hydroxypregnenolone↗

The use and safety profile of non-steroidal antiinflammatory drugs among Turkish patients with osteoarthritis.

BACKGROUND/AIMS: To determine the use and safety profile of non-steroidal anti-inflammatory drugs (NSAIDs) among Turkish osteoarthritis patients. METHODS: Osteoarthritis patients were interviewed by 138 doctors from clinics in nine different cities. Doctors completed a questionnaire regarding non-steroidal anti-inflammatory drugs use and safety profile while interviewing the patients. RESULTS: Totally 3,755 patients (female/male: 3/1, mean age 59.0 +/- 12.2 years), 3,442 under non-steroidal anti-inflammatory drugs treatment, were included in the study. The use of meloxicam (5.5% vs. 14.4%) and specific cyclooxygenase-2 (COX-2) inhibitors (for celecoxib 3.3% vs. 12.2%; for rofecoxib 3.0% vs. 11.2%) increased more than that of other non-selective non-steroidal anti-inflammatory drugs. The most common side effects were epigastric burning (37%), other dyspeptic symptoms (25.3%), abdominal pain (17.0%), constipation (12.7%), nausea (10.6%) and diarrhea (3.0%). COX-2 selective and specific inhibitors had significantly lower incidence of dyspeptic complaints compared to non-selective non-steroidal anti-inflammatory drugs. No difference was found between the different non-steroidal anti-inflammatory drugs regarding the ratio of discontinuation of therapy due to inefficacy. The ratios of discontinuation due to side effects were lower in patients using COX-2 specific inhibitors compared to non-selective and selective non-steroidal anti-inflammatory drugs: celecoxib (7.7%), rofecoxib (10.3%), etodolac (12.4%), meloxicam (12.6%), tenoxicam (16.5%), diclofenac (16.8%), ibuprofen (19.4%), and naproxen (27.4%). Discontinuation of the non-steroidal anti-inflammatory drugs due to dyspeptic complaint was significantly less for specific COX-2 inhibitors than for non-selective and selective non-steroidal anti-inflammatory drugs: celecoxib (2.5%), rofecoxib (8.4%), meloxicam (9.5%), etodolac (13.4%), tenoxicam (14.0%), diclofenac (14.1%), ibuprofen (17.2%), and naproxen (24.4%). CONCLUSIONS: The use of meloxicam and specific COX-2 inhibitors seems to have increased more than that of other non-selective non-steroidal anti-inflammatory drugs, if previously used non-steroidal anti-inflammatory drugs are considered. Fewer dyspeptic complaints have been reported with specific COX-2 inhibitors.

Aged↗

The effect of steroids on the biophysical profile and Doppler indices of umbilical and middle cerebral arteries in healthy preterm fetuses.

OBJECTIVE: To examine the effect of antenatal steroids on the biophysical profile and the Doppler parameters of umbilical and middle cerebral arteries of healthy fetuses. STUDY DESIGN: Thiry-five singleton pregnancies between the gestational ages of 28 and 34 weeks, who received two consecutive doses of betamethasone 24h apart to accelerate pulmonary maturation were prospectively studied. Fetal biophysical profile and Doppler assessment were performed at 0 (pre-steroid), 24, 48, 72, 96 and 120 h after the administration of first dose. We compared the percentage of the fetuses with biophysical parameters present for each of the five components of the biophysical profile and the Doppler indices, using Cochran's Q-test, Friedman's test and one way analysis of variance of repeated measures where appropriate. The statistical significance was defined as P<0.05. RESULTS: The mean delivery time was 36.9(+/-1.8) weeks. There was a statistically significant difference in the frequency of the following findings in the pre- compared to post-steroid measurements: absence of body movements (48 h, P<0.05), non-reassuring fetal heart rate tracings (24, 48 and 72 h, P<0.05) and absence of breathing movements (24, 48 and 72 h, p<0.05). Initially none of the biophysical profile score was <or=6, whereas at 24, 48 and 72 h, 13.3, 76.7, 16.7% of them, respectively, were <or=6 (P<0.05). None of the Doppler indices was found to be affected by the steroid administration. CONCLUSION: Maternal betamethasone administration can cause a significant but transient, reduction in biophysical profile scores, however the middle cerebral and umbilical artery Doppler indices were found to be unaffected suggesting the reliability of this modality for the evaluation of the fetuses previously exposed to the antenatal steroids.

Adult↗

Fifty years with bile acids and steroids in health and disease.

Cholesterol and its metabolites, e.g., steroid hormones and bile acids, constitute a class of compounds of great biological importance. Their chemistry, biochemistry, and regulation in the body have been intensely studied for more than two centuries. The author has studied aspects of the biochemistry and clinical chemistry of steroids and bile acids for more than 50 years, and this paper, which is an extended version of the Schroepfer Medal Award lecture, reviews and discusses part of this work. Development and application of analytical methods based on chromatography and mass spectrometry (MS) have been a central part of many projects, aiming at detailed characterization and quantification of metabolic profiles of steroids and bile acids under different conditions. In present terminology, much of the work may be termed steroidomics and cholanoidomics. Topics discussed are bile acids in human bile and feces, bile acid production, bacterial dehydroxylation of bile acids and steroids during the enterohepatic circulation, profiles of steroid sulfates in plasma of humans and other primates, development of neutral and ion-exchanging lipophilic derivatives of Sephadex for sample preparation and group separation of steroid and bile acid conjugates, profiles of steroids and bile acids in human urine under different conditions, hydroxylation of bile acids in liver disease, effects of alcohol-induced redox changes on steroid synthesis and metabolism, alcohol-induced changes of bile acid biosynthesis, compartmentation of bile acid synthesis studied with 3H-labeled ethanol, formation and metabolism of sulfated metabolites of progesterone in human pregnancy, abnormal patterns of these in patients with intrahepatic cholestasis of pregnancy corrected by ursodeoxycholic acid, inherited and acquired defects of bile acid biosynthesis and their treatment, conjugation of bile acids and steroids with N-acetylglucosamine, sulfate-glucuronide double conjugates of hydroxycholesterols, extrahepatic 7alpha-hydroxylation and 3-dehydrogenation of hydroxycholesterols, and extrahepatic formation of C27 bile acids. The final part discusses analysis of free and sulfated steroids in brain tissue by capillary liquid chromatography-electrospray MS and suggests a need for reevaluation of the function of steroid sulfates in rat brain.

Animals↗

[The metabolism of 4-14C-pregnenolone in tissue sections of human ovaries and their modification by chlormadinone acetate].

In vitro incubations with slices of two normal human ovaries and 4-14C-pregnenolone as precursor were carried out to study the possibility of a direct influence of chlormadinone acetate on the metabolism of pregnenolone. In agreement with our previous studies the incubations of the ovary from the follicle phase of the cycle yields a profile of steroids different from that of the ovary from the corpus luteum phase of the cycle. Under the experimental condition chosen, the presence of enzymes of the steroidogenic pathway responsible for the synthesis of 17alpha-hydroxy-pregnenolone, DHA, androstenediol (basic metabolites) and androstenedione represents a characteristic profile of steroids of the ovaries from the follicle phase. After the addition of chlormadinone acetate to the incubation medium, the formation of androstenedione was inhibited, whereas the basic metabolites increased. The biosynthesis of progesterone, 17alpha-hydroxyprogesterone, estrone and estradiol represents a characteristic profile of steroids of the ovaries from the corpus luteum phase. After a addition of chlormadinone acetate to the incubation medium, the formation of this characteristic profile of steroids was inhibited. The influence of chlormadinone acetate on the two different profiles of steroids indicated, that chlormadinone acetate exerts an inhibitory effect on the 3beta-hydroxysteroid-dehydrogenase-delta5-4-isome

Aromatase↗

The effect of growth hormone replacement therapy on cortisol-cortisone interconversion in hypopituitary adults: evidence for growth hormone modulation of extrarenal 11 beta-hydroxysteroid dehydrogenase activity.

OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults has been associated with a decreased urinary ratio of 11-hydroxy/11-oxo-cortisol metabolites (CoM). This could result from GH regulation of the activity of hepatic or renal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1 and 2), the enzymes responsible for cortisol-cortisone interconversion, or alternatively it might reflect decreased cortisol availability. To elucidate this, we examined the effect of GH on urinary cortisol, cortisone and cortisol metabolites in hypopituitary adults at increasing doses of hydrocortisone replacement. DESIGN: Patients received increasing twice daily doses of hydrocortisone (HC) (10/10, 20/10, 40/20 mg) each week, before and during 2 months of GH replacement (0.25 U/kg/week). PATIENTS: Seven hypopituitary adults (three men and four women, age range 47-64 years) with combined GH and ACTH deficiency. Three additional patients with GH deficiency, but intact ACTH reserve, were also studied. MEASUREMENTS: Urine steroid metabolite profiles were measured in 24-hour urine collections by gas chromatography after each week of treatment. Urinary free cortisol and free cortisone were measured by radioimmunoassay as a measure of renal 11 beta-HSD-2 activity. RESULTS: Total urinary CoM increased with rising doses of HC, but at each particular HC dose, were unchanged after GH (before versus after GH, median (range): 9.67 (7.86-12.59) versus 9.93 (8.31-14.08); 15.87 (12.37-31.39) versus 17.07 (12.64-23.81); 26.68 (19.07-42.14) versus 26.77 (8.01-37.62) mg/24 hours). The urine ratio 11-hydroxy/11-oxo-CoM decreased significantly with GH treatment, at each HC dose schedule (1.22 (1.02-1.96) versus 0.92 (0.83-1.63) P = 0.018; 1.53 (1.30-2.23) versus 1.23 (0.93-1.46) P = 0.018; 1.87 (1.45-2.70) versus 1.56 (1.22-1.79) P = 0.018). The urinary ratio tetrahydrocortisols/tetrahydrocortisone, an alternative index of 11 beta-HSD activity, also fell with GH therapy at each HC dose (P = 0.049; P = 0.018; P = 0.043). In contrast, the urinary 20-hydroxy/20-oxo-CoM ratio exhibited a small increase with GH, suggesting that the changes observed above were not simply due to changes in redox status. The patients with GH deficiency, but intact ACTH reserve, demonstrated changes in urine steroid profiles similar to the group receiving hydrocortisone replacement. Urinary free cortisone and urinary free cortisol/free cortisone ratios did not change with GH therapy, but the serum cortisol/ cortisone ratio fell significantly with GH therapy at each hydrocortisone dose. CONCLUSIONS: GH therapy decreases the urinary ratios 11-hydroxy/11-oxo-cortisol metabolites and tetrahydrocortisols/tetrahydrocortisone, but not urinary free cortisone or the urinary free cortisol/free cortisone ratio. This effect is not secondary to reduced cortisol availability. These findings provide further evidence for direct or indirect modulation of cortisol metabolism by growth hormone and suggest that this occurs at hepatic or an alternative site of 11 beta-hydroxysteroid dehydrogenase-1 activity.

11-beta-Hydroxysteroid Dehydrogenases↗

Adrenal function in the Mongolian gerbil (Meriones unguiculatus): influence of confinement stress upon glucocorticosteroid, progesterone, dehydroepiandrosterone, testosterone and androstenedione plasma levels, adrenal content and in-vitro secretion.

The pattern of adrenal steroid secretion and the response to confinement stress were investigated in male Mongolian gerbils (Meriones unguiculatus). Steroid levels of glucocorticosteroids (GC), progesterone (P), dehydroepiandrosterone (DHEA), testosterone (T) and androstenedione (A) in plasma, adrenal tissue and superfusates of adrenals superfused in-vitro were measured by radioimmunoassay. The sensitivity of the assay systems and the low cross-reactivity of the antisera used allowed the determination of steroid levels in small samples (5-200 microliters), without prior chromatography. GC plasma levels were much higher than values of P, DHEA, T or A (176.7, 2.4, 3.3, 2.6 and 2.8 ng/ml, respectively). Confinement stress resulted in a significant increase of GC and DHEA plasma levels; similarly, adrenal content of GC, DHEA and P was markedly increased. In contrast, the applied stress factor had no significant effects on either plasma levels of P, T or A or on adrenal T or A content. Compared to plasma levels or adrenal content, amounts of steroids secreted from adrenals superfused in-vitro were very low (GC: 57.1, P: 2.1, DHEA: 23.0, T: 1.8, A: 3.0 pg/mg/min, respectively). Confinement stress significantly stimulated GC, P and DHEA secretion in-vitro but had no effects on T or A release. The secretion of GC, P, DHEA and T, but not of A was significantly increased by in-vitro stimulation with 0.01-10.0 mIU (1-24) ACTH. Interestingly, the amounts of GC and P, and of GC and DHEA secreted from incubated adrenal slices stimulated with (1-24) ACTH and from adrenals of controls and stressed gerbils superfused in-vitro were significantly correlated. By measuring steroid plasma levels and profiles of steroids secreted from adrenocortical and testicular tissue it now seems possible to characterize in more detail the effects of chronic intermittent stress upon the adrenalgonadal axis and the possible interrelationship between glucocorticosteroid and androgen secretion, especially in small laboratory animals from which only limited amounts of blood can be obtained repeatedly.

Adrenal Glands↗

Growth and reproductive development in freemartins hormonally treated from 1 to 79 weeks of age.

Postnatal growth, steroid hormone profiles and response to steroid hormone treatment were studied in 18 freemartins and one normal female born co-twin with a bull. They were either treated postnatally with testosterone or estrone at one week of age, or left untreated until 50 weeks of age when they received silastic implants calculated to release either 12.9 microgram of estrone or 2.6 microgram of estradiol per day per kg of body weight. Later a dihydrotestosterone-treated group was added. Reproductive development was studied by palpation per rectum and by examination when animals were slaughtered at 79 weeks of age. Treated animals grew slightly faster than untreated animals. Testosterone in untreated freemartins averaged 76 and 87 pg/ml of blood plasma during weeks 1 to 48 and 52 to 56. Corresponding values for those animals with small testosterone implants (weeks 1 to 48) and with larger implants (weeks 52 to 56) were 130 and 272 pg/ml. Estrone and estradiol values appeared to fluctuate between 10 and 50 pg/ml but values are uncertain because they were below the sensitivity of the assay then available. Thus, circulating steroid hormone concentrations were similar to those reported for castrates. Testosterone stimulated clitoral development prenatally and postnatally. None of the treatments influenced vaginal depth, which averaged 4.0, 9.0 and 10.9 cm at 1, 24 and 52 weeks of age. Vaginal depth at birth was not a reliable indicator of freemartinism. Androgen may have inhibited udder development, whereas estrogen appeared to be stimulatory. The reproductive organs of the freemartin were characterized by differences in underdevelopment and the general presence of seminal vesicles. The latter structures, plus clitoral development at birth in 3 animals and postnatal response of the clitoris to testosterone is interpreted to indicate that the presence of androgens is one factor in abnormal development. Otherwise, gross morphology of the reproductive tract was not related to hormone treatment, postnatal gonadal histology, endocrinology or lymphocyte chromosomal karyotypes.

Animals↗

Relationship between urinary profile of the endogenous steroids and postmenopausal women with stress urinary incontinence.

AIMS: The aims of this study were to investigate whether endogenous steroid hormones are (1) related to pathogenesis of stress urinary incontinence after menopause, (2) are related to severity of stress urinary incontinence, and (3) are related to prognostic parameters of stress urinary incontinence. METHODS: Twenty post-partum women with clinically diagnosed stress urinary incontinence and 20 age-matched postmenopausal women without stress urinary incontinence (control group) were evaluated. We compared urinary profile of the endogenous steroid hormones patients with stress urinary incontinence and controls, and between grade I and grade II of stress urinary incontinence. We also investigated the relationship between urinary profile of the endogenous steroid hormones and prognostic parameters of stress urinary incontinence (maximal urethral closure pressure, functional urethral length, Valsalva leak point pressure, cough leak point pressure, posterior urethrovesical angle, bladder neck descent, and stress urethral axis). The ages of the patients and those in the control group were 64.3 +/- 5.6 and 57.5 +/- 3.8 years old and the body mass indexes were 24.96 +/- 3.14 and 22.11 +/- 2.73 kg/m2 in patients and in normal subjects, respectively. Nine patients were grade I and 11 were grade II. Estrone and 17beta-estradiol only were detected in all subjects, regardless of control or patient group. It is noteworthy that there were no significant differences (P > 0.05) in the levels of estrone and 17beta-estradiol in the urine of postmenopausal normal subjects compared with in the urine of postmenopausal patients with urinary incontinence. E2/E1 ratio was not different between the two groups (P > 0.05). Among the objective steroids, DHEA, Delta4-dione, Delta5-diol, Te, DHT, 16alpha-DHT, 11-keto An, THDOC, and THB were not detected either in the urine of normal subjects and nor in the urine of the patients. After comparing androgen levels between normal subjects and patients, no significant differences (P>0.05) were detected, except for 5alpha-THB and 5alpha-THF. Neither 5alpha-THB or 5alpha-THF were detected in the patients' urine. Et/An (11beta-OH Et/11beta-OH An) concentration ratios were not significantly different between the two groups, either (P > 0.05). There were not significant differences of concentrations (micromol/g creatinine) of urinary steroids between grade I and grade II of stress urinary incontinence. Pregnanediol was significantly related to bladder neck descent in supine and sitting positions (R = 0.79, P = 0.01, and R = 0.73, P = 0.03, respectively), and pregnanetriol was significantly related to maximal urethral closure pressure and functional urethral length (R = 0.68, P = 0.04, and R = -0.79, P = 0.01, respectively). Androsterone was significantly related to bladder neck descent in supine and sitting positions (R = 0.68, P = 0.04, and R = 0.78, P = 0.01, respectively). 5-AT was significantly related to bladder neck descent in sitting position and stress urethral axis (R = 0.72, P = 0.03, and R = -0.71, P = 0.03). 11-keto Et was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.82, P = 0.01, and R = 0.81, P = 0.01, R = -0.67, P = 0.04, respectively). THS was significantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R = 0.76, P = 0.02, and R = 0.74, P = 0.02, R = -0.68, P = 0.04, respectively). THE was significantly related to bladder neck descent in sitting position (R = 0.67, P = 0.04).beta-Tetrahydrocortisol/alpha-tetrahydrocortisol (beta-THF/alpha-THF) and alpha-cortol were significantly related to maximal urethral closure pressure and functional urethral length (R = 0.74, P = 0.02, and R = -0.92, P = 0.01; R = 0.71, P = 0.36, and R = -0.87, P = 0.000, respectively). 17beta-estradiol (E2) was significantly related to bladder neck descent in supine position (R = -0.62, P = 0.04) and 17beta-estradiol/estrone (E2/E1) was significantly related to cough leak point pressure (R = 0.79, P = 0.01). In conclusion, the urinary concentrations of endogenous steroid metabolites in postmenopausal patients with stress urinary incontinence were not significantly different from normal patients and were not significantly different between grade I and grade II patients with stress urinary incontinence. Some endogenous steroid metabolites were positively or negatively significantly related to prognostic parameters of stress urinary incontinence.

Adrenal Cortex Hormones↗

Automated metabolic profiling analysis of urinary steroids by a gas chromatography mass spectrometry data system.

A computer system (MSSMET), using methylene unit retention indices for an off-line reverse library search analysis of selected ion chromatograms from gas-liquid chromatographic mass spectrometric data, has been applied for the qualitative and quantitative determination of daily variations in the excreted levels of urinary steroids of two individuals, using capillary column gas-liquid chromatography. Aliquots of 24 h urine collections and morning spot urine samples were examined. The daily excretion pattern of most of the major steroid metabolites was fairly consistent from day to day (i.e. 3 alpha-hydroxy-5 alpha-androstane-17-one, androsterone; 3 alpha-hydroxy-5 beta-androstane-17-one, etiocheolanolone; 3 alpha, 17 alpha, 21-trihydroxy-5 beta-pregnane-11,20-dione, THE; 3 alpha, 11 beta, 17 alpha, 21-tetrahydroxy-5 beta-pregnane-20-one, THF; 3 alpha, 11 beta, 17 alpha, 21-tetrahydroxy-5 alpha-pregnane-20-one; allo-THF; 3 alpha, 17 alpha, 20 alpha, 21-tetrahydroxy-5 beta-pregnane-11-one, cortolone; 3 alpha, 17 alpha, 20 beta, 21-tetrahydroxy-5 beta-pregnane-11-one, beta-cortolone; 5 beta-pregnane-3 alpha, 11 beta,17 alpha,20 alpha,21-pentol, cortol; 5 beta-pregnane-3 alpha, 11 beta, 17 alpha, 20 beta, 21-pentol, beta-cortol), while certain other steroid metabolites had a less consistent excretion pattern (3 beta-hydroxy-5-androstene-17-one, for example). Advantages and disadvantages of using capillary columns for the automated metabolic profile analysis of urinary steroids by reverse library search of selected mass chromatograms.

Adult↗