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[Comparison of treatments in senile osteoporosis: follow up for 12 months (author's transl)].

We randomly divided senile osteoporotic patients into 8 groups. Eleven patients of A-Group were treated daily with 900 mg of calcium and 50 mg of sodium fluoride and 50,000 units of vitamin D twice weekly. Fourteen patients of B-Group were treated daily with 900 mg of calcium and 50 mg of sodium fluoride. Twelve patients of C-Group were treated daily with 50 mg of sodium fluoride. Ten patients of D-Group were treated daily with 900 mg of calcium, 50 mg of sodium fluoride and 2 mg of estriol. Ten patients of E-Group were treated daily with 2 mg of estriol. Ten patients of F-Group were treated daily with 900 mg of calcium. Ten patients of G-Group were treated daily with 900 mg of calcium and 2 mg of estriol. The treatments were given for 12 months. Ten patients without treatment served as the non-treated control group. In each group, mineral contents were measured with Norland Bone Mineral Analyzer at the level of the distal third of the left radius and ulna before and after treatment. Mineral contents of ulnar bone in A-Group, of radial and ulnar bones in E-Group, F-Group, and G-Group increased with statistical significance after 12 months of the therapy. Mineral contents of radial and ulnar bones in C-Group and Nontreated Group decreased with statistical significance after 12 months. In laboratory examination, we observed no severe side-effect in our patients. But it was very interesting that the values of serum alkaline phosphatase in F-Group and G-Group decreased with statistical significance after 12 months of the therapies.

Aged↗

[Effect of vaginal estrogen therapy on urinary incontinence in postmenopause].

A depot preparation of Estriol (Ortho Gynest D; 3.5 mg Estriol, intravaginal) was applied for 3 months to 135 postmenopausal women with urinary incontinence. Before and after treatment the symptoms of incontinence were scaled by the Gaudenz questionnaire. 8 symptoms were tested for statistical significance. All of them had significantly improved after treatment. 63% of patients showed improvement of their incontinence, urinary stress incontinence improved in 50%. Dysuria was reported by 14 patients before treatment, by none after treatment. Daytime and nighttime micturition frequency both decreased significantly, also subjective impairment by incontinence. Thus the local application of Estriol ovula represents an effective mode of primary treatment (maintenance therapy, one dose per week) in postmenopausal patients with urinary incontinence.

Administration, Intravaginal↗

Long-term responses of women to indole-3-carbinol or a high fiber diet.

We test the hypothesis that the estrogen metabolite ratio 2-OH-estrone:estriol can be raised via dietary indole-3-carbinol (I3C) and that this higher ratio can be sustained over a 3-month test period. We also explore the possible role of pure fiber on estradiol metabolism. Using a randomized clinical trial with three arms, each containing 20 subjects, arm 1 received 400 mg/day of I3C daily for 3 months, arm 2 received 20 g of alpha-cellulose daily for the same time period as a source of added fiber, and arm 3 received a placebo dose. Blood levels of a variety of biochemical parameters were measured. The urinary 2-OH-estrone:estriol estrogen metabolite ratio was measured monthly at the same time of the menstrual cycle. While no changes were observed in the control and alpha-cellulose-treated arms, a substantial mean increase in the ratio was observed in the I3C-treated arm at month 1; that increase was maintained over the 3-month time period. Three of the 20 subjects in this I3C-treated group differed from the others in that no significant change in the metabolite ratio was observed at any time point. The results suggest that I3C can serve to increase the 2-OH-estrone:estriol metabolite ratio in a sustained manner without detectable side effects and that some individuals may be resistant to such change.

Adolescent↗

Glucuronidation of N-acetylbenzidine by human liver.

N-Glucuronidation is an important pathway in aromatic amine metabolism. This study assessed N-glucuronidation of N-acetylbenzidine by human liver slices and microsomes. With slices, considerable metabolism of [3H]N-acetylbenzidine (0.2 mM) was observed during a 2-hr incubation. N-Acetylbenzidine N'-glucuronide represented significant metabolism in four different human liver samples (6-33% of the total recovered radioactivity following HPLC). Benzidine (11-43%), benzidine N-glucuronide (8-11%), and N,N'-diacetylbenzidine (0-2%) were also formed. The kinetics of N-acetylbenzidine N'-glucuronide formation were investigated using Triton X-100-pretreated microsomes. Data were best described by a two-component Michaelis-Menten model composed of both high-affinity (low KM) and low-affinity (high KM) UDP-glucuronsyltranosferases. The high- and low-affinity KMs were 0.36 +/- 0.02 and 1.07 +/- 0.12 mM, respectively. To help identify the UDP-glucuronosyltransferases metabolizing N-acetylbenzidine, 23 transferase substrates were tested for their ability to inhibit glucuronidation. At 0.25 mM, bilirubin, estriol, and 17-epiestriol were good inhibitors (< 50% of control). Dose-response inhibition studies with estriol and 4-aminobiphenyl demonstrated that each agent reached a plateau as its concentration was increased. IC50 for estriol and 4-aminobiphenyl was 0.15 +/- 0.03 and 0.57 +/- 0.06 mM, respectively. Complimentary inhibition was observed when these agents were combined at maximal inhibitory concentrations. These results suggest that more than one UDP-glucuronosyltransferase metabolizes N-acetylbenzidine. N-Glucuronidation represents a major pathway for N-acetylbenzidine metabolism in humans.

Aged↗

17 beta-Estradiol metabolism by hamster hepatic microsomes. Implications for the catechol-O-methyl transferase-mediated detoxication of catechol estrogens.

We have shown that the metabolism of 17 beta-estradiol in hamster liver microsomes is concentration-dependent. At low (< 25 microM) concentrations of 17 beta-estriol, 16 alpha-hydroxylase activity predominated, and estriol was the major metabolite. At higher concentrations (25-75 microM), 16 alpha-hydroxylation and aromatic hydroxylation at C2 contributed equally to 17 beta-estradiol metabolism. Aromatic C4-hydroxylation was maximal at 75 microM of 17 beta-estradiol and was always less than C2-hydroxylation. Dehydrogenation of the 17 beta-hydroxyl group to the ketone (estrone) was also observed, but both estrone and 2-hydroxyestrone were minor (approximately 3%) metabolites of 17 beta-estradiol, only detectable at concentrations of 50 microM and above. Catechol-O-methyl transferase (COMT) effectively converted both 2- and 4-hydroxyl-17 beta-estradiol to their corresponding monomethoxy metabolites. Effective reducing conditions are required for COMT activity, because catechol estrogens are readily oxidized to their corresponding ortho-quinones, and ascorbic acid is routinely added to assays of COMT activity. Interestingly, although ascorbic acid (1 mM) increased the recovery of 2- and 4-hydroxy-17 beta-estradiol from microsomal incubations, it decreased the recovery of the methoxy metabolites (approximately 40%). Since the enediol function of ascorbate resembles that of a catechol group, ascorbate is a substrate for COMT and probably competes with the catechol estrogens for methylation. Because previous studies describing the ability of COMT to inhibit the covalent binding of electrophilic reactive metabolites of [4-(14)C]17 beta-estradiol to microsomal protein were performed in the presence of high (100 mM) Mg2+ concentrations, we also investigated the effects of Mg2+ on 17 beta-estradiol metabolism. Concentrations of Mg2+ > 10 mM inhibited the metabolism of 17 beta-estradiol, as evidenced by i) the increased recovery of substrate; ii) a decrease in the formation of estriol, estrone, and 2-, and 4-hydroxy-17 beta-estradiol; iii) a decrease in the recovery of water-soluble metabolites when incubations were performed in the presence of glutathione (GSH) to trap the reactive electrophilic metabolites; and iv) a decrease in the amount of reactive electrophilic metabolites bound to microsomal protein. GSH also decreased the covalent binding of electrophilic metabolites of [4-(14)C]17 beta-estradiol to microsomal protein, with the concomitant formation of water-soluble metabolites. Thus, both COMT and GSH combine to limit the formation of electrophilic metabolites from 17 beta-estradiol. The relative importance of each of these pathways to the disposition of the catechol estrogens remains to be determined.

Animals↗

Effects of sex hormones on oncogenesis in rat urinary bladder by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

The effects of testosterone propionate, estradiol, and estriol on the oncogenesis of male rats' bladder induced by oral administration of the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) were examined. There were significant differences between the testosterone propionate-administered and estradiol-administered groups and also between the testosterone propionate-administered and estriol-administered groups in the incidence of bladder tumors.

Animals↗

Prospective study of postpartum blues. Biologic and psychosocial factors.

Potential biologic and psychosocial causative factors for the postpartum blues were tested in a prospective study of 182 women followed up from the second trimester of pregnancy until postpartum week 9. Personal and family history of depression, depressive symptoms, stressful life events, and social adjustment were all assessed during the second trimester. Levels of progesterone, prolactin, estradiol, free and total estriol, and free and total cortisol were measured on several occasions during late pregnancy and early puerperium. Obstetric and child-care stressors and the postpartum blues were assessed after delivery. Predictors of the postpartum blues were personal and family history of depression, social adjustment, stressful life events, and levels of free and total estriol. Our results support the hypothesis that the postpartum blues is within the spectrum of affective disorders.

Adult↗

Isoluminol as a marker in direct chemiluminescence immunoassays for steroid hormones.

We have used isoluminol steroid hormone conjugates in competitive heterogeneous chemiluminescence immunoassays (CIA) for estradiol, progesterone and estriol in body fluids. The assays did not require prior extraction of the steroid hormone with an organic solvent. Polyclonal or monoclonal antibodies, covalently coupled to polyacrylamide microspheres or adsorbed onto the plastic surface of microtritation plates via an intermediate second antibody, were used as solid-phase. The latter solid-phase system allows rapid processing of incubation mixtures. Sensitive and reliable direct CIAs for estradiol in serum, progesterone in serum and in saliva and for estriol in saliva have been developed and their clinical utility has been assessed. Sensitivities ranged from 0.54 to 0.04 nmol/l, and precision (% CV) ranged from 10% to 16%.

Estradiol↗

Collagenolytic activity and steroid levels after administration of dehydroepiandrosterone sulfate.

Seventy-five pregnant women in the 38th to 41st weeks of gestation were given a single intravenous injection of 200 mg of dehydroepiandrosterone sulfate (DHAS). The changes in estriol, 17beta-estradiol and progesterone levels in the serum, the uterine cervix and the myometrium of the placenta-implanting site were then determined. Estriol levels remained unchanged both in serum and tissue, but the level of 17beta-estradiol increased sharply both in serum and tissue after four hours. The increases of 17beta-estradiol in the serum and the portio vaginalis of the same patient were well correlated (r = 0.79898), but the percentage of increase was much higher in the portio vaginalis than in the serum (p less than 0.001). Serum progesterone levels did not change initially, but always decreased within four or eight hours in cases in which labor had started or delivery was accomplished within 24 hours (p less than 0.01 at four hours). The total amount of collagenase was determined in ten subjects before and after the administration of DHAS. The total collagenase activity was elevated by an average of 152.3%. The peak of activity was accelerated from the fourth to the second day (p less than 0.001) of the culture. A probable mechanism of DHAS action in accelerating cervical ripening is presented.

Cervix Uteri↗

Effects of feto-placental markers with plasma exchange in pregnancy.

To evaluate changes in feto-placental markers with plasma exchange in pregnancy, two patients at varying stages of pregnancy referred to a tertiary care hospital and requiring plasma exchange for intercurrent problems were evaluated. Alpha-fetoprotein, human chorionic gonadotropin, and free estriol were sequentially measured in the patients' plasma and in the fluid removed, thus permitting calculations of permeability rates and clearances. Despite markedly different molecular weights, all three feto-placental markers had similar permeabilities and clearances. While in both patients maternal levels of alpha-fetoprotein and human chorionic gonadotropin decreased rapidly with plasma separation and rebounded rapidly to baseline, free estriol responded differently and did not appear to decrease with therapy. Maternal levels of feto-placental markers only transiently changed with plasma exchange during pregnancy and rapidly returned to baseline with no apparent consequences to the pregnancy.

Adult↗

Maternal serum marker medians in Aboriginal Canadian women.

OBJECTIVES: The study evaluates the differences between Aboriginal and Caucasian women in the levels of maternal serum markers used in second-trimester Down syndrome screening (alpha-fetoprotein, unconjugated estriol, and total human chorionic gonadotrophin). METHODS: A case-control study compared the levels of serum markers in 401 Aboriginal women and 1565 matched controls selected from 7717 Caucasian women. The cases and controls were screened in a single centre and matched for maternal age, parity, and sample date. Women with multiple pregnancies and pregnancies associated with Down syndrome, open neural tube defects, trisomy 18, and insulin-dependent diabetes mellitus as well as women without weight recorded were excluded from the study. RESULTS: No differences in the levels of maternal serum alpha-fetoprotein and total human chorionic gonadotrophin were observed between the two groups. Maternal serum unconjugated estriol was 12% higher in Aboriginal women. DISCUSSION: Since Aboriginal women make up only a small proportion of women screened, correcting the level of uE3 for this group will have little effect on the overall screening performance. However, if these results are confirmed by further study, individual centres may consider making this correction, so optimal screening performance can be achieved in Aboriginal women.

Adult↗

Intrauterine development, feto-placental function and pregnancy outcome after induction of ovulation with bromoergocryptine.

18 pregnancies occurred after treatment with bromoergocryptine in 17 patients who wished to conceive, but who suffered from anovulation of varying aetiology. The course of 15 pregnancies was uneventful. Three pregnancies ended in abortion. Nine of the 17 women had hyperprolactinemic amenorrhea. Furthermore, one woman had normoprolactinemic post-pill amenorrhea, another normoprolactinemic anovulatory oligomenorrhea and a third normoprolactinemic anovulatory regular menstruations. With the exception of one woman, all had galactorrhea. The courses of pregnancy were monitored by frequent ultrasound measurements of the fetal biparietal diameter, maternal urinary estriol excretion and radioimmunological measurements of plasma estrone, estradiol, unconjugated and immunoreactive estriol, progesterone, and HPL. All data were within the normal ranges and all babies were healthy at birth and had no teratogenic defects. The data prove the great value of bromoergocryptine in the treatment of hyperprolactinemic anovulation, sometimes even in the treatment of normoprolactinemic anovulation. Moreover, the results indicate no adverse effect on either the course or the outcome of pregnancy.

Abortion, Spontaneous↗

When applied to facial skin, does estrogen ointment have systemic effects?

We examined cytological vaginal smears of 17 women before and after three months of dermal estrogen (1 g of 0.01% estradiol ointment or 0.3% estriol ointment once daily), applied to the face for dermatological indications. The mean age was 57.1 +/- 7.6 years (range from 46 to 66). Seven women had estrogenic smears (more than 10% superficial cells) before therapy. Nine women were treated with 0.01% estradiol ointment and 8 were treated with 0.3% estriol ointment. Both groups had gynecological examinations including cervical and vaginal smears before and after treatment and also monthly measurements of serum follicle-stimulating hormone, prolactin and estradiol levels. Serum hormone levels and the appearance of vaginal smears showed no significant change during treatment.

Aged↗

Placental steroid metabolism in a case of placental sulfatase deficiency.

The importance of the placental 3 beta-steroid sulfatase for placental biosynthesis of estrogens is demonstrated by a case report of a placental sulfatase deficiency. The absolute deficiency of this enzyme in our case is demonstrated in vivo by the intravenous dehydroepiandrosterone sulfate loading test and in vitro by placental enzyme tests. Steroid concentrations in serum after injection of dehydroepiandrosterone sulfate (DHEA-S) are compared with those in a group of pregnant women without placental enzyme defects and in a group of nonpregnant women. Placental in vitro tests demonstrate the intact 3 beta-hydroxysteroid dehydrogenase-delta 4,5 isomerase-aromatase-system in the placenta with sulfatase deficiency. The lack of placental hydrolysis results in low concentrations of estrone and estradiol-17 beta in the maternal serum, which are only 5.9% and 12.5%, respectively, of the mean values of the control group. This indicates that more than 90% of estrone and more than 85% of estradiol-17 beta measured in the maternal serum are from DHEA-S as precursor. The remaining concentrations are converted mainly from dehydroepiandrosterone (DHEA), which needs no hydrolysis. Maternal serum concentrations of estriol are under the detection limit of the radioimmunoassay. This is due to the absence of the so called "neutral pathway" and the "phenolic pathway" with 16 alpha-hydroxydehydroepiandrosterone sulfate (16 alpha-OH-DHEA-S) and DHEA-S respectively as precursors. The insignificance of the "placental pathway" for the total biosynthesis of estriol is demonstrated. The placental sulfatase seems to have no great importance for the biosynthesis of the C21-steroids.

Androstenedione↗

A comparison of two glucocorticoid regimens for acceleration of fetal lung maturation in premature labor.

This study compares fetal corticoid response from conventional dose (12.0 mg) intramuscular betamethasone to large dose (1,000 mg) intravenous cortisol administered to women in premature labor for acceleration of fetal lung maturity. To compare these two regimens, 14 women selected at random were treated in groups of seven with either cortisol or betamethasone. Peripheral levels of unconjugated estriol were measured by specific radioimmunoassay prior to the cortisol dose and at 1, 4, 8, and 12 hours following the dose. The rate of corticoid delivery to the fetal hypothalamic-adrenal axis was estimated by the per cent suppression of unconjugated estriol at each post-treatment interval. Least-squares regression lines fitted (P less than 0.01) for each regimen were compared for time saved (delta t) when cortisol was used. Mean delta t (1, 4, 8, and 12 hours) was 9.0 +/- 0.2 S.E.M. hours. It is concluded that: (1) Intravenous cortisol delivers a fetal corticoid effect that is significantly more rapid in onset and more profound in magnitude than does intramuscular betamethasone and that (2) the cortisol regimen is probably better suited to the acceleration of fetal lung maturation in premature labor when time is short and rapid action is essential.

Adolescent↗

Fetal movement, biochemical and biophysical parameters, and the outcome of pregnancy.

Fetal movements, fetal heart rate patterns, and serum estriol levels were prospectively monitored in 91 high-risk and normal pregnant women. In four women, there was cessation of fetal movements. In three of these cases, there were pathologic changes in fetal heart rate patterns, with one neonatal death. Of the 87 women who did not demonstrate cessation of fetal movements, one had changes in fetal heart rate patterns. The difference between the two groups was statistically significant (Z test: p less than 0.001). No correlation was found between fetal movements and serum estriol levels in this study. Daily recording of fetal movements can be used as an effective screening test, with high sensitivity and specificity for the fetus in utero. Cessation of fetal movement places the fetus in a high-risk category and should alert the physician to the need for non-stress tests.

Estriol↗

Indications for and timing of delivery in diabetic pregnancies.

The management of 430 diabetic pregnancies is presented. Our protocol emphasized "tight" metabolic control and assessment of fetal well-being by antepartum fetal heart rate testings and estriol levels. Spontaneous labor was allowed in uncomplicated Class A diabetic patients. Labor in complicated cases and insulin-dependent diabetic pregnancies was induced after establishing fetal lung maturity, except when a maternal or fetal complication dictated otherwise. A significant drop in estriol was observed in 4% of Class A diabetic patients and 10.2% of insulin-dependent diabetic patients. None developed a positive contraction stress test. Abnormal fetal well-being tests contributed minimally to the indications for induction of labor. The incidence of induced preterm delivery was 2.8% in Class A diabetic patients and 18.4% in insulin-dependent diabetic ones. The perinatal mortality was 5.6:1000 and 13:1000, respectively. The incidence of respiratory distress syndrome was very low, and none of the cases were associated with a "mature" amniotic fluid lecithin phosphorus measurement.

Adult↗

Predicting postnatal emotional adjustment with psychosocial and hormonal measures in early pregnancy.

This prospective study showed that scores on a socioenvironmental stress questionnaire were related to numbers of crying spells and to estriol levels in pregnancy. Estriol levels in turn were correlated with numbers of antenatal and postnatal crying spells. Stress, hormonal response in pregnancy, and crying during pregnancy each contributed independently to predicting postpartum emotional adjustment.

Adult↗