Estrogen Excretion Research Articles

Effect of diet on the plasma levels, metabolism, and excretion of estrogens

Effect of diet on the plasma levels, metabolism, and excretion of estrogens

Modulation of male mouse genital sniff, attack, and mount behaviors by urogenital substances from estrous females

The modulation of attacks, genital sniffs, and mounts in male SJL/J mice by ovarian-dependent urogenital substances in the urine voided by estrous females was examined. Urogenital substances were applied onto the external urogenital areas of ovariectomized mice. When compared with urine voided by estrous females, which stimulated genital sniffing, mounting, and reduced aggression, bladder urine was ineffective. Genital sniffing and mounting was stimulated by estradiol-17 beta, vaginal fluids, and preputial extract. Aggression was reduced by estradiol-17 beta, urethral catheterized urine, and vaginal fluids. Preputialectomy reduced, but did not eliminate, urinary stimulation of genital sniffing and mounting. Preputial extract stimulated aggression. Urogenital substances from ovariectomized females were ineffective in reducing attacks and stimulating genital sniffs and mounts. It was concluded that the ovarian-dependent chemosignals in the urine voided by estrous females are contributed by the urethra, vagina, and preputial gland, perhaps in part through the excretion of unconjugated estrogens.

Diet and the excretion and enterohepatic cycling of estrogens

Urinary and fecal excretion and plasma levels of estrogens were measured in pre- and postmenopausal women eating different diets. When premenopausal U.S. women eating a comprising high fat (40% of calories) and low fiber, were compared with age-matched vegetarians eating a moderate-fat (30%), high-fiber diet, it was found that the vegetarians excreted threefold more estrogen in their feces, had lower urinary excretion, and had 15-20% lower plasma estrogen levels. When U.S. pre- and postmenopausal women eating a Western diet were compared with recent Asian immigrants eating a very low-fat diet (20-25% of calories), similar results were obtained except that plasma estrogen levels were 30% lower among Orientals compared with those among Western omnivore women. Correlation analysis of dietary components and plasma estrogen showed that plasma estrogen was positively associated with fat and was negatively associated with fiber. The results indicate that diet can alter the route of excretion of estrogen by influencing the enterohepatic circulation and that this, in turn, influences plasma estrogen levels.

Increased urinary catechol estrogen excretion in female smokers

Premenopausal female smokers show significantly increased estrogen 2-hydroxylation, which may account in part for the anti-estrogenic effects of cigarette smoking. We have measured five major urinary estrogens, including estradiol (E 2), estrone (E 1), 16α-hydroxyestrone (16αOHE 1), estriol (E 3), and 2-hydroxyestrone (2OHE 1), in premenopausal female smokers and non-smokers, to determine whether increased C-2 hydroxylation affected the urinary excretory patterns in these subjects. While total measured estrogen excretion in the follicular phase did not differ significantly between the two groups, urinary 2OHE 1 among the smokers constituted a significantly greater proportion of the total (31.1 vs 18.2%, P < 0.02). This difference was largely caused by significantly increased urinary 2OHE 1 and decreased E 3 observed in smokers. A urinary catechol estrogen index, defined by [2OHE 1] [E 3] , was significantly elevated in smokers compared with non-smokers (1.67 ± 0.21 vs 0.56 ± 0.08, P<0.001), and this urinary index correlated strongly with radiometrically determined estrogen 2-hydroxylation ( r=0.84, P <0.01). Ratios of the various estrogen metabolites did not vary substantially throughout the menstrual cycle. Urinary estrogen indices as described here may therefore be useful in demonstrating differences in estrogen metabolism, specifically 2-hydroxylation vs 16α-hydroxylation, in selected populations.

The return to ovulation following early abortion: a comparison between vacuum aspiration and prostaglandin

The return to ovulation following early abortion (less than or equal to 56 days amenorrhea) has been assessed after both vacuum aspiration under general anesthesia (N = 14) and menstrual induction with 16,16 dimethyltrans-delta 2PGE1 methyl ester in pessary form (N = 18). The urinary excretion of hCG, total estrogen and pregnanediol was similar in each group. There was an initial rapid decline in hCG excretion (t1/2 48 h), reaching 10% of the pre-treatment value after 6 days. Twenty-nine (91%) women showed a luteal phase rise in pregnanediol excretion, with ovulation occurring on day 29 (16-37) and 24 (16-32) in the vacuum aspiration and prostaglandin groups, respectively (median (range) NS). The wide range in the return of ovarian activity was related to the variation in decline of progesterone secretion (as reflected by excretion of pregnanediol) by the corpus luteum. Asynchrony between the ovarian and menstrual cycles resulting from a delay to ovulation presents a major constraint to the use of early pregnancy interruption as a routine method of fertility control.

Antenatal detection of placental steroid sulphatase deficiency by measurement of urinary 16 alpha-hydroxydehydroepiandrosterone sulphate.

A simple gas chromatographic technique for the measurement of 16 alpha-hydroxydehydroepiandrosterone sulphate in urine from pregnant women is described. An assessment was made of the effectiveness of the measurement of this oestriol precursor for the antenatal diagnosis of placental steroid sulphatase deficiency. Twenty-two patients whose pregnancies were complicated by subnormal oestrogen excretion for gestation were studied. In nine of these, where placental steroid sulphatase activity was found subsequently in vitro to be normal, the excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate was less than 27 mumol/24 h. In the remaining 13 patients, in whom postnatal in vitro assay demonstrated absence of placental steroid sulphatase activity, urinary excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate was 59-360 mumol/24 h. The excretion of this metabolite was below the limit of detection (20 mumol/24 h) in 30 uncomplicated pregnancies. It is concluded that urinary excretion of 16 alpha-hydroxydehydroepiandrosterone sulphate greater than 50 mumol/day or a ratio of urinary 16 alpha-hydroxydehydroepiandrosterone sulphate to urinary oestrogen greater than 2.0 correctly identifies, before delivery, those pregnancies in which fetus and placenta are deficient in steroid sulphatase activity.

Excretion of radiolabeled estradiol metabolites in the slow loris (Nycticebus coucang).

The excretion pattern of estradiol was studied in the slow loris Nycticebus coucang) and the ring-tailed lemur (Lemur catta) in order to compare steroid excretion in two representative prosimian species. Daily urinary estrone conjugate measurements in the female loris provided little information when applied over prolonged periods. As a result of these negative data, a metabolic study was performed to determine if estrogen excretion patterns in the slow loris differed from those in the lemur, where urinary assays proved a useful tool in characterizing reproductive cycles. Radio-labeled estradiol was injected intravenously, and serial urine and fecal collections were analyzed for radiolabeled metabolites. The results of these studies demonstrate that more than 92% of the radiolabel was excreted in the feces of the loris, in contrast to only 16% excreted in the feces of the lemur.

Urinary hormone analysis as a diagnostic tool to evaluate the ovarian function of female gorillas (Gorilla gorilla).

Daily urine samples were collected from 4 adult female gorillas over 7 menstrual cycles. Urinary oestrone conjugate and pregnanediol-3-glucuronide (PDG) were measured by radioimmunoassay; LH was measured by enzyme immunoassay and each hormone was indexed by creatinine. The quantity of urinary LH during the ovulatory surge was positively correlated with the quantity of PDG excreted during the luteal phase (r = 0.87, P = 0.0013). The observations indicate a relationship between the quality of the LH surge and the levels of PDG in the luteal phase and suggest that both the LH surge and subsequent luteal phase function may be predictable from the oestrogen excretion profile during the follicular phase.

Weight percentile at birth. II. Prediction by endocrinological and sonographic measurements

In a prospective study of 847 singleton pregnancies, the importance of various endocrine methods (serum estriol, HPL, SP1, β-HCG, estradiol-17β, urinary estrogen excretion) and of two sonographic measurements (biparietal and thoracic diameter) for the diagnosis of growth retardation in the third trimester was studied. HPL and estriol determinations were best suited for the diagnosis of growth retardation. The thoracic diameter correlated most closely with the birthweight of the newborns. Sensitivity in relationship to growth retardation was between 17 and 35% for the HPL and estriol determinations as well as for both sonographic methods. Specificity was around 90% for these methods. The validity for all methods improved as the time of birth approached. Through the simultaneous measurement of one of the hormones and the thoracic diameter, an antepartal diagnosis of up to 50% of the hypo- and hypertrophic growth disorders was achieved. In the first two years of life a relationship between development and the HPL and estriol concentrations could be observed which was independent of the weight percentile at birth.

Monitoring follicular maturation through measurement of urinary estrogen excretion by latex agglutination inhibition reaction

We evaluated the clinical utility of the MS 8601 kit, which is a new method of measurement of estrogens in urine. Changes in daily urinary estrogen excretion measured with the kit were highly correlated with that in daily serum E2. This kit was sensitive enough to detect the rises in estrogens in the follicular phase not only in women with normal menstrual cycle, but also in hMG-hCG treated patients.

Induction of first cycles in primary hypothalamic amenorrhea with pulsatile luteinizing hormone-releasing hormone: a mirror of female pubertal development

During pubertal development in girls, the attainment of regular ovulatory menstrual cycles usually is preceded by cycles that are either anovulatory or show a defective luteal phase. It is not known whether these defective cycles are caused by inadequate luteinizing hormone-releasing hormone (LH-RH) secretion or by an inadequate response of the pituitary-ovarian axis to LH-RH stimulation. To shed new light on this matter, the authors analyzed endocrine data from 12 menstrual cycles induced by pulsatile LH-RH therapy in five women with primary amenorrhea of hypothalamic origin. Anovulatory cycles occurred with and without an increase in estrogen excretion and with and without a luteinizing hormone surge. In addition, ovulatory cycles with and without deficient corpus luteum function were observed. Most of these types of anovulatory and ovulatory menstrual cycles also have been described during normal puberty. Therefore, these observations suggest that, during normal pubertal development, maturation of the pituitary gonadotropes and of the ovary occurs, as well as the increased secretion of LH-RH from the hypothalamus, which the overall process depends upon.

Diet and the excretion and enterohepatic cycling of estrogens

Urinary and fecal excretion and plasma levels of estrogens were measured in pre- and postmenopausal women eating different diets. When premenopausal U.S. women eating a “Western diet,” comprising high fat (40% of calories) and low fiber, were compared with age-matched vegetarians eating a moderate-fat (30%), high-fiber diet, it was found that the vegetarians excreted threefold more estrogen in their feces, had lower urinary excretion, and had 15–20% lower plasma estrogen levels. When U.S. pre- and postmenopausal women eating a Western diet were compared with recent Asian immigrants eating a very low-fat diet (20–25% of calories), similar results were obtained except that plasma estrogen levels were 30% lower among Orientals compared with those among Western omnivore women. Correlation analysis of dietary components and plasma estrogen showed that plasma estrogen was positively associated with fat and was negatively associated with fiber. The results indicate that diet can alter the route of excretion of estrogen by influencing the enterohepatic circulation and that this, in turn, influences plasma estrogen levels.

Androgens and oestrogens before and following oral testosterone administration in male patients with and without alcoholic cirrhosis.

Compared with controls (N = 9), alcoholic cirrhotic men (N = 14) showed: significantly (P less than 0.05) higher serum concentrations of sexual hormone binding globulin (SHBG), androstenedione, oestrone, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol; significantly (P less than 0.05) lower concentrations of albumin and non-SHBG bound testosterone; no significant differences regarding concentrations of testosterone, dihydrotestosterone, non-protein bound testosterone, oestrone sulphate, and SHBG bound oestradiol. Following oral administration of 400 mg of micronized testosterone, serum concentrations of testosterone, dihydrotestosterone, androstenedione, and oestrone increased significantly (P less than 0.05) in both groups, cirrhotic patients reaching significantly (P less than 0.01) higher concentrations than controls. Further, in the cirrhotic group, the serum concentrations of oestrone sulphate, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol, and the urinary excretion of oestrogen increased significantly P less than 0.05). In conclusion, peroral testosterone administration decreases the serum oestradiol/testosterone ratio in patients with normal livers as well as in patients with alcoholic cirrhosis, but the latter group obtains significantly higher oestrogen concentrations.

The effect of a low fat diet on estrogen metabolism.

Women who consume a diet low in fat are at lower risk for breast cancer than women whose diet is relatively high in fat. To investigate the effects of a low fat diet on estrogen metabolism, six normal young women were studied while eating a Western-style high fat diet and again after 2 months of consuming a defined low fat diet. Both studies involved the simultaneous administration of [3H]estradiol [( 3H]E2) orally and [14C]E2 iv and the subsequent collection of multiple blood samples and urine for 96 h. The blood samples were analyzed for radioactivity as estrone (E1), E2, their glucuronides, and E1 sulfate. An aliquot of the pooled 96-h urine was analyzed for radioactivity as the glucuronides and sulfates of E1, E2, estriol, 16 alpha-hydroxyestrone (16 alpha-OHE1), and the catechol estrogens, i.e. 2-hydroxy and 2-methoxy metabolites of E1 and E2. The low fat diet resulted in a consistent and significant (P less than 0.05) decrease in urinary excretion of both 16-hydroxylated metabolites, estriol and 16 alpha-OHE1, expressed as a percentage of administered dose of [3H]E2 and [14C]E2, and an increase in the excretion of the catechol estrogens. These changes in metabolite excretion were not, however, mirrored by changes in the MCRs or conversion ratios of either [3H]E2 or [14C]E2. Thus, while neither the clearance of E2 from the blood nor its absorption from the intestinal tract was altered by a relatively short term decrease in dietary fat, there was a shift in the pattern of urinary metabolites away from the purported carcinogenic estrogen (16 alpha-OHE1) and toward the less active catechol estrogens. This may represent an important mechanism whereby low fat diets decrease the risk of breast cancer.

Effect of oxytetracycline administration on intestinal metabolism of oestrogens and on plasma sex hormones in healthy men.

The effect of oxytetracycline (1 g/day for five days) on the enterohepatic recycling of oestrogens and on plasma sex hormone concentrations was assessed in healthy men. Plasma oestrone (E1), oestradiol-17 beta (E2), 4-androstenedione (A), 5 alpha-dihydrotestosterone (5 alpha-DHT), total and free testosterone (T and free T), binding capacity of sex hormone binding globulin, luteinizing hormone, dehydroepiandrosterone-sulphate, urinary total E1, E2, and oestriol (E3), and oestriol-3-glucuronide (E3-3G) and faecal unconjugated and conjugated E1, E2, and E3 were measured by radioimmunoassay (RIA). Treatment with the antibiotic significantly increased the excretion of faecal conjugated oestrogens, which parallelled a decrease in urinary oestrogen excretion, especially of E3. The effect on urinary E3 could be explained almost entirely by the simultaneous decrease of urinary E3-3G concentrations. In urine and faeces the E2/E3 and E1 + E2/E3 ratios increased, probably because of the diminished reductive metabolism of oestrogens in the gut. No significant effects on plasma unconjugated oestrogen concentrations were observed. Moreover, in the present study oxytetracycline had no remarkable effect on plasma total, or free T concentrations, nor on other plasma hormones measured. Our results suggest that enterohepatic recycling and intestinal metabolism of oestrogens may be significant in men. The mechanism of action of antibiotics on oestrogen metabolism probably involves decreased hydrolysis by beta-glucuronidase of oestrogen conjugates by the intestinal contents, diminishing the reabsorption of aglycones of oestrogen conjugates and resulting in faecal loss of the steroids.

Diurnal variation in the excretion of 6 beta-hydroxycortisol and estriol at 32 weeks gestation.

We have previously shown a marked diurnal variation in the excretion of cortisol and 6 beta-hydroxycortisol at 36-38 weeks pregnancy with no variation in estrogen excretion. Since others have shown a reciprocal relationship between plasma levels of estriol and cortisol at 30-35 weeks of pregnancy, we decided to determine whether a similar relationship was present in urinary concentrations of cortisol, 6 beta-hydroxycortisol and estriol at this gestational age. A significant variation in excretion of both cortisol and 6 beta-hydroxycortisol was found. The variation in urinary levels of estriol was less than that of the corticosteroids but followed the same pattern.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG)

A brief account of our present knowledge on the enterohepatic metabolism of estrogens and on the origin, metabolism and biological effects of mammalian lignans and phytoestrogens is undertaken. Furthermore, recently published results on the effects of dietary fiber, fat and carbohydrates on estrogen metabolism are reviewed. New preliminary results are presented on quantitative assays of lignans and phytoestrogens in urine of women belonging to various dietary and population groups and in a group of chimpanzees. The highest values of lignans and phytoestrogens were found in the non-human primates, and in macrobiotic, lactovegetarian and Japanese women, all groups considered having a low risk for the development of breast and other hormone-dependent cancer. New results on correlations between intake of various fibers, lignan and phytoestrogen excretion and plasma levels of estrogens, free testosterone and SHBG in women are presented. There is a significant positive correlation between the intake of fiber and urinary excretion of lignans and phytoestrogens, and the concentration of plasma SHBG. Fiber intake and urinary excretion of lignans and equol correlated negatively with plasma percentage free estradiol. Enterolactone excretion correlated negatively with plasma free testosterone. It is concluded that dietary macro- and micronutrients seem to play an important role in estrogen metabolism.

Synchronization of ovarian cycles within and between social groups in golden lion tamarins (Leontopithecus rosalia).

Synchronization of ovarian events has been reported in a number of primate species, with the temporal resolution of synchrony ranging from the occurrence of seasonal breeding within the annual cycle to a close matching of ovarian events within a single ovarian cycle. However, ovarian synchrony has not been reported in a New World primate. The temporal association of ovarian events was examined in female golden lion tamarins (Leontopithecus rosalia) living in the same or different social groups. Ovarian cyclicity was monitored by measuring the excretion of urinary estrogen metabolites. There was a high degree of synchronization in the occurrence of urinary estrogen peaks for females in different social groups (mean peak discrepancy = 2.1 days) and in females housed in the same social group (mean peak discrepancy = 1.3 days). Contrary to previous reports on callitrichid primates, daughters housed in their natal family group exhibited cyclic patterns of urinary estrogen excretion. These findings represent the first explicit demonstration of ovarian synchrony in a New World primate, and the tight coupling of ovarian cycles in female tamarins resembles the nature of menstrual synchrony in human females.

The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women

The relationship between diet and estrogens was studied in two groups of women with different dietary habits and breast cancer risks. Plasma estrogens and androgens and 24-h urinary and fecal excretion of estrogens were measured in premenopausal and postmenopausal Caucasians and recent Oriental immigrants from Southeast Asia to Hawaii. Premenopausal Caucasians had 30–75% higher plasma estrone and estradiol levels than their age-matched cohorts in Hawaii, and the postmenopausal Caucasians had 3-fold higher plasma levels of estradiol. The Oriental women excreted more than twice the amount of estrogen in their feces but they excreted significantly less in their urine. Thus, the ratio of urinary-to-fecal excretion was ∼3–5 times higher in young Caucasian women. Analysis of dietary components and plasma estrogens in premenopausal women showed a positive correlation between daily intake of total fat and saturated fat and plasma estrone and estradiol concentrations.

Assessment of follicular function in women by measurement of urinary estrogen conjugates

Daily early morning urine samples from 23 women during their conception cycles were evaluated for urinary estrone (E1) conjugates and pregnanediol-3-glucuronide (PdG) levels and indexed by creatinine (Cr) concentrations. These 23 cycles were classified into two groups according to the rate of E1 conjugates increase following implantation. Urine from 16 nonconception cycles was available for 11 of the women. The two groups differed significantly both before and after, but not during, the midcycle E1 conjugates peak. The length of the follicular phase was significantly shorter in the group of women with the lower E1 conjugate levels. These data suggest that differences in estrogen excretion at times other than the preovulatory estrogen surge represent the endocrine activity of subdominant ovarian follicles. Further, such urinary estrogen profiles may represent useful parameters for defining ovarian follicular populations and/or indicating the effects of hazards to female reproduction.