Excretion Of Oestrone Research Articles

Urinary excretion of sex steroid hormone metabolites after consumption of cow milk: a randomized crossover intervention trial

Current cow milk production practices introduce considerable levels of pregnancy hormones into the milk. Humans are exposed to these hormones when cow milk is consumed, and this may explain the observed association between cow milk consumption and several hormone-sensitive cancers. The aim of the study was to evaluate whether cow milk consumption is associated with an increase in urinary excretion of sex steroid hormones and their metabolites in humans. We conducted a randomized crossover intervention feeding experiment. A total of 109 postmenopausal women consumed 1 L of semiskimmed milk (1.5% fat) per day for 4 d and 1 L of whole milk (3.5% fat) per day for 4 d, intersected by 4-d wash-out periods. Sex steroid hormone levels were measured in 24-h urine samples collected at the end of each intervention and wash-out period. Estrogens, androgens, and progesterone were detected in the examined milk samples used for our intervention. Although a very high proportion of the estrogens were conjugated, only small proportions of the androgens and progesterone were conjugated. Milk consumption resulted in a significant increase in urinary estrone (E1) excretion, whereas estradiol (E2), estriol (E3), and 16ketoE2 excretion only increased after semiskimmed milk consumption. Urinary pregnanediol glucuronide excretion was not significantly affected. Cow milk consumption increases urinary excretion of E1 in humans. Ingestion of semiskimmed milk appears also to raise E2, E3, and 16ketoE2 excretion, but future studies need to confirm these associations. This trial was registered at https://www.drks.de as DRKS00003377.

Excresión urinaria de estrógenos fraccionados en mujeres con ciclos normales

Al utilizar el procedimiento del Marrón los autores han medido la excreción urinaria de estrona, estradiol y estriol en un grupo de 10 mujeres normales. Se observaron dos picos de excreción: el primero correspondiente a la ovulación y una segunda en la fase lútea; ambos fueron significativamente diferentes de los valores obtenidos en la primera fase del ciclo.

Estrógenos urinarios en el ciclo menstrual

El método de Brown, basado en la cromatografía de absorción en columnas alúmina, fue aplicado para determinar, por primera vez en nuestro medio, las variaciones de la excreción urinaria de estrona, 17B-estradiol y estriol, en un grupo de 8 mujeres normales, entre los 18 y 38 años de edad, en tres momentos del ciclo menstrua!: fase foliculor, pico ovulatorio y fase luteínica. Los resultados obtenidos estuvieron de acuerdo con los comunicados por varios autores, usando el mismo método o métodos similares. Se demostró las variaciones cíclicas de la excreción de los tres estrógenos, obteniéndose evidencia de ovulación en 6 casos; en los dos restantes no se pudo descartar, aunque tampoco se comprobó definitivamente la posibilidad de ciclos anovulatorios . Se observó buena correlación entre las variaciones estrogénicas y las curvas de temperatura basal, así como entre la excreción de estriol y el peso corporal. En un caso de feminización testicular, los dosajes de estrógenos se correlacionaron muy bien con el grado de feminización detectable clínicamente, con otras pruebas de laboratorio y con los hallazgos anatómicos.

Total dietary fat and omega-3 fatty acids have modest effects on urinary sex hormones in postmenopausal women

BackgroundTotal fat and omega-3 fatty acids in the diet may affect breast cancer risk by altering estrogen metabolism. The purpose of this study was to elucidate the effects of differing total fat and omega-3 fatty acid content of diets on a panel of urinary estrogens and metabolites.FindingsA controlled, cross-over feeding trial was conducted in postmenopausal women using three test diets: high fat diet (HF; 40% energy from fat), low fat diet (LF; 20% of energy from fat) and low fat, high omega-3 diet (LFn3; 23% energy from fat; 3% omega-3 fatty acids) for 8 week periods. Urinary hormone concentrations for 16 women were compared among diets using a linear mixed model, and within diet comparisons were made using paired t-tests. Urinary excretion of estrone was greater after the LF and LFn3 compared to the HF (P = 0.004). Estrone excretion was increased from baseline within the LF only (P = 0.02). Total estrone + estradiol + estriol increased from baseline with LF (P = 0.02) and was greater than the other two diets at 8 weeks (P = 0.03). There were no effects on estrogen metabolites, including the 2-hydroxy estrone:16α-hydroxy estrone ratio.ConclusionsThe results of this study indicate that urinary sex hormone metabolism was modestly altered in postmenopausal women by a low fat dietary intervention.

Excretion of estrogens, catecholestrogens and phytoestrogens in carriers of BRCA1 gene mutations: effects of metformin

BRCA1 gene mutation is associated with a combination of excessive aromatase activity/expression, predominantly estrogen receptor-negative phenotypes of tumors, and only scarce information about estrogen contents in body fluids. In the present work, isotope dilution capillary gas chromatography/mass spectrometry was used to study urinary excretion of estrogens, their catechol metabolites, and phytoestrogens in 22 women (11 with BCRA1 gene mutations and 11 without these mutations) in average 5.1+/-0.4 years before surgery for breast cancer. BCRA1 mutation carriers (including 3 premenopausal females) compared with respective controls showed significantly higher urinary estradiol and estrone excretion and a trend to an increased 2-OH-E2 excretion. In the subgroup of untreated postmenopausal women, BCRA1 mutation carriers showed a trend to increased estradiol and estrone excretion and to a higher value of the mean levels of all estrogen metabolites tested. The treatment after the baseline laboratory investigation of 6 women from postmenopausal group with the antidiabetic biguanide metformin for 3 months was associated with decreases in the excretion rates of 4-hydroxyestradiol, 2-methoxyestradiol, and 16-epiestriol and did not influence phytoestrogen excretion. The decrease in 2-methoxyestrogen excretion was more consistent in women without BCRA1 mutations than in BCRA1 mutation carriers. The data suggest the possibility that aromatase complex activation in BCRA1 mutation carriers is combined with increases in both, estrogen metabolism into catecholestrogens and their inactivation by methoxylation, and that metformin may affect both of these pathways.

Excretion of urinary steroids in pre- and postpartum female baboons

Steroid hormones are important regulators of a wide variety of reproductive and behavioral functions. We investigated the ability to track sex steroids and glucocorticoids in urine samples collected noninvasively from pre- and postpartum female baboons. Paired plasma and urine samples were collected every 2 weeks prior to and following birth in 10 females. Changes in concentrations of plasma steroids (estradiol, progesterone, and cortisol) were reflected in changes in urinary metabolite excretion (estrone conjugates, pregnanediol conjugates, and cortisol; r’s > 0.36, p’s < 0.001). A low correlation between prepartum plasma and urinary cortisol may reflect late-gestational changes in the production and/or metabolism of glucocorticoids. Steroid excretion profiles in a large sample of females giving birth and caring for healthy infants ( n=108) were compared with profiles obtained from females with poor maternal–fetal outcomes (late-term stillbirth, n=14) and from females with significant postpartum problems with maternal care ( n=20). Mothers giving birth to stillborn infants had lower prepartum levels of urinary estrone conjugates and cortisol, suggesting reduced placental steroidogenesis. Mothers with postpartum behavioral difficulties had higher concentrations of prepartum estrone excretion, lower cortisol excretion, and elevated E/P ratios throughout the peripartum period. Noninvasive sample collection and enzyme immunoassay, therefore, have predictive utility regarding circulating steroid concentrations and can identify important endocrine correlates of physiological and behavioral abnormalities in baboons.

Emergency Contraception With Mifepristone and Levonorgestrel

In Brief OBJECTIVE To study the effect of mifepristone and levonorgestrel on ovarian function and endometrial development in doses effective as emergency contraception. METHODS Twelve fertile women were treated with either 10 mg of mifepristone as a single dose (n = 6) or two doses of 0.75 mg of levonorgestrel, 12 hours apart (n = 6) before and after ovulation. An endometrial biopsy performed during the implantation period was analyzed for endometrial maturation and expression of markers of endometrial receptivity. The markers tested for were integrin α4 and β3, cyclooxygenase-1 and -2, progesterone receptors, Dolichos biflorus agglutinin lectin binding, and pinopodes. Urinary excretion of luteinizing hormone, estrone, and pregnanediol were also determined RESULTS Treatment with mifepristone and levonorgestrel before ovulation inhibited the luteinizing hormone surge showing no significant differences between the means of luteinizing hormone measurements. When mifepristone was administered in the early luteal phase, downregulation of progesterone receptors was inhibited in five of six women. No significant alteration was found in any of the remaining markers of endometrial receptivity. CONCLUSION The mode of action of emergency contraception with mifepristone or levonorgestrel is primarily due to inhibition of ovulation rather than inhibition of implantation. Emergency contraception with mifepristone and levonorgestrel acts mainly by inhibition of ovulation rather than inhibition of implantation.

Emergency contraception with mifepristone and levonorgestrel: mechanism of action

OBJECTIVE: To study the effect of mifepristone and levonorgestrel on ovarian function and endometrial development in doses effective as emergency contraception. METHODS: Twelve fertile women were treated with either 10 mg of mifepristone as a single dose ( n = 6) or two doses of 0.75 mg of levonorgestrel, 12 hours apart ( n = 6) before and after ovulation. An endometrial biopsy performed during the implantation period was analyzed for endometrial maturation and expression of markers of endometrial receptivity. The markers tested for were integrin α4 and β3, cyclooxygenase-1 and -2, progesterone receptors, Dolichos biflorus agglutinin lectin binding, and pinopodes. Urinary excretion of luteinizing hormone, estrone, and pregnanediol were also determined RESULTS: Treatment with mifepristone and levonorgestrel before ovulation inhibited the luteinizing hormone surge showing no significant differences between the means of luteinizing hormone measurements. When mifepristone was administered in the early luteal phase, downregulation of progesterone receptors was inhibited in five of six women. No significant alteration was found in any of the remaining markers of endometrial receptivity. CONCLUSION: The mode of action of emergency contraception with mifepristone or levonorgestrel is primarily due to inhibition of ovulation rather than inhibition of implantation.

Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia.

We assessed adult hypothalamic-pituitary-ovarian function following treatment with chemotherapy and cranial irradiation for childhood acute lymphoblastic leukaemia. The patients (n = 12) had median age at diagnosis of 4.7 years, and at assessment of 20.8 years. They collected a daily urine sample over two to five consecutive menstrual cycles (total of 41 cycles) for analysis of LH and steroid excretion. Blood sampling and ovarian ultrasound examination was performed in the early follicular phase. Sixteen healthy women with regular menstrual cycles were recruited as controls. Urinary LH excretion was significantly lower in patients throughout the cycle, particularly during the LH surge (P < 0.0001). The length of the luteal phase was significantly shorter in patients than in normal controls (12.2 +/- 0.3 versus 13.6 +/- 0.4 days, P = 0.01) with a high prevalence of short (< or =11 days) luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly but not significantly lower. Follicular and luteal phase excretion of oestrone was lower in patients than in controls (P = 0.01). Early follicular phase plasma oestradiol was also lower in the patient group (P = 0.032) although LH, FSH, inhibin A and B concentrations were similar. These data indicate that treatment for childhood leukaemia results in subtle ovulatory disorder in some patients, probably related to cranial irradiation. Follow-up of these women is required to detect any effect on reproductive potential.

Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study

We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximately 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g.MJ-1.d-1, respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P < or = 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men.

Characterization of reproductive hormonal dynamics in the perimenopause.

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.

Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in healthy postmenopausal women.

We have performed a phase I study of the effect of a single dose of CGS 20267, an oral nonsteroidal aromatase inhibitor, in 12 healthy volunteer postmenopausal women. Each subject received 2 single doses of CGS 20267 (0.1, 0.5, or 2.5 mg) or placebo separated by a washout period of at least 6 weeks. There was statistically significant suppression of serum estrone and estradiol at all three doses of CGS 20267 tested. Serum estrone and estradiol concentrations were maximally suppressed by 76% and 79% from baseline levels, respectively. Urinary excretion of estrone and estradiol was also suppressed, although this did not reach statistical significance. Serum concentrations of aldosterone, cortisol, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, FSH, LH, and TSH were unaffected by CGS 20267. The drug was well tolerated, with no significant side-effects. This study has shown CGS 20267 to be a potent and specific aromatase inhibitor, and further studies are now needed to assess its clinical efficacy.

Peripheral and not central suppression of ovarian function during osmotic pump infusion of adrenocorticotropin-(1-24) for one menstrual cycle in the cynomolgus monkey and its partial compensation by a transitory elevation of sex hormone-binding globulin levels.

The purpose of our study was to assess the impact of subchronic administration of ACTH-(1-24) on ovarian function in the primate using a repeated measures experimental design. Osmotic pumps that released ACTH-(1-24) at a dose of 67 micrograms/day were implanted sc in four cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed peptide infusion. Administration of ACTH-(1-24) elevated cortisol levels in serum 1.6-fold and those in urine 2.2-fold, without affecting adrenal androgen concentrations. In the follicular phase (FP) of the menstrual cycle, infusion of ACTH-(1-24) did not alter serum levels of estradiol, FSH, or LH. However, immunoreactive estrone excretion in urine was decreased by 71% (P less than 0.05), and serum concentrations of sex hormone-binding globulin (SHBG) were increased by 100% (P less than 0.01). In the luteal phase (LP) of the menstrual cycle, infusion of ACTH-(1-24) suppressed levels of serum estradiol by 54% (P less than 0.001), urinary immunoreactive estrone by 72% (P less than 0.05), serum progesterone by 53% (P less than 0.001), and urinary immunoreactive pregnanediol by 71% (P less than 0.01). Serum FSH concentrations were increased during treatment by 100% (P less than 0.001) in LP, but LH concentrations were not altered. Also, serum levels of SHBG returned to control values in the LP. The lengths of menstrual cycles and the lengths of FP or LP were not affected during or after treatment. These data provide evidence that subchronic infusion of ACTH-(1-24) in primates: 1) suppresses estradiol production by the ovarian follicle as well as estradiol and progesterone production by the corpus luteum, 2) compromises ovarian function without concomitant suppression of serum gonadotropin levels, and 3) induces a transitory elevation of SHBG levels in the circulation, which may compensate for reduced estrogen output.

Effects of subchronic infusion of dehydroepiandrosterone sulfate on serum gonadotropin levels and ovarian function in the cynomolgus monkey

To assess the impact of elevated adrenal androgen levels on ovarian function in a nonhuman primate using a repeated measures experimental design. Osmotic pumps that released dehydroepiandrosterone sulfate (DHEAS) were implanted subcutaneously in five cynomolgus monkeys (Macaca fascicularis) for one menstrual cycle. The pumps were filled with saline for the two control cycles, one preceding and the other following DHEAS infusion. Administration of DHEAS elevated its levels in serum fourfold and in urine sevenfold, which returned to pretreatment values in the next cycle. Serum concentrations of estradiol (E2) were reduced by 55% during DHEAS administration in both follicular and luteal phases and were still decreased in the following cycle by 69% in follicular phase and 48% in luteal phase (P less than 0.01). Luteal serum progesterone (P) levels were diminished by 52% during treatment and were accompanied by 56% reduction in immunoreactive pregnanediol excretion in urine (P less than 0.05). Serum luteinizing hormone (LH) levels were decreased during DHEAS infusion by 51% in follicular phase and 58% in luteal phase (P less than 0.01) but returned to baseline in the next cycle. Conversely, serum follicle-stimulating hormone (FSH) concentrations were increased during treatment by 70% in follicular phase and 101% in luteal phase and remained increased by 58% in follicular phase of the next cycle (P less than 0.05). Estrone excretion in urine was higher during DHEAS infusion (1.5-fold increase) but was below pretreatment values in the following cycle by 57% in follicular phase and 51% in luteal phase (P less than 0.001). Administration of DHEAS did not change significantly serum levels of sex hormone-binding globulin. The length of menstrual cycles was not affected by increased levels of adrenal androgens either. However, in the cycles that followed DHEAS infusion, follicular phase was prolonged by an average of 9 days, and luteal phase was shortened by an average of 5 days (P less than 0.01). These data document that subchronically elevated adrenal androgen levels in primates: (1) suppress E2 and P levels, which may affect fertility; (2) differentially affect gonadotropin secretion, decreasing LH and increasing FSH serum concentrations; and (3) result in disturbances of ovarian function that persist for at least one menstrual cycle after normalization of androgen levels.

Increased catechol estrogen metabolism as a risk factor for nonfamilial breast cancer.

The metabolism of estrone (E1) or estradiol-17 beta (E2) to catechols seldom has been investigated in biochemical studies related to the risk of development of human breast cancer, as a result of the extreme lability and reactivity of these hormones. A method of indirect calculation was developed in which estimated catechol estrogen excretion (ECE) from urinary excretion of E1, E2, and estriol (E3) was used, based on the obligate reciprocal relation between 16 alpha-hydroxylase activity (r3) and estrogen 2/4 hydroxylase function (r2). This relationship is expressed by r2 x r3 = K, the estrogen oxidative constant. From published data relating chiefly to 2-OH estrone excretion, K = 12.4 +/- 0.8 (standard error of the mean). Urinary E1 + E2 excretion rates reflect nonprotein-bound plasma ovarian estrogen concentrations available for cell metabolism, which influence the value of K. The equation: r2 = [E1 + E2] K/[E3 + 16 alpha OH E1] = ECE gives a median correlation coefficient between actual catechol estrogen excretion and ECE in micrograms/24 hours of +0.88 (range, 0.61 to 0.97). When tested against the best product isolation analysis of catechol estrogen excretion, ECE was 95% accurate. Using this method a metaanalysis was conducted of published fractional estrogen excretion collected from 2846 healthy women worldwide aged 15 to 59 years, with a risk of breast cancer varying fivefold. Overall ECE was 78% to 97% higher in high-risk women of all ages and menstrual cycle phases (P less than 0.001, by Wilcoxon test). With increasing cancer risk (as estimated by the authors), ECE rose linearly exponentially with a slope of 0.149 (follicular phase) and 0.136 (luteal phase). The correlation coefficient (R2) between the two variables was 0.77 and 0.57, respectively (P less than 0.05). These data derived from calculations of ECE in healthy women confirmed recent analytic results of a twofold increase in the ratio of 2-OH E1/4-OH E1 in healthy Finnish women compared with recent Japanese migrants to Hawaii. In Finnish women with breast cancer, this ratio increased further (almost twofold). Metaanalysis supported the conclusion that increased rates of oxidation of estradiol 17-beta to 2-OH catechols supply the principal proximal human mammary carcinogens active after menarche.

Long‐acting gonadotrophin releasing hormone agonist implant causes variable duration of suppression of ovarian steroid and inhibin secretion

The duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretion. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long-term GnRH agonist treatment was attributable to changes in inhibin secretion. The implants of slowly biodegradable polylactide/glycolide (molar ratio 75:25) containing 3.3 mg buserelin, D-Ser (But)6-GnRH (1-9)-nonapeptide-ethylamide, in a rod 1 cm long and 0.13 cm diameter were injected s.c. in patients with endometriosis (3.3 mg buserelin in four patients, 6.6 mg buserelin in six patients). Urinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week. In all patients ovarian hormone secretion was suppressed successfully but considerable variability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100-194 days (median 118 days) (3.3 mg group) and 79-290 (median 178 days) (6.6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3.3 mg implant and 11 days for 6.6 mg implant. This was followed by a second phase representing a plateau of release, t1/2 = 50 days (3.3 mg implant) and 90 days (6.6 mg implant). During this second phase, an excretion rate of greater than 0.2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0.1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0.1 and 0.2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4-5 weeks. While this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long-term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but these events are not closely correlated.

Influence of wheat bran on NMU-induced mammary tumor development, plasma estrogen levels and estrogen excretion in female rats

In our animal experiments the hypothesis was tested that a high-fiber (HF) diet reduces tumor promotion by interruption of the enterohepatic circulation resulting in lowered estrogen exposure of the estrogen-sensitive tissue. In the first experiment the development of N- nitrosomethylurea (NMU) induced mammary tumors was investigated. One group of rats (HF) was fed a HF diet (11% fibe, based on wheat bran), the other group (LF) fed a low-fiber diet (0.5% fiber, based on white wheat flour). Tumor incidence (90 and 80%, respectively) and latency (121 and 128 days, respectively) were similar in the HF and LF groups. Compared to the LF group, HF rats had lower tumor weights (0.16 vs 0.55 g; P < 0.01) and a slightly lower tumor multiplicity (1.8 vs 2.8 tumors per tumor-bearing rat). These differences were reduced after adjustment for body weight. In a second experiment rats, not treated with the carcinogen, were kept on the same HF and LF diets. From these rats 24-h urine and feces and orbital blood samples were collected for analysis of (un)conjugated estrogens. The excretion of both free and conjugated estrogens in fecal samples was about 3-fold higher in HF rats than in LF rats. During the basal period of the cycle urinary excretion of estrone was lower in HF rats (mean 9.7 ng/day) than in LF rats (mean 13.0 ng/day; P < 0.05). It is concluded that wheat rain interrupts the enterohepatic circulation of estrogens, but plasma levels are not affected. Whether the development of mammary tumors is reduced by the introduction of specific components of wheat bran, or by a reduced body weight due to a lower (effective) energy intake remains to be determined.

Assessing reproductive status in orang‐utans by using urinary estrone

AbstractThe aim of this work was to compare normal menstrual cycle patterns of urinary estrone excretion in orang‐utans with those of an orang‐utan in her late 40s, an orang‐utan before and after rehabilitation for anorexia, and an orang‐utan during prolonged lactation. A detailed menstrual and sexual activity record was kept for each orang‐utan subject. Urine samples for estrone radioimmunoassay were collected daily for two cycles whenever possible. “Mawas,” in her late 40s, was monitored for two cycles in each of 3 successive years. While the normal pattern of estrone excretion was initially seen, some of the later cycles were shorter and appeared to lack the large luteal‐phase peak. “Puspa,” anorexic and amenorrhoeic at the age of 9½ years, had very low urinary estrone concentrations. After rehabilitation, followed by a late menarche, she had regular menstrual cycles with a normal estrone excretion pattern. She gave birth to a normal infant in 1990. “Puteri,” who had been lactating for 2 years, had consistently low estrone concentrations during an 8‐week monitoring period, with no evidence of cyclic variation in estrone excretion. Daily urinary estrone measurements, together with observation, were found to be useful in assessing the reproductive status of orangutans.

RETURN OF OVARIAN FUNCTION FOLLOWING SPONTANEOUS ABORTION

Assays of first morning urine samples for oestrone-3-glucuronide, LH and pregnanediol-3-glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post-partum (range 13-103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P less than 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68.8 IU/g C; P less than 0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P less than 0.02). The mean luteal phase length of 12.9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P less than 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.

The influence of boar stimulation on puberty attainment in tethered and group penned gilts

The objective of this experiment was to determine the influence of boar exposure on sexual development of tethered and group penned gilts. At 140 d of age, a total of 120 Large White gilts were moved into four stalls, each for one treatment, during three successive replicates. Gilts in treatments TB and T were tethered, and those in treatments GB and G were penned in groups of five animals. Two weeks later, females in treatments TB and GB were exposed to a mature boar for 20 min twice daily, while those in treatments T and G remained isolated from the male. From that age, all gilts were checked daily for estrus with the back pressure test and controlled weekly for ovulation by measuring progesterone concentration in plasma. Recording of social interactions between the male and the females was carried out in the second replicate at 6 and 7 mo of age. Estrone excretion was estimated just before and after relocation and 4 wk after boar introduction in the first and second replicates. Boar exposure advanced puberty attainment of gilts whatever the type of housing (median age at puberty = 233, 260, 215, 264 in treatments TB, T, GB and G, respectively, P<0.05), but in tethered gilts, its effectiveness varied between replicates. Influence of the housing system on sexual development was obvious only in presence of the male and varied also between replicates. Efficacy of estrus detection was similar in tethered and group penned gilts but was highly decreased when performed without a boar (78% with and 38% without the male). Behavioral interactions of the male towards the females were directed more to the head and body of group penned gilts and more to the ano-genital area of tethered gilts. Interactions performed by the females towards the male were highly reduced by tethering. Estrone excretion was not influenced by the type of housing or by boar introduction. Thus, it was found that boar introduction is more important for puberty attainment of gilts than type of housing. However, when gilts are tethered male effectiveness is lower and depends on other environmental factors which remain to be identified.