Chronotropic competence in endurance trained heart transplant recipients: heart rate is not a limiting factor for exercise capacity

Soy isoflavones are hypothesized to be responsible for changes in hormone action associated with reduced breast cancer risk. To test this hypothesis, we studied the effects of isoflavone consumption in 14 premenopausal women. Isoflavones were consumed in soy protein powders and provided relative to body weight (control diet, 10 +/- 1.1; low isoflavone diet, 64 +/- 9.2; high isoflavone diet, 128 +/- 16 mg/day) for three menstrual cycles plus 9 days in a randomized cross-over design. During the last 6 weeks of each diet period, plasma was collected every other day for analysis of estrogens, progesterone, LH, and FSH. Diet effects were assessed during each of four distinctly defined menstrual cycle phases. Plasma from the early follicular phase was analyzed for androgens, cortisol, thyroid hormones, insulin, PRL, and sex hormone-binding globulin. The low isoflavone diet decreased LH (P = 0.009) and FSH (P = 0.04) levels during the periovulatory phase. The high isoflavone diet decreased free T3 (P = 0.02) and dehydroepiandrosterone sulfate (P = 0.02) levels during the early follicular phase and estrone levels during the midfollicular phase (P = 0.02). No other significant changes were observed in hormone concentrations or in the length of the menstrual cycle, follicular phase, or luteal phase. Endometrial biopsies performed in the luteal phase of cycle 3 of each diet period revealed no effect of isoflavone consumption on histological dating. These data suggest that effects on plasma hormones and the menstrual cycle are not likely to be the primary mechanisms by which isoflavones may prevent cancer in premenopausal women.     

Serum levels of the pregnancy zone protein during the normal menstrual cycle

pregnancy zone protein (PZ), low polar estrogen, progesteorne, luteinizing hormone, and follicle stimulating hormone levels during normal menstrual cycles were studied. Serum samples were taken from 12 healthy women of different ages throughout their menstrual cycle. PZ levels showed no significant pattern and no statistically significant association was shown between PZ levels and any of the hormones. PZ levels were higher in older women and varied within each women's cycle. The study results indicate that peak estrogen levels during the menstrual cycle are not sufficient in duration or magnitude to cause increased serum levels of PZ.     

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome

OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.     

Effects of subchronic implantation of hydrocortisone phosphate-releasing osmotic pumps on peripheral gonadotropin levels and estradiol feedback to gonadotropin secretion in the cynomolgus monkey

The purpose of our study was to investigate subchronic effects of moderate hypercortisolemia on serum gonadotropin and estradiol (E2) levels in the primate using a repeated-measures experimental design. Osmotic pumps which released hydrocortisone 21-phosphate (HP) at a dose of 5 mg/day were implanted subcutaneously (s.c.) in each of five 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 hormone infusion. Subsequently, osmotic pumps which released HP at a higher dose of 15 mg/day were implanted s.c. in four of the initial five monkeys for the longer period of two menstrual cycles. The pumps were filled with saline for the two additional control cycles, one of which preceded and one of which followed HP infusion at 15 mg/day. The control cycle which followed HP infusion at 5 mg/day and the control cycle which preceded HP infusion at 15 mg/day were separated by at least one menstrual cycle. Administration of HP at the lower dose elevated serum cortisol levels 1.4-fold and decreased serum adrenal androgens to 0.6 of the pretreatment baseline. The higher dose of HP elevated serum cortisol levels 1.7-fold and suppressed serum adrenal androgens to 0.4 of the baseline. In the menstrual cycle following HP infusion serum cortisol levels were depressed to 0.8 and 0.6 of the pretreatment levels after the lower and the higher dose of HP, respectively. Serum levels of adrenal androgens returned to the baseline after the lower dose of HP, but were still suppressed to 0.5 of the baseline after the higher treatment dose. Implantation of pumps which released 5 mg/day of HP did not affect gonadotropin levels in the serum, either in the follicular phase (FP) or the luteal phase (LP) of the menstrual cycle. Serum E2 levels were increased by 77% in the FP during HP infusion at 5 mg/day (p < 0.001), but returned to control values in the LP. Implantation of pumps which released 15 mg/day of HP raised serum luteinizing hormone (LH) levels throughout the two menstrual cycles of treatment, by 111 and 96% in FPs (p < 0.001), and by 84 and 70% in LPs (p < 0.001). Conversely, serum follicle-stimulating hormone (FSH) levels were decreased by 45 and 50% in FPs (p < 0.05), and by 54 and 50% in LPs (p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)     

A mild form of Proteus syndrome

An increased level of serum estrogen is one marker of breast cancer risk. We have recently reported that increased risk of advanced breast cancer is associated with a common allele of the cytochrome P450c17alpha gene (CYP17), designated A2. We now show that CYP17 genotype is associated with serum hormone levels among 83 young, nulliparous women. Serum estradiol (E2) levels measured around day 11 of the menstrual cycle were 11 and 57% higher (P = 0.04), respectively, among women hetero- and homozygous for the CYP17 A2 allele compared to A1/A1 women. Similarly, around cycle day 22, E2 levels were 7 and 28% higher (P = 0.06), and progesterone levels were 24 and 30% higher (P = 0.04), respectively. These data provide direct evidence of genetic control of serum hormone levels.     

The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients

The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15-20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (> or = 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p < 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.     

Response of the primate secretory endometrium to subchronic hypercortisolemia

OBJECTIVE: To assess the impact of subchronic and moderate hypercortisolism on the secretory endometrium of the cynomolgus monkey. METHODS: Osmotic pumps containing hydrocortisone phosphate (HP) were implanted subcutaneously in each monkey on the first day of the menstrual cycle; each monkey also received pumps containing saline in another cycle. Blood was obtained three times per week and urine was collected daily for hormone analyses. Endometriectomy was performed 13 +/- 1 days after the serum estradiol (E2) peak in each study cycle. RESULTS: Infusion of HP elevated serum cortisol levels by an average of 70%. Mean serum progesterone (P) levels were decreased by 50% during the secretory phase of HP-treatment cycles by comparison with self-control cycles (P < .01); as a result, the mean endometrial glycogen concentration was reduced by 30% (P < .05) and the activity of 17 beta-hydroxysteroid dehydrogenase was decreased by 70% (P < .05). Serum E2 levels were not consistently elevated by HP treatment, but cytosolic estrogen receptor levels of the endometrium were decreased by 50% (P < .01), indicating increased estrogenic stimulation. Histologic development of the secretory endometrium was retarded, but the length of the secretory phase was not affected by the treatment. CONCLUSION: A moderate elevation of serum cortisol levels over one menstrual cycle consistently produced a reduction in serum P and a hypoprogestogenic-hyperestrogenic response of the secretory endometrium in the cynomolgus monkey.     

The use of estrogen preparations after the menopause and the risk of endometrial carcinoma

Studies have shown that the risk of endometrial cancer increases 4-7 times among women who undergo post-menopausal estrogen treatments. Certain factors can be associated with an increase inpost-menopausal estrogen levels in the body: acyclic anovulatory menstrual cycles, estrogen-producing ovarial carcinomas, use of post-menopausal estrogen treatments, and obesity. In obese women, estrone is produced from androstendion in fatty and other peripheral tissues. Cyclical therapy; avoiding progestative substances; and using preparations based on estriol, which does not affect the endometrium as strongly, are suggested as possibilities for post-menopausal estrogen treatment.     

Estradiol concentrations in premenopausal women with coronary heart disease

BACKGROUND: Because of the beneficial effects of estrogen, premenopausal women are normally protected against coronary heart disease (CHD) and are at lower risk for myocardial infarction; consequently, CHD occurs very rarely in menstrually active women. Given this background, the aim of the present study was to test the hypothesis that decreased concentrations of estrogen are associated with CHD in premenopausal women. METHODS: Fourteen premenopausal women with CHD were investigated and compared with a healthy control group comparable for age and cardiovascular risk factors. Relevant characteristics of patients and controls were assessed: age, blood pressure, body mass index, total cholesterol and high-density lipoprotein cholesterol, triglycerides, former pregnancies, ovariectomy and related surgical interventions, smoking history and former use of oral contraceptives. To ensure the premenopausal status of the participants, the regularity of the menstrual cycle and the follicle-stimulating hormone concentrations were also assessed. Plasma estradiol and progesterone and urine estrone concentrations (24 h urine collection) were measured at day 6 after estimated ovulation to assess the relative increase in plasma estradiol and progesterone during the second half of the menstrual cycle. RESULTS: Compared with the control group, premenopausal women with CHD had significantly lower concentrations of plasma estradiol (408.9 +/- 141 pmol/l and 287.8 +/- 109 pmol/l respectively; P = 0.0228) and total estrogen (2061 +/- 693 pg/mumol creatinine and 1607 +/- 448 pg/mumol creatinine respectively; P = 0.025) in the urine. However, the progesterone concentrations were not significantly different between the groups. These findings might be explained by a partial ovarian dysfunction, as the patient group had a significantly higher number of tubal sterilizations (eight compared with one). CONCLUSION: Our data provide support for the hypothesis that decreased concentrations of estradiol might be an additional pathogenetic factor for the development of CHD in menstrually active premenopausal women.     

Thrombosis of mechanical heart valve prosthesis. Predisposing factors and results of surgical treatment

There is both epidemiologic and experimental support for the hypothesis that a high-fiber diet can reduce breast cancer risk; this may be due, at least in part, to a reduction in circulating estrogens. This study examined the effects of three levels of wheat bran supplementation (5, 10, and 20 g/d for 2 mo) on the major serum estrogens during both the luteal and follicular phases of the menstrual cycle. The 10- and 20-g supplements, which increased the total dietary fiber intakes to approximately 20 and 32 g/d, respectively, resulted in significant decreases in the luteal serum estrone (P < 0.05 and < 0.02, respectively). The serum estradiol was significantly reduced in the 10-g wheat bran group after 2 mo (P < 0.05); the 20-g supplemented group showed a significant decrease in estradiol at 1 mo (P < 0.02), but not at 2 mo. No changes occurred in the estrone sulfate concentrations. During the follicular phase, the 10-g wheat bran group exhibited a significant reduction in the serum estrone (P < 0.02). Only the serum estrone sulfate showed any reduction with the 20-g supplement, and this just failed to achieve significance (P = 0.07). Serum sex hormone-binding globulin levels were unaffected by wheat bran. When of long duration, these effects may be sufficient to favorably influence breast cancer risk in Western women.     

Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis

Soy isoflavones exhibit a number of biological effects, suggesting that they may have a role in cancer prevention. Our objectives are to determine whether components of soy products or purified soy isoflavones can inhibit the progression of bladder cancer. We compared the in vitro effects of pure soy isoflavones and soy phytochemical concentrate on growth curves, cell cycle progression, and apoptosis in murine and human bladder cancer cell lines. Pure soy isoflavones (genistein, genistin, daidzein, and biochanin A) and soy phytochemical concentrate exhibit dose-dependent growth inhibition of murine (MB49 and MBT-2) and human (HT-1376, UM-UC-3, RT-4, J82, and TCCSUP) bladder cancer cell lines, although the degree of inhibition varies among lines. Soy isoflavones induce a G2-M cell cycle arrest in all human and murine lines evaluated by flow cytometry. In addition, some bladder cancer lines show DNA fragmentation consistent with apoptosis. We next evaluated the ability of genistein, soy phytochemical concentrate, and soy protein isolate, respectively, to inhibit the growth of transplantable murine bladder cancer in vivo. C57BL/6 mice were randomly assigned to treatment groups (n = 12/group): (a) AIN-76A diet; (b) AIN-76A diet plus genistein, i.p., 50 mg/kg body weight/day; (c) AIN-76 diet with soy phytochemical concentrate at 0.2% of the diet; (d) AIN-76 diet with soy phytochemical concentrate at 1.0% of the diet; and (e) AIN-76A diet with soy protein isolate, 20% by weight. Mice were inoculated s.c. with 5 x 10(4) syngeneic MB49 bladder carcinoma cells, and tumor growth was quantitated. Neither genistein nor soy products reduced body weight gain. Tumor volumes from mice treated with genistein, dietary soy phytochemical concentrate at 1%, or dietary soy protein isolate were reduced by 40% (P < 0.007), 48% (P < 0.001), or 37% (P < 0.01), respectively, compared with controls. We characterized the effects of treatment on several biomarkers in tumor tissue: proliferation index by proliferating cell nuclear antigen staining, apoptotic index by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining, and angiogenesis by microvessel quantitation. Soy products reduced angiogenesis, increased apoptosis, and slightly reduced proliferation while showing no histopathological effects on the normal bladder mucosa. Our data suggest that soy isoflavones can inhibit bladder tumor growth through a combination of direct effects on tumor cells and indirect effects on the tumor neovasculature. Soy products warrant further investigation in bladder cancer prevention and treatment programs or as antiangiogenic agents.     

Menstruation, sex hormones, and migraine

All women with migraine are susceptible to the effects of hormonal changes. For a minority with menstrual migraine, fluctuating hormones of the normal ovarian cycle are a specific trigger, particularly during perimenopause. The author proposes that the term menstrual migraine should be restricted to migraine attacks occurring on day 1 +/- 2 days of the menstrual cycle with freedom from migraine during the rest of the cycle. This definition is compatible with the mechanism of estrogen withdrawal. Other mechanisms such as prostaglandin release also may be important for some women. The changing hormonal environment at various stages of life provides further evidence of the role of estrogen in migraine. Treatments that stabilize hormone levels in the form of estrogen supplementation for menstrual migraine, elimination of the pill-free week, and adequate, stable levels of estrogen for HRT, all are associated with an improvement in migraine. The control of the menstrual cycle, however, is extremely complex, and until further studies are undertaken using strict criteria, the mechanism of migraine triggered by hormonal events remains uncertain.     

Development of aviation medicine in Germany

BACKGROUND: Despite some findings to the contrary, it would appear that pharmacological doses of progesterone and estrogen (alone or in combination) can influence intraocular pressure (IOP). The relationship between hormonal changes associated with the menstrual cycle and intraocular pressure is not clearly understood. After elimination of those factors that can affect IOP, the present study investigated whether physiological hormonal changes associated with the menstrual cycle have a correlation with intraocular pressure. METHODS: Intraocular pressure and the concentrations of circulating hormones, namely, the luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, and testosterone, of twenty married women of the same age groups were recorded daily throughout a menstrual cycle. None was taking any contraceptives in any form. The intraocular pressure was measured using a Goldmann applanation tonometer. RESULTS: The intraocular pressure values fluctuated in each of the twenty subjects at various times of the cycle; however, they were not definitely correlated with the different phases of the cycle. This study failed to find any correlation between IOP and progesterone or estradiol levels.     

Ischemic but not thermal pain sensitivity varies across the menstrual cycle

OBJECTIVE AND METHOD: Findings from both animal and human research suggest that pain sensitivity changes across the menstrual cycle; however, among humans the nature of these menstrual cycle effects remains unclear. The present study used a repeated-measures design to evaluate changes in thermal and ischemic pain responses during three phases of the menstrual cycle, midfollicular (postmenstrual), ovulatory, and mid-to-late luteal (premenstrual), in 11 healthy women. The cycle phase during which subjects began their participation was determined randomly. Plasma levels of estrogen, progesterone, luteinizing hormone (LH), testosterone, and beta-endorphin were determined at each experimental session. Participants also completed a daily diary of physical and emotional symptoms for two complete menstrual cycles before the experimental sessions. RESULTS: The results indicated that women showed less ischemic pain sensitivity during the midfollicular compared with the ovulatory and mid-to-late luteal phases, but thermal pain responses did not vary significantly across menstrual cycle phases. Physical and emotional symptoms were minimal and did not change significantly across the menstrual cycle. CONCLUSIONS: These findings indicate greater ischemic but not thermal pain sensitivity among women after the midcycle LH surge. The practical relevance and potential mechanisms of these findings are discussed.     

Factors associated with serum levels of estradiol and sex hormone-binding globulin among premenopausal Japanese women

We measured serum levels of estradiol (E(2)) and sex hormone-binding globulin (SHBG) among 50 healthy premenopausal Japanese women in 1994 in Gifu, Japan, to investigate the relationships between potential risk factors for breast cancer and hormone levels. Using a self-administered questionnaire, we collected data on body size, physical activity, and previous disease history, as well as menstrual and reproductive histories of the woman and her mother. Blood samples were drawn from each subject on the 11th and 22nd days of her menstrual cycle. Higher serum E(2) levels were observed for women with shorter menstrual cycles. Age as well as cycle length were included in the regression models to determine the associations between hormone levels and study variables. Body mass index (BMI) was inversely related to SHBG level measured at the 11th day of the cycle, after adjusting for age and cycle length (r = -0.33; p = 0. 03). Women born in spring/summer had higher levels of E(2) on the 22nd day (p = 0.07) and higher levels of SHBG on both the 11th and 22nd days of the cycle (p = 0.01 and p = 0.06, respectively) than those born in other seasons. Physical activity at 13-15 years of age was inversely related to E(2) level on the 11th day of the cycle after controlling for age, cycle length, BMI, and birth month (r = -0.35; p = 0.04).     

Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women

OBJECTIVE: To determine the association between serum estrogen levels, cognitive performance, and risk of cognitive decline in older women. DESIGN: Prospective cohort study with an average follow-up of 5 years. SETTING: Clinical centers in Baltimore, MD, Minneapolis, MN, Portland, OR, and the Monongahela Valley in Pennsylvania. PARTICIPANTS: 532 women aged 65 years or older who were the controls from two nested case-control studies in the ongoing Study of Osteoporotic Fractures. OUTCOME MEASURES: Three cognitive tests--a modified Mini-Mental Status Exam, Digit Symbol, and Trails B--were administered at study initiation and were then repeated approximately 5 years later. Estrone and estradiol levels were determined by radioimmunoassay at two laboratories from baseline stored serum. RESULTS: The characteristics of the women in the four serum estrogen quartiles did not differ except that body weight and change in weight since age 50 increased directly with higher quartile of serum estrogen (P < .001, for both estrone and estradiol). Initial cognitive performance on all three tests did not differ consistently by quartile of estradiol or by the estradiol to estrone ratio. Women in the higher estrone quartiles had 15% lower (worse) scores on Digit Symbol compared with the lower quartiles (P=.004) but there was no difference by quartile on the modified MMSE or on Trails B. Cognitive function test scores declined over the 5 years of follow-up. There was no difference in amount of change by quartile of estradiol, but women in the higher estrone quartiles had greater reduction of scores on Trails B compared with those in the lower quartiles (P=.012), even after adjusting for age, education, depression, stroke history, weight, and change in weight since age 50. The age-adjusted odds of cognitive decline (defined as tenth percentile of women with the largest decline in cognitive performance) did not vary across quartile of estrone or estradiol. CONCLUSIONS: Endogenous estrogens are not associated consistently with cognitive performance or risk of cognitive decline on a selected battery of cognitive tests in older community-dwelling women. Worse performance on two cognitive tests among women with higher estrone levels was surprising and warrants further investigation.     

A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues

The long-term clinical effects of soy protein containing various amounts of isoflavones on lipoproteins, mononuclear cell LDL receptor messenger RNA concentrations, and other selected cardiovascular risk factors are not well known. Sixty-six hypercholesterolemic, free-living, postmenopausal women were investigated during a 6-mo parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, all subjects were randomly assigned to 1 of 3 dietary groups (all with 40 g protein): a National Cholesterol Education Program (NCEP) Step 1 diet with protein from casein and nonfat dry milk (control), an NCEP Step 1 diet with protein from isolated soy protein containing moderate amounts of isoflavones (ISP56), or an NCEP Step 1 diet with protein from isolated soy protein containing high amounts of isoflavones (ISP90). Non-HDL cholesterol in both the ISP56 and ISP90 groups was reduced compared with the control group (P < 0.05), whereas total cholesterol was not changed. HDL cholesterol increased in both the ISP56 and ISP90 groups (P < 0.05), whereas the ratio of total to HDL cholesterol decreased significantly in both groups compared with the control (P < 0.05). Mononuclear cell LDL receptor messenger RNA concentrations increased in subjects consuming ISP56 or ISP90 compared with the control (P < 0.05). These results indicate that soy protein, with different amounts of isoflavones, may decrease the risk of cardiovascular disease via improved blood lipid profiles, and that the mechanism by which apolipoprotein B-containing lipoproteins were depressed may be via alterations in LDL receptor quantity or activity.     

Effect of post-coital contraceptive methods on the endometrium and the menstrual cycle

STUDY OBJECTIVE: To evaluate the effect of treatment with ethinylesteradiol-levonorgestrel or danazol on ovarian function, gonadotrophin release and endometrial development during the time when a pregnancy may occur following unprotected intercourse. METHODS: Women with regular menstrual cycles were followed during one control, one treatment and one follow-up month. The women obtained either a combination of 0.5 mg levonorgestrel and 0.1 mg ethinylestradiol (Yuzpe regimen: n = 16) or 600 mg danazol orally and repeated after 12 hours (n = 16). The treatment was administered on either cycle day (cd) 12 or day LH +2. An endometrial biopsy was obtained once on cd LH +6 to +8 in the subjects treated on cd LH +2 both in control and treatment cycles, and morphometric analysis was performed. The concentrations of LH, pregnandiol (P2G), and estrone (EIG) glucuronide were followed daily in morning urine during control and treatment cycles. RESULTS: Following treatment with the Yuzpe regimen on cd 12 the LH surge was either undetectable (three subjects), postponed to cd 16 to 22 (three subjects) or cd 38 to 39 (two subjects) with lower P2G and LH levels than in the control cycle. Following preovulatory treatment with danazol, no LH peak could be detected in four subjects and in the remaining four subjects the LH peak varied between cd 13 and cd 24. The mean area under the curve for LH was significantly lower, the levels of EIG were slightly higher and the P2G levels were unaffected in comparison with the control cycle. Neither of the two treatments administered on cd LH +2 affected the hormonal pattern and only a discreet effect on the development of the endometrium was seen after the EE/LNG treatment. CONCLUSION: The findings indicate that the contraceptive effect of postcoital treatment with EE/LNG and danazol is mainly due to an inhibition or delay of ovulation and insufficient corpus luteum function. The direct effect on the endometrium is limited, if any.     

Estrogen metabolism and excretion in Oriental and Caucasian women

BACKGROUND: Caucasian and Oriental women have different incidence rates of breast cancer. Among the underlying risk factors for the development of breast cancer in the women of these two groups may be their different diets and patterns of estrogen metabolism and excretion. The absolute levels and relative ratios of 16 alpha-hydroxylated estrogens and 2-hydroxylated estrogens (catechol estrogens) in the body may have a role in the etiology of breast cancer, but studies so far have provided only conflicting results. PURPOSE: Our goal was to study estrogen metabolism, in particular, the extent of 2-hydroxylation and 16 alpha-hydroxylation of estrogens in two groups of women, one Caucasian and one Oriental, with inherently different breast cancer risks. METHODS: Dietary records were analyzed over 3-day periods in the mid-follicular phase, twice, at 6-month intervals for 13 premenopausal Oriental women, recent immigrant arrivals in Hawaii with presumed low risk of breast cancer, and for 12 premenopausal Finnish women with presumed higher risk. The urinary estrogen profile was measured by gas chromatography-mass spectrometry and plasma and fecal estrogens were assayed by chromatographic radioimmunoassays. RESULTS: Mean fat intake per 1000 kcal was 73% higher (P < .001) in the Finnish women, but the mean fiber intake and fecal weights were similar to those of the Oriental women. Compared with Oriental women, Finnish women had 46% higher plasma estradiol (P < .01) and 124% higher plasma estrone sulfate (P < .01); however, after adjustment for differences in age and body mass index, only the difference in estrone sulfate remained statistically significant (P < .05). Mean plasma levels of estrone and estradiol correlated with height after adjustment for body mass index (P < .05). Mean plasma levels of estrone and sex hormone-binding globulin were similar. The Finns had higher mean urinary estrone (193%), estradiol (166%), various catechol estrogens (130%-439%), and total estrogen excretion (123%) (all P < .001), but similar 16 alpha-hydroxylated estrogen excretion. As calculated, 16 alpha-hydroxylation of estrone was significantly increased (P < .01) in the Oriental women, but 2-hydroxylation, 4-hydroxylation, and 16 beta-hydroxylation of estrone were similar in both groups. The ratio of catechol estrogen to 16 alpha-hydroxylated estrogen was four to five times higher (P < .001) in the Finnish women. The Oriental women had two to three times higher fecal excretion of estrogens than the Finnish women (P < .01). CONCLUSIONS: Our results indicate that high catechol estrogen formation may be a greater risk factor for breast cancer than high 16 alpha-hydroxylation of estrogens. However, the main risk factor for the Finnish women, as opposed to the Oriental women, may be their higher estrogen levels that result from a higher fat diet, higher estrogen production related to their greater height, and lower fecal estrogen excretion.     

Immunohistochemical identification and effects of atrial natriuretic peptide, pancreastatin, leucine-enkephalin, and galanin in the porcine pancreas

OBJECTIVE: To examine the fertility and pregnancy wastage rates in a group of presumably fertile couples. DESIGN: Prospective observational study of 200 couples desiring to achieve pregnancy over 12 menstrual cycles coupled with pregnancy outcome follow-up. SETTING: A university-based obstetrics and gynecological center. PATIENTS: Personal interviews and questionnaires were used to screen couples for entry into the study. Couples were counseled to have intercourse centered on predicted day of ovulation. Phase 1 included the first three cycles in which women collected daily morning urine samples, underwent midcycle postcoital tests, and, if late for their menses, presented for serum hCG testing. Phase 2 encompassed the next nine cycles in which women were contacted monthly by phone and underwent serum hCG testing if menses was delayed. Urine samples from cycles in which clinical (serum hCG) pregnancy did not occur underwent sensitive hCG testing to detect occult pregnancies. Pregnancies were followed until delivery to ascertain outcome. RESULTS: Eighty-two percent of the 200 couples followed for the entire study period conceived. The maximal fertility rate was approximately 30% per cycle in the first two cycles. This rate quickly tapered over the remainder of the study. Pregnancy wastage during phase 1 accounted for 31% of the pregnancies detected. Forty-one percent (15/36) of these losses were seen only by urine hCG testing and were categorized as occult. Eleven of these same patients later achieved clinically recognized conceptions during the study. CONCLUSIONS: These results support the concept that the efficiency of human reproduction is maximum at approximately 30% per cycle. A very significant number of these pregnancies end in spontaneous abortion. In addition, pregnancy loss before missed menses occurs in a significant proportion of women.