Differential survival throughout the full annual cycle of a migratory bird presents a life-history trade-off.

Long-distance migrations are among the most physically demanding feats animals perform. Understanding the potential costs and benefits of such behaviour is a fundamental question in ecology and evolution. A hypothetical cost of migration should be outweighed by higher productivity and/or higher annual survival, but few studies on migratory species have been able to directly quantify patterns of survival throughout the full annual cycle and across the majority of a species' range. Here, we use telemetry data from 220 migratory Egyptian vultures Neophron percnopterus, tracked for 3,186 bird months and across approximately 70% of the species' global distribution, to test for differences in survival throughout the annual cycle. We estimated monthly survival probability relative to migration and latitude using a multi-event capture-recapture model in a Bayesian framework that accounted for age, origin, subpopulation and the uncertainty of classifying fates from tracking data. We found lower survival during migration compared to stationary periods (ß = -0.816; 95% credible interval: -1.290 to -0.318) and higher survival on non-breeding grounds at southern latitudes (<25°N; ß = 0.664; 0.076-1.319) compared to on breeding grounds. Survival was also higher for individuals originating from Western Europe (ß = 0.664; 0.110-1.330) as compared to further east in Europe and Asia, and improved with age (ß = 0.030; 0.020-0.042). Anthropogenic mortalities accounted for half of the mortalities with a known cause and occurred mainly in northern latitudes. Many juveniles drowned in the Mediterranean Sea on their first autumn migration while there were few confirmed mortalities in the Sahara Desert, indicating that migration barriers are likely species-specific. Our study advances the understanding of important fitness trade-offs associated with long-distance migration. We conclude that there is lower survival associated with migration, but that this may be offset by higher non-breeding survival at lower latitudes. We found more human-caused mortality farther north, and suggest that increasing anthropogenic mortality could disrupt the delicate migration trade-off balance. Research to investigate further potential benefits of migration (e.g. differential productivity across latitudes) could clarify how migration evolved and how migrants may persist in a rapidly changing world.

Immune response to the hepatitis B vaccine among HIV-infected adults in Uganda.

BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in sub-Saharan Africa (SSA) and can rapidly progress to cirrhosis and hepatocellular carcinoma. Recent data demonstrate ongoing HBV transmission among HIV-infected adults in SSA, suggesting that complications of HIV/HBV co-infection could be prevented with HBV vaccination. Because HBV vaccine efficacy is poorly understood among HIV-infected persons in SSA, we sought to characterize the humoral response to the HBV vaccine in HIV-seropositive Ugandan adults. METHODS: We enrolled HIV-infected adults in Kampala, Uganda without serologic evidence of prior HBV infection. Three HBV vaccine doses were administered at 0, 1 and 6 months. Anti-HBs levels were measured 4 weeks after the third vaccine dose. "Response" to vaccination was defined as anti-HBs levels ≥ 10 IU/L and "high response" as ≥ 100 IU/L. Regression analysis was used to determine predictors of response. RESULTS: Of 251 HIV-positive adults screened, 132 (53%) had no prior HBV infection or immunity and were enrolled. Most participants were women [89 (67%)]; median (IQR) age was 32 years (27-41), and 68 (52%) had received antiretroviral therapy (ART) for > 3 months. Median (IQR) CD4 count was 426 (261-583), and 64 (94%) of the 68 receiving ART had undetectable plasma HIV RNA. Overall, 117 (92%) participants seroconverted to the vaccine (anti-HBs ≥ 10 IU/L), with 109 (86%) participants having high-level response (anti-HBs ≥ 100 IU/L). In multivariate analysis, only baseline CD4 > 200 cells/mm3 was associated with response [OR = 6.97 (1.34-34.71), p = 0.02] and high-level response [OR = 4.25 (1.15-15.69)], p = 0.03]. CONCLUSION: HBV vaccination was effective in eliciting a protective humoral response, particularly among those with higher CD4 counts. Half of the screened patients did not have immunity to HBV infection, suggesting a large at-risk population for HBV infection among HIV-positive adults in Uganda. Our findings support including HBV vaccination as part of routine care among HIV-positive adults.

Ovarian remnant removal using minimally invasive laparoscopic techniques in four dogs.

Four partially intact, female dogs with a median age of 6 · 5 years were presented to Angell Animal Medical Center for laparoscopic treatment of ovarian remnant syndrome. Dogs were positioned in dorsal recumbency and a three-port laparoscopic technique was used to identify and remove en bloc any abnormal tissue in the area of the ovarian pedicles. None of the dogs required conversion to open coeliotomy and there were no major complications. Abnormal tissue, including granulosa thecal cell tumour (n = 1), was identified bilaterally in three dogs and unilaterally in one dog. Clinical signs associated with ovarian remnant syndrome resolved in all dogs following surgery.

Do power lines and protected areas present a catch-22 situation for Cape vultures (Gyps coprotheres)?

Cape vulture Gyps coprotheres populations have declined across their range due to multiple anthropogenic threats. Their susceptibility to fatal collisions with the expanding power line network and the prevalence of carcasses contaminated with illegal poisons and other threats outside protected areas are thought to be the primary drivers of declines in southern Africa. We used GPS-GSM units to track the movements and delineate the home ranges of five adult (mean ±SD minimum convex polygon area = 121,655±90,845 km(2)) and four immature (mean ±SD minimum convex polygon area = 492,300±259,427 km(2)) Cape vultures to investigate the influence of power lines and their use of protected areas. The vultures travelled more than 1,000 km from the capture site and collectively entered five different countries in southern Africa. Their movement patterns and core foraging ranges were closely associated with the spatial distribution of transmission power lines and we present evidence that the construction of power lines has allowed the species to extend its range to areas previously devoid of suitable perches. The distribution of locations of known Cape vulture mortalities caused by interactions with power lines corresponded to the core ranges of the tracked vultures. Although some of the vultures regularly roosted at breeding colonies located inside protected areas the majority of foraging activity took place on unprotected farmland. Their ability to travel vast distances very quickly and the high proportion of time they spend in the vicinity of power lines and outside protected areas make Cape vultures especially vulnerable to negative interactions with the expanding power line network and the full range of threats across the region. Co-ordinated cross-border conservation strategies beyond the protected area network will therefore be necessary to ensure the future survival of threatened vultures in Africa.

Foraging ranges of immature African white-backed vultures (Gyps africanus) and their use of protected areas in southern Africa.

Vultures in the Gyps genus are declining globally. Multiple threats related to human activity have caused widespread declines of vulture populations in Africa, especially outside protected areas. Addressing such threats requires the estimation of foraging ranges yet such estimates are lacking, even for widespread (but declining) species such as the African white-backed vulture (Gyps africanus). We tracked six immature African white-backed vultures in South Africa using GPS-GSM units to study their movement patterns, their use of protected areas and the time they spent in the vicinity of supplementary feeding sites. All individuals foraged widely; their combined foraging ranges extended into six countries in southern Africa (mean (± SE) minimum convex polygon area =269,103±197,187 km(2)) and three of the vultures travelled more than 900 km from the capture site. All six vultures spent the majority of their tracking periods outside protected areas. South African protected areas were very rarely visited whereas protected areas in northern Botswana and Zimbabwe were used more frequently. Two of the vultures visited supplementary feeding sites regularly, with consequent reduced ranging behaviour, suggesting that individuals could alter their foraging behaviour in response to such sites. We show that immature African white-backed vultures are capable of travelling throughout southern Africa, yet use protected areas to only a limited extent, making them susceptible to the full range of threats in the region. The standard approach of designating protected areas to conserve species is unlikely to ensure the protection of such wide-ranging species against threats in the wider landscape.

Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis.

BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by approximately 20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones ( approximately 14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.

Probiotic capsules do not lower plasma lipids in young women and men.

OBJECTIVE: To investigate the effect of probiotic capsules on plasma lipids. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: Fifty-five normocholesterolemic subjects ages 18-36 (33 premenopausal women and 22 men). INTERVENTION: Each subject consumed either three probiotic capsules each containing a total of 10(9) colony-forming units Lactobacillus acidophilus and Bifidobacterium longum and 10-15 mg fructo-oligosaccharide or three placebo capsules daily for 2 months (men) or two menstrual cycles (women). Plasma lipids were measured before and following the intervention (during the early follicular phase for women). RESULTS: Plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride were not altered by consumption of probiotic or placebo capsules and were not different between treatment groups following the intervention. CONCLUSIONS: These results do not support a beneficial effect of Lactobacillus acidophilus strain DDS-1 and Bifidobacterium longum strain UABL-14 on plasma lipids in normocholesterolemic young women and men. SPONSORSHIP: Supported by the Minnesota Agricultural Experiment Station and UAS Laboratories.

Syphilis, chlamydia, and gonorrhea screening in HIV-infected patients in primary care, San Francisco, California, 2003.

The Centers for Disease Control (CDC) recommends sexually transmitted disease (STD) screening among HIV-infected persons in order to reduce HIV transmission. We evaluated the results of routine screening for syphilis and for urogenital, pharyngeal, and rectal gonorrhea (GC) and chlamydia (CT) among asymptomatic HIV-infected patients at an HIV primary care clinic in San Francisco, California. We found 15 new syphilis infections of 814 tested (1.8%) and 60 new cases of CT or GC infection of 586 tested (10.2%), with 88% of GC and CT infections occurring at nonurethral sites. Our study reveals a high rate of asymptomatic STDs among HIV-infected patients in primary care and supports the CDC recommendations to screen HIV-infected patients for STDs at all relevant anatomic sites.

Antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV.

BACKGROUND: Cryptococcal disease is an opportunistic infection that causes significant morbidity and mortality in adults with HIV. Primary prophylaxis with antifungal interventions may decrease cryptococcal disease incidence and associated mortality. OBJECTIVES: To assess the efficacy of antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV. SEARCH STRATEGY: We searched the following databases: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Database of Abstracts of Reviews of Effectiveness (DARE), Latin American and Caribbean Literature on the Health Sciences (LILACS), and the Cochrane Controlled Trials Register (CCTR). We reviewed abstracts from the following relevant conferences: International AIDS Conference, International AIDS Society Conference on HIV Pathogenesis and Treatment, and Conference on Retroviruses and Opportunistic Infections. We searched reference lists for all primary and other pertinent articles identified. We attempted to contact experts in the field, particularly primary authors of included studies, to better ensure completeness of included studies. We also approached pharmaceutical companies for any available and relevant unpublished data. The time period searched was from 1980 to August 2004. We placed no language restrictions on the search. Key words used include: meningitis, cryptococcal, cryptococcus, cryptococcosis, acquired immunodeficiency syndrome, human immunodeficiency virus, prophylaxis, chemoprevention, antifungal agents, and the Cochrane screen for randomized controlled trials. SELECTION CRITERIA: Randomized controlled trials using antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. Trial authors, experts, and pharmaceutical companies were contacted for additional and/or missing information. Data were abstracted by two reviewers. Data were pooled, where appropriate, to yield summary estimates. MAIN RESULTS: Five studies (N=1316) were identified. All study patients had CD4 cell counts <300 cells/microl, and the majority of patients had CD4 cell counts <150 cells/microl. When all five studies are analyzed as a single group (N=1316), the incidence of cryptococcal disease was decreased in those taking primary prophylaxis (RR 0.21, 95% CI 0.09, 0.46) compared to those taking placebo. However, there was no significant difference in overall mortality observed (RR 1.01, 95% CI 0.71, 1.44). When the three studies using itraconazole as the intervention were analyzed together (N=798), the incidence of cryptococcal disease was decreased in those taking itraconazole for primary prophylaxis (RR 0.12, 95% CI 0.03, 0.51) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 1.12, 95% CI 0.70, 1.80). When the two studies using fluconazole as the intervention were analyzed together (N=518), the incidence of cryptococcal disease was decreased in those taking fluconazole for primary prophylaxis (RR 0.25, 95% CI 0.07, 0.87) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 0.59, 95% CI 0.14, 2.62). AUTHORS' CONCLUSIONS: Antifungal primary prophylaxis with either itraconazole or fluconazole is effective in reducing the incidence of cryptococcal disease in adults with advanced HIV disease. However, neither of these interventions has a clear effect on overall mortality. Further research is needed to better understand these interventions and the populations in which they may be most effective.

Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women.

OBJECTIVE: To confirm the results of an earlier study showing premenopausal equol excretors to have hormone profiles associated with reduced breast cancer risk, and to investigate whether equol excretion status and plasma hormone concentrations can be influenced by consumption of probiotics. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: In all, 34 of the initially enrolled 37 subjects completed all requirements. INTERVENTION: All subjects were followed for two full menstrual cycles and the first seven days of a third cycle. During menstrual cycle 1, plasma concentrations of estradiol (E(2)), estrone (E(1)), estrone-sulfate (E(1)-S), testosterone (T), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured on cycle day 2, 3, or 4, and urinary equol measured on day 7 after a 4-day soy challenge. Subjects then received either probiotic capsules (containing Lactobacillus acidophilus and Bifidobacterium longum) or placebo capsules through day 7 of menstrual cycle 3, at which time both the plasma hormone concentrations and the post-soy challenge urinary equol measurements were repeated. RESULTS: During menstrual cycle 1, equol excretors and non-excretors were not significantly different with respect to subject characteristics, diet, or hormone concentrations. Significant inverse correlations were found between E(2) and body mass index (BMI) (P=0.02), SHBG and BMI (P=0.01), DHEA-S and dietary fiber (P=0.04), and A and protein:carbohydrate ratio (P=0.02). Probiotic consumption failed to significantly alter equol excretor status or hormone concentrations during menstrual cycle 3, although there were trends towards decreased concentrations of T (P=0.14) and SHBG (P=0.10) in the probiotic group. CONCLUSIONS: We were unable to verify a previously reported finding of premenopausal equol excretors having plasma hormone concentrations different from those of nonexcretors. Furthermore, a 2-month intervention with probiotic capsules did not significantly alter equol excretion or plasma hormone concentrations.

Clinical outcomes following interval laparoscopic transabdominal cervico-isthmic cerclage placement: case series.

The purpose of this report is to describe outcomes following laparoscopic transabdominal cervico-isthmic cerclage placement in cases of cervical incompetence not amenable to a conventional transvaginal procedure. We reviewed records of the first 11 patients at an academic teaching hospital who underwent laparoscopic transabdominal cerclage placement as an interval procedure, using a technique we previously first described. For all patients, the clinical course, including surgical complications and outcome of all subsequent pregnancies, is briefly described. One case was complicated by a small bowel injury secondary to concomitant extensive enterolysis. Otherwise there were no complications. Mean estimated blood loss was <40 ml. To date, 10 patients have conceived a total of 12 pregnancies following the procedure. Two pregnancies resulted in spontaneous losses at 8 weeks gestation, two in deliveries by Caesarean section at 34.5 weeks, and eight in deliveries by elective Caesarean section at 38 weeks or more. Each delivery resulted in the birth of a healthy infant. In conclusion, patients who require a transabdominal cerclage may undergo a laparoscopic interval procedure and achieve outcomes similar to those following placement via laparotomy during pregnancy.

Lack of effect of isoflavonic phytoestrogen intake on leptin concentrations in premenopausal and postmenopausal women.

OBJECTIVE: To assess the effect of soy isoflavone ingestion on plasma leptin concentrations in premenopausal and postmenopausal women. DESIGN: Randomized, crossover studies, with blinding of participants and laboratory personnel. SETTING: Procedures involving free-living individuals were carried out at the University of Minnesota General Clinical Research Center. PATIENT(S): Fourteen regularly cycling premenopausal women, and 18 postmenopausal women. INTERVENTION(S): Each premenopausal participant consumed, on a daily basis, each of three soy protein powders containing different levels of isoflavones for three menstrual cycles plus 9 days, with plasma samples collected every other day the last 6 weeks of each diet period. Similarly, each postmenopausal participant consumed each of the three powders for 93 days, with plasma samples collected daily on days 64 to 66 and 92 to 94 of each diet period. The powders, dosed on a per-kilogram body weight basis, provided mean isoflavone intakes of 8, 65, and 130 mg/day, for the control, low-isoflavone, and high-isoflavone diet periods, respectively. MAIN OUTCOME MEASURE(S): Plasma leptin concentrations. RESULT(S): Isoflavone intake had essentially no effect on leptin concentrations in either premenopausal or postmenopausal participants. Concentrations in the premenopausal women were higher during the periovulatory and midluteal phases as compared to the early follicular and midfollicular phases. CONCLUSION(S): Despite the well-documented effect of estrogens to enhance leptin production, even high levels of isoflavone consumption do not alter leptin concentrations in women. Further studies are needed to more precisely delineate the nature of estrogenic and/or antiestrogenic effects of isoflavones in humans.

Polycystic ovary syndrome and ovulation induction.

Before initiating treatment to induce ovulation in cases of PCOS, an appropriate evaluation of the patient and her partner, based on individual considerations, is important to optimize outcome. For obese patients with PCOS, weight-loss measures should be pursued before pharmacologic treatment is initiated. For most patients, the pharmacologic agent of choice to induce ovulation is clomiphene citrate, alone or in combination with a glucocorticoid. Treatment with metformin, alone or in combination with clomiphene citrate, may also be beneficial. For patients not responsive to clomiphene citrate, injectable gonadotropin treatment is usually warranted, although, depending on individual circumstances, laparoscopic ovarian drilling may be appropriate.

Initial IVF-ET experience with assisted hatching performed 3 days after retrieval followed by day 5 embryo transfer.

OBJECTIVE: To report our initial IVF-ET experience combining assisted hatching performed 3 days after oocyte retrieval with day 5 embryo transfer (ET). DESIGN: Retrospective review of 110 consecutive IVF cycles not involving donor oocytes, including 16 cycles that involved assisted hatching performed 3 days after oocyte retrieval in combination with day 5 ET. SETTING: Academic teaching hospital IVF center. PATIENT(S): Eighty-six consecutive IVF patients undergoing ET. INTERVENTION(S): Assisted hatching using acid Tyrode's solution performed 3 days after oocyte retrieval in selected cases in combination with day 3 or 5 ETs. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per ET. RESULT(S): Of the 16 women undergoing day 5 ET following day 3 assisted hatching, 14 had a clinical pregnancy. These included 11 ongoing/delivered singletons and 2 ongoing/delivered twin pregnancies, neither of which was monochorionic. These clinical and ongoing/delivered pregnancy rates compared very favorably with those of 54% and 46%, respectively, for the 35 patients undergoing day 5 ETs without assisted hatching, even though the latter group appeared to be better IVF candidates based on the prognostic factors commonly used to predict success. CONCLUSION(S): Our experience suggests that day 3 assisted hatching followed by day 5 ET may be a useful combination in selected patients. Although not seen in our small series, an increased risk of monochorionic pregnancies remains a theoretical concern when such a combination is used, since both assisted hatching and blastocyst transfers have been independently linked to an increased risk in some reports.

Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women.

Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life. In 2 randomized, cross-over studies, 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [control, 0.13; low isoflavone (low-iso), 1.00; and high-iso, 2.01 mg/kg body wt/day, averaging 8, 65, and 130 mg/day, respectively], for over 3 months each. Food records, blood samples, and 24-h urine collections were obtained throughout the studies. The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase, osteocalcin, insulin-like growth factor-I (IGFI), IGF binding protein-3 (IGFBP3), and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen. In premenopausal women, IGFI and IGFBP3 concentrations were increased by the low-iso diet, and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle. In postmenopausal women, bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets, and there were trends toward decreased osteocalcin, IGFI, and IGFBP3 concentrations with increasing isoflavone consumption. Although soy isoflavones do affect markers of bone turnover, the changes observed were of small magnitude and not likely to be clinically relevant. These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women.

Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer.

Increased urinary excretion of equol, a metabolite of the isoflavone daidzein, has been associated with a reduced risk of breast cancer. This risk reduction has generally been presumed to be a consequence of increased isoflavone consumption. However, only 30-40% of the population excretes more than trace amounts of equol, regardless of isoflavone intake. Accordingly, we hypothesized that the observed apparent protective effect of equol is at least in part attributable to hormonal differences between equol excretors and non-excretors, and that these differences are largely independent of isoflavone intake. We measured plasma hormone and sex hormone binding globulin (SHBG) concentrations in 14 normally cycling premenopausal women during each of three diet periods in which they consumed differing isoflavone doses (0.15, 1.0, and 2.0 mg/kg of body weight/day) as a component of soy protein isolate. The plasma hormone and SHBG concentrations of equol excretors (n = 5) were then compared with those of the non-excretors (n = 9). Results showed that even at the lowest dose, urinary equol excretion values for excretors far exceeded those for non-excretors consuming the highest dose. At all doses, equol excretors generally had lower concentrations of estrone, estrone-sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, and cortisol and higher concentrations of SHBG and midluteal progesterone, a hormonal pattern overall consistent with lowered breast cancer risk. In conclusion, the association of equol excretion and lowered breast cancer risk may largely reflect the tendency of equol excretors to have more favorable hormonal profiles, as opposed to merely reflecting increased isoflavone intake. Equol may be a marker for the presence of colonic bacterial enzymatic activity that increases fecal steroid excretion. Alternatively, equol itself, even with very modest isoflavone intake, may exert beneficial effects on the regulation of endogenous hormones.

Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women.

BACKGROUND: Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. OBJECTIVE: The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. DESIGN: Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. RESULTS: Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). CONCLUSIONS: Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.

Menstrual cycle effects on urinary estrogen metabolites.

Endogenous estrogen metabolism may play an important role in the pathogenesis of hormone-related cancers, most notably breast cancer. Despite the importance of estrogen metabolism, little is known about estrogen metabolite profiles during different phases of the menstrual cycle. This study was performed to evaluate the effects of the menstrual cycle on endogenous estrogen metabolism. Twenty-four-hour urine samples were collected daily during 4 precisely defined phases of the menstrual cycle (early follicular, midfollicular, periovulatory, and midluteal phases) from 6 healthy premenopausal women. Urine samples were analyzed for 15 endogenous estrogens and their metabolites by an ion exchange chromatography and the capillary gas chromatography-mass spectrometry method. The patterns of urinary estrogen metabolites (including potentially genotoxic 16alpha-hydroxyestrone, 4-hydroxyestradiol, and 4-hydroxyestrone) followed those of plasma estradiol and estrone, showing significant increases in the periovulatory and midluteal phases. Compared to the early and midfollicular phases, the ratios of 2-hydroxyestrogens/16alpha-hydroxyestrogens and 2-hydroxyestrogens/4-hydroxyestrogens were significantly increased during the periovulatory and midluteal phases (by 28% and 72%, respectively; P < 0.05), suggesting that estrogen metabolism is significantly affected by menstrual cycle phase. These data indicate that menstrual cycle phase must be considered in studies of estrogen metabolism in premenopausal women.

Modest hormonal effects of soy isoflavones in postmenopausal women.

Soy isoflavones have been hypothesized to exert hormonal effects in postmenopausal women. To test this hypothesis, we studied the effects of three soy powders containing different levels of isoflavones in 18 postmenopausal women. Isoflavones were consumed relative to bodyweight [control: 0.11 +/- 0.01; low isoflavone (low-iso): 1.00 +/- 0.01; high isoflavone (high-iso): 2.00 +/- 0.02 mg/kg/day] for 93 days each in a randomized crossover design. Blood was collected on day 1 of the study (baseline) and days 36-38, 64-66, and 92-94 of each diet period, for analysis of estrogens, androgens, gonadotropins, sex hormone binding globulin (SHBG), prolactin, insulin, cortisol, and thyroid hormones. Vaginal cytology specimens were obtained at baseline and at the end of each diet period, and endometrial biopsies were performed at baseline and at the end of the high-iso diet period, to provide additional measures of estrogen action. Overall, compared with the control diet, the effects of the low-iso and high-iso diets were modest in degree. The high-iso diet resulted in a small but significant decrease in estrone-sulfate (E1-S), a trend toward lower estradiol (E2) and estrone (E1), and a small but significant increase in SHBG. For the other hormones, the few significant changes noted were also small and probably not of physiological importance. There were no significant effects of the low-iso or high-iso diets on vaginal cytology or endometrial biopsy results. These data suggest that effects of isoflavones on plasma hormones per se are not significant mechanisms by which soy consumption may exert estrogen-like effects in postmenopausal women. These data also show that neither isoflavones nor soy exert clinically important estrogenic effects on vaginal epithelium or endometrium.

Soy isoflavones exert modest hormonal effects in premenopausal women.

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.