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The authors investigated the relations of demographic, anthropometric, and lifestyle factors with endometriosis in the Nurses' Health Study II prospective cohort. During 10 years of follow-up (1989-1999), 1,721 cases of laparoscopically confirmed endometriosis were reported among women with no past infertility. The incidence rate was greatest among women aged 25-29 years and lowest among women over 44 years (p(trend) < 0.0001). In multivariate Cox proportional hazards models, African-American women had a lower rate of disease compared with Caucasian women (rate ratio = 0.6, 95% confidence interval: 0.4, 0.9). The authors also observed an inverse relation with body mass index at age 18 years (for body mass index of >30 vs. 19-20.4 kg/m(2): rate ratio = 0.8, 95% confidence interval: 0.6, 1.1; p(trend) = 0.004) and with current alcohol intake (for >10 vs. 0 g/day: rate ratio = 0.7, 95% confidence interval: 0.6, 0.8; p(trend) < 0.0001) but no association with height, waist/hip ratio, or caffeine intake. An inverse relation with current body mass index and current cigarette smoking was observed only when cases were concurrently infertile. The authors conclude that age, race, body mass index, alcohol use, and cigarette smoking are associated with the incidence of endometriosis and that some of these relations may differ by infertility status at the time of laparoscopic diagnosis. [ABSTRACT FROM AUTHOR]

The historical meeting between originally American people, European colonizers, and slaved peoples from Africa in the biome Pampa in South Brazil and Uruguay involved a cultural syncretism and a great genetic diversity of landraces of cultivated species. Genetic richness evolved by selection and cultural processes in response to different environments, cultural backgrounds, and needs. This review summarized the knowledge on vegetable and maize landraces in South Brazilian and Uruguayan Pampa biome, to design a strategy towards the rediscovery, conservation, and sustainable use. Landraces diversity maintained in situ and ex situ is described, specific case studies are presented, and the main problems and tools towards landraces re-valorization are discussed. We show that traditional family farming systems maintain diverse vegetable species, mainly squashes ( Cucurbita spp.), sweet potato ( Ipomoea batatas ), beans ( Phaseolus spp.), onion ( Allium cepa ), peppers ( Capsicum spp.), tomato ( Solanum lycopersicum ), next to leafy vegetables and maize, among others. We propose the priority of systematic surveys as a basis for monitoring genetic erosion, increasing complementariness between in situ and ex situ conservation, and implementing sustainable conservation and utilization. The case studies highlight genetic diversity within each cultivated species, with different crop physiological responses; disease resistances, different quality traits and associated uses, from animal feeding in maize to a range of culinary uses linked to traditional culture in maize and vegetable species, and ornamental uses of specific Capsicum and Cucurbita . Some landraces were the basis for breeding, where improved cultivars allowed the competitiveness of landrace germplasm in the markets. Renewed industrialized products allowed the competitive and sustainable use of Capsicum landraces in Brazilian farmers communities. Strategies towards in situ conservation improvements and valorization are discussed; emphasizing the role played by agroecology, community seed banks and custodian farmers, participatory plant breeding, promotion of landraces specialties among consumers, and the need of research and capacity building, among others. Farmers' participation in the decisions is a key factor, along with the academia and the public sector. Landraces and associated knowledge are treasures to be used to benefit from farmers to consumers, directing the course of agriculture towards sustainable directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivas, Vidal, Neitzke, Priori, Almeida, Antunes, Galván and Barbieri.)

Background: Lifetime ovulatory years (LOY) is estimated by the difference between ages at menopause and menarche subtracting time for events interrupting ovulation. We tested whether LOY influences sex hormone levels in postmenopausal women with at least one intact ovary not using hormones., Methods: Estradiol, estrone, estrone sulfate, total testosterone, dehydroepiandrostendione sulfate, prolactin, and sex hormone binding globulin were measured in 1,976 postmenopausal women from the Nurses' Health Study. Associations of age, body mass index (BMI), smoking, alcohol use, and other factors on hormones were assessed by t tests and ANOVA. Linear regression was used to assess multivariable adjusted associations between LOY and hormones and trends in hormone levels per 5-year increases in LOY were estimated., Results: Women averaged 61.4 years old, 11.0 years since menopause, with BMI of 25.8 kg/m2. A total of 13.6% had irregular cycles, 17.5% hysterectomy, 6.4% unilateral oophorectomy, and 13.8% were current smokers. Variables associated with one or more hormone levels were included as covariates. Each 5-year increase in LOY was significantly associated with a 5.2% increase in testosterone in women with BMI < 25 kg/m2 and a 7.4% increase in testosterone and 7.3% increase in estradiol in women with above-average BMI., Conclusions: This is the first study to show that greater LOY is associated with higher testosterone in postmenopausal women and higher estradiol in those with elevated BMI, suggesting accumulation of functioning stromal and thecal cells from repeated ovulations and peripheral conversion of testosterone., Impact: A possible explanation for why greater LOY increases risk for breast, endometrial, and ovarian cancer is offered., (©2023 American Association for Cancer Research.)

Objective: Understand the meanings people attribute to the use of plants in self-care practices during situations of ailment., Method: Qualitative, exploratory-descriptive research with ethnographic orientation, based on health anthropology with informants selected from a relations network. The sampling was done by semi-structured interviews and participant observations, from April 2015 to February 2017., Results: Seventeen informants participated. The thematic axis emerged in the content analysis: meanings attributed by the informants to the use of medicinal plants. Feelings of love and happiness were unveiled, meanings of helping others, cure practices, family care through plants, comfort, the sense of welfare, among others., Conclusion: The importance of the nursing professional in establishing a therapeutic alliance with the subjects and social groups, aiming at the promotion of health and care completeness.

Capsicum baccatum is one of the main pepper species grown and consumed in South America. In Brazil, it is commonly cultivated by family farmers, using mostly the genotypes bishop's hat genotypes (locally cambuci) and red chili pepper (dedo-de-moça). This study had the objective of characterizing 116 C. baccatum accessions from different regions of Brazil, based on morphological fruit descriptors and AFLP (Amplified Fragment Length Polymorphisms) markers. Broad phenotypic variability among the C. baccatum accessions was detected when using morphological fruit descriptors. The Ward modified location model (Ward-MLM) discriminated five groups, based mainly on fruit shape. Six combinations of AFLP primers detected polymorphism in 97.93% of the 2466 identified bands, indicating the high genetic variability in the accessions. The UPGMA coincided with the Bayesian clustering analysis and three large groups were formed, separating the wild variety C. baccatum var. praetermissum from the other accessions. There was no relation between genetic distance and geographical origin of the accessions, probably due to the intense exchange of fruits and seeds between farmers. Morphological descriptors used together with AFLP markers proved efficient in detecting the levels of genetic variability among the accessions maintained in the germplasm collections. These results can be used as an additional source of helpful information to be exploited in C. baccatum breeding programs.

Background: Extramedullary hematopoiesis depends on complex pathophysiological mechanisms linked to hematopoietic stem cells and the proteins considered mediators of the inflammation. The identification of hematopoietic cells outside bone marrow in the adult is an occurrence that can occasionally follows the inflammatory response, was considered a secondary occurrence, but current biomolecular studies have changed that concept., Aim: Describe the presence of clusters of precursor cells of platelets (megakaryocytes), and cells of the inflammatory response in the abdominal wall and spleen of rats with experimentally induced incisional hernias and repaired with different synthetic prostheses., Methods: Twenty-five rats with incisional hernias previously performed, were divided into groups of five animals each: Group 1, repair of the hernia defect without prosthetic implant; Group 2, repair with polypropylene prosthesis; Group 3, repair using polypropylene with low weight; Group 4, the use of polypropylene and polyglecaprone prosthesis; Group 5, of polypropylene and polyglactin prosthesis. All prostheses were cut in rhombus format with area 2,625 cm². The animals were reoperated after 10 days, the abdominal walls were removed with the viscera attached to them and the material was processed for histological study., Results: Megakaryocyte niches in the abdominal wall and spleen, occasionally removed together with the adhesions produced in animals with implantation of prostheses and significant inflammatory reaction., Conclusion: The intense inflammatory reaction due to the prostheses with polypropylene in their composition was disproportionate to the expected response, indicating that further studies should be accomplished including immunophenotyping evaluation and specific panels of monoclonal antibodies to better understand the findings.

Study Question: Is there a temporal relationship between endometriosis and infertility?, Summary Answer: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years., What Is Known Already: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown., Study Design, Size, Duration: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort., Participants/materials, Setting, Methods: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis., Main Results and the Role of Chance: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years., Limitations, Reasons for Caution: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates., Wider Implications of the Findings: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses., Study Funding/competing Interests: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To compare renal dysfunction after right nephrectomy and ligation of the right renal vein with preservation of kidney., Methods: Animals' weight, pH, density, protein in urine and histological samples of the kidneys were evaluated. Fifteen female rats (Wistar) were divided into three groups. In the control group, right renal vein dissections were performed. In the second group, the right nephrectomy was performed. In the third group, the right renal vein was ligated and the kidney was preserved. Urine samples were taken before, three and seven days after the procedure. On the seventh postoperative day the kidneys were removed to histopathological study. Analysis by Student's t test was performed., Results: weight loss, alterations of urine pH (p<0.05), in specific gravity, proteinuria (p<0.05) were found in groups 2 and 3; hemorrhagic infarction and edema were found after ligation of the right renal vein; changes in the left kidney were also observed on the seventh day.

Background: Adhesions induced by biomaterials experimentally implanted in the abdominal cavity are basically studied by primary repair of different abdominal wall defects or by the correction of incisional hernias previously performed with no precise definition of the most appropriate model., Aim: To describe the adhesions which occur after the development of incisional hernias, before the prosthesis implantation, in an experimental model to study the changes induced by different meshes., Methods: Incisional hernias were performed in 10 rats with hernia orifices of standardized dimensions, obtained by the median incision of the abdominal wall and eversion of the defect edges. Ten days after the procedure adhesions of abdominal structures were found when hernias were repaired with different meshes., Results: The results showed hernia sac well defined in all rats ten days after the initial procedure. Adhesions of the greater omentum occurred in five animals of which two also showed adhesions of small bowel loops besides the omentum, and another two showed liver adhesions as well as the greater omentum, numbers with statistical significance by Student's t test (p<0.05)., Conclusion: Although it reproduces the real clinical situation, the choice of experimental model of incisional hernia repair previously induced implies important adhesions, with possible repercussions in the evaluation of the second operation, when different implants of synthetic materials are used.

Objective: To evaluate the use of fertility treatments among a large cohort of women in the United States., Design: Cohort study., Setting: Nurses' Health Study II., Patient(s): Ten thousand thirty-six women who reported having used fertility treatment on biennial questionnaires from 1993-2009., Intervention(s): None., Main Outcome Measure(s): Data on patterns of treatment modality were collected via self-report from validated mailed questionnaires. Information on clomiphene, gonadotropin injections alone, and gonadotropin injections as part of intrauterine insemination (IUI) and in vitro fertilization (IVF) was queried., Result(s): Most women who reported fertility treatment used clomiphene (94%), with a large majority reporting clomiphene as their only form of treatment (73%). Of women who reported treatment more advanced than clomiphene, 13% had used gonadotropin injections alone, 11% IUI treatment, and 11% IVF. Several subgroups were more likely to use multiple treatment modalities and to initiate treatment with gonadotropins rather than clomiphene, including women living in states with insurance coverage of fertility procedures, with higher household income, younger in age, who remained nulliparous at the study close, and treated after 2000., Conclusion(s): Results should be interpreted cautiously, but to our knowledge, this represents the first study of fertility treatment patterns in the United States and could inform public health planning., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Prior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women., Methods: We evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses., Results: In analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9), Ptrend = 0.02). Luteal estrone, free estradiol and progesterone were not associated with risk. Androgens were suggestively or significantly associated with risk when the sample was restricted to invasive tumors (for example, testosterone: OR: 1.4 (1.0 to 2.0), Ptrend = 0.23) and ER+/PR+ disease (testosterone: OR: 1.7 (1.1 to 2.6) Ptrend = 0.10; dehydroepiandrosterone sulfate (DHEAS) OR: 1.3 (0.8 to 2.0) Ptrend = 0.05). SHBG was not associated with breast cancer risk. The results varied by menopausal status at diagnosis, with follicular estradiol suggestively positively associated with breast cancers in women premenopausal at diagnosis (OR: 1.1 (0.9 to 1.3) and significantly inversely associated with postmenopausal disease (OR: 0.6 (0.4 to 0.9); Pheterogeneity < 0.01)., Conclusions: Androgens were associated with modestly increased risk of breast cancer in this population, with stronger associations for invasive and ER+/PR+ disease. Luteal phase estradiol levels were suggestively associated with ER+/PR+ tumors but no other strong associations were observed with estrogens. Associations with follicular phase estrogens may vary by menopausal status at diagnosis, but case numbers were limited. Additional studies to confirm the role of premenopausal hormones in the etiology of both premenopausal and postmenopausal breast cancer are needed.

Ovarian testosterone increases the response of antral follicles to stimulation, declines with age, and has effects mediated or potentiated by insulin-like growth hormone I (IGF-I). Increased circulating insulin and IGF-I, exogenous testosterone, and increased local ovarian testosterone concentrations due to aromatase inhibition or exogenous luteinizing hormone/human chorionic gonadotropin are all associated with an increased ovarian response to gonadotropins. These factors should be further investigated alone or in combination for enhancing oocyte yield with fertility treatments, particularly in older reproductive-age women., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk., (©2011 AACR.)

The aim of this study was to investigate the process of knowledge transmission related to medicinal plants among family generations in the context of ecological farmers in Southern Rio Grande do Sul. This qualitative study was conducted with eight farming families, comprising 19 respondents living in the municipalities of Pelotas, Morro Redondo, Canguçu and Arroio do Padre. The interviews took place from January to May 2009. Data analysis was performed using the hermeneutic-dialectic method. The family was referred to as the main source in the transmission of knowledge about medicinal plants. Most subjects reported first completing treatment with medicinal plants, to then seek formal health service. The construction of knowledge related to medicinal plants by the families is predominantly oral, and takes place by the daily contact between its members and is shared with other members of the community to which they belong.

Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies., Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires., Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62-0.99; P-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17-1.88; Pt = 0.001)., Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply.

Objective: To examine in detail the geographic distribution of reproductive endocrinology and infertility (REI) fellowships in the United States., Design: Ecological., Setting: University-based REI fellowship program., Patient(s): None., Intervention(s): None., Main Outcome Measure(s): Number and location of REI fellowship positions., Result(s): A significant association was found between the number of REI fellowship positions and the number of categorical postgraduate year-1 (PGY-1) obstetrics and gynecology (OBGYN) residency positions within states. No association was observed among the land area, population, or population density within states. However, despite the fact that in the East, as in the United States overall, there was no association between population density and number of fellowships, West of the Mississippi River, as the population density increased, the number of REI fellowships increased linearly (test for heterogeneity = 0.007)., Conclusion(s): First-year REI fellowship positions in the United States are correlated with the number of categorical PGY-1 OBGYN residency positions within a state. The geographically uneven distribution of fellowship positions may limit the choices for OBGYN residents wishing to pursue further training in REI.

Context: Female reproduction spans a developmental life arc from fetal life and childhood, through puberty to the reproductive years, and, finally, ovarian follicle depletion and the onset of menopause., Objective: This invited review highlights a selection of reports from leading journals over the past 2 yr that have significantly advanced our understanding of female reproduction from conception to menopause., Synthesis: During fetal life, in utero exposures may be important determinants of later pubertal and adult endocrine physiology. Epigenetic mechanisms are likely involved in the fetal programming of adult endocrine function. With regards to the polycystic ovary syndrome, recent clinical trials have confirmed the central role of clomiphene for ovulation induction in women with this disease. In addition, an expert panel has recommended that all women with polycystic ovary syndrome have a glucose tolerance test because of the high prevalence of impaired glucose tolerance in this population. In menopausal women the precise impact of estrogen therapy on cardiovascular biology remains to be delineated fully. Evolving data indicate that when initiated near the onset of menopause, estrogen therapy has fewer cardiovascular risks than when it is administered decades after the menopause., Conclusions: The essence of reproduction is the successful transmission of germ-line DNA to a succeeding generation. Advances in genetics and endocrinology are converging to advance significantly our understanding of the biology of reproduction and our ability to influence reproductive processes. These advances will translate into new treatments for the prevalent medical problems of reproduction.

An association between physical activity and premenopausal breast cancer risk may be due, in part, to relationships with sex hormones or growth factors. Therefore, we assessed whether MET-h/week of total physical activity (moderate-to-vigorous intensity), walking, or vigorous physical activity, and h/week of standing or sitting were associated with plasma concentrations of several hormones. We examined levels of estrogens, androgens, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and growth hormone (GH) in 565 premenopausal women, ages 33-52 years, from the Nurses' Health Study II (NHSII). About 87% of women had both timed follicular and luteal samples; other women had one untimed sample. In general we observed few associations between sex hormone or IGF levels and measures of physical activity or inactivity. However, free testosterone was modestly inversely associated with total physical activity (p-trend = 0.02). Luteal estradiol, free estradiol, and estrone also were inversely associated with total physical activity (p-trend = 0.10, 0.04, 0.01, respectively); however, the trend was substantially attenuated when excluding women with anovulatory cycles or irregular cycles. These cross-sectional results suggest that physical activity and inactivity have limited associations with premenopausal sex hormone and growth factor levels, except possibly luteal estrogens.

The association of birthweight and body size throughout life with premenopausal breast cancer risk may be due, in part, to relationships with sex hormones. Therefore, we assessed whether birthweight, body shape at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, adult waist circumference and waist-to-hip ratio (WHR), and attained height were associated with the plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone-binding globulin (SHBG) in 592 premenopausal women, ages 33 to 52 years old, from the Nurses' Health Study II. About 85% of women provided blood samples during follicular and luteal menstrual phases; other women had a single untimed sample. We observed few associations between sex hormone levels and birthweight or body shape in childhood. However, adult BMI was inversely associated with SHBG (P trend < 0.001) and positively associated with free testosterone (P trend < 0.001) concentrations. Adult BMI was not associated with follicular or luteal free estradiol levels (P trend >or= 0.15) because it was inversely associated with total estradiol levels (P trend < 0.001 for follicular and luteal estradiol levels). Testosterone, androstenedione, and progesterone were inversely associated with BMI. Comparing women with a BMI of >or=30 versus <20 kg/m2, levels were higher by 53% for free testosterone and lower by 51% for SHBG, 39% for follicular estradiol, 20% for luteal estradiol, 14% for androstenedione, 13% for testosterone, and 20% for progesterone. We observed no clear associations between BMI at age 18, waist circumference, WHR, or height, and sex hormone concentrations. Our results suggest that effects on premenopausal sex hormone levels may be one mechanism through which adult adiposity, but not birthweight or childhood body size, affects premenopausal breast cancer risk.

Background: Higher levels of endogenous sex steroid hormones are associated with increased risks of breast cancer in postmenopausal women. Data for premenopausal women are sparse, in part because of the complexity of measuring hormone levels that vary cyclically. We prospectively evaluated associations between plasma sex hormone levels and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II., Methods: From 1996 to 1999, blood samples were collected from 18,521 premenopausal women during the early follicular and midluteal phases of their menstrual cycles. A total of 197 cases of breast cancer were diagnosed among these women after blood collection and before June 1, 2003; these case subjects were matched to 394 control subjects. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided., Results: Women in the highest (versus the lowest) quartiles of follicular total and free estradiol levels had statistically significantly increased risks of breast cancer (RR = 2.1 [95% CI = 1.1 to 4.1], P(trend) = .08, and RR = 2.4 [95% CI = 1.3 to 4.5], P(trend) = .01, respectively); the associations were stronger for invasive breast cancer and for estrogen and progesterone receptor-positive (ER+/PR+) tumors. Luteal estradiol levels were not associated with breast cancer risk. Higher levels of total and free testosterone and androstenedione in both menstrual cycle phases were associated with modest, non-statistically significant increases in overall risk of breast cancer and with stronger, statistically significant increases in risks of invasive and ER+/PR+ cancers (e.g., RR of invasive cancers for the top [versus bottom] quartile of luteal total testosterone levels = 2.0 [95% CI = 1.1 to 3.6], P(trend) = .05, and RR of ER+/PR+ cancers = 2.9 [95% CI = 1.4 to 6.0], P(trend) = .02). Levels of estrone, estrone sulfate, progesterone, and sex hormone-binding globulin were not associated with breast cancer risk. The absolute number of cases observed over 3 years were 30 among women in the lowest 25% of follicular total estradiol levels and 50 among women in the highest 25%., Conclusions: Levels of circulating estrogens and androgens may be important in the etiology of premenopausal breast cancer.

Concentrations of adrenal androgens are positively associated with postmenopausal breast cancer risk; however, results in premenopausal women are conflicting. Therefore, we conducted a prospective nested case-control study within the Nurses' Health Study II cohort to examine the relationship of DHEA and DHEA sulfate (DHEAS) with breast cancer risk in predominantly premenopausal women. Blood samples were collected from 1996 to 1999. The analysis included 317 cases of breast cancer diagnosed after blood collection and before June 1, 2003; for each case, two controls were matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. No associations were observed between DHEA or DHEAS levels and breast cancer risk overall [in situ and invasive; DHEA relative risk (RR), top versus bottom quartile, 1.2; 95% confidence interval (95% CI), 0.8-1.8, P(trend) = 0.53; DHEAS RR, 1.3; 95% CI, 0.9-2.0; P(trend) = 0.07]. However, both DHEA and DHEAS were positively associated with estrogen receptor-positive/progesterone receptor-positive breast cancer (DHEA RR, 1.6; 95% CI, 0.9-2.8, P(trend) = 0.09; DHEAS RR, 1.9; 95% CI, 1.1-3.3, P(trend) = 0.02). We observed a significant interaction by age, with an RR for DHEAS of 0.8 (95% CI, 0.4-1.5, P(trend) = 0.62) for women <45 years old and 2.0 (95% CI, 1.2-3.5, P(trend) = 0.003) for women >/=45 years old; results were similar for DHEA. Our results suggest that adrenal androgens are positively associated with breast cancer among predominately premenopausal women, especially for estrogen receptor-positive/progesterone receptor-positive tumors and among women over age 45 years.

Few studies have evaluated whether a single blood hormone measurement, as is available in most epidemiologic studies, sufficiently characterizes a premenopausal woman's long-term hormone levels; there is particular concern whether sex steroid hormones, which fluctuate during the menstrual cycle, are reliable. We conducted a prospective study within the Nurses' Health Study II to examine the reproducibility of plasma estrogens, androgens, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). One blood sample per year over 3 years was collected from 113 premenopausal women during both the follicular and luteal phases of the menstrual cycle. We calculated intraclass correlation coefficients (ICC) across the three samples for all women. Among estrogens, ICCs ranged from 0.38 (estradiol) to 0.60 (estrone sulfate) in the follicular phase and from 0.44 (estrone) to 0.69 (estrone sulfate) in the luteal phase. Among androgens, ICCs ranged from 0.58 (androstenedione) to 0.94 [dehydroepiandrostenedione sulfate (DHEAS)] in the follicular phase and from 0.56 (testosterone) to 0.81 (DHEAS) in the luteal phase. When values were averaged across the follicular and luteal phases, the ICC for prolactin was 0.64 whereas ICCs for IGF-I and IGFBP-3 were 0.86 and 0.82, respectively. The ICC for progesterone in the luteal phase was only 0.29. These data suggest that for androgens, estrone sulfate, prolactin, IGF-I, and IGFBP-3, a single measurement can reliably categorize average levels over at least a 3-year period in premenopausal women. For estrone and estradiol, where ICCs were relatively low, it is important to use reproducibility data such as those to correct for measurement error in epidemiologic studies.

Objective: To investigate a previously hypothesized relation between natural hair color and endometriosis., Design: Prospective cohort study., Setting: Nurses' Health Study II with 10 years of follow-up., Participant(s): A total of 90,065 women, 25-42 years old, who had never been diagnosed with endometriosis, infertility, or cancer at baseline in 1989., Main Outcome Measure(s): Incidence of laparoscopically confirmed endometriosis according to natural hair color., Result(s): During 379,422 person-years of follow-up, 1,130 cases of laparoscopically confirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at age 18, we observed no association overall. However, compared with women with any other hair color, we observed an increased rate of endometriosis among women with naturally red hair who had never been infertile (incidence rate = 1.3, 95% confidence interval [CI] = 1.0-1.7), but a decreased rate among women with naturally red hair among women who were infertile (incidence rate = 0.4, 95% CI = 0.2-1.2); P value, test for heterogeneity = .03., Conclusion(s): Overall, we did not observe a significant relation between red hair color and the rate of endometriosis, however this prospective cohort study suggests that the relation may differ by infertility status.

The effect of dehydroepiandrosterone (DHEA) on pancreatic islet function of aged rats, an animal model with impaired glucose-induced insulin secretion, was investigated. The following parameters were examined: morphological analysis of endocrine pancreata by immunohistochemistry; protein levels of insulin receptor, IRS-1, IRS-2, PI 3-kinase, Akt-1, and Akt-2; and static insulin secretion in isolated pancreatic islets. Pancreatic islets from DHEA-treated rats showed an increased beta-cell mass accompanied by increased Akt-1 protein level but reduced IR, IRS-1, and IRS-2 protein levels and enhanced glucose-stimulated insulin secretion. The present results suggest that DHEA may be a promising drug to prevent diabetes during aging.

Differences in breast cancer incidence across racial groups are well documented. African Americans have the highest rates of premenopausal breast cancer and Asians have lower breast cancer rates across all age groups. We hypothesized that levels of premenopausal endogenous hormones and growth factors, risk factors that have been predictive of breast cancer, would differ by race. Using a cross-sectional study design, we tested this hypothesis in the Nurses' Health Study II. We assayed estradiol, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-I (IGF-I), and IGFBP-3 in 111 African American and 111 Asian American women, matched to 111 Caucasian women on age, day of luteal phase, and day, time, and fasting status at blood collection. We analyzed the association between race and hormone levels using robust linear regression methods. In multivariate models, compared with Caucasians, African Americans had 18% higher levels of estradiol (P < 0.01), 17% higher free estradiol (P < 0.01), 11% lower SHBG (P = 0.05), 11% higher IGF-I (P < 0.01), 25% higher free IGF-I (P < 0.01), and 9% lower IGFBP-3 (P < 0.01) levels. In multivariate models, compared with Caucasian women, Asian Americans had 22% higher calculated free estradiol (P < 0.01), 31% lower SHBG (P < 0.01), and 25% higher free IGF-I (P < 0.01) levels. No racial differences were found in progesterone and prolactin levels. Our study showed hormone differences consistent with breast cancer risk between Caucasians and African Americans but inconsistent with breast cancer risk between Asian Americans and Caucasians. Further research is needed to explore differences across racial groups and the link between endogenous hormones and breast cancer risk.

Assisted reproductive technology (ART) is catalyzing a renaissance in reproductive endocrinology and infertility (REI), manifested by the rapid growth of new technologies, such as intracytoplasmic sperm injection, oocyte cryopreservation, preimplantation genetic manipulation of embryos, and embryonic stem cell biology. Because of advances in ART, REI will be a vibrant and growing discipline, both in academic and independent practice settings, for many decades.

Background: Sex hormone concentrations are associated with breast cancer risk among women not using postmenopausal hormones (PMH); however, whether a relationship exists among PMH users is unknown. Therefore, we conducted a prospective, nested case-control study within the Nurses' Health Study (NHS) cohort to examine the association between plasma sex hormone concentrations and postmenopausal breast cancer among women using PMH at blood collection., Methods: Blood samples were collected from 1989 to 1990. During follow-up through May 31, 2000, 446 women developed breast cancer and were matched by age, date and time of day of blood collection, and fasting status to 459 control subjects (PMH users) who did not develop cancer. We used conditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). We compared hormone concentrations of the 459 control subjects with those of 363 postmenopausal NHS participants not taking PMH. All statistical tests were two-sided., Results: PMH users had statistically significantly higher estradiol, free estradiol, sex hormone-binding globulin, and testosterone, and lower free testosterone concentrations than non-PMH users. Among PMH users, we found modest associations with breast cancer risk when comparing the highest versus lowest quartiles of free estradiol (RR = 1.7, 95% CI = 1.1 to 2.7; P(trend) = .06), free testosterone (RR = 1.6, 95% CI = 1.1 to 2.4; P(trend) = .03), and sex hormone-binding globulin (RR = 0.7, 95% CI = 0.5 to 1.1; P(trend) = .04), but not of estradiol or of testosterone. However, estradiol and free estradiol were statistically significantly positively associated with breast cancer risk among women older than 60 years (RR = 2.8, 95% CI = 1.5 to 5.0; P(trend) = .002 and 2.6, 95% CI = 1.4 to 4.7; P(trend) = .001, respectively) and among women with a body mass index of less than 25 kg/m2 (RR = 1.8, 95% CI = 1.1 to 3.1, P(trend) = .01 and 2.4, 95% CI = 1.4 to 4.0, P(trend) = .003, respectively)., Conclusion: Although women using PMH have a different hormonal profile than those not using PMH, plasma sex hormone concentrations appear to be associated with breast cancer risk among PMH users.

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Objective: [1] To examine the effects of body mass index (BMI), age, cigarette smoking, cause of infertility, and use of oral contraceptives on baseline serum testosterone (T), and [2] to examine associations between baseline serum T and IVF outcomes such as pre-hCG serum E(2), number of oocytes retrieved, oocyte fertilization rate, and pregnancy outcome in regularly cycling women., Design: Prospective, cohort study., Setting: Three IVF programs in eastern Massachusetts., Patient(s): Four hundred twenty-five regularly cycling women planning to undergo IVF. Women with polycystic ovary syndrome, ovulatory infertility, or irregular cycles were excluded from this study., Intervention(s): Collection of epidemiological data and baseline serum in women undergoing IVF., Main Outcome Measure(s): Baseline serum total T, sex hormone binding globulin (SHBG), and calculation of free androgen index., Result(s): Body mass index >26 kg/m(2) was associated with a significant increase in serum T (P<.01) and free androgen index (P<.0001). Serum T decreased significantly throughout the fourth decade of life (P<.03). A history of cigarette smoking >10 pack years was associated with increased serum T (P<.01). A diagnosis of endometriosis was associated with decreased serum T. Serum T correlated positively with pre-hCG serum E(2) and number of oocytes retrieved. However, serum T did not significantly influence fertilization or pregnancy rates., Conclusion(s): In cycling infertile women, increasing BMI and cigarette smoking are associated with increased serum T. Advancing age and endometriosis are associated with decreased serum T.

Background: Levels of endogenous hormones have been associated with the risk of breast cancer among postmenopausal women. Little research, however, has investigated the association between hormone levels and tumor receptor status or invasive versus in situ tumor status. Nor has the relation between breast cancer risk and postmenopausal progesterone levels been investigated. We prospectively investigated these relations in a case-control study nested within the Nurses' Health Study., Methods: Blood samples were prospectively collected during 1989 and 1990. Among eligible postmenopausal women, 322 cases of breast cancer (264 invasive, 41 in situ, 153 estrogen receptor [ER]-positive and progesterone receptor [PR]-positive [ER+/PR+], and 39 ER-negative and PR-negative [ER-/PR-] disease) were reported through June 30, 1998. For each case subject, two control subjects (n = 643) were matched on age and blood collection (by month and time of day). Endogenous hormone levels were measured in blood plasma. We used conditional and unconditional logistic regression analyses to assess associations and to control for established breast cancer risk factors., Results: We observed a statistically significant direct association between breast cancer risk and the level of both estrogens and androgens, but we did not find any (by year) statistically significant associations between this risk and the level of progesterone or sex hormone binding globulin. When we restricted the analysis to case subjects with ER+/PR+ tumors and compared the highest with the lowest fourths of plasma hormone concentration, we observed an increased risk of breast cancer associated with estradiol (relative risk [RR] = 3.3, 95% confidence interval [CI] = 2.0 to 5.4), testosterone (RR = 2.0, 95% CI = 1.2 to 3.4), androstenedione (RR = 2.5, 95% CI = 1.4 to 4.3), and dehydroepiandrosterone sulfate (RR = 2.3, 95% CI = 1.3 to 4.1). In addition, all hormones tended to be associated most strongly with in situ disease., Conclusion: Circulating levels of sex steroid hormones may be most strongly associated with risk of ER+/PR+ breast tumors.

Objective: To investigate the relation between the fetal environment and endometriosis., Design: Prospective cohort study., Setting: Nurses' Health Study II with 10 years of follow-up., Participant(s): Eighty-four thousand, four hundred forty-six women aged 25-42 who had never been diagnosed with endometriosis, infertility, or cancer at baseline in 1989., Main Outcome Measure(s): Incidence of laparoscopically confirmed endometriosis according to birthweight, prematurity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed., Result(s): During 566,250 woman-years of follow-up, 1,226 cases of laparoscopically-confirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at age 18, we observed a linear increase in the incidence rate with decreasing birthweight (rate ratio [RR] = 1.3 for birthweight <5.5 pounds versus 7.0-8.4 pounds, 95% confidence interval [CI] = 1.0-1.8, P value, test for trend = .01). In addition, women who were born as one of a multiple gestation (i.e., twins or greater number) were at increased risk even after controlling for birthweight (RR = 1.7, CI = 1.2-2.5). The rate of endometriosis was also 80% greater among women exposed to diethylstilbestrol in utero (RR = 1.8, CI = 1.2-2.8). Neither premature delivery nor having been breastfed were associated with the incidence of endometriosis. None of these effect estimates were modified by infertility status at the time of endometriosis diagnosis., Conclusion(s): The fetal environment is associated with subsequent laparoscopically confirmed endometriosis in this cohort of US women.

Objectives: Plasma DHEA and its sulfate (DHEA-S) are positively associated with breast cancer risk in postmenopausal women; but the relationships have not been studied in detail in premenopausal women. We prospectively evaluated relationships between plasma levels of DHEA and DHEA-S in blood samples provided by a group of primarily premenopausal women and subsequent breast cancer, by use of case-control sampling from the Nurses' Health Study cohort., Method: Blood samples were collected from 1989 to 1990. Among women who were not postmenopausal at blood collection, 302 were diagnosed with breast cancer between blood collection and June 1998. Two controls were selected per case and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at blood collection. Statistical analyses using conditional logistic regression were done to adjust for potential confounders., Results: At time of blood collection, the median age was 49 (10th to 90th percentiles 45 to 53). In multivariable analyses, the highest quartile of DHEA was associated with an odds ratio of breast cancer of 0.92 (95% confidence interval, 0.59-1.43) relative to the lowest quartile (P value for log-linear trend 0.11). A similar analysis revealed an odds ratio of 1.08 (0.69-1.69) for DHEA-S (P value for log-linear trend 0.83). No statistically significant interactions were noted according to certainty of menopausal status, age, or past oral contraceptive use., Discussion: Our analysis did not reveal a relationship between DHEA or DHEA-S and subsequent breast cancer in middle-aged premenopausal women. In the future, this relationship should be studied in younger women.

Purpose: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned., Methods: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001., Results: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model., Conclusion: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Objective: To evaluate the relation between tubal ligation, change in menstrual cycle characteristics, and early follicular phase hormones., Design: Cross-sectional analysis of women 36-44 years of age., Setting: The greater Boston area., Patient(s): Nine hundred seventy-six premenopausal women with intact uteri., Intervention(s): A comparison of women with and without a history of tubal ligation., Main Outcome Measure(s): Menstrual and reproductive histories were self-reported. Early follicular phase blood samples were obtained to assess FSH, LH, and E(2). We compared menstrual cycle changes from the first 5 years after menarche with completion of the baseline questionnaire in women with and without a prior history of tubal ligation., Result(s): Cycle length, cycle regularity, menses length, flow volume, dysmenorrhea, and hormone levels were similar in women with and without a history of tubal ligation. However, among parous women with a history of cesarean section, those with a tubal ligation >5 years ago experienced a marginal increase in volume of menstrual flow compared with women with no tubal ligation history., Conclusion(s): We found no significant change in menstrual cycle characteristics or hormone levels in women with or without a history of tubal ligation. However, tubal ligation may have a modest effect on the change in menstrual flow volume over time among parous women with a history of cesarean section.

Background: FSH and estradiol measured during the menstrual (basal) phase of cycles predict the success of infertility treatment; but the role of these hormones as markers for ovarian reserve in normal populations needs further study., Methods and Results: From a cohort study of depressed and non-depressed women, a subset of 406 non-depressed women between the ages of 36 and 45 years with spontaneous periods were selected and their concentrations and determinants of basal hormones measured at study entry, 6 and 12 months later were described. FSH and LH increased significantly over the 12 months of observation (P

Objective: To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG)., Design: Cross-sectional study., Setting: Academic medical center., Patient(s): Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones., Intervention(s): A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine., Main Outcome Measure(s): FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle., Result(s): Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase., Conclusion(s): Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

Objective: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles., Design: Prospective observational study., Setting: IVF clinic., Patient(s): One hundred sixteen ovulatory subjects undergoing IVF., Intervention(s): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle., Main Outcome Measure(s): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups., Result(s): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups., Conclusion(s): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.

A variant of the beta-subunit of luteinizing hormone (v-LH) is more common among populations also at higher risk for breast and ovarian cancer. To explore the possible relationship between these cancers and v-LH, we examined its frequency in premenopausal women, including 100 with a family history of ovarian cancer, 94 with carcinoma- in-situ of the breast, and 153 age and residence-matched controls. Reproductive histories were assessed and v-LH status measured by immunological assays from plasma drawn during the early follicular phase of cycles. For the entire study population, 283 (81.5%) were wild type; 61 (17.6%) were heterozygous; and three (0.9%) were homozygous for v-LH. Carrier frequency was not elevated among women with a family history of ovarian cancer or personal history of carcinoma-in-situ of the breast compared with controls. Women with the v-LH variant were less likely to report menstrual weight gain or ovarian cysts, more likely to report infertility, and have higher early follicular phase LH concentrations compared with women who were wild type. While there is no evidence from this study that v-LH increases risk for ovarian or breast cancer, we conclude that possession of v-LH may impact on some aspects of reproductive history and LH concentrations.

Purpose: Basal follicle-stimulating hormone (FSH) and age are predictors of successful outcome in in vitro fertilization (IVF). More recently, the clomiphene citrate challenge test (CCCT) has been proposed as a better way to predict IVF outcome than FSH alone. The purpose of this study was to determine which indicator of ovarian reserve--basal (day 3) FSH or the CCCT--is the better predictor of IVF success in the critical age group of women over the age of 40., Methods: In this retrospective study, basal FSH and clomiphene-stimulated FSH levels from 104 women who underwent 175 cycles of IVF were analyzed., Results: Neither basal FSH level nor stimulated FSH level alone were statistically significant predictors of IVF success; however, no patient with a day 3 FSH level > 11.1 mIU/ml or a stimulated day 10 FSH level > 13.5 mIU/ml conceived and carried a pregnancy. All ongoing pregnancies occurred in the first two cycles of IVF., Conclusions: Clear prognostic cutoff values were found to predict IVF success in women over age 40. IVF programs should consider limiting the number of cycles of IVF in women above age 40.

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Although endogenous sex steroid hormones in premenopausal women may be associated with the risk of breast cancer and other illnesses, direct evidence to support this hypothesis is limited in large part by methodological issues in the conduct of relevant studies. One major unresolved issue is whether a single blood sample (such as is available in most epidemiological studies), collected in a specific phase of the menstrual cycle, reflects long-term levels in that phase. To address this issue, two sets of blood and urine samples were obtained from 87 premenopausal women over a 1-year period in both the follicular and luteal phases. Plasma estradiol, estrone, and estrone sulfate were measured in the blood samples obtained in both phases, whereas progesterone and urinary 2- and 16a-hydroxyestrone were measured in luteal-phase samples only. For all of the women combined, intraclass correlation coefficients (ICCs) ranged, with one exception, from 0.52 to 0.71 for the plasma estrogens and the urinary estrogen metabolites. The sole exception was for estradiol in the luteal phase (ICC = 0.19); inclusion of only women who were ovulatory in both cycles and who collected each sample 4-10 days before their next period resulted in a substantially higher ICC for estradiol in the luteal phase (ICC = 0.62; 95% confidence interval, 0.43-0.78). These data indicate that, for several plasma and urinary sex hormones, a single follicular- or luteal-phase measurement in premenopausal women is reasonably representative of hormone levels in that phase for at least a 1-year period.