Biomedical subjects

John F Randolph

Publications and source records attributed to John F Randolph.

At least 19 recordsLinked to original sources

PubMed2006

Vacuolar hepatopathy in dogs: 336 cases (1993-2005).

OBJECTIVE: To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs. DESIGN: Retrospective case series. Animals-336 dogs with histologically confirmed moderate or severe VH. PROCEDURES: Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity. RESULTS: 12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.

Alkaline Phosphatase↗

PubMed2006

Low bone mineral density in the early menopausal transition: role for ovulatory function.

UNLABELLED: OBJECTIVE AND CONTEXT: The objective of the study was to determine whether luteal abnormalities or measures of sex steroid hormones collected across a menstrual cycle were associated with bone mineral density (BMD) at the total hip or lumbar spine. DESIGN AND SETTING: The Study of Women's Health Across the Nation is a longitudinal, community-based study conducted at seven clinical sites. Study of Women's Health Across the Nation includes a daily hormone study substudy in which daily urine samples are collected for one menstrual cycle (up to a maximum of 50 d) each year. PARTICIPANTS: Participants included 643 pre- and perimenopausal women, aged 43-53 yr. MAIN OUTCOME MEASURES: BMD of the lumbar spine and total hip was measured by dual-energy x-ray densitometry. Daily urine samples were assayed for estrone conjugates, pregnanediol glucuronide, LH, and FSH, and the information from across the menstrual cycle was expressed as area under the curve (AUC). BMD levels were evaluated in relation to three menstrual cycle attributes: 1) absence or presence of ovulation; 2) luteal phase length to menstrual cycle length ratio; and 3) ovulatory disturbances, defined as anovulatory cycles or cycles with short luteal phases (<10 d). RESULTS: Lower urine estrone conjugate AUC and higher urine FSH AUC were significantly associated with lower BMD. However, luteal abnormalities based on menstrual cycle attributes were not significantly associated with BMD at the total hip or lumbar spine after adjustment for age, body mass index, urinary hormone concentrations, menopausal status, and race/ethnicity. CONCLUSIONS: Direct measures of urinary hormones, not menstrual cycle luteal abnormalities, were associated with lower levels of BMD.

Adult↗

PubMed2006

Evaluation of four proposed bleeding criteria for the onset of late menopausal transition.

CONTEXT: The current criterion for onset of late menopausal transition is amenorrhea of 90 d or more. The Stages of Reproductive Aging Workshop proposed alternative criteria based on a shorter period of amenorrhea. Empirical data comparing proposed criteria are not available. OBJECTIVE: This paper evaluates the several bleeding criteria that served as the basis of these recommendations. The goal was to provide empirically based guidance regarding which bleeding criterion may be optimal for widespread application in clinical and research settings. DESIGN/SETTING: The study used prospective menstrual calendar data from four community and population-based cohort studies: TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation. PARTICIPANTS: The study included 735 TREMIN, 279 Seattle Midlife Women's Health Study, 216 Melbourne Women's Midlife Health Project, and 2270 Study of Women's Health Across the Nation women aged 35-57 yr at baseline who contributed 10 menstrual cycles or more. MAIN OUTCOME MEASURE(S): The main measures were the frequency of and median age at occurrence and time from occurrence to final menstrual period (FMP) for four criteria: skipped segment, 10-segment running range, 60- and 90-d amenorrhea. RESULTS: A skipped segment, 10-segment running range greater than 42 d and 60-d amenorrhea identify a similar time in women's reproductive lives. The latter two identify the exact same date in two thirds of women. All three criteria occur in a greater proportion of women than the 90-d criterion and are equally predictive of the FMP, although they occur 1-2 yr earlier. CONCLUSIONS: These findings support the recommendation of the Stages of Reproductive Aging Workshop that 60 d of amenorrhea be used to define onset of the late menopausal transition.

Adult↗

PubMed2006

The value of follicle-stimulating hormone concentration and clinical findings as markers of the late menopausal transition.

CONTEXT: The Stages of Reproductive Aging Workshop proposed bleeding and hormonal criteria for the menopausal transition, but operational definitions of hormone parameters were not specified. OBJECTIVE: This paper investigates the longitudinal relationship of annual serum FSH levels with four proposed bleeding criteria for the late menopausal transition in two cohort studies. The goal is to provide empirically based guidance regarding application of hormonal criteria that may be optimal for widespread application in clinical and research settings for assessing menopausal stage. DESIGN/SETTING: Prospective menstrual calendar and annual serum FSH data were collected from two population-based cohort studies: the Melbourne Women's Midlife Health Project and the Study of Women's Health Across the Nation. PARTICIPANTS: Participants in the study were 193 Melbourne Women's Midlife Health Project and 2223 Study of Women's Health Across the Nation women aged 42-57 yr at baseline who contributed 10 or more menstrual cycles and at least one annual serum FSH value. MAIN OUTCOME MEASURE(S): Association between bleeding criteria for the late menopausal transition and FSH was a main outcome measure. Associations of bleeding criteria, FSH, and hot flashes with the final menstrual period were also measured. RESULTS: A single FSH measure is an independent marker of the late menopausal transition, but FSH concentrations are less predictive of menopausal stage than any of four proposed bleeding criteria. Criterion FSH values for the late transition are similar across both studies. Experience of hot flashes adds no information in the presence of hormonal and bleeding criteria. CONCLUSIONS: An annual serum FSH concentration of 40 IU/liter could be incorporated, in conjunction with bleeding markers, into the Stages of Reproductive Aging Workshop paradigm for markers of the late menopausal transition.

Adult↗

PubMed2006

Endogenous estradiol and its association with estrogen receptor gene polymorphisms.

We evaluated potential associations between single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol (E2) concentrations in women of 4 races/ethnicities. The study population was drawn from participants in the Study of Women's Health Across the Nation (SWAN). A total of 1,538 African American, Caucasian, Chinese, and Japanese women from SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood for sex steroid hormone analyses and consenting to lymphocyte transformation from which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 ESR2 SNPs (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Mean E2 level was 196.0 +/- 4.0 pmol/L in women who were premenopausal and perimenopausal (with blood drawn on days 2 through 5 of the menstrual cycle follicular phase); however, mean E2 levels in Chinese and Japanese women were lower (155.7 +/- 10.6 pmol/L and 170.0 +/- 10.3 pmol/L, respectively) than in African American (196.4 +/- 8.1 pmol/L, P <0.05) or Caucasian women (210.7 +/- 5.9 pmol/L, P <0.002). The ESR1 rs3798577 CC genotype was associated with lower circulating E2 concentrations in African American women (P <0.07) and explained about 1% of the variation in circulating E2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was associated with significantly lower circulating E2 concentrations that explained about 4% of the variation. Circulating E2 concentrations were not strongly or consistently associated with selected polymorphisms for the estrogen receptor genes. The 2 strongest associations explained <4% of the total variation in the circulating E2 concentrations.

Adult↗

PubMed2006

Menstrual cycle markers of ovarian aging and sex steroid hormone genotypes.

We related variation in 4 sex steroid genes to 3 phenotypic indicators of ovarian aging, including no evidence of luteal activity as a marker of anovulatory cycles, shorter or longer menstrual cycle lengths, and the profiles of metabolites of estrogens, progesterone, follicle-stimulating hormone, and luteinizing hormone measured in urine samples collected daily across a menstrual cycle in women aged 43 to 53 years. The study sample included 485 menstruating women without hormone therapy who had collected daily urine hormone samples across 1 menstrual cycle or 50 days, whichever occurred first. There were 14 single nucleotide polymorphisms from 4 genes, including estrogen receptor-alpha (ESR1), estrogen receptor-beta, aromatase, and 17beta hydroxysteroid dehydrogenase type 1, related to ovarian aging phenotypes that include the presence or absence of luteal activity, menstrual cycle lengths < or > 24 to 31 days, and profiles of urinary hormone metabolites. Women with the TT genotype of ESR1 rs3798577 have evidence of advanced ovarian aging compared with women with the CT or CC genotypes, after adjustment for race/ethnicity, chronologic age, and race/ethnicity-specific body mass index. Further, women with the TC and CC genotypes of ESR1 rs2234693 may have a greater likelihood of more advanced ovarian aging than do women with the TT genotype, adjusting for covariates. Using a candidate gene approach, 2 ESR1 polymorphisms are related to 3 phenotypic markers of ovarian aging, suggesting a possible role for the ESR1 gene in the timing of the menopausal transition.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

The association of bone mineral density with estrogen receptor gene polymorphisms.

The purpose of this investigation was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4 races/ethnicities who were premenopausal or in early perimenopause. The sample consisted of 1,301 participants from the Study of Women's Health Across the Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the ESR1 gene (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 SNPs from the ESR2 gene (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Unadjusted mean LS-BMD values ranged from 1.141+/-0.14 g/cm(2) in African American women to 1.031+/-0.11 g/cm2 in Japanese women; unadjusted mean hip BMD values ranged from 1.053+/-0.14 g/cm2 in African American women to 0.862+/-0.10 g/cm2 in Chinese women. African American and Japanese women with the ESR1 rs2234693 (PvuII) CC genotype had higher LS-BMDs than did their peers with the TT genotype (P=0.009 and P=0.04, respectively). Japanese women with the ESR1 rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT genotype (P=0.02 and P=0.01, respectively). Caucasian women with the TC genotype for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype (P=0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2 rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent groups for each of these SNPs (CC and AA, respectively). Associations between BMD and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our results differ from those previously reported for 2 ESR1 genotypes (ESR1 rs2234693 [PvuII] and ESR1 rs9340799 [XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we studied have not previously been examined with respect to BMD. Among these, ESR2 rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine and hip in Chinese women and may warrant further study.

Adult↗

PubMed2006

Selected diet and lifestyle factors are associated with estrogen metabolites in a multiracial/ethnic population of women.

Diet and lifestyle factors, body size, and smoking behavior may influence estrogen metabolism, but the nature of these relations may vary according to race/ethnic groups. We evaluated the association of lifestyle factors with estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) in a racially diverse population. With a cross-sectional study design, urine samples from 1881 African-American, Caucasian, Chinese, Japanese, and Hispanic women, aged 42-52 y, from the Study of Women's Health Across the Nation (SWAN) were assayed by EIA for 2-OHE1 and 16alpha-OHE1. Dietary factors and beverages were measured using a modified Block FFQ. Dietary fiber, vegetable and fruit servings, Brassica vegetables, polyphenols, coffee, caffeine, green and black tea, and total alcohol and wine were related to metabolite values using multiple variable regression analyses. In adjusted analyses, 2-OHE1 concentrations were significantly associated with race/ethnicity, weight, smoking, and consumption of hydroxybenzoic acid, anthocyanidins, wine, and caffeine (P < 0.05). Regression models incorporating these variables explained 19-20% of the variation in 2-OHE1 concentrations. Regression models for 16alpha-OHE1, which explained 16-17% of the variability, included race/ethnicity, smoking, caffeine, total dietary fiber, and fiber from fruits and vegetables as variables. These associations may reflect why increased consumption of polyphenol-containing foods and fruit as well as decreased smoking, caffeine intake, and body size would be consistent with hypothesized benefits and risks for selected health outcomes.

Anticarcinogenic Agents↗

PubMed2005

The relationship of longitudinal change in reproductive hormones and vasomotor symptoms during the menopausal transition.

CONTEXT: The relationship of reproductive hormones to vasomotor symptoms (VMS) has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65-76% of women traversing the menopausal transition and are a primary reason for medical intervention during this life stage. OBJECTIVE: The purpose of this report was to relate longitudinal serum concentrations of the reproductive hormones estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), and SHBG and the free hormone indices free E2 index (FEI) and free T index (FTI) with the occurrence of VMS in women traversing the menopausal transition. DESIGN AND SETTING: The Study of Women's Health Across the Nation is a multisite, longitudinal, cohort study of the menopausal transition being conducted in community-based groups of women. PARTICIPANTS AND MAIN OUTCOME MEASURES: At baseline, 3302 menstruating women who belonged to one of five ethnic/racial groups were recruited and followed up with annual visits. Frequencies of symptoms (hot flashes, night sweats) for the prior 2 wk and measures of other covariates as well as potentially confounding variables were self-reported in the annual interview. Serum was obtained annually, on d 2-5 of a spontaneous cycle in cycling women or within 90 d of the anniversary of the baseline study visit in noncycling women and assayed for FSH, E2, T, SHBG, and DHEAS. FTI and FEI were calculated. This analysis incorporated available longitudinal data from 3293 women, excluding information collected at or after first report of hormone therapy use or hysterectomy. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. RESULTS: After adjusting for age, body mass index, and other related covariates, VMS prevalence increased with higher (log)FSH concentrations, and the increase was greater when blood was drawn more than 5 d after menses began. FSH concentrations were positively associated with the frequency of either hot flashes or night sweats, and higher FSH concentrations were associated with greater odds of reporting more frequent symptoms. Vasomotor symptom prevalence decreased with higher (log)E2, (sqrt)SHBG, and (log)FEI but only when these hormone values were modeled independently of (log)FSH values and the specimens were obtained outside the d 2-5 window. When modeled simultaneously with (log)FSH, (log)E2, (sqrt)SHBG, and (log)FEI were no longer significantly associated with symptom prevalence. (Cubic root)T and (sqrt)DHEAS concentrations and (log)FTI were not associated with the prevalence of VMS. CONCLUSIONS: Annual serum FSH concentrations, but not E2, T, DHEAS, FTI, or FEI when collectively modeled longitudinally, are associated with both the prevalence and frequency of VMS in women at midlife.

Adult↗

PubMed2005

Hemostatic factors and estrogen during the menopausal transition.

BACKGROUND: It has been speculated that gender differences in cardiovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. Therefore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. METHODS: Longitudinally, we studied 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%). Serum samples from baseline and years 2001, 2003, and 2005 were assayed for estradiol and FSH. Hormone concentrations were related to CVD markers, including fibrinogen, factor VII-c, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator, and human serum C-reactive protein (hsCRP). RESULTS: Lower estradiol levels were associated with higher levels of PAI-1 and tissue plasminogen activator, but there were no significant relationships with fibrinogen, factor VII-c, or hsCRP. Higher FSH concentrations were associated with higher PAI-1 and factor VII levels, but lower fibrinogen and hsCRP levels. Transitions from premenopause and early perimenopause to postmenopause were not associated with significant differences in levels of hemostatic factors. The hsCRP concentrations were approximately 25% higher, and the PAI-1 concentrations approximately 20% lower among women who initiated hormone therapy, compared with nonusers. SUMMARY: Endogenous estrogens may reduce CVD risk via modulation of fibrinolytic factors, but not coagulation or inflammatory markers. Notably, conclusions derived from studies of exogenous hormones and CVD risk may not parallel or explain the effects of endogenous hormones or perimenopausal hormone changes on CVD risk.

Adult↗

PubMed2005

Androgens are associated with hemostatic and inflammatory factors among women at the mid-life.

GOAL: The goal of this study was to relate annually measured endogenous androgens to hemostatic and inflammation markers in women longitudinally. METHODS: A total of 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandrosterone sulfate, and SHBG at four time points in 5 yr. Cardiovascular disease markers were fibrinogen, activated factor VII-c, C-reactive protein (hsC-RP), and the fibrolytic factors, plasminogen activator inhibitor type 1 (PAI-1), and tissue plasminogen activator [t(PA)]. RESULTS: T and free androgen index (FAI) were associated highly positively with PAI-1 and t(PA), and FAI was associated highly and positively with hsC-RP. Lower SHBG levels, associated with greater bioavailable T, were associated significantly with higher levels of PAI-1, t(PA), hsC-RP, and factor VII-c. SHBG was lower in Chinese and Japanese women markedly, resulting in FAI values that, on average, were higher among Chinese and Japanese women compared with African-American, Caucasian, and Hispanic women. IMPLICATIONS: There were strong, positive associations of androgens with fibrolytic and inflammation markers, even after considering age, body size, smoking, and race/ethnicity. It is important to study androgens, their precursors, and their carrier protein as part of the risk profile for heart disease in mid-aged women.

Androgens↗

PubMed2005

Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).

OBJECTIVE: To evaluate prognostic factors, survival, and treatment protocols for immune-mediated hemolytic anemia (IMHA) in dogs. DESIGN: Retrospective study. ANIMALS: 151 dogs with IMHA not associated with underlying infectious or neoplastic disease. PROCEDURE: lnformation recorded from review of medical records included signalment at the time of initial evaluation; vaccination history; 30-, 60-, and 365-day follow-up outcomes; laboratory data; results of imaging studies; and necropsy findings. Dogs were grouped according to the presence of spherocytes, autoagglutination, a regenerative erythrocyte response, and treatments received (azathioprine, azathioprine plus ultralow-dose aspirin, azathioprine plus mixed-molecular-weight heparin [mHEP], or azathioprine plus ultralow-dose aspirin plus mHEP) for comparisons. All dogs received glucocorticoids. RESULTS: Cocker Spaniels, Miniature Schnauzers, neutered dogs, and female dogs were overrepresented. Alterations in certain clinicopathologic variables were associated with increased mortality rate. Rates of survival following treatment with azathioprine, azathioprine plus ultralow-dose aspirin, azathioprine plus mHEP, and azathioprine plus ultralow-dose aspirin plus mHEP were 74%, 88%, 23%, and 70%, respectively, at hospital discharge; 57%, 82%, 17%, and 67%, respectively, at 30 days; and 45%, 69%, 17%, and 64%, respectively, at 1 year. In comparison, mean survival rates at discharge and at 30 days and 1 year after evaluation collated from 7 published reviews of canine IMHA were 57%, 58%, and 34%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with a combination of glucocorticoids, azathioprine, and ultralow-dose aspirin significantly improved short- and long-term survival in dogs with IMHA.

Anemia, Hemolytic, Autoimmune↗

PubMed2004

Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age.

Serum reproductive hormone concentrations were measured longitudinally in a community-based, multiethnic population of midlife women to assess whether ethnic differences exist in the patterns of change in estradiol (E2) and FSH and, if so, whether these differences are explained by host characteristics. We studied 3257 participants from seven clinical sites in the Study of Women's Health Across the Nation (SWAN) who were aged 42-52 yr at baseline and self-identified as African American (28.2%), Caucasian (47.1%), Chinese (7.7%), Hispanic (8.4%), or Japanese (8.6%). E2 and FSH were assayed in serum collected primarily in the early follicular phase of a spontaneous menstrual cycle in three consecutive annual visits. The primary explanatory variables included in repeated-measures regression analyses were race/ethnicity, menopausal status, age, body mass index (BMI), day of the cycle, smoking, parity, socioeconomic status, study site, and the self-report of diabetes at baseline. At the baseline visit, 46.2% of the women were classified as being early perimenopausal, with the remaining being premenopausal. By the second follow-up visit, 5.5% of the women in that cohort were postmenopausal, 66.8% were early perimenopausal, 8.3% were late perimenopausal, and 19.4% remained premenopausal. Serum E2 concentrations decreased significantly with age, with a steeper decline at higher ages. FSH concentrations increased significantly with age, with a steeper increase at higher ages. Similar patterns in the decline of E2 and the increase in FSH with age were found across ethnic groups, but the levels of these hormones differed by race/ethnicity. Specifically, over time, Chinese and Japanese women had lower E2 concentrations but similar FSH levels, compared with Caucasian women, and African American women had higher FSH concentrations but comparable E2 levels with those of Caucasian women. These ethnic differences in E2 and FSH were independent of menopausal status. The effect of BMI on serum E2 and FSH levels varied by menopausal status. Increasing BMI was associated with decreasing concentrations of E2 among premenopausal and early perimenopausal women but was associated with increasing concentrations of E2 among late perimenopausal and postmenopausal women. Increasing BMI was associated with decreasing concentrations of FSH, with the effect of BMI becoming larger as women transitioned through menopause. We conclude that serum E2 levels decrease and FSH concentrations increase with increasing age in midlife women, that ethnic differences in E2 over time differ from ethnic differences in FSH and suggest ethnic differences in the pituitary-ovarian relationship, and that the effect of BMI on E2 and FSH concentrations varies by menopausal status.

Adult↗

PubMed2003

Evaluation of urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in dogs.

OBJECTIVE: To evaluate 3 methods for measuring urine bile acids (UBA) and compare their diagnostic performance with that of the serum bile acids (SBA) test and other routine screening tests in dogs with hepatic disorders. DESIGN: Prospective study. ANIMALS: 15 healthy dogs, 102 dogs with hepatic disorders, and 9 dogs with clinical signs of hepatic disorders that were found to have nonhepatic disorders. PROCEDURES: Blood and urine samples were collected from sick dogs and healthy dogs for serum biochemical analyses, and determination of concentrations of SBA and UBA. Urine samples were obtained from 15 healthy dogs to establish an upper cutoff value for UBA concentrations. The UBA were measured by use of a quantitative-linked enzymatic colorimetric method. Three analytical modifications were evaluated; 1 quantified only urine sulfated bile acids (USBA), 1 only urine nonsulfated bile acids (UNSBA), and 1 quantified both (USBA plus UNSBA). The UBA values were standardized with the urine creatinine concentration. RESULTS: The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio tests had the best diagnostic performance of the UBA tests; each had a substantially higher specificity, slightly higher positive predictive value, slightly lower negative predictive value, and lower sensitivity than the SBA test. These UBA-to-creatinine values were positively correlated with SBA values. The USBA-to-creatinine ratio had poor sensitivity, indicating a low rate of bile acid sulfation in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The UBA can be measured in dogs with sufficient repeatability and accuracy for clinical application. The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio identified dogs with hepatic disorders nearly as well as the SBA test.

Animals↗

PubMed2003

Central abdominal fat and endogenous hormones during the menopausal transition.

OBJECTIVE: To investigate the effect of endogenous hormone levels on central abdominal fat during the menopausal transition in a population-based cohort of Australian-born women. DESIGN: Prospective observational study. SETTING: Population-based sample. Body composition was assessed in the Royal Melbourne Hospital, and interviews were conducted at the patient's home. SUBJECT(S): One hundred two women from the Melbourne Women's Midlife Health Project. Data, physical measures, and blood were obtained by interview when the longitudinal study commenced (baseline) and at the time of the total body scan approximately 5 years later. Body composition was measured using dual-energy X-ray absorptiometry. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Total body fat and central abdominal fat. RESULT(S): The 102 women were either premenopausal or in the early menopausal transition at baseline. At the time of their dual-energy X-ray absorptiometry scan, 31 were in the early menopausal transition, 22 were in the late menopausal transition, and 49 were postmenopausal. Multiple regression analysis found that total percentage of body fat was associated with weight measures, whereas central abdominal fat was also positively associated with baseline free T index (FTI) and with the increase in FTI since baseline. CONCLUSION(S): The major hormonal change associated with central adiposity during the menopausal transition is the increase in the FTI. This effect is significant even after allowing for baseline and final weight.

Abdomen↗

PubMed2003

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics.

OBJECTIVE: To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. DESIGN: Prospective observational study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. MAIN OUTCOME MEASURE(S): Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. RESULT(S): Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. CONCLUSION(S): These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.

Adult↗

PubMed2003

Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status.

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.

Adult↗

PubMed2002

Processed total motile sperm count correlates with pregnancy outcome after intrauterine insemination.

OBJECTIVES: To determine the impact of processed total motile sperm (PTMS) count on pregnancy after partner intrauterine insemination (IUI). IUI is generally attempted before proceeding to more expensive and invasive assisted-reproductive techniques such as intracytoplasmic sperm injection. Several semen parameters have been shown to correlate with IUI outcome and may be useful when counseling couples. METHODS: Four hundred thirty-eight couples with diverse causes of infertility underwent 1114 cycles of husband IUI during a 39-month period. The clinical and semen parameters were recorded for each couple and each insemination. The parameters were compared between those couples who achieved a pregnancy and those who did not. RESULTS: The total number of pregnancies was 120, resulting in a pregnancy rate per cycle of 10.8% and a couple pregnancy rate of 27.4%. On multivariable logistic regression analysis, the PTMS count was independently associated with fertility after IUI (P = 0.0014). Moreover, the pregnancy rate was significantly lower for couples with less than 10 million PTMS (P <0.05). CONCLUSIONS: The results of this study have demonstrated that the PTMS count independently predicts success with IUI. Cycles with less than 10 million total motile sperm are significantly less likely to result in a pregnancy. If cause-specific therapy has failed, alternatives to IUI should be considered for couples when the PTMS count is less than 10 million.

Adult↗