Serum Estrone Sulfate Research Articles

Adipose Tissue Sex Steroids in Postmenopausal Women with and without Menopausal Hormone Therapy.

The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized. We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women. Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction. HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users. Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.

Adipose tissue estrogen production and metabolism in premenopausal women

ObjectiveAlthough the ovaries produce the majority of estrogens in women before menopause, estrogen is also synthesized in peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated in subcutaneous and femoro-gluteal regions, is estrogen-mediated, but the significance of estrogen synthesis in AT of premenopausal women is poorly understood. Design and MethodsSerum and subcutaneous and visceral AT homogenates from 28 premenopausal women undergoing non-malignant surgery were analyzed for estrone, estradiol, and serum estrone sulfate (E1S) concentrations with liquid chromatography-tandem mass spectrometry. Isotopic precursors were used to measure enzyme activities of estrone-producing steroid sulfatase and estradiol-producing 17β-hydroxysteroid dehydrogenases (17β-HSD). Messenger RNA (mRNA) expression levels of genes for estrogen-metabolizing enzymes were analyzed using real-time reverse transcription quantitative polymerase chain reaction. ResultsWhile estradiol was the predominant circulating active estrogen, estrone dominated in AT, with a higher concentration in visceral than subcutaneous AT (median, 2657 vs 1459 pmol/kg; P = 0.002). Both AT depots converted circulating E1S to estrone, and estrone to estradiol. Median levels of estrone were five to ten times higher in subcutaneous and visceral AT than in serum (P < 0.001) and the estradiol level in visceral AT was 1.3 times higher than in serum (P < 0.005). The local estrone concentration in visceral AT correlated positively with mRNA expression of estrone-producing enzyme aromatase (r = 0.65, P = 0.003). Waist circumference correlated positively with increased estradiol production in subcutaneous AT (r = 0.60, P = 0.039). ConclusionsPremenopausal AT demonstrated high estrogenic enzyme activity and considerable local estrogen concentrations. This may be a factor promoting female-typical AT distribution in premenopausal women.

Serum progesterone and oestrone sulphate concetrations for monitoring fertility in Sows

Blood samples were taken from 161 sows the days 19-21 (serum progesterone assessments), from 306 sows on days 24-30 (serum oestrone sulphate assessments) and from 150 sows on day 20 (serum progesterone assessments) and on days 26-29 (serum oestrone sulphate assessments) after service. Actual farrowing or abortion and signs of return to oestrus were used as criteria for pregnancy and non-pregnancy, respectively. Litter size was also recorded at each farrowing. The results showed that the overall accuracy of progesterone and oestrone sulphate for predicting pregnant sows was 90.7% and 97.2%, respectively. The highest accuracy of oestrone sulphate (100%) was noticed on days 27 and 28 after service. The overrall accuracy of the combination of both progesterone and oestrone sulphate assessments to detect pregnant sows was 97% and to detect non-pregnant sows was 100%. Significant correlation coefficients between serum oestrone sulphate concentration and litter size were found on days 24,26,27, 28,29 and 30, but the highest correlation coefficient was noticed on day 28 after service (r=0.51, Ρ, 0.001). Moreover, it was also found that mean litter size was significantly higher (P &lt;0.05). in sows with serum oestrone sulphate concentrations &gt; 1 ng/ml compared with concentrations &lt; 1 ng/ml from day 26 up to day 30 after service. It is concluded that serum progesterone assessment helps in the determination of the non-pregnant sows early enough for problems related to failure of fertilization to be promptly dealt with. Serum oestrone sulphate concentration on day 28 after service can be used as an indicator of conception, as a predictor of small litter size and also can help in the estimation of embryonic mortality. The combination of these two assessments, in addition to their value in pregnancy diagnosis, can be useful in identifying concurrent reproductive problems in units with sub-optimal productivity.

Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women.

In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

Serum estrone concentration, estrone sulfate/estrone ratio and BMI are associated with human epidermal growth factor receptor 2 and progesterone receptor status in postmenopausal primary breast cancer patients suffering invasive ductal carcinoma.

BackgroundWe investigated in postmenopausal women with primary breast cancer prior to surgical intervention whether, serum levels of different steroid hormones and hormonal precursors associated with tumor tissue estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status.MethodsWe enrolled 1,042 patients suffering invasive ductal carcinoma undergoing surgical resection in the National Institute of Oncology, Hungary between 2003 and 2011. Serum parameters were measured by RIA/IRMA assays; tumor tissue ER, PR and HER2 status was assessed histologically. Patients were classified according to tumor receptor status. Case–case analysis subjects were categorized into four subgroups based on serum hormone concentrations in ER, PR and HER2 receptor-negative cases, respectively.ResultsSerum estrone sulfate and dehydroepiandrosterone sulfate levels correlated with each other and also with serum estrone and estradiol levels. According to case–case study the odds ratios in the highest quartile were 1.517 (p = 0.0305, Ptrend = 0.0394) for androstenedione, 1.495 (p = 0.0317, Ptrend < 0.0105) for estrone and 0.654 (p = 0.0273, Ptrend < 0.0151) for estrone sulfate/estrone ratio in PR+ vs. PR− tumors. Regarding HER2 status (HER2+ vs. HER2−), the odds ratios for estrone, estrone sulfate and estrone sulfate/estrone ratio were 0.530 (p = 0.0234, Ptrend = 0.0595), 2.438 (p = 0.0042, Ptrend < 0.0066) and 3.118 (p = 0.0001, Ptrend < 0.0001) in the highest quartile, respectively. Of note significantly increased BMI associates with PR+ and ER +/PR+ status while significantly decreased BMI was observed in HER2+ cases.ConclusionsTaken together, measurement of serum estrone and estrone sulfate concentrations prior to surgical intervention might support the individualization of regime in postmenopausal primary breast cancer patients.

What is the best test for cryptorchidism?

Cryptorchidism is a common heritable condition in horses and ponies and while retained testicles rarely release viable sperm, Leydig cells produce testosterone leading to undesirable stallion-like behaviour. Endocrine assays are frequently required to definitively diagnose retained testicular tissue. A literature search of the Medline database was performed using the PubMed search engine. The search term ‘equine cryptorchidism’ was entered and the results filtered using the contents of the abstracts to retain articles relating specifically to diagnostic testing for cryptorchidism. The initial search yielded 139 articles which after filtering were reduced to 6 articles included for analysis. Retrospective analysis of clinical cases comprising level IV evidence was used to evaluate the use of serum oestrone sulphate and serum testosterone (alone and after human chorionic gonadotropin (hCG) administration) for the detection of cryptorchidism (Cox et al. 1986). Leung et al. (2011) also analysed a large number of normal horses but few cryptorchid animals (n = 25, only 18 confirmed) were diagnosed using urine steroid profiling. The remaining prospective experimental studies evaluated the use of serum testosterone following administration of hCG (Silberzahn et al. 1989), serum anti-Müllerian hormone (AMH) (Claes et al. 2013), serum androstenedione (Illera et al. 2003) and faecal oestrogens (Palme et al. 1994) to distinguish between gelded, entire and cryptorchid horses. This data was then variably extrapolated to provide inferred relevance for the use of each test for the detection of suspected cryptorchid animals. Of the 4 prospective experimental studies those by Silberzahn et al. (1989) and Palme et al. (1994) lack sufficient numbers or appropriate methodology to provide quality evidence. Illera et al. (2003) evaluated the use of serum androstenedione but inconsistency in their results significantly weakens the evidence provided by this paper. The most recent experimental study by Claes et al. (2013) provides the strongest evidence for the use of serum AMH. The quality of the evidence provided by the retrospective studies (Cox et al. 1986; Leung et al. 2011) is weak as the cryptorchid status of all the animals in the study, particularly those testing negative, was not confirmed. Testosterone may be measured directly but serum levels vary greatly between individuals and fluctuate with age and season (Cox et al. 1986; Claes et al. 2013) making it unsuitable as a definitive test. Measurement of testosterone pre and 30 min post administration of hCG was reported to be more reliable with an accurate diagnosis achieved in 95% of cases (Cox et al. 1986). However, other studies have questioned the reliability of this elevation in testosterone so soon after hCG administration (Silberzahn et al. 1989; Illera et al. 2003) and accuracy may be improved by testosterone measurement up to 72 h post hCG (Silberzahn et al. 1989). This claim has not been validated and such a time delay is less suitable for use in clinical practice. Measurement of serum oestrone sulphate in horses and ponies (not donkeys) >3-years-old was 96% accurate in weak early retrospective studies (Cox et al. 1986). However, evaluation of serum oestrone sulphate in a more clearly defined population yielded reduced positive predictive values (PPV) and negative predictive values (NPV) of 85% and 91% respectively for this test (Illera et al. 2003). Illera et al. (2003) reported serum androstenedione to have increased accuracy (92%) compared with both oestrone sulphate (86%) and testosterone pre and post hCG stimulation (88%) for the detection of cryptorchids. However, this finding is weakened by anomalies in the results of the study and, on the basis of this, evidence serum androstenedione cannot be recommended. Anti-Müllerian hormone (AMH) is produced in elevated amounts from Sertoli cells in cryptorchid testes (Ball et al. 2008) making it a potentially reliable and specific test for the presence of testicular tissue. Claes et al. (2013) evaluated the serum AMH concentrations in stallions, geldings and cryptorchids. Serum AMH concentrations were significantly higher in cryptorchid stallions (32.7 ± 5.3 ng/ml) compared with intact stallions (14.7 ± 2.4 ng/ml); geldings were below or fractionally above the lower limit of detection for the test. Only animals of >2 years of age were included in the study and AMH levels require investigation in cryptorchid pubertal animals. The calculated biological half-life was 1.5 days (Claes et al. 2013) making AMH a useful test if there is doubt over the success of a recent castration procedure. The evidence for many of the available endocrine assays is based on poor quality retrospective or experimental studies. Currently, the strongest evidence exists for the use of AMH for the detection of cryptorchidism, although the test warrants validation in a large number of confirmed cryptorchid animals and in animals <2 years of age. No conflicts of interests have been declared.

Use of a deslorelin implant for influencing sex hormones and male behaviour in a stallion — Case report

This case report describes the use of a subcutaneously applied 4.7-mg deslorelin acetate implant in a three-year-old Arabian crossbred stallion showing unwanted strong male behaviour. Following deslorelin acetate implantation the stallion showed a short transitional increase in male behaviour. A 'gelding-like' behaviour was noted 15 days (D15) after treatment. The horse was surgically castrated at the owners request at D52 after treatment. Serum testosterone, oestradiol-17β and oestrone sulphate values decreased after deslorelin acetate implantation, but serum LH and FSH levels remained unchanged. Histopathological analysis of both testes and sperm analysis revealed a reduced spermatogenesis at D52. The testicular volume decreased after treatment. The use of a subcutaneously applied deslorelin acetate implant might be a promising tool to change the behaviour of aggressive stallions.

Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes

Estrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. We measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. The increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. Our results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.

Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: A pilot study

Vaginal promestriene was tested in gynecological cancer patients who suffered from severe vaginal dryness and dyspareunia. This form of estrogen has a low level of vaginal absorption and proved to be effective for vaginal atrophy. Method17 patients were treated with a 10mg soft vaginal suppository daily for one month. Plasma levels of estrone sulfate (E1S), used as the marker of overall estrogenicity, were measured by liquid chromatography in combination with mass spectrometry. ResultsMean E1S levels changed from 533 (22–2920) to 374 (81–856) pg/ml (p=0.39). ConclusionIn highly symptomatic gynecological cancer patients the level of circulating estrone sulfate was not significantly affected by vaginal promestriene treatment overall, but a wide range of levels was noted pre and post treatment in individual patients.

Changes in Breast Density and Circulating Estrogens in Postmenopausal Women Receiving Adjuvant Anastrozole

Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes.

Moderate Alcohol Consumption and 24-Hour Urinary Levels of Melatonin in Postmenopausal Women

Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

A randomized trial exploring the biomarker effects of neoadjuvant sequential treatment with exemestane and anastrozole in post-menopausal women with hormone receptor-positive breast cancer

Several adjuvant endocrine strategies exist for postmenopausal women with breast cancer. This study compared the effect of two sequences of aromatase inhibitor use [steroidal (exemestane) and non-steroidal (anastrozole)] on serological and pathological biomarkers when given in the neoadjuvant setting to postmenopausal women with breast cancer. Thirty women were assigned to receive exemestane 25 mg or anastrozole 1 mg each given for 8 weeks in a randomized sequence. The effect of this treatment on serum estrone sulfate and estradiol levels, as well as tumor changes in the proliferation biomarker Ki67 were evaluated at baseline, 8 weeks and 16 weeks. WHO clinical response criteria, patient preference, and quality of life were also assessed. Assessable data was available from 28 patients. There were no differences in concentration changes of serum estradiol or Ki67 between patients in the two arms. Overall clinical response rate was 68% (19/28 assessable patients) and clinical benefit was 93% (26/28 assessable patients). There was no significant difference in toxicity or quality of life scores. The majority of patients expressed a personal preference for anastrozole over exemestane. Results suggest that the order of steroidal and non-steroidal aromatase inhibitors has little effect on outcome. The majority of patients express clear preferences for drug treatments.

Laparoscopic‐assisted castration of a monorchid male pseudohermaphrodite pony

SummaryA pseudohermaphrodite possesses gonads of one sex, but with external genitalia of the opposite sex. Although cases of male pseudohermaphroditism have been published, there is no report of a monorchid male pseudohermaphrodite. This Case Report documents a 12‐year‐old monorchid male pseudohermaphrodite displaying stallion‐like behaviour, with an elevated serum oestrone sulphate concentration confirming the presence of functional testicular tissue. A complete resolution of all behavioural signs occurred after laparoscopic‐assisted castration under general anaesthesia, along with a drop in serum oestrone sulphate concentrations to &lt;0.01 ng/ml and no response in serum testosterone concentration following administration of hCG.

Increases in Serum Estrone Sulfate Level Are Associated with Increased Mammographic Density during Menopausal Hormone Therapy

Menopausal hormone therapy increases mammographic density. We determined whether increases in serum estrone sulfate (E(1)S) levels during menopausal hormone therapy predict increased mammographic density. We measured percent mammographic density and serum E(1)S levels in 428 participants of the Postmenopausal Estrogen/Progestin Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum E(1)S levels were determined by RIA. Information about covariates was determined by annual questionnaire. Using linear regression, we determined the association between change in E(1)S level from baseline to 12 months and change in percent mammographic density (by semiquantitative interactive threshold method). After controlling for baseline mammographic density, age, body mass index, alcohol intake, parity, smoking, ethnicity, physical activity, and age at first pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in E(1)S level (P < 0.0001). The association between change in E(1)S level and change in mammographic density differed by treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment group, change in the ratio of E(1)S to E(1) was also positively associated with change in mammographic density. Increases in serum E(1)S levels during menopausal hormone therapy are associated with increases in mammographic density. The relative contribution of E(1)S and E(1) to stimulation of breast tissue awaits further elucidation.

Steroid sulfatase in breast carcinoma and change of serum estrogens levels after operation

Fifty-four breast carcinomas were studied for the expression of steroid sulfatase (STS) by immunohistochemistry. Correlations between the expression of STS and clinical parameters were determined. Concentrations of serum estrone (E1), estrone sulfate (E1S), estradiol (E2) and estradiol sulfate (E2S) in 12 postmenopausal patients with STS positive tumor were measured by radioimmunoassay. Positive expression of STS was obtained in 72% of tumors. The incidence of STS positive tumor was significantly more frequent in postmenopausal patients (p = 0.01). In our postmenopausal patients, serum E1, E1S, E2, E2S and E2S levels in STS high score group were decreased postoperatively, and those in both STS high and low score group were stabilized after operation. Results from this study suggest STS in breast carcinoma may play an important enzyme of the intratumoral estrogen synthesis in postmenopausal women, and it would be interesting that locally produced STS might be closely related to the control of estrogens environment in breast carcinoma.

Differences in Serum Sex Hormone and Plasma Lipid Levels in Caucasian and African-American Premenopausal Women

Risk of coronary heart disease is higher in African-American than in Caucasian women. The aim of this study was to evaluate the contribution of sex hormone levels, race, and measures of body fat to the variation in plasma lipid levels, a well-established risk factor for coronary heart disease. This was a cross-sectional study. The study was conducted in the general community. Sixty Caucasian and 117 African-American premenopausal women participated. Body weight, body mass index (BMI), and waist to hip circumference ratio (WHR), as well as plasma lipid and serum sex hormone levels, were assessed. Relative to Caucasian women, African-American women had significantly higher mean BMI (23.92 +/- 3.87 vs. 26.99 +/- 5.87 kg/m2, respectively; P < 0.001), and WHR (0.733 +/- 0.052 vs. 0.757 +/- 0.068; P < 0.03). Also, plasma triglyceride (TG) levels were significantly lower in African-American women (81 +/- 61 vs. 55 +/- 24 mg/dl; P < 0.0001). Serum estrone sulfate (556 +/- 323 vs. 442 +/- 332 pg/ml, Caucasian vs. African-American; P < 0.001), estradiol (E2) (55.1 +/- 43.6 vs. 35.8 +/- 17.7 pg/ml; P < 0.0001), androstenedione (2.6 +/- 0.9 vs. 1.6 +/- 0.7 ng/ml; P < 0.0001), and testosterone (0.36 +/- 0.12 vs. 0.31 +/- 0.19 ng/ml; P < 0.002) levels were significantly lower in African-American women than in Caucasian women. After correction for the effects of age, BMI, and WHR, serum E2 levels were significantly and positively associated with plasma high-density lipoprotein cholesterol levels in all women, and serum estrone sulfate levels with plasma total cholesterol and TG levels in African-American women. Our results indicate that race is an important determinant of plasma TG and serum sex hormone levels, even after adjustment for differences in body size. A significant association between endogenous E2 and high-density lipoprotein cholesterol levels exists in premenopausal women, independent of their race.

Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women

Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer. We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women. There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (> or = 3.00 microg/g creatinine) than in those with low urinary cadmium (< 2.00 microg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results. Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.

Pregnancy status determination in mares using a rapid lateral flow test for measuring serum oestrone sulphate

AIMS: To develop a means of determining pregnancy status in horses based on measuring serum oestrone sulphate (OS) concentrations using a rapid lateral flow immunoassay, and to determine the assay's effectiveness using a visual end-point. METHODS: Serum samples from mares >100 days post-mating (n=701) were assayed using a nitrocellulose membrane-based lateral flow immunoassay device. The device was developed using membrane-bound 1,3,5 (10)-estratrien-3-ol-17-one conjugated to bovine serum albumin as the capture antigen, and an OS-detection monoclonal antibody coupled to colloidal gold as the visible detection reagent. Concentrations of the coating antigen and OS monoclonal antibody were optimised so that the working range would allow pregnancy status to be determined from a visual end-point. The test was run by adding 0.1 ml serum to the sample well of a plastic cassette encasing the test membrane. As the serum migrated along the membrane, a test dot and control line were generated on it within 5–10 min. The intensity of the test dot was inversely proportional to the concentration of OS in the serum sample being tested. Results were compared with those from a validated OS enzyme immunoassay (EIA) and subsequent foaling or return to oestrus of the mares. RESULTS: Serum samples with OS concentrations <10 ng/ml, indicative of non-pregnancy in mares >100 days post-mating, generated a test end-point consisting of a highly visible test dot and control line, whereas serum OS concentrations >50 ng/ml, indicative of pregnancy, generated a control line only. The test correctly identified 384/389 (98.7%) non-pregnant mares tested, and 303/312 (97.1%) pregnant mares tested that were >100 days post-mating. The lateral flow test devices were stable for at least 12 months when stored at 4°C, sealed in aluminium pouches with desiccant. CONCLUSION: This novel, rapid, easy-to-use, lateral flow immunoassay offers a practical alternative to traditional laboratory-based immunoassays for measuring serum OS concentra- tions in mares for determining their pregnancy status.

Endometrial thickness and uterine diameter not affected by ultralow doses of 17β-estradiol in elderly women

Objective: Our purpose was to monitor changes in endometrial thickness and uterine diameter during treatment with ultralow doses of estradiol, which might improve the serum lipid profile in elderly women. Study Design: Ultrasonographic changes were monitored in 60 women with an intact uterus in a group of 70 healthy women who were previously evaluated for changes in serum lipid levels. Subjects were 60 years and older and were randomly assigned to receive parenteral 17β-estradiol (7.5 μg/24 h), delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malmö, Sweden), or no treatment for 12 months. Results: Estring treatment yielded minor increases in serum estrone sulfate and 17β-estradiol levels within the normal postmenopausal range. The maximal endometrial thickness was 2.8 mm at baseline and 2.6 mm at 12 months. No significant changes within or between the study groups were found in endometrial thickness or uterine diameter. There were no significant interactions between age and baseline serum estrone sulfate or 17β-estradiol levels. Conclusions: Ultralow doses of 17β-estradiol, which might improve serum lipid levels, did not significantly change endometrial thickness or uterine diameter. This might indicate that there is a “therapeutic window” for systemic effects of ultralow doses of estradiol in elderly women without any apparent increase in endometrial thickness. (Am J Obstet Gynecol 2002;186:944-7.)

Bioavailability of oestradiol from the Alora TM (0.1 mg/day) oestradiol matrix transdermal delivery system compared with Estraderm (0.1 mg/day)

Summary This open-label, randomised, two-way crossover study compared the steady-state bioavailability of oestradiol administered by way of a new oestradiol matrix transdermal delivery system (Alora TM 0.1 mg/day) with that of Estraderm (0.1 mg/day) in 24 subjects. Serum oestradiol, oestrone and oestrone sulphate concentrations were determined by measurement of blood samples. Mean SD pre-dosing, nonadjusted oestradiol levels for Alora (71.9 27.0 pg/ml) were substantially higher than those for Estraderm (26.7 9.7 pg/ml), while peak oestradiol concentrations were comparable. Consequently, fluctuations in steady-state levels were substantially smaller for Alora than for Estraderm; the fluctuation index values (\\[C- C ])/ max min C ) were significantly lower for Alora (0.97 0.23) than av for Estraderm (1.68 0.45). Oestradiol levels remained constant over the dosing interval with Alora but decreased significantly after 48 hours with Estraderm. The bioavailability of oestradiol with Alora was 127 56% that of Estraderm. Oestrone and oestrone sulphate data showed the same qualitative and quantitative differences between the two systems. Both systems were well tolerated. In summary, Alora delivered more oestradiol to the systemic circulation with greater consistency and over a longer time than did Estraderm.