Bioavailable Estradiol Levels Research Articles

Sex-specific causal effects of serum sex hormones on COVID-19 susceptibility and severity: Evidence from the UK Biobank and COVID-19 Host Genetics Initiative

BackgroundSeveral hormone therapies, such as androgen receptor signaling inhibition, are being investigated for their potential effectiveness against coronavirus disease 2019 (COVID-19). However, the causal relationships between serum sex hormones and the predisposition to, as well as the severity of, COVID-19, with a particular emphasis on potential gender-specific impacts, remain elusive. MethodsIn this study, using the latest data from the UK Biobank (up to 424,907 individuals) and COVID-19 Host Genetics Initiative (up to 1,878,143 individuals), we conducted a two-sample Mendelian randomization (MR) to systematically assess the sex-specific causal effects of serum sex hormone levels, total testosterone (TT), bioavailable testosterone (BT) in particular, on COVID-19 outcomes. The inverse-variance weighted method was used in the main MR analysis. Furthermore, we additionally performed a series of sensitivity analyses to assess the robustness of MR effect estimates against potential biases caused by invalid genetic variants. ResultsOur MR analysis revealed novel causal associations between bioavailable testosterone and serum estradiol levels, and SARS-CoV-2 infection in women, but not men, except for a suggestive inverse causal association between estradiol levels and COVID-19 severity in men. ConclusionThese novel findings improve our understanding of the sex-specific causal nature of androgen and estrogen in relation to COVID-19 outcomes, and suggest that bioavailable testosterone and estradiol levels may serve as potential therapeutic targets for preventing SARS-CoV-2 infection and improving patient outcomes.

Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study

BackgroundSex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset. MethodsWe retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198,058 males; 250,830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking. ResultsAD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls (padjusted<0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls (padjusted<0.001). These differences remained after accounting for current drinking frequency (p < 0.001). SHBG moderated TT’s effect on AD in males (pinteraction<0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males (p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males (p < 0.001). ConclusionsTestosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations.

LBSAT139 Osteoporosis Screening In Men As Per Endocrine Society Clinical Practice Guidelines: A Cross-sectional Study

Abstract Introduction With the aging of the population, osteoporosis in men is a significant public health problem. Both hip and vertebral fractures are associated with increased mortality in men, as compared to women. One out of every five men experiences fragility fractures at least once in their lifetime. Declining sex steroid levels and bioavailable estradiol levels contributes to age-related bone loss in men. The objective of this study was to identify the underdiagnosis and the lack of guideline-based screening for osteoporosis in men. Method: Endocrine Society Clinical Practice Guidelines published in June 2012 recommends screening for osteoporosis in all men aged ≥70y, and all men aged between 50-69y who have risk factors including delayed puberty, hypogonadism, hyperparathyroidism, hyperthyroidism, chronic obstructive pulmonary disease; drugs such as glucocorticoids or GnRH agonists; life choices such as alcohol abuse or smoking; or other causes of secondary osteoporosis, using a dual-energy x-ray absorptiometry (DXA) of the spine and hip. The National Osteoporosis Foundation has similar recommendations. | Using a cross-sectional study design, charts of male patients eligible for osteoporosis screening, between the period of September 2020 to December 2021, were reviewed. Patients seen in the internal medicine residents’ clinic, family medicine residents’ clinic and endocrinology clinic were included in the study. Results A total of 90 out of the 1120 male patients aged ≥70y had ever undergone a DXA scan. Of these 90 patients, on reviewing their problem list from the electronic health record, 15 had osteoporosis listed and 9 had fragility fracture/compression fracture/fracture listed. Of the 135 patients aged ≥50y with ho HIV, only 21 received a DXA scan. Additionally, it was observed that only 20% (23/120) of the patients on testosterone therapy were screened for osteoporosis. As compared to this, almost 40% (1012 out of 2479) of all women aged ≥65y received screening DXA scan. Conclusion This project highlighted the inconsistencies in ordering screening DXA scans for male patients at risk for osteoporosis. Fewer than 10% of the at-risk males had a DXA. Additionally, 10% of the patients who underwent DXA had already suffered from a fracture, further emphasizing the burden of this disease. Although osteoporosis is appreciated in post-menopausal women, we must not overlook our male patients, who have 2-3 times higher morbidity and mortality associated with a hip fracture. Based on this data, we plan to initiate a quality improvement project with an aim to improve guideline directed screening for osteoporosis. Enhanced DXA screening for at risk patients will not only reduce rates of fragility fracture but will also help reduce healthcare cost. For a sustainable and broader impact, we are working further on EPIC Best Practice Alert to prompt providers to order DXA scans for these patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Tree nut consumption is associated with a lower risk of hyperestrogenism in men

Hyperestrogenism may affect 2% to 8% of men globally. Previous studies indicate that tree nut consumption is associated with sex hormones in women. Whether this is the case in men remains unknown. This study hypothesized that consumption of tree nuts was inversely associated with circulating estradiol and prevalence of hyperestrogenism in men. This cross-sectional study included 3340 men aged ≥20 years from the US National Health and Nutrition Examination Survey from 2013 to 2016. Associations of tree nut consumption with circulating estradiol and prevalence of hyperestrogenism were assessed using weighted linear regression and binary logistic regression, respectively. Among the 3340 men, 207 consumed tree nuts. The mean usual intake of tree nuts among tree nut consumers was 34.2 g/d. Amounts of usual intake of tree nuts were inversely associated with bioavailable estradiol (β=-0.032, P=.037) after adjustment for all confounders. Usual intake of tree nuts of ≥ 30 g/d (vs <30 g/d) or ≥42.52 g/d (vs <42.52 g/d) was associated with a 24% or 7% lower multivariate-adjusted risk of hyperestrogenism, respectively. Further analyses showed that usual intake of tree nuts was positively associated with circulating folate, and the latter was inversely associated with circulating estradiol. In conclusion, higher tree nut consumption was independently associated with lower circulating levels of bioavailable estradiol and a lower risk of hyperestrogenism in men. Further research is needed to verify the effectiveness of using tree nuts to treat hyperestrogenism in men.

Associations between Polymorphisms in Phase II Enzymes and Circulating Sex-Steroid Hormones in White Postmenopausal Women.

ObjectivesThe purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association.MethodsBaseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Free, bioavailable, and total serum levels of reproductive hormones were measured through liquid chromatography/tandem mass spectrometry. For genotyping of UGT1A1 (rs10928303), UGT1A4 (rs10929301, rs11673726), UGT1A6 (rs1105879, rs2070959, rs6759892), UGT1A8 (rs10167119), UGT2B7 (rs7439366), and SULT1A1 (rs9282861, rs1968752), mass spectrometry based on multiplex methods and TaqMan assays were performed. Adjusted linear models were fit to assess the associations between SNPs and blood hormones using age, body mass index (BMI), and MHT as covariates.ResultsThe mean age was 59.8 years, and the mean BMI was 25.1 kg/m2. Past or recent use of MHT was reported by 41.2% of the participants. SNPs in SULT1A1 (rs1968752 and rs9282861) and UGT1A4 (rs11673726) genes were significantly associated with estrone levels, whereas SNPs in UGT1A6 (rs6759892) and UGT1A8 (rs10167119) genes were significantly associated with bioavailable estradiol levels.ConclusionsThere was no evidence that MHT use modified the association between SNPs and sex-steroid hormone levels; however, further studies are needed to establish the potential clinical significance of UGT1A4 (rs11673726), UGT1A6 (rs6759892), and UGT1A8 (rs10167119) SNPs and the modulation of hormone levels in postmenopausal women.

Epidemiology of estrogen and dementia in women with Down syndrome.

Several lines of investigation have shown a protective role for estrogen in Alzheimer's disease through a number of biological actions. This review examines studies of the role of estrogen-related factors in age at onset and risk for Alzheimer's disease in women with Down syndrome, a population at high risk for early onset of dementia. The studies are consistent in showing that early age at menopause and that low levels of endogenous bioavailable estradiol in postmenopausal women with Down syndrome are associated with earlier age at onset and overall risk for dementia. Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk. To date, no clinical trials of estrogen or hormone replacement therapy (ERT/HRT) have been published for women with Down syndrome. While findings from clinical trials of ERT or HRT for dementia have generally been negative among women in the neurotypical population, the short interval between menopause and onset of cognitive decline, together with a more positive balance between potential benefits and risks, suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved.

Bioavailable estradiol concentrations are elevated and predict mortality in septic patients: a prospective cohort study.

BackgroundExperimental studies demonstrate beneficial immunological and hemodynamic effects of estradiol in animal models of sepsis. This raises the question whether estradiol contributes to sex differences in the incidence and outcomes of sepsis in humans. Yet, total estradiol levels are elevated in sepsis patients, particularly nonsurvivors. Bioavailable estradiol concentrations have not previously been reported in septic patients. The bioavailable estradiol concentration accounts for aberrations in estradiol carrier protein concentrations that could produce discrepancies between total and bioavailable estradiol levels. We hypothesized that bioavailable estradiol levels are low in septic patients and sepsis nonsurvivors.MethodsWe conducted a combined case-control and prospective cohort study. Venous blood samples were obtained from 131 critically ill septic patients in the medical and surgical intensive care units at the University of Rochester Medical Center and 51 control subjects without acute illness. Serum bioavailable estradiol concentrations were calculated using measurements of total estradiol, sex hormone-binding globulin, and albumin. Comparisons were made between patients with severe sepsis and control subjects and between hospital survivors and nonsurvivors. Multivariable logistic regression analysis was also performed.ResultsBioavailable estradiol concentrations were significantly higher in sepsis patients than in control subjects (211 [78–675] pM vs. 100 [78–142] pM, p < 0.01) and in sepsis nonsurvivors than in survivors (312 [164–918] pM vs. 167 [70–566] pM, p = 0.04). After adjustment for age and comorbidities, patients with bioavailable estradiol levels above the median value had significantly higher risk of hospital mortality (OR 4.27, 95 % CI 1.65–11.06, p = 0.003). Bioavailable estradiol levels were directly correlated with severity of illness and did not differ between men and women.ConclusionsContrary to our hypothesis, bioavailable estradiol levels were elevated in sepsis patients, particularly nonsurvivors, and were independently associated with mortality. Whether estradiol’s effects are harmful, beneficial, or neutral in septic patients remains unknown, but our findings raise caution about estradiol’s therapeutic potential in this setting. Our findings do not provide an explanation for sex-based differences in sepsis incidence and outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1525-9) contains supplementary material, which is available to authorized users.

Fundamental Frequency of Crying in Two-month-old Boys and Girls: Do Sex Hormones During Mini-puberty Mediate Differences?

To evaluate whether the puberty-like sex hormone surge during the first months of life (mini-puberty) affects fundamental frequency (fo) in infant crying as one would derive from hormone influences on voice in adults. Populational prospective study. Twenty healthy normal-hearing infants (nine boys) were recruited for participation. Spontaneously uttered cries were collected from each infant at 8 weeks of age. The cries were acoustically analyzed for mean fo and fo range. The fo properties were correlated to the average serum levels of bioavailable estradiol (E2) (mean E2/sex hormone-binding globulin [SHBG]) and testosterone (T) (mean T/SHBG) across the second month of life. Whereas no significant hormone effect was found for mean fo, a significant negative correlation (r = -0.55) was found between fo range and mean E2/SHBG. No indication for a T influence on fo features was found at this age. Although girls showed a slightly higher mean E2 concentration than boys did, the observed differences in cry fo range were judged to be reflective of an infant's serum concentration of E2 rather than a sex-based difference. In the absence of laryngeal size differences between female and male infants, the result was interpreted as indicative of an E2 influence on viscoelastic properties of the vocal folds. In our opinion, the investigation of young infants' vocalizations during the early postnatal surge of sex steroids (mini-puberty) may advance our understanding of the mechanisms mediating average sex differences in vocal development and early communication.

The perinatal androgen to estrogen ratio and autistic-like traits in the general population: a longitudinal pregnancy cohort study.

BackgroundPrenatal androgen exposure has been hypothesized to be linked to autism spectrum disorder (ASD). While previous studies have found a link between testosterone levels in amniotic fluid and autistic-like traits, a similar relationship has not been found for testosterone in umbilical cord blood. However, it may be the net biological activity of multiple androgens and estrogens that influences postnatal effects of prenatal sex steroids. Accordingly, composite levels of androgens (A) and estrogens (E) were investigated, along with their ratio, in relation to autistic-like traits in young adulthood.MethodsSex steroid data in umbilical cord blood were available from 860 individuals at delivery. Samples were analyzed for androgens (testosterone, androstenedione, and dehydroepiandrosterone) and estrogens (estrone, estradiol, estriol, and estetrol). Levels of bioavailable testosterone, estradiol, and estrone were measured and used to calculate A and E composites and the A to E ratio. Participants were approached in early adulthood to complete the autism-spectrum quotient (AQ) as a self-report measure of autistic-like traits, with 183 males (M = 20.10 years, SD = 0.65 years) and 189 females (M =19.92 years, SD = 0.68 years) providing data.ResultsMales exhibited significantly higher androgen composites and A to E composite ratios than females. Males also scored significantly higher on the details/patterns subscale of the AQ. Subsequent categorical and continuous analyses, which accounted for covariates, revealed no substantial relationships between the A/E composites or the A to E ratio and the AQ total or subscale scores.ConclusionsThe current study found no link between the A/E composites or the A to E ratio in cord blood and autistic-like traits in the population as measured by the AQ. These outcomes do not exclude the possibility that these sex steroid variables may predict other neurodevelopmental traits in early development.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-015-9114-9) contains supplementary material, which is available to authorized users.

Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis

Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat. We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States. Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant. On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Elevation of C-reactive protein during the luteal phase in healthy adolescents

Introduction: Variations in inflammatory markers have been reported in adult women during the luteal phase, but whether these findings are observed during adolescence is unknown. We postulate that higher ultrasensitive C-reactive protein (usCRP) and lower 2-hydroxyestrone (2OHE) levels, an estrogen metabolite with cardioprotective actions, are present during the luteal phase in young women.Aim: To evaluate usCRP levels during the menstrual cycle and to determine its association with 2OHE and 16α-hydroxyestrone (16OHE) in adolescents.Methods: Healthy postmenarcheal adolescents (N = 37) were studied during one menstrual cycle in follicular phase (FP) and luteal phase-like period (LP-L).Results: Elevations in usCRP levels in the LP-L were observed in the entire group and in anovulatory cycles (1.9 ± 1.1 mg/L in FP to 2.5 ± 1.8 mg/L in LP-L; p < 0.0001). Increases in estrone, estradiol, free and bioavailable estradiol, testosterone, usCRP and 2OHE levels were observed in LP-L compared with FP (p < 0.01), with a borderline elevation in IFG-I levels (p = 0.06).Conclusions: We report an elevation of usCRP and 2OHE levels during the luteal phase in healthy adolescents. Elevations of this inflammatory marker in anovulatory adolescents without an increase in 2OHE may play a role in metabolic risks associated with chronic anovulation.

여성의 혈중 남성호르몬 수치와 성기능 장애의 상관관계 연구

Introduction and Aim. Sex hormones might induce significant changes in sexual desire, arousal, orgasm, and satisfaction. Decreased sexual desire and sexual dysfunctions in females have been associated with low levels of androgen. This study was to explore the relationship of sex hormones and sex hormone-binding globulin (SHBG) with female sexual dysfunction. Materials and Methods. Seventy-four women with sexual dysfunction were taken their medical history, personal history and physical examination. A self-reporting questionnaire on sexual problems and satisfaction was administered to them. Also levels of total, free, and bio-available testosterone, LH, FSH, estradiol, DHEAS and SHBG were measured, and free androgen index were calculated. Using Wilcoxon rank-sum test, the hormone levels of the sexual dysfunction groups were compared to those of control group. Nine patients were treated by testogel®. Results. The mean levels of LH, FSH, DHEA and DHEAS were lower in women with lack of sexual desire. The levels of DHEA was lower in the arousal disorder group (p&lt;.05) and lower in the orgasmic disorder group (p&lt;.01) than the control group. Sexual pain disorder groups showed lower estradiol level (p&lt;.05). Among the nine patients receiving testosterone replacement therapy by using testogel®, 4 patients reported that symptoms were improved subjectively, the other 4 patients had not significant change, and the remaining 1 patient stopped the therapy due to side effect. Conclusion. The findings supported the concept that sex hormones significantly affect sexual response in women with sexual dysfunction. An androgenic hormone profile was associated with lack of libido, orgasmic disorder, and estrogen with pain disorder.

Sex Hormone Levels and Risk of Breast Cancer With Estrogen Plus Progestin

Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer. We conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided. Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04). Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.

Relationship of adiposity to bone volumetric density and microstructure in men and women across the adult lifespan

Recent evidence suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm that increased fat mass, through mechanical loading or endogenous estrogen production, is beneficial to the skeleton. We hypothesized that it is primarily the visceral compartment of body fat that is detrimental to bone metabolism, resulting in impaired bone density and architecture. In an age-stratified population sample of 218 women and 291 men (age 20–97years), we assessed visceral (VAT) and subcutaneous (SAT) adipose tissue areas at the L2–L3 interspace level by single slice quantitative computed tomography (QCT) and measured total body fat mass (TBF) by dual-energy X-ray absorptiometry. We then correlated these findings with volumetric bone mineral density (vBMD) at the femoral neck (FN) and lumbar spine (LS) assessed by central QCT, and with vBMD and microstructural parameters at the ultradistal radius (UDR) by high resolution peripheral QCT (HRpQCT). In unadjusted analyses in postmenopausal women, TBF and SAT were positively correlated with total, trabecular, and cortical vBMD at the FN, LS, and UDR and with trabecular microstructure at the UDR. By contrast, VAT was not correlated with vBMD at the FN or LS but was positively correlated with UDR total and trabecular vBMD but not cortical vBMD. Adjustment for age or for bioavailable estradiol and testosterone levels reduced these correlations, while adjustment for body weight eliminated most positive associations. Assessment of the VAT/SAT ratio, however, demonstrated a negative relationship with vBMD at the FN and LS in postmenopausal women, a relationship eliminated when adjusted for age. Correlations between skeletal parameters and adipose measurements in pre-menopausal women and older men were weaker and mostly non-significant. In younger men, VAT was negatively associated with vBMD, cortical thickness, and trabecular microstructure at the UDR, and with LS vBMD and FN cortical vBMD. These associations generally remained after adjustment, with some negative associations (e.g. UDR cortical area) being accentuated. Similar results were found when the VAT/SAT ratio was correlated with FN vBMD in younger men; in contrast, VAT/SAT was positively correlated with FN vBMD in older men and this relationship was strengthened by age-adjustment. Together, our data suggest that adiposity has associations with bone that are age-, gender-, menopausal status-, adipose depot-, and bone compartment-specific. These novel observations warrant further investigations to establish any causal relationships.

Associations between sex hormones and cognitive and neuropsychiatric manifestations in vascular dementia (VaD)

Although numerous studies have been carried out to determine the effects of sex hormones on Alzheimer's disease (AD), little is known about the associations between sex hormones and VaD. The aim of this study was to compare serum sex hormone levels between VaD patients and normal controls, and to further determine the link between sex hormones and cognitive and neuropsychiatric manifestations of VaD. Serum levels of total estradiol (TE2), total testosterone (TT), luteinizing hormone (LH), and sex hormone binding globulin (SHBG) were measured in 87 VaD patients and 110 cognitive normal controls. The levels of bioavailable estradiol (BE2) and bioavailable testosterone (BT) were calculated. The VaD patients underwent the tests of global cognitive function, verbal memory, and visuospatial, and executive ability. The Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. Compared to controls, the testosterone and SHBG levels were lower in male VaD patients, and the estradiol levels were higher in female VaD patients. The hormones levels were not correlated with cognitive functions among either male or female VaD patients. There were no associations between hormone levels and neuropsychiatric symptoms among male patients, while the TE2 and TT levels were positively associated with apathy and anxiety, respectively among female patients. Our findings suggested there were sex hormone level changes in VaD patients in comparison with cognitive normal controls. Sex hormones were associated with neuropsychiatric symptoms among female but not male VaD patients.

The use of dehydroepiandrosterone in the treatment of hypoactive sexual desire disorder: A report of gender differences

Data regarding the efficacy of dehydroepiandrosterone (DHEA) in the treatment of hypoactive sexual desire disorder (HSDD) are scarce and inconsistent. We aimed to determine possible gender differences in the efficacy of DHEA as a treatment for HDSS. Postmenopausal women (n=27), and men (n=21) with HSDD, were randomized to receive either DHEA 100mg daily or placebo for 6 weeks in a controlled, double blind study. Primary outcome measures were sexual function questionnaires. Hormone serum levels of DHEAS, total and bioavailable testosterone, estradiol, and urine levels of DHEA and androsterone were also measured. Participants on active treatment showed a significant increase in circulating serum levels of DHEAS, while bioavailable testosterone levels increased in women only. In women only, significant interaction effects were observed for sexual arousal (p<0.05), satisfaction (p<0.05), and cognition (trend; p=0.06). For arousal, a significant improvement was observed for the DHEA treated group at 6 weeks (p=0.001). Significant correlations were observed between bioavailable T and sexual cognitions, arousal and orgasm, while DHEAS was correlated with satisfaction. In the men, significant correlations were observed between testosterone and arousal (r=.45), sexual drive (r=.50) and orgasm (r=.55). In women with HSDD, DHEA treatment had a significant beneficial effect on arousal, whereas no efficacy was demonstrated in men, indicating a possible gender difference. This improvement seems to be mediated via DHEA's metabolism to testosterone. Our positive results suggest that the neurosteroid DHEA may be effective as a treatment for women with HSDD if administered at a dose of at least 100mg per day.

Serum Osteoprotegerin and Sex Steroid Levels in Patients With Prostate Cancer

The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.

High Level of Plasma Estradiol as a New Predictor of Ischemic Arterial Disease in Older Postmenopausal Women: The Three‐City Cohort Study

BackgroundDespite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain.Methods and ResultsIn the Three-City prospective cohort study of subjects (n=9294) >65 years of age, we investigated the association of total 17β-estradiol, bioavailable 17β-estradiol, and total testosterone with the 4-year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case–cohort study including a random sample of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional-hazards models with age as the time scale were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for ischemic arterial disease by a 1–standard deviation increase in sex steroid hormones. In univariate analysis, HR of ischemic arterial disease was positively and significantly associated with both total and bioavailable estradiol levels. These associations remained significant after adjustment for traditional cardiovascular risk factors, including body mass index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR: 1.42, 95% CI: 1.12–1.79, P<0.01; and HR: 1.42, 95% CI: 1.12–1.78, P<0.01, respectively). Separate analysis for coronary heart disease yielded similar results (adjusted HR: 1.49, 95% CI: 1.10–2.02, P=0.01; and adjusted HR: 1.50, 95% CI: 1.11–2.04, P<0.01, respectively), and a borderline significant trend was observed for ischemic stroke (HR: 1.34, 95% CI: 0.95–1.89, P=0.08; and HR: 1.32, 95% CI: 0.94–1.84, P=0.11, respectively). By contrast, no significant association was found between total testosterone and ischemic arterial disease in both univariate and adjusted analyses.ConclusionsHigh plasma level of endogenous estradiol emerges as a new predictor of ischemic arterial disease in older postmenopausal women. (J Am Heart Assoc. 2012;1:e001388 doi: 10.1161/JAHA.112.001388.)

Associations of Ionizing Radiation and Breast Cancer-Related Serum Hormone and Growth Factor Levels in Cancer-Free Female A-Bomb Survivors

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

Sex Hormone Levels and Risks of Estrogen Receptor-Negative and Estrogen Receptor-Positive Breast Cancers

Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.