Endogenous Estradiol Levels Research Articles

Hormone levels and cognitive function in postmenopausal midlife women

Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.

Prospective Study of Endogenous Circulating Estradiol and Risk of Stroke in Older Women

The incidence of stroke increases after menopause, when endogenous estrogen levels fall. Paradoxically, recent randomized clinical trials have shown that use of exogenous estrogen increases both circulating estrogen levels and the risk of stroke among older postmenopausal women. The influence of endogenous estrogen on stroke pathogenesis and the risk of stroke in postmenopausal women are unclear. This prospective case–control study tested the hypothesis that circulating endogenous estradiol may increase the risk of stroke in older postmenopausal women. The study population was comprised of 415 white women who were 65 years or older not taking estrogen at baseline, nested in the Study of Osteoporotic Fractures. Among these women, the odds for a first-ever atherothrombotic stroke associated with the endogenous free estradiol index (FEI) was determined in 196 who had a subsequent validated stroke (at a median follow-up of 8 years) and was compared with that of 219 controls who did not. The FEI was estimated by dividing total estradiol (protein-bound plus unbound) by sex hormone-binding globulin in molar concentrations. Multivariable models were used to estimate odds ratios for incident stroke by levels of endogenous estradiol and to adjust for potential confounders. Over the 8 years of follow-up, women with increasing FEI by quartiles had an increasing age-adjusted odds of having an atherothrombotic stroke (Ptrend = 0.007). The odds of a stroke were higher among women in the highest FEI quartile (age-adjusted odds ratio, 2.31; 95% confidence interval, 1.28–4.17) in comparison with women in the lowest quartile. There was suggestion of a stronger association between FEI and stroke among women with greater central adiposity (P = 0.08). Potential effect modifiers of the relation between endogenous estrogen and the risk of stroke were atherogenic dyslipidemia, diabetes (insulin resistance), and inflammation (level of C-reactive protein). These findings show an age-independent association between endogenous estradiol levels and the risk of stroke among older postmenopausal women, and especially those with greater central adiposity. It is unclear whether endogenous estradiol, independent of atherogenic adiposity, affects potential effect mediators in atherothrombotic stroke.

Ovarian Suppression in Normal-Weight and Obese Women During Oral Contraceptive Use

To assess ovarian suppression during oral contraceptive pill (OCP) use among normal-weight and obese women using two OCP doses. This was a prospective, double-blind, randomized trial of two 21-day monophasic OCP formulations (20-microgram ethinyl estradiol [E2],/100-microgram levonorgestrel compared with 30-microgram ethinyl E2/150-microgram levonorgestrel) among normal-weight (body mass index 19.0-24.9) and obese (body mass index 30.0-39.9) women with regular menses and normal ovarian ultrasonography. Participants underwent transvaginal ultrasonography and phlebotomy twice weekly for 4 weeks during the third or fourth OCP cycle. We assessed OCP compliance using serum levonorgestrel levels. Outcomes included follicular development, endogenous E2 levels, ovulation, and self-reported bleeding patterns. Two hundred twenty-six women enrolled. One hundred eighty-one participants completed the study; we retained 150 consistent OCP users in the main analysis (96 normal weight, 54 obese). Consistent users of either OCP dose had substantial suppression of follicular development; obesity and follicular development were not related. Among the consistent OCP users, 2.7% ovulated during the study cycle (3 of 96 normal-weight and 1 of 54 obese participants). Two ovulations occurred with each OCP formulation. Inconsistent OCP use or nonuse during the study cycle was associated with more ovulation (P<.001). Normal-weight and obese participants had similar follicular development, endogenous estradiol levels, Hoogland scores, and bleeding patterns. Normal-weight and obese participants who were consistent OCP users experienced substantial and comparable ovarian suppression during OCP use. Higher OCP failure rates among obese women reported elsewhere are thus unlikely to be attributable to physiological differences in OCP effect. ClinicalTrials.gov, www.clinicaltrials.gov; NCT00827632. : I.

Influence of oral contraceptives on endogenous pain control in healthy women

This study investigated the influence of oral contraceptives (OC) on diffuse noxious inhibitory control (DNIC) in healthy women. Fifteen women taking OC and 17 normally menstruating women (No-OC) were tested during high and low endogenous estrogens sessions. Saliva was sampled for analysis of endogenous estradiol level. Mechanical pressure (test stimuli) was applied to the masseter muscle and finger. The pain induced by this pressure was assessed on a 0-10 numerical rating scale (NRS) before, during, and after immersion of the contralateral hand in ice-cold water (cold pressor test, CPT) to induce DNIC. For all subjects, pain induced by the test stimuli decreased significantly during the CPT (P < 0.001). The decrease in general was larger in the No-OC group, with a significant difference between groups in the masseter muscle in the low session (P < 0.027). There were no significant differences between groups or sessions in estradiol levels. These results indicate that endogenous pain modulation may be less effective in OC users.

VARIATIONS IN THE DEFICIENCY LEVELS OF ENDOGENOUS ESTRADIOL ON THE RATE OF POSTMENOPAUSAL BONE RESORPTION

Over a period of three years, 257 healthy postmenopausal women (mean age of 51.7 years) and 47 premenopausal women (control group, mean age of 34.23 years) were selected into the study. The postmenopausal women were divided into three estradiol‐deficient (study) groups based on the endogenous estradiol levels such as Group – I (10–25 pg/ml), Group ‐ II (&gt;25–50 pg/ml) and Group ‐ III (&gt;50 pg/ml). Bone formation marker (total alkaline phosphatase), bone resorption markers (tartrate‐resistant acid phosphatase, calcium, free hydroxyproline, free deoxypyridinoline and calcium/creatinine) and intact paratharmone levels were estimated in every subject. The bone formation marker and bone resorption markers were found to be elevated in all the three study groups over controls (P&lt;0.0010) When the study groups compared among one another, the bone resorption markers were found elevated in Group‐I over Group ‐ II and III and in Group ‐ II over Group ‐ III. But, the intact paratharmone levels were found to be normal in all the groups.This study concludes that the degree of bone resorption was high in Group ‐ III (&gt;50 pg/ml, higher in Group – II (&gt; 25–50 pg/ml) and highest in Group ‐ I (10–25 pg m/l) over controls. This view portends that the endogenous estradiol levels are the important determinants of bone resorption risk and also the variations in deficient endogenous estradiol levels in postmenopausal women might contribute to differences in the rate of postmenopausal bone resorption.

Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding

Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT(2A)) receptor binding in men. In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6-81.7) we studied the effect of plasma sex hormone levels on neocortical 5-HT(2A) receptor binding as imaged with [(18)F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. Mean neocortical 5-HT(2A) receptor binding was positively correlated with estradiol (p=0.0001), whereas no independent effects of testosterone could be demonstrated. Correction for other factors of importance for 5-HT(2A) receptor binding did not change the result. A voxel-based analysis suggested that there were no regional differences in the estradiol effect on cortical 5-HT(2A) receptor binding. Our data show a positive correlation between endogenous plasma estradiol levels and cortical 5-HT(2A) receptor binding in healthy men, whereas, no independent effect of testosterone was demonstrated. We speculate that this association could be mediated through effects on gene transcription.

Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women

BackgroundThis study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal-weight [body mass index (BMI) 19.0–24.9] and obese (BMI 30.0–39.9) women. Study DesignDuring the third week of the third cycle of OC use, we admitted 15 normal-weight and 15 obese women for collection of 12 venous specimens over 24 h. Using radioimmunoassay techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels. ResultsObese women had a lower area under the curve (AUC; 1077.2 vs. 1413.7 pg⁎h/mL) and lower maximum values (85.7 vs. 129.5 pg/mL) for EE than normal-weight women (p=.04 and <0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (Cmax) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal-weight women (2.6 and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p=.05) and lower E2 levels (p=.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant. ConclusionOC hormone peak levels are lower among obese women compared to normal-weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users.

Prospective Study of Endogenous Circulating Estradiol and Risk of Stroke in Older Women

To test the hypothesis that circulating endogenous estradiol is associated with stroke risk in older postmenopausal women. Stroke incidence increases after menopause, when endogenous estrogen levels fall, yet exogenous estrogen increases strokes in older postmenopausal women. The relation between endogenous estrogen and stroke is unclear. Prospective case-control study. Study of Osteoporotic Fractures. Women at least age 65 years (99% follow-up) who were not taking estrogen at baseline. Free estradiol index (FEI) was calculated by dividing total estradiol by sex hormone-binding globulin concentrations measured in banked baseline serum. Using logistic regression, odds ratios were estimated for a first-ever atherothrombotic stroke associated with endogenous FEI in 196 women who had a subsequent validated stroke (median follow-up, 8 years) compared with 219 randomly selected women who did not. Potential mediators were assessed in multivariable models. The age-adjusted odds of atherothrombotic stroke increased with increasing FEI quartiles (P(trend) = .007). Women in the highest FEI quartile had an age-adjusted 2.31-fold (odds ratio, 2.31; 95% confidence interval, 1.28-4.17) higher odds than women in the lowest quartile. Women with greater central adiposity had a suggestively stronger association (P = .08). Atherogenic dyslipidemia, type 2 diabetes mellitus, and C-reactive protein level were potential mediators of this relation. Endogenous estradiol level is an indicator of stroke risk in older postmenopausal women, especially in those with greater central adiposity. Potential mediators, including atherogenic dyslipidemia, insulin resistance, and inflammation, might underlie this association. Whether estradiol, independent of atherogenic adiposity, influences such mediators and stroke risk needs to be determined. Estrogen-altering agents might be harmful or beneficial depending on endogenous estradiol levels, especially in women with greater central adiposity.

Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study

BackgroundSeveral studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored.MethodsWe utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR.ResultsSeveral variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4) and triglycerides (p = 1.3 × 10-3) and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women <45 years old (p = 0.002).ConclusionsEstrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

Baseline Endogenous Estradiol and the Association of Hormone Therapy with Breast Cancer Risk, the Women's Health Initiative Clinical Trials.

Abstract Background: The effect of exogenous hormones on breast cancer risk may depend on baseline endogenous levels of estradiol (E2). We investigated whether women with lower E2 levels will have the greatest increase in breast cancer risk during treatment with estrogen plus progestin ((E+P); combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate) or estrogen-alone ((E-alone); CEE) therapy. Additionally, we examined whether the risk of breast cancer varies by untreated levels of endogenous E2.Methods: We performed an ancillary study within the Women's Health Initiative E+P and E-alone clinical trials. We used a case-only design to test for interactions between untreated levels of E2 and hormone therapy (E+P or E-alone) on breast cancer risk. We measured baseline levels of bioavailable E2 in 346 cases of invasive breast cancer from the E+P trial and 231 cases from the E-alone trial. To estimate the risk of breast cancer by endogenous E2 levels (expressed as quartiles), we used a case-cohort design which included the cases described above in addition to a randomly selected comparison group (N=387; 203 from the E+P and 184 from the E-alone trial). Incident breast cancer cases were identified over an average follow-up of 4.1 years in the E+P trial and 5.4 years in the E-alone trial. All analyses were performed separately for the E+P and the E-alone trials.Results: In the case-only study, the effect of E+P therapy on breast cancer risk did not seem to vary by endogenous E2 quartiles (p-heterogeneity= 0.16). Breast cancer risk associated with E-alone treatment tended to be greater among women with the lowest E2 levels; however this association was not significant (hazard ratio (HR)= 1.44, 95% confidence interval (CI)= 0.79-2.59).Table 1. Effects of E+P and E-alone treatments on breast cancer risk (HR (95% CI)) by quartiles of baseline estradiol: case-only results E+PE-aloneEstradiol Quartile 11.20 (0.80-1.80)1.44 (0.79-2.59)Quartile 20.88 (0.58-1.34)0.98 (0.58-1.67)Quartile 31.27 (0.81-2.00)0.79 (0.47-1.33)Quartile 40.67 (0.43-1.06)0.92 (0.57-1.49)P-heterogeneity0.160.51P-trend0.160.20 In the case-cohort analysis, higher endogenous E2 levels were associated with increased breast cancer risk (p-trend= 0.01), independent of hormone therapy.Table 2. Effects of baseline estradiol and hormone therapy (E+P vs. E-alone) on breast cancer risk (HR (95% CI)): case-cohort results E+PE-aloneHormone therapy treatment (Reference= placebo group)1.01 (0.96-1.07)0.84 (0.56-1.26) Estradiol Quartile 1 (Reference)1.001.00Quartile 21.22 (0.75-2.00)1.30 (0.77-2.17)Quartile 31.41 (0.87-2.32)1.32 (0.77-2.27)Quartile 41.85 (1.12-3.03)2.38 (1.32-4.35)P-trend0.010.01 Conclusion: The risk of breast cancer increases with higher levels of untreated endogenous E2. However, untreated E2 level does not modify the effect of E+P or E-alone therapy on breast cancer risk. Estradiol measurement is unlikely to identify women where hormone therapy may substantially increase the risk of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 906.

Endogenous estradiol levels are associated with attachment avoidance and implicit intimacy motivation

Estradiol has been linked with attachment and caregiving processes in humans and other mammals; however, relations between estradiol and personality constructs relevant to intimate relationships have not yet been explored. In the present sample of 100 adult participants (52 men, 48 women), we examined endogenous estradiol levels in relation to two personality constructs that predict comfort with and desire for close, intimate relationships—attachment style and implicit intimacy motivation. In both men and women, estradiol levels were predicted by an interaction between a dimension of attachment style—attachment avoidance—and implicit intimacy motivation. Specifically, the highest estradiol levels were observed among participants whose explicit traits support the expression of their implicit motives, that is, those characterized by both low avoidance and high intimacy motivation. Our findings provide novel evidence that endogenous estradiol levels are associated with relationship-relevant personality constructs in theoretically meaningful ways. These findings also highlight the importance of considering interactions between implicit and explicit personality constructs in the study of the biological bases of personality.

POSTMENOPAUSAL HORMONE THERAPY AND REGIONAL BRAIN VOLUMES: THE WHIMS-MRI STUDY

We read the article by Resnick et al.1 regarding findings from the Women's Health Initiative Memory (WHIMS)–MRI Study on hormone therapy (HT) and brain volumes on MRI. The investigators found slightly lower hippocampal volumes on MRI after a 3-year follow-up in women assigned to HT compared to placebo. This confirms our previous observation in the Rotterdam Scan Study, a population-based MRI study in nondemented elderly where we found no beneficial effect of high endogenous plasma estradiol levels on manually measured hippocampal volumes on MRI in 210 randomly selected women.2 If anything, we found that higher estradiol levels were associated with lower hippocampal volumes. For a portion of this cohort (n = 94), follow-up MRIs are now available and were made an …

The physiology of women’s power motive: Implicit power motivation is positively associated with estradiol levels in women

This study examined the relationship between implicit power motivation ( n Power) and salivary estradiol in women. Forty participants completed the Picture Story Exercise, a measure of n Power, and salivary estradiol levels from two saliva samples were determined with radioimmunoassay. We found that n Power was positively associated with estradiol levels. The positive correlation between n Power and estradiol was stronger in single women and women not taking oral contraceptives than in the overall sample of women. These findings replicate those of Stanton and Schultheiss (2007), giving further credence to the argument that women’s dominance striving is positively associated with their endogenous estradiol levels and that both social and biological factors influence the nature of that association.

Postmenopausal Levels of Endogenous Sex Hormones and Risk of Colorectal Cancer

Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women.

Effect of endogenous estradiol levels on bone resorption and bone mineral density in healthy postmenopausal women: a prospective study

Objective To investigate the effect of endogenous estrogens on bone mineral density (BMD) and bone markers in postmenopausal women over 24 months.Methods Fifty out of 99 postmenopausal women seen previously were re-assessed after 24 months. Levels of BMD, bone markers, serum estradiol (E2) and total testosterone were determined.Results BMD decreased in the femoral neck (∼2%) (p < 0.008), but remained stable in the other skeletal areas; E2 and serum Crosslaps (sCTX) decreased by 34% (p < 0.001) and 21% (p < 0.003), respectively. Women aged ≤ 65 years exhibited decreased BMD only in the femoral neck (2%, p < 0.01), without changes in bone markers. Women aged > 65 years exhibited a decrease in sCTX levels and stable BMD values at all skeletal sites. E2 levels decreased similarly in both groups (∼35%). Women with baseline E2 levels ≥ 10 pg/ml showed stable BMD in spite of their E2 levels decreasing by 42% (p < 0.001); sCTX decreased by 21% (p < 0.01). Women with baseline E2 levels < 10 pg/ml showed a 2% decrease (p < 0.001) in femoral neck BMD and a 19% decrease (p < 0.002) in E2 levels, without changes in bone markers.Conclusion Although endogenous E2 decreased to around 7 pg/ml in these menopausal women, this level would seem to be sufficient to maintain BMD in almost all skeletal areas, and to be more effective in older women.

Associations of endogenous sex hormones and sex hormone-binding globulin with lipid profiles in aged Japanese men and women

Background The associations of endogenous estrogen with lipid profiles and insulin resistance were conflicting in both men and women. We determined the associations of serum estradiol level and free estradiol index (FEI) with lipid profiles and insulin resistance in aged Japanese men and women. Methods One hundred seventy-four men and 208 postmenopausal women aged from 50 to 85 y were included in this study. Lipid profiles, fasting glucose and insulin as well as estradiol, testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and sex hormone-binding globulin (SHBG) in serum were measured. Results Serum estradiol concentration in men showed a significant and negative correlation with high density lipoprotein-cholesterol (HDL-C) concentration and a significant and positive correlation with triglyceride (TG) after adjustment for age and body mass index (BMI). In addition, estradiol level was positively correlated with insulin and HOMA index. In women, serum levels of estradiol and testosterone were not correlated with lipid profiles and insulin resistance. SHBG concentration was negatively correlated with TG after adjustment for age and BMI in women. Conclusion Endogenous estradiol level is associated with unfavorable lipid profiles and insulin resistance in aged men. In aged women, SHBG level is associated with favorable lipid profiles.

Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis

Pregnancy is known to influence the course of rheumatoid arthritis (RA) in women, as well as type II collagen-induced arthritis (CIA) in DBA/1 mice. A characteristic feature is the remission during gestation and the exacerbation of the diseases during the post-partum period. In the case of CIA in DBA 1 mice, two hormonal changes have been assumed to be critical for the induction of the post-partum flare: (i) the fall in steroid hormone levels from those present during pregnancy; and (ii) surges of prolactin (PRL) release at and after delivery. Our results show that treatment with oestradiol during a short period immediately after parturition protects the mouse from a post-partum flare of the disease, and that treatment with bromocriptine, a drug known to inhibit the endogenous PRL release, has a significant though less marked effect. Studies of lactating (i.e. animals with physiological stimulation of endogenous PRL release) and non-lactating arthritic mice revealed no clear-cut differences, indicating that PRL is of minor importance for the induction of the post-partum flare. Some steroids other than oestradiol, which may be implicated in the exacerbation of arthritis, namely progesterone and hydrocortisone, had no clinical effect. Analyses of agalactosyl IgG levels in mice with CIA, and anti-collagen II antibodies in sera collected at the end of the experiments revealed no significant differences between the oestradiol and the control groups. The successful oestradiol treatment of the mice indicates that the drop in endogenous oestradiol levels prior to delivery ends the oestrogen-mediated protection against arthritis during pregnancy.

Endogenous estradiol may influence IGF-I levels in acromegalic women treated with pegvisomant

We present the case of a 46-year-old woman with acromegaly currently being treated with the growth hormone (GH) receptor antagonist pegvisomant showing strongly fluctuating IGF-I levels. We prospectively measured estradiol, IGF-I, IGF-I binding protein, acid labile subunit, basal endogenous GH, binding protein and pegvisomant levels for 6 months every week. Estradiol levels showed a strongly negative correlation with IGF-I (r = -0.733, P < 0.001), and less so with ALS (r = -0.433, P < 0.05) and IGFBP3 (r = -0.590, P < 0.01). Estradiol was not significantly correlated with endogenous GH or pegvisomant levels. Likewise, IGF-I did not correlate with endogenous GH or pegvisomant levels. In our patient, endogenous estradiol levels have a significant influence on IGF-I levels. When female acromegalic patients on permanent pegvisomant treatment show fluctuating IGF-I levels, estradiol levels should be taken into consideration.

The association of endogenous sex hormones with lipoprotein subfraction profile in the Multi-Ethnic Study of Atherosclerosis

The traditional lipid profile differs by sex hormone levels. However, associations of sex hormones with lipoprotein subfractions, which may more accurately represent metabolic pathways to atherosclerosis, are not well studied. We quantified the cross-sectional associations of endogenous sex hormones with lipoprotein subfractions in 3143 men and 2038 postmenopausal women who were not on hormone replacement therapy, aged 45 to 84 years, in the Multi-Ethnic Study of Atherosclerosis baseline examination. Particle sizes and numbers of very low-density (VLDL), low-density (LDL), and high-density (HDL) lipoproteins were measured by nuclear magnetic resonance. In both men and women, after multivariable adjustment, higher sex hormone binding globulin (SHBG) levels are associated with smaller, fewer VLDL; larger, fewer LDL; and larger, more numerous HDL particles, whereas higher endogenous estradiol levels are associated with smaller VLDL and smaller, more numerous HDL and LDL particles (all P < .05). Testosterone (adjusted for SHBG) is associated with smaller VLDL particles in men but not women (sex difference P = .040). Higher dehydroepiandrosterone levels are associated with more numerous, smaller VLDL particles only in women (sex difference P = .030, .004, respectively). In conclusion, we found sex differences in the association of endogenous androgens with lipoprotein particle sizes and numbers. Higher endogenous estradiol, but lower SHBG, is associated with a more atherogenic lipoprotein particle profile. These findings highlight the potential to improve the lipoprotein profile with sex hormones, but emphasize the intricacies of the interactions.

Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats

The current study investigated whether, for spatial reference memory, age impacts (1) sensitivity to surgical ovarian hormone loss (Ovx), (2) response to estradiol therapy (ET), and (3) the relation between circulating estradiol levels and memory scores in ovary-intact sham and Ovx plus ET rats. Young, middle-aged and aged Fischer-344 rats received sham, Ovx or Ovx plus ET treatments, and were then tested on the Morris maze. After the last test trial, a probe trial was given whereby the platform was removed. Circulating estradiol levels were then determined and correlated with performance. In Study 1, Ovx facilitated learning on day one, but impaired performance after day one, in young rats. Ovx did not influence performance in middle-aged rats. In young and middle-aged Ovx rats, ET enhanced performance with higher exogenous estradiol levels correlating with better performance during testing and the probe trial. There was no relationship between endogenous estradiol levels and performance in sham young or middle-aged rats. Study 2 showed that, like middle-aged rats, aged rats were not impacted by Ovx. Further, for aged Ovx rats, the ET regimen that was beneficial at earlier ages was no longer effective during test trials, and had only minor benefits for platform localization as assessed by the probe trial. Collectively, the findings suggest that the effects of Ovx as well as responsivity to the currently utilized ET regimen changes with age. Further, there appears to be a distinction between sensitivity to Ovx and responsiveness to ET after Ovx for spatial reference memory performance.