Impact of luteoma during pregnancy on fetal development and its long-term effects into adulthood.

A woman in her 30s presents to the Differences in Sexual Development Programme at a tertiary care academic medical centre with vaginal stenosis and scarring. Her medical history is significant for virilisation in utero due to a maternal luteoma of pregnancy. Laboratory investigations at the time of birth showed elevated androgens in both mother and daughter. During infancy, she underwent clitoroplasty and vaginoplasty for correction of posterior vaginal fusion. She represented as an adult with vaginal stenosis, with associated physical and psychosocial implications. She was not able to insert a tampon or have penetrative intercourse. After examination and shared decision-making, the patient underwent cystoscopy, vaginoscopy and posterior vaginoplasty with the goal to create a normal calibre vagina. Postoperative dilator use was recommended to prevent restenosis of the introitus. In clinic follow-up, the patient was observed to have a normal calibre vagina.

Role of sex steroids in colorectal cancer: pathomechanisms and medical applications.

Given that the colon represents the most extensive hormone-responsive tissue in the human body, it prompts a compelling inquiry into whether the progression of its cancer is intimately linked to hormonal dynamics. Consequently, the interplay between sex steroids - a pivotal constituent of hormones - and colorectal cancer has increasingly captivated scientific interest. Upon a comprehensive review of pertinent literature both domestically and internationally, this study delineates the present landscape of three pivotal steroids - estrogen, progestin, and androgen - in the context of colorectal cancer. More specifically, this investigation probes into the potential utility of these steroids in providing therapeutic interventions, diagnostic insights, and prognostic indicators. Furthermore, this study also delves into the mechanistic pathways through which sex steroid interventions exert influence on colorectal cancer. It was discovered that the trio of sex steroid hormones partakes in an array of biological processes, thereby influencing the onset and progression of colorectal cancer. In conclusion, this study posits that a profound interconnection exists between colorectal cancer and sex steroids, suggesting that elucidating the targets of their action mechanisms could unveil novel avenues for the diagnosis and prevention of colorectal cancer.

Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health.

This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.

Ionic liquid-functionalized covalent organic frameworks on the surface of silica for online solid-phase extraction.

A covalent organic framework (COF) was gown on porous silica with 1,3,5-tri(4-aminophenyl)benzene and 2,5-divinyl-1,4-phenyldiformaldehyde as monomers, and two ionic liquids were grafted to COF by a click reaction. The materials before and after the modification of ionic liquids were separately packed into solid-phase extraction columns (10 × 4.6 mm, i.d.), which were coupled with liquid chromatography to construct online analysis systems. The extraction mechanisms of polycyclic aromatic hydrocarbons, bisphenols, diphenylalkanes and benzoic acids were investigated on these materials. There were π-π, hydrogen-bond and electrostatic interactions on ionic liquid-functionalized sorbents. After the comparison among these materials, the best sorbent was used, and the analytical method was established and successfully applied to the detection of some estrogens from actual samples. For the analytical method, the detection limit was as low as 0.005 µg L-1, linear range was as wide as 0.017-10.0 µg L-1, and enrichment ratio was as high as 3635. The recoveries in actual samples were 70 %-129 %.

The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.

The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment.

Effect of Menopausal Hormone Therapy on Cellular Immunity Parameters and Cytokine Profile.

BACKGROUND: A woman's entry into the menopause period is associated with a number of changes in the body, including those related to the immune system. Immune aging is a consequence of age-related changes in the function of immune cells and the composition of their subpopulations. Menopausal hormone therapy (MHT) is thought to partially neutralize the negative effects of aging on the immune system. OBJECTIVE: We aimed to evaluate the effect of oral and transdermal MHT on cellular immunity parameters and cytokine profile in menopausal women. METHODS: Fifty peri- and early postmenopausal women were included. Immune parameters were assessed by flow cytometry and multiplex analysis. RESULTS: We showed that different routes of MHT administration led to significant changes in monocyte phenotype and a decrease in monocyte chemoattractant protein-1 (MCP-1) level in menopausal patients. In addition, oral MHT resulted in a significant increase in NK and B cells. A significant increase in the number of T-helper cells was observed with transdermal MHT. In addition, oral MHT resulted in a significant decrease in IL-1ß level. CONCLUSIONS: We have demonstrated for the first time that oral therapy, in contrast to transdermal therapy, has a more pronounced effect on specific immune subpopulations of blood cells in menopausal women. This effect is likely to be responsible for its anti-aging properties in the context of immune aging as well as its protective effects in infectious diseases. Perhaps testing blood immune parameters or assessing immune status before prescribing MHT could become a routine step in clinical practice before choosing a patient management strategy.

Altered extracellular matrix and mechanotransduction gene expression in rat bone tissue following long-term estrogen deficiency.

Osteoporosis is primarily associated with bone loss, but changes in bone tissue matrix composition and osteocyte mechanotransduction have also been identified. However, the molecular mechanisms underlying these changes and their relation to bone loss are not fully understood. The objectives of this study were to (1) conduct comprehensive temporal gene expression analyses on cortical bone tissue from ovariectomized rats, with a specific focus on genes known to govern matrix degradation, matrix production, and mechanotransduction, and (2) correlate these findings with bone mass, trabecular and cortical microarchitecture, and mineral and matrix composition. Microarray data revealed 35 differentially expressed genes in the cortical bone tissue of the ovariectomized cohort. We report that catabolic gene expression abates after the initial accelerated bone loss period, which occurs within the first 4 wk of estrogen deficiency. However, in long-term estrogen deficiency, we report increased expression of genes associated with extracellular matrix deposition (Spp1, COL1A1, COL1A2, OCN) and mechanotransduction (Cx43) compared with age-matched controls and short-term estrogen deficiency. These changes coincided with increased heterogeneity of mineral-to-matrix ratio and collagen maturity, to which extracellular matrix markers COL1A1 and COL1A2 were positively correlated. Interestingly, mineral heterogeneity and collagen maturity, exhibited a negative correlation with PHEX and IFT88, associated with mechanosensory cilia formation and Hedgehog (Hh) signaling. This study provides the first insight into the underlying mechanisms governing secondary mineralization and heterogeneity of matrix composition of bone tissue in long-term estrogen deficiency. We propose that altered mechanobiological responses in long-term estrogen deficiency may play a role in these changes.

Cross-sex hormonal replacement: Some effects over mitochondria.

Transgender is a term for people whose gender identity or expression differs from their natal sex. These individuals often seek cross-hormonal therapy to simulate the individual´s desired gender. However, the use of estrogens and testosterone has side effects such as a higher propensity to cancer, weight changes and cardiovascular diseases. Testosterone has also been linked with hypertension. Still, little is known about the outcomes and prevalence of metabolic perturbations in the trans community. Here we aim to analyze if cross-administering sexual hormones affects heart mitochondrial function. Mitochondria produces the ATP needed for heart function. In fact, different studies show that mitochondrial dysfunction precedes cardiac damage. In this work we used either female rats castrated and injected with testosterone or male rats castrated and injected with estrogens for 4 months. We performed an electrocardiogram, and then we isolated heart mitochondria to measure the rate of oxygen consumption, calcium fluxes, membrane potential, superoxide dismutase activity, lipoperoxidation and cytokines. We detected wide modifications in all parameters associated to cross-hormonal administration.

The Influence of Sex Steroid Hormone Fluctuations on Capsaicin-Induced Pain and TRPV1 Expression.

Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.

Effect of Menstrual Cycle and Hormonal Contraception on Musculoskeletal Health and Performance: Protocol for a Prospective Cohort Design and Cross-Sectional Comparison.

BACKGROUND: Women of reproductive age experience cyclical variation in the female sex steroid hormones 17ß-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew tissues (ie, ligaments and tendons), which may influence injury risk and physical performance. OBJECTIVE: The purpose of the study is to understand the effect of the menstrual cycle and hormonal contraceptive use on bone and calcium metabolism, and musculoskeletal health and performance. METHODS: A total of 5 cohorts of physically active women (aged 18-40 years) will be recruited to participate: eumenorrheic, nonhormonal contraceptive users (n=20); combined oral contraceptive pill (COCP) users (n=20); hormonal implant users (n=20); hormonal intrauterine system users (n=20); and hormonal injection users (n=20). Participants must have been using the COCP and implant for at least 1 year and the intrauterine system and injection for at least 2 years. First-void urine samples and fasted blood samples will be collected for biochemical analysis of calcium and bone metabolism, hormones, and metabolic markers. Knee extensor and flexor strength will be measured using an isometric dynamometer, and lower limb tendon and stiffness, tone, and elasticity will be measured using a Myoton device. Functional movement will be assessed using a single-leg drop to assess the frontal plane projection angle and the qualitative assessment of single leg loading. Bone density and macro- and microstructure will be measured using ultrasound, dual-energy x-ray absorptiometry, and high-resolution peripheral quantitative computed tomography. Skeletal material properties will be estimated from reference point indentation, performed on the flat surface of the medial tibia diaphysis. Body composition will be assessed by dual-energy x-ray absorptiometry. The differences in outcome measures between the hormonal contraceptive groups will be analyzed in a one-way between-group analysis of covariance. Within the eumenorrheic group, the influence of the menstrual cycle on outcome measures will be assessed using a linear mixed effects model. Within the COCP group, differences across 2 time points will be analyzed using the paired-samples 2-tailed t test. RESULTS: The research was funded in January 2020, and data collection started in January 2022, with a projected data collection completion date of August 2024. The number of participants who have consented at the point of manuscript submission is 66. It is expected that all data analysis will be completed and results published by the end of 2024. CONCLUSIONS: Understanding the effects of the menstrual cycle and hormonal contraception on musculoskeletal health and performance will inform contraceptive choices for physically active women to manage injury risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05587920; https://classic.clinicaltrials.gov/ct2/show/NCT05587920. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50542.

Associations of endogenous estrogens, plasma Alzheimer's disease biomarkers, and APOE4 carrier status on regional brain volumes in postmenopausal women.

Background: Women carrying the APOE4 allele are at greater risk of developing Alzheimer's disease (AD) from ages 65-75 years compared to men. To better understand the elevated risk conferred by APOE4 carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and APOE4 carrier status on regional brain volumes in a sample of late midlife postmenopausal women. Methods: Participants were enrolled in MsBrain, a cohort study of postmenopausal women (n = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, APOE4 carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography-tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aß42/Aß40, Aß42/p-tau181), and APOE4 carrier status predict regional brain volume (21 regions per hemisphere, selected a priori); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by APOE4 carrier status. Results: There was no main effect of APOE4 carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and APOE4 carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aß42/40, lower Aß42/p-tau181 ratios). In APOE4-stratified analyses, these interactions were driven by non-APOE4 carriers. Conclusion: We demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-APOE4 carriers, suggesting that APOE4 carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.

The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

The Estrous Cycle Coordinates the Circadian Rhythm of Eating Behavior in Mice.

The estrous cycle regulates rhythms of locomotor activity, body temperature, and circadian gene expression. In female mice, activity increases on the night of proestrus, when elevated estrogens cause ovulation. Exogenous estradiol regulates eating behavior rhythms in female mice fed a high-fat diet, but it is unknown whether endogenous estrogens regulate eating rhythms. In this study, we investigated whether diurnal and circadian eating behavior rhythms change systematically across the estrous cycle. We first studied diurnal eating behavior rhythms in female C57BL/6J mice in 12L:12D. Estrous cycle stages were determined by vaginal cytology while eating behavior and wheel revolutions were continuously measured. The mice had regular 4- to 5-day estrous cycles. Consistent with prior studies, the greatest number of wheel revolutions occurred on the night of proestrus into estrus when systemic levels of estrogens peak. The amplitude, or robustness, of the eating behavior rhythm also fluctuated with 4- to 5-day cycles and peaked primarily during proestrus or estrus. The phases of eating behavior rhythms fluctuated, but not at 4- or 5-day intervals, and phases did not correlate with estrous cycle stages. After ovariectomy, the eating behavior rhythm amplitude fluctuated at irregular intervals. In constant darkness, the amplitude of the circadian eating behavior rhythm peaked every 4 or 5 days and coincided with the circadian day that had the greatest number of wheel revolutions, a marker of proestrus. These data suggest that fluctuations of ovarian hormones across the estrous cycle temporally organize the robustness of circadian eating behavior rhythms so that it peaks during ovulation and sexual receptivity.

Steroid sulfatase and sulfotransferases in the estrogen and androgen action of gynecological cancers: current status and perspectives.

Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis and action of steroid hormones. STS catalyzes the hydrolysis of estrone-sulfate (E1-S) and dehydroepiandrosterone-sulfate (DHEA-S), while sulfotransferases catalyze the reverse reaction and require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control the concentration of active estrogens and androgens in peripheral tissues. Aberant expression of STS and SULT genes has been found in both, benign hormone-dependent diseases and hormone-dependent cancers. The aim of this review is to present the current knowledge on the role of STS and SULT in gynecological cancers, endometrial (EC) and ovarian cancer (OC). EC is the most common and OC the most lethal gynecological cancer. These cancers primarily affect postmenopausal women and therefore rely on the local production of steroid hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) or organic anion transporters (OAT), STS and SULT regulate the formation of active estrogens and androgens, thus disturbed balance between STS and SULT can contribute to the onset and progression of cancer. The importance of these enzymes in peripheral estrogen biosynthesis has long been recognized, and this review provides new data on the important role of STS and SULT in the formation and action of androgens, their regulation and inhibition, and their potential as prognostic biomarkers.

Steroid metabolism and hormonal dynamics in normal and malignant ovaries.

The ovaries are key steroid hormone production sites in post-pubertal females. However, current research on steroidogenic enzymes, endogenous hormone concentrations and their effects on healthy ovarian function and malignant development is limited. Here, we discuss the importance of steroid enzymes in normal and malignant ovaries, alongside hormone concentrations, receptor expression and action. Key enzymes include STS, 3ß-HSD2, HSD17B1, ARK1C3, and aromatase, which influence ovarian steroidal action. Both androgen and oestrogen action, via their facilitating enzyme, drives ovarian follicle activation, development and maturation in healthy ovarian tissue. In ovarian cancer, some data suggest STS and oestrogen receptor α may be linked to aggressive forms, while various oestrogen-responsive factors may be involved in ovarian cancer metastasis. In contrast, androgen receptor expression and action vary across ovarian cancer subtypes. For future studies investigating steroidogenesis and steroidal activity in ovarian cancer, it is necessary to differentiate between disease subtypes for a comprehensive understanding.

Association between Disgust Sensitivity during Pregnancy and Endogenous Steroids: A Longitudinal Study.

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/ß-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/ß-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

Chorio-retinal vessel density in women affected by functional hypothalamic amenorrhea: a monocentric observational cross-sectional study to evaluate the impact of hypoestrogenism on chorio-retinal vascularization.

PURPOSE: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization. RESULTS: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district. CONCLUSION: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance.

Endogenous estrogens and brain activation during verbal memory encoding and recognition in the postmenopause.

OBJECTIVE: Determine associations of endogenous estrogens with memory systems in the postmenopausal brain and evaluate clinical significance. STUDY DESIGN: In the MsBrain cohort (n=199, mean age 59.3+3.9 years, 83.9% white), we examined the cross-sectional association of serum estradiol and estrone, measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), during a functional magnetic resonance imaging (fMRI) task of word encoding and recognition. To characterize the clinical significance of those associations, we examined the magnitude of activation in relation to a neuropsychological measures of memory and affect. RESULTS: Endogenous estradiol was positively associated with activation in temporal and frontal cortices during encoding and negatively associated with one prefrontal region during recognition (p<.05). Activation in the left inferior frontal gyrus was associated with memory performance (ß(SE)= 0.004(0.002), p<.05), and anxiety (ß(SE)= -0.100(0.050), p<.05). The left middle frontal gyrus was associated with memory performance (ß(SE)= 0.006(0.002), p<.01), depression, and anxiety. The left superior temporal gyrus (STG) was associated with depression (ß(SE)= -0.083(0.036), p<.05) and anxiety (ß(SE)= -0.134(0.058), p<.05). Estrone was positively associated with activation in a range of brain areas including bilateral STG and right superior frontal gyrus during encoding (p<.05). Activation of the left insula an precental gyrus were associated with symptoms of depression and anxiety. None related to memory. CONCLUSION: The function of brain areas critical to memory performance varies with estrogen levels in the postmenopause, even though those levels are low. Higher levels of estradiol may facilitate memory performance through enhanced function of temporal and frontal cortices during encoding of verbal material.