Changes In Hormonal Milieu Research Articles

Our Patient Lost Weight But Also Her Heartbeat

Purpose: Symptomatic bradycardia has been reported in morbidly obese individuals and is often attributed to untreated obstructive sleep apnea. Development of this complication de novo in patients after successful gastric bypass surgery and weight loss is rare. Case description: We present the unique case of a 46 year old woman with past medical history of HTN, osteoarthritis and morbid obesity. She complained of intermittent episodes of lightheadedness and syncope which started 5 months after a successful Roux-en-Y gastric bypass surgery. She denied any history of hypothyroidism and was not on any medication which would precipitate bradycardia. Symptoms would appear at any time during the day without any triggers. In the post surgery period, she lost > 50 Kg of weight and her BMI improved from 49.9 to 28.1. She felt very active otherwise and had no complaints of day time sleepiness, snoring or apneic episodes during sleep. Physical exam during the episode revealed heart rate of 32- 36/ min, blood pressure of 100/70. There was no icterus, thyromegaly, pedal edema, heart murmurs or hyporeflexia. EKG showed sinus bradycardia with intermittent pauses. Echocardiogram showed normal ejection fraction and surprisingly revealed normalization of left ventricular hypertrophy which was reported in a previous study done 6 months prior to surgery. Metabolic profile, thyroid function and cortisol levels were with in normal limits. Patient was evaluated by cardiology and it was concluded that her symptoms were due to an increased resting vagal tone and decreased resting oxygen uptake after surgery. This condition is considered to be benign and does not require a pacemaker. She was started on scopolamine patch with complete resolution of bradycardia and her symptoms. Discussion: Pathophysiology of bradycardia developing after successful weight loss involves decreased cardiac output and resting oxygen uptake by tissues. Bariatric surgery leads to increased Glucagon-like peptide-1 and Ghrelin levels stimulating the enterocardiac hormonal axis. This axis modulates decrease in sympathetic outflow and strengthening of resting vagal tone resulting in bradycardia. The favorable change in hormonal milieu and decreased cardiac output leads to regression of ventricular hypertrophy as was observed in our patient. Clinicians should be aware of this relatively rare and benign condition in this era of increasing use of Bariatric surgery for weight loss.

Postpartum changes in maternal and infant erythrocyte fatty acids are likely to be driven by restoring insulin sensitivity and DHA status

Introduction Perinatal changes in maternal glucose and lipid fluxes and de novo lipogenesis (DNL) are driven by hormones and nutrients. Docosahexaenoic acid (DHA) reduces, whereas insulin augments, nuclear abundance of sterol-regulatory-element-binding-protein-1 (SREBP-1), which promotes DNL, stearoyl-CoA-desaturase (SCD, also Δ9-desaturase), fatty acid-(FA)-elongation (Elovl) and FA-desaturation (FADS). Decreasing maternal insulin sensitivity with advancing gestation and compensatory hyperinsulinemia cause augmented postprandial glucose levels, adipose tissue lipolysis and hepatic glucose- and VLDL-production. Hepatic VLDL is composed of dietary, body store and DNL derived FA. Decreasing insulin sensitivity increases the contribution of FA from hepatic-DNL in VLDL-triacylglycerols, and consequently saturated-FA and monounsaturated-FA (MUFA) in maternal serum lipids increase during pregnancy. Although other authors described changes in maternal serum and RBC essential-FA (EFA) after delivery, none went into detail about the changes in non-EFA and the mechanisms behind -and/or functions of- the observed changes. Hypothesis Postpartum FA-changes result from changing enzymatic activities that are influenced by the changing hormonal milieu after delivery and DHA-status. Empirical data We studied FA-profiles and FA-ratios (as indices for enzymatic activities) of maternal and infant RBC at delivery and after 3 months exclusive breastfeeding in three populations with increasing freshwater-fish intakes. DNL-, SCD- and FADS2-activities decreased after delivery. Elongation-6 (Elovl-6)- and FADS1-activities increased. The most pronounced postpartum changes for mothers were increases in 18:0, linoleic (LA), arachidonic acid (AA) and decreases in 16:0, 18:1ω9 and DHA; and for infants increases in 18:1ω9, 22:5ω3, LA and decreases in 16:0 and AA. Changes were in line with the literature. Discussion Postpartum increases in 18:0, and decreases in 16:0 and 18:1ω9, might derive from reduced insulin-promoted DNL-activity, with more reduced SCD- than Elovl-activity that leaves more 16:0 to be converted to 18:0 (Elovl-activity) than to MUFA (SCD-activity). Postpartum changes in ΣDNL, saturated-FA and MUFA related negatively to RBC-DHA. This concurs with suppression of both SCD- and Elovl-6 activities by DHA, through its influence on SREBP. Infant MUFA and LA increased at expense of their mothers. Sustained transport might be important for myelination (MUFA) and skin barrier development (LA). Maternal postpartum decreases in FADS2-, and apparent increases in FADS1-activity, together with increases in LA, AA, and 22:5ω3, but decrease in DHA, confirm that FADS2 is rate limiting in EFA-desaturation. Maternal LA and AA increases might be the result of rerouting from transplacental transfer to the incorporation into milk lipids and discontinued placental AA-utilization. Implications Perinatal changes in maternal and infant FA status may be strongly driven by changing insulin sensitivity and DHA status.

FC29-06 - Psychological stress causes relative infertility through direct change in the frequency pattern of GnRH release from the hypothalamus

ObjectivesEvaluation of oscillation pattern of GnRH release by the hypothalamus in different mental statesMaterials and methodsTwenty two patients were evaluated by a computer algorithm to find oscillation of LH/GnRH pulsation measured on four sessions (day 6 and 14) every 10 minutes within two consecutive cycles in addition to the MCMI-III and Hamilton test.ResultsThe pattern of oscillation was indirectly correlated with Hamilton scale and the anxiety state and showed statistically significant lowering of frequency during anxiety and depression states. Besides, the slope of GnRH between two consecutive sessions (d0GnRH0/GnRH1dt) showed also a prominent reduction and even flattening. In addition the time to ovulation was also postponed in cycles with prominent anxiety.Conclusions1.Psychological stress exerts its effect through a reduction of pulsation frequency in GnRH release.2.Pattern of GnRH pulsation changes in the range of ¼ to 1/15 of the baseline and external stimuli have strength of changing hormonal milieu in this range.3.MCMI-III is an excellent tool for evaluating psychological state of the patient.4.Patients with borderline, schizoid, dependent, depressed and passive aggressive personality suffer most from irregularity of menstruation cycles.5.Patients with chronic major depression are subject to menstrual irregularity highest during stabilization of disease and in the early phases of recovery after treatment with SSRI.6.Treatment of depression/anxiety causes a reduction of menstrual cycles length.7.Measurement of GnRH, FSH, LH and Estradiol on two sessions one week apart is a nice marker for regularity and ovulation.

Protein metabolism in women and men: similarities and disparities

To provide an objective and comprehensive review of the recent literature addressing the effects of sex on protein metabolism. We also evaluate whether these differences can be attributed to physiology or methodology. Because of the developmental changes in hormonal milieu and body composition that occur across life, the literature has been examined in a longitudinal manner across the lifespan. Throughout most points of life, men and women of similar health status and BMI display fairly similar protein turnover rates. However, some investigators have reported sexual dimorphism in protein metabolism, which may be partly attributable to differences in fat-free mass and/or methodology. In periods of significant changes in the hormonal milieu (puberty and menopause), sex differences may become more evident. Finally, anabolic stimuli such as feeding and exercise may help highlight any discrepancies in protein turnover between men and women. Sex differences in protein metabolism, if any, are most evident during the main phases of hormonal changes, and may be also due to differences in body composition. However, methodological issues and sample size must be considered when designing and evaluating these studies.

Associations of depression with the transition to menopause

The aims of this study were to identify the risk of depression in the transition to menopause in women with and without a history of depression and to consider that the changing hormonal milieu is one of multiple risk factors for perimenopausal depression. A review of epidemiologic studies of depressed mood in the menopausal transition since the State-of-Science Report of the National Institutes of Health in 2005 was conducted. Recent longitudinal cohort studies indicate that the likelihood of depressed mood in the menopausal transition is approximately 30% to three times greater compared with that during premenopause. Women with a history of depression are nearly five times more likely to have a diagnosis of major depression in the menopausal transition, whereas women with no history of depression are two to four times more likely to report depressed mood compared with premenopausal women. In some studies, the changing hormonal milieu is significantly associated with depressive symptoms in the menopausal transition. Other risk factors for depressed mood in perimenopausal women include poor sleep, hot flashes, stressful or negative life events, employment status, age, and race. The findings support the concept that the menopausal transition is a "window of vulnerability" for some women and is framed by the changing hormonal milieu of ovarian aging.

Ventricular hypertrophy and cavity dilatation in relation to body mass index in women with uncomplicated obesity

ObjectiveThe traditionally accepted mechanism for ventricular adaptation to obesity suggests that cavity dilatation in response to increased blood volume and elevated filling pressure results in ventricular hypertrophy as a compensatory...

The hormonal profile of hip fracture female patients differs from community-dwelling peers over a 1-year follow-up period

Hormone levels were compared over a 1-year period between elderly women who had sustained a hip fracture and women of similar age and functional ability. Our study suggests progressive hormonal changes that may contribute to severe bone loss during the year following hip fracture. Alterations in hormones affecting the musculoskeletal system may increase risk of hip fracture or poor post-fracture recovery in postmenopausal women. Most studies lack appropriate reference groups, and thus cannot assess the extent to which these alterations are attributable to hip fracture. Women aged ≥65years hospitalized for an acute hip fracture (Baltimore Hip Studies, BHS-3; n = 162) were age-matched to 324 women enrolled in the Women's Health and Aging Study I, a Baltimore-based cohort with similar functional status to the pre-fracture status of BHS-3 women. Both studies enrolled participants from 1992 to 1995. Insulin-like growth hormone-1 (IGF-1), parathyroid hormone (PTH), 1,25 dihydroxyvitamin D [1,25(OH)2D], and osteocalcin were evaluated at baseline and 2, 6, and 12months post-fracture, and at baseline and 12months in the comparison group. Between-group differences in trajectories of each hormone were examined. Baseline mean IGF-1 levels were significantly lower in hip fracture patients than the comparison group (75.0 vs. 110.5μg/dL; p < 0.001). Levels increased by 2months post-fracture, but remained significantly lower than those in the comparison group throughout the 12-month follow-up (p < 0.01). Levels of PTH and osteocalcin were similar between groups at baseline, but rose during the year post-fracture to significantly differ from the comparison women (p < 0.001). 1,25(OH)2D levels did not differ between the hip fracture and comparison women at any time. Older women who have sustained a hip fracture have progressive changes in hormonal milieu that exceed those of women of similar health status during the year following fracture.

Myocardial Fatty Acid Metabolism in Health and Disease

There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the beta-oxidation of long-chain fatty acids. The control of fatty acid beta-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via beta-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid beta-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid beta-oxidation and how alterations in fatty acid beta-oxidation can contribute to heart disease. The implications of inhibiting fatty acid beta-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.

Temporal associations of hot flashes and depression in the transition to menopause

The aim of this study was to evaluate associations between hot flashes and depressed mood in the menopausal transition and associations of these symptoms with reproductive hormone changes. A 10-year follow-up in a population-based cohort of women who had no experience of hot flashes or depressed mood at baseline was conducted. The incidence of hot flashes significantly increased compared with the incidence of depressed mood in the 10-year follow-up (P < 0.001). Sixty-seven percent of the women reported hot flashes, 50% reported depressed mood, and 41% reported both symptoms during the study interval. Reporting of both hot flashes and depressed mood was greater than expected if the processes operated independently (P < 0.001). Of the women who experienced both symptoms, depressed mood was more likely to precede hot flashes (relative risk = 2.1; 95% CI, 1.5-2.9). Within-woman increases in follicle-stimulating hormone levels were associated with the onset of depressed mood in unadjusted analysis (P = 0.05). Increased follicle-stimulating hormone levels, decreased inhibin B levels, and the variability of estradiol were significantly associated with hot flashes. Follicle-stimulating hormone and inhibin B remained significantly associated with hot flashes in the final multivariable models (P < 0.001). Both hot flashes and depressive symptoms occur early in the menopausal transition in women with no previous experience of these symptoms. Depressive symptoms are more likely to precede hot flashes in women who report both symptoms. The findings support the concept that the changing hormonal milieu of the menopausal transition is one of multiple factors associated with the onset of symptoms.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status

To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. Multicenter, randomized, controlled clinical trial. University hospitals. A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. Measurement of myoma volume and E(2), FSH, LH, and T levels. Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma.

Sarcopenic obesity: definition, cause and consequences.

Older obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, rather, muscle weakness should be used for the definition. Excess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so-called 'sarcopenic obesity'. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term 'sarcopenic obesity' should be revisited. Recognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome.

Psychosocial and cultural contributions to depression in women: considerations for women midlife and beyond.

Women share a greater burden of mood disorders than men and have twice the prevalence rate of depression. To highlight some of the psychosocial and cultural contributions to depression in women. Multiple factors contribute directly or interact to precipitate the onset of depression. Genetics, stress life events, previous history of depression, and cognitive factors have been shown to be significant risk factors for future depression episodes. Life stressors contribute to the onset of depression in both men and women, but particular stressors affect the genders differently, with women identifying more closely with relationship issues, lack of adequate housing, and poverty. Women are also more frequently affected by physical and sexual abuse, which will significantly influence future episodes of depression. Depression does not discriminate on the basis of race. Women of all ethnic groups suffer from depression. However, research indicates that there may be differences in prevalence and treatment-seeking behavior in black Americans, Mexican Americans, and white Americans. Many factors contribute to the occurrence of depression. Some of these occurrences may be explained by the changing hormonal milieu, susceptibility after physical or sexual abuse, poverty, housing problems, or loss of a close friend. One of the explanations for the higher rate of depression in women is that women have a greater incidence of first depressive episodes, which often begin during adolescence or young adulthood.

Proliferation, Hyperplasia, Neogenesis, and Neoplasia in the Islets of Langerhans

Pancreatic disease is responsible for significant morbidity and mortality as a result of pancreatic carcinoma and diabetes mellitus. Regulation of endocrine cell mass is thought to have a central role in the pathogenesis of both these diseases. Islet cell proliferation, hypertrophy, neogenesis, and apoptosis are the main determinants of endocrine cell mass in the pancreas, and their understanding has been improved by new clues of their genetic and molecular basis. Beta cells have attracted most research interest because of potential implications in the treatment of diabetes mellitus and hypoglycemic disorders. The processes that operate during pancreatic adaptation to a changing hormonal milieu are important in pancreatic carcinogenesis. There is evidence that somatostatin and its receptors are fundamental regulators of endocrine cell mass and are involved in islet tumorigenesis.

Cognitive side-effects of adjuvant treatments

Symptoms associated with cognitive dysfunction—difficulties with memory, concentration, and language—are frequent among breast cancer survivors after chemotherapy. The true incidence, functional significance, and causes of these symptoms remain unclear. Models of cognitive dysfunction suggest multiple possible contributors including changes in hormonal milieu, direct effects of chemotherapy, medications given as supportive care, psychiatric changes including depression and anxiety, and mediators of inflammation. Novel neuro-cognitive testing and imaging methods are being evaluated in breast cancer survivors to better understand cognitive side-effects of therapy.

Hormonal Changes Throughout Life in Women

The changes in hormonal milieu associated with menarche, pregnancy, lactation, and menopause are frequently accompanied by changes in the patterns and frequency of migraine. Migraine headache is more common in females and, for many women, the onset of this condition occurs at menarche. As many as 60% of women migraineurs report an association between migraine and menstruation, and evidence suggests that estrogen withdrawal may be a trigger for menstrual migraine in susceptible women. Moreover, in the majority of women, migraine frequency increases during the pill-free interval with oral contraceptive use and during the postpartum period, which are other times of decreasing estrogen levels. Migraine frequency tends to decrease during periods of increasing or stable estrogen levels. For these reasons, the numerous neuroendocrine effects elicited by estrogen have been evaluated to explain its role in migraine. Overall, estrogen appears to be a key factor in menstrual migraine, but it is likely to be only one of several factors that act in concert to trigger migraine in susceptible women. Understanding the relationship of the different hormonal milieus through the natural course of women's lives can guide diagnosis and treatment.

Application of functional genomics to primate endometrium: insights into biological processes.

Endometrium is a dynamic tissue that responds on a cyclic basis to circulating levels of the ovarian-derived steroid hormones, estradiol and progesterone. Functional genomics has enabled a global approach to understanding gene regulation in whole endometrial tissue in the setting of a changing hormonal milieu. The proliferative phase of the cycle, under the influence of estradiol, has a preponderance of genes involved in DNA synthesis and cell cycle regulation. Interestingly, genes encoding ion channels and cell adhesion, as well as angiogenic factors, are also highly regulated in this phase of the cycle. After the LH surge, different gene expression profiles are uniquely observed in the early secretory, mid-secretory (window of implantation), and late secretory phases. The early secretory phase is notable for up-regulation of multiple genes and gene families involved in cellular metabolism, steroid hormone metabolism, as well as some secreted glycoproteins. The mid-secretory phase is characterized by multiple biological processes, including up-regulation of genes encoding secreted glycoproteins, immune response genes with a focus on innate immunity, and genes involved in detoxification mechanisms. In the late secretory phase, as the tissue prepares for desquamation, there is a marked up-regulation of an inflammatory response, along with matrix degrading enzymes, and genes involved in hemostasis, among others. This monograph reviews hormonal regulation of gene expression in this tissue and the molecular events occurring therein throughout the cycle derived from functional genomics analysis. It also highlights challenges encountered in using human endometrial tissue in translational research in this context.

Perimenopausal Depression Often Overlooked or Undertreated

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessPerimenopausal Depression Often Overlooked or UndertreatedJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:19 May 2006https://doi.org/10.1176/pn.41.10.0032As women who have made the journey to menopause know, mood swings are often part of the baggage. Exactly how susceptible women are to depression during the months and years preceding menopause, however, has been unclear, as has the role of various hormones in that depression.A carefully designed longitudinal study has now documented not only that many women without a history of depression do get depressed during the perimenopausal period, but that changes in levels of specific hormones coincide with their getting depressed.The study was headed by Ellen Freeman, Ph.D., a research professor in the University of Pennsylvania's Department of Obstetrics and Gynecology. Results appear in the April Archives of General Psychiatry.Freeman and her colleagues enrolled 231 women with no history of depression in their investigation. All were premenopausal and ranged in age from 35 to 47 years. The subjects were interviewed in their homes by trained research interviewers 10 times over the following eight years about their menstrual cycle dates, reproductive history, general health status, and health behaviors.Subjects were also assessed for current depressive symptoms with the CES-D, a self-report questionnaire, and for clinical depression with the PRIME-MD or its self-report version, the Patient Health Questionnaire. Both versions yield DSM-IV diagnoses.Each assessment period included two visits, scheduled in the first six days of two consecutive menstrual cycles, to obtain blood samples, and these samples were measured for levels of three reproductive hormones— luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol.The investigators then analyzed the information to determine whether the subjects had developed depression during the course of the study, and if so, whether the depression could be linked with the status of LH, FSH, or estradiol in their bodies at the time of depression.Half of the subjects reported high depression scores at least once during the study, and a quarter met criteria for a depressive disorder during it. Moreover, subjects were four times more likely to experience depression symptoms during their menopausal transition than when they were premenopausal. This difference was highly significant statistically. Subjects were 2.5 times more likely to have a depressive disorder when they were perimenopausal than when they were premenopausal. This difference was also statistically significant.Furthermore, after possibly confounding factors such as smoking, body mass index, premenstrual syndrome, health status, hot flashes, and poor sleep were considered, increased levels of LH and FSH and increased variability in LH, FSH, and estradiol were significantly linked with subjects' depressive symptoms or diagnosis of depression.For example, when subjects were diagnosed for a depressive disorder, they were, on average, nine times more likely to have higher FSH levels and five times more likely to have higher LH levels than before they were diagnosed. And at the time of depression diagnosis, a woman was much more likely to have an increased variability in her levels of estradiol and FSH than before the diagnosis.“Our data indicate that transition to menopause and its changing hormonal milieu are strongly associated with both new onset of high depressive symptoms and new onset of diagnosed depressive disorders in women with no history of depression,” the researchers concluded.“This is a very important study that will benefit the area of women's mental health,” Marlene Freeman, M.D., an assistant professor of psychiatry and obstetrics and gynecology at the University of Arizona and director of the university's Women's Mental Health Program, told Psychiatric News. “These investigators carefully demonstrated that perimenopausal status and hormone variability appear to increase the risk of depression in a large segment of women. These findings should compel further research into screening and treatment for perimenopausal depression.” (Marlene Freeman, M.D., is not related to study author Ellen Freeman, M.D.)These results, Marlene Freeman said, also “speak to the need for primary care providers, gynecologists, and other health care providers to receive appropriate education in the identification and treatment of major depression. We might expect that women who have not previously experienced mood disorders.. .may feel more comfortable seeking help from a primary care doctor than a psychiatrist. In addition, considering the current controversies surrounding hormone-replacement therapy, this study's findings suggest that psychiatrists need to understand the risks and benefits of hormonal therapies for perimenopause, as well as nonhormonal options.”The study was financed by the National Institutes of Health.An abstract of “Associations of Hormones and Menopausal Status With Depressed Mood in Women With No History of Depression” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/63/4/375.▪ ISSUES NewArchived

Associations of Hormones and Menopausal Status With Depressed Mood in Women With No History of Depression

Whether depressed mood reported in the transition to menopause by women with no history of depression is associated with menopausal status and changes in reproductive hormones is controversial and lacks scientific information. To identify new onset of depressive symptoms and diagnosed depressive disorders in the menopausal transition and to determine the associations of menopausal status, reproductive hormones, and other risk factors with these cases. A within-woman, longitudinal (8-year) study to identify risk factors of depressed mood. A subset of a randomly identified, population-based cohort. Premenopausal women with no history of depression at cohort enrollment. The Center for Epidemiological Studies of Depression scale (CES-D) was used to assess depressive symptoms, and the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify clinical diagnoses of depressive disorders. High CES-D scores (> or=16) were more than 4 times more likely to occur during a woman's menopausal transition compared with when she was premenopausal (odds ratio, 4.29; 95% confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal status, increased levels of follicle-stimulating hormone and luteinizing hormone, and increased variability of estradiol, follicle-stimulating hormone, and luteinizing hormone around the woman's own mean levels were each significantly associated with high CES-D scores after adjusting for smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status. A diagnosis of depressive disorder was 2(1/2) times more likely to occur in the menopausal transition compared with when the woman was premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the hormone measures were also significantly associated with this outcome. Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression.

Hormones and Menopausal Status as Predictors of Depression in Womenin Transition to Menopause

Associations between depressed mood and hormonal changes during transition to menopause are controversial. To our knowledge, there has been no prospective study of these associations in women commencing when they are premenopausal. To longitudinally study the associations among reproductive hormones, menopausal status, and other predictors of depressed mood in midlife women. Cohort study with 6 assessment periods during a 4-year interval. Blood samples were collected 12 times during the follicular phase (days 2-6). Philadelphia County, Pennsylvania. A randomly identified, population-based, stratified sample of African American (n = 218) and white (n = 218) women aged 35 to 47 years with regular menstrual cycles, no hormonal or psychotropic medication use, and no serious physical or mental health problems at enrollment. Center for Epidemiologic Studies Depression Scale score and history of depression via the Primary Care Evaluation of Mental Disorders. There was an increased likelihood of depressive symptoms during transition to menopause and a decreased likelihood after menopause after adjustment for other predictors of depression, including history of depression, severe premenstrual syndrome, poor sleep, age, race, and employment status (P =.03). The likelihood of depressive symptoms decreased for individuals with a rapidly increasing follicle-stimulating hormone profile (P< or =.001) and also decreased with age compared with premenopausal women (P =.02). Participant aggregate profiles with increasing estradiol levels were significantly associated with depressive symptoms in bivariate analysis (P =.053). Depressive symptoms as assessed herein increased during transition to menopause and decreased in postmenopausal women. Hormone associations provided corroborating evidence that the changing hormonal milieu contributes to dysphoric mood during transition to menopause.

Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization.

Microarrays comprise an efficient approach to discovering large numbers of differentially expressed mRNA transcripts in the CNS resulting from changes in hormonal milieu. We used high-density oligonucleotide microarrays to examine the short- and long-term actions of estradiol (E(2)) on the transcriptomes from the medial basal hypothalamus and other brain regions of E(2)-treated (10 microg) adult female mice. Our results have revealed several unanticipated gene regulations. Most striking is lipocalin prostaglandin D(2) synthase (L-PGDS), which catalyzes the conversion of prostaglandin (PG) H(2) to PGD(2), a neuromodulator involved in a variety of functions, including sleep, pain, and odor responses. In situ hybridization revealed significant increases in L-PGDS expression in the arcuate and ventromedial nucleus of the medial basal hypothalamus compared with vehicle controls. The magnitude of these changes is approximately 2-fold and suggests a modulatory role for PGD(2) in E(2)-controlled neuroendocrine secretions and behaviors. Surprisingly, L-PGDS gene expression is reduced 2-fold after E(2) treatment in the ventrolateral preoptic area (VLPO), the suspected site of action for the sleep-promoting effects of PGD(2). Finally, whereas L-PGDS has been reported to be expressed primarily in oligodendrocytes of the adult rodent brain, we demonstrate, immunocytochemically, that L-PGDS is also expressed in a population of VLPO neurons. Thus, our data suggest the intriguing possibility that E(2) modulation of L-PGDS plays a role in the regulation of sleep-wake states through hitherto unknown mechanisms in VLPO neurons and through hormone-dependent neuronal-glial cooperation.