Postmenopausal Women Receiving Hormone Replacement Research Articles

The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion

Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promotes the generation of suppressive cortical actin bundles that inhibit motility dynamics, and is crucial for the ER-mediated suppression of invasion in vitro and in vivo. Interestingly, despite its benefits in suppressing tumor growth, anti-estrogenic endocrine therapy decreases EVL expression and increases local invasion in patients. Our results highlight the dichotomous effects of estrogen on tumor progression and suggest that, in contrast to its established role in promoting growth of ER+ tumors, estrogen has a significant role in suppressing invasion through actin cytoskeletal remodeling.

Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia.

SummaryMeningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0–1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (<6.5 nmol/L). CT abdomen was performed as the patient complained of rapid-onset increasing abdominal girth and revealed bilateral large adrenal myelolipomata. MRI brain revealed a large meningioma involving the right sphenoid wing with anterior displacement of the right eye and associated bony destruction. Surgical debulking of the meningioma was performed and histology demonstrated a meningioma, which stained positive for the progesterone receptor. Growth of meningioma has been described in postmenopausal women receiving hormone replacement therapy, in women receiving contraceptive therapy and in transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth.Learning points:Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels.Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours.Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.

Complicaciones de la terapia hormonal de reemplazo en posmenopáusicas sanas

OBJETIVO: Identificar las principales complicaciones asociadas al uso de la terapia hormonal de reemplazo. MATERIALES Y MÉTODOS: Estudio observacional, transversal y retrospectivo de 514 mujeres posmenopáusicas sanas que recibían terapia hormonal de reemplazo con 0,625 mg de estrógenos equinos conjugados más 2,5 mg de acetato de medroxiprogesterona por día, durante el período comprendido entre enero 1998 y diciembre 2002. RESULTADOS: La edad media fue 57,5 ± 5,75 años (rango, 50-76). El índice de masa corporal fue anormal en 87,0% (n=447) de pacientes, y se encontró sobrepeso y desnutrición en 12,5% (n=64) y 0,6% (n=3), respectivamente. La incidencia de complicaciones asociadas a la terapia hormonal fue 40,1%. La más frecuentes fueron hipertrigliceridemia (31,7%), hipercolesterolemia (25,9%), enfermedad coronaria (6,2%), hiperplasia endometrial (2,4%) y cáncer de mama (2,4%), presentándose más frecuentemente (63,2%) en pacientes mayores de 70 años. No se registró caso de embolia pulmonar. CONCLUSIONES: Las principales complicaciones de la terapia de reemplazo hormonal en este grupo de mujeres fueron hipertrigliceridemia, hipercolesterolemia, enfermedad coronaria, hiperplasia endometrial y cáncer de mama, las que se presentaron con mayor frecuencia después de los 70 años.

Evaluation of uterine perfusion in postmenopausal women receiving hormone replacement therapy

Objectives: The authors evaluated uterine perfusion in postmenopausal women receiving hormone replacement therapy (HRT) by using transvaginal Doppler ultrasonography. Materials and methods: A total of 60 postmenopausal women receiving HRT were included in this prospective case control study. The patients were divided into two groups. The study group received HRT for at least one year. Uterine perfusion was evaluated by transvaginal Doppler ultrasonography and pulsatility index (PI) and resistance index (RI) of uterine arteries were also recorded with a 5-7.5 MHz transvaginal probe. All patients gave informed consent to the study. Statistical analyses were carried out by using the statistical packages for SPSS 15.0 for Windows. Results: Demographic characteristics of the cases showed no statistically significant difference between the groups. There was a statistically significant difference between PI and RI of uterine arteries. In the study group PI and RI were lower than in the control group. As the duration of HRT use was prolonged, a decline in PI and RI increased (p Conclusion: The current study showed that HRT has positive effects on uterine blood flow in postmenopausal women and may be evaluated by transvaginal Doppler ultrasonography.

Oestrogen induced downregulation of TFPI expression is mediated by ERα

IntroductionOestrogens influence the pathophysiology and development of hormone-sensitive cancers, such as breast cancer. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor of the extrinsic coagulation pathway and has recently been associated with breast cancer cell development. Moreover, reduced TFPI levels have been reported in plasma of healthy post-menopausal women receiving hormone replacement therapy, indicating a possible link between oestrogen and TFPI. In our study, we aimed to examine the effects of oestrogen and oestrogen analogues on TFPI expression in breast cancer cells and to identify underlying mechanism(s). MethodsOestrogen receptor alpha (ERα) positive MCF7 and negative MDA-MB-231 cells were treated with 17-β-oestradiol, 17-β-ethinyloestradiol, raloxifene and fulvestrant. TFPI mRNA and protein was measured using qRT-PCR and ELISA, respectively. Transient ERα knockdown was achieved using siRNA. ResultsIn ERα expressing MCF7 cells, but not in MDA-MB-231 cells, the TFPI mRNA and protein levels were significantly downregulated by more than 50% after four or six hours of incubation with 17-β-ethinyloestradiol and 17-β-oestradiol, respectively. Moreover, a significant increase in FXa generation was detected in response to oestrogens. Breast tissue ER antagonists, raloxifene and fulvestrant, did not affect TFPI mRNA, however, fulvestrant blocked oestrogen mediated reduction of TFPI mRNA. Transient knockdown of ERα abolished the oestrogenic effect on TFPI and co-treatment of MCF7 cells with the protein synthesis inhibitor cycloheximide and 17-β-oestradiol also led to reduction of TFPI mRNA. ConclusionOur data establish a direct and time dependent regulation of TFPI expression by oestrogens through the ERα at the transcriptional level.

Medroxyprogesterone Acetate Enhances Monocyte-Endothelial Interaction Under Flow Conditions by Stimulating the Expression of Cell Adhesion Molecules

Monocyte adhesion to endothelial cells is an important initial event in atherosclerosis and is partially mediated by adhesion molecule expression on the cell surface. Although estrogens inhibit atherosclerosis development, effects of coadministered progestogen remain controversial. We examined the effects of progestogen on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. In HUVECs, adhesion molecule mRNA levels were measured by real-time PCR. Protein expression was quantified by immunocytochemistry and ELISAs. To mimic the monocyte adherence to endothelial cells, we used a flow chamber system to assess progestogen effects on U937 monocytoid cell adherence to HUVEC monolayers. We also examined the suppression effects of adhesion molecules with small interference RNAs. mRNA levels of adhesion molecules in HUVECs treated with medroxyprogesterone acetate (MPA) or 17β-estradiol + MPA were 1.7- to 2.5-fold higher than those in the control. MPA increased the protein expression of E-selectin, P-selectin, and intercellular adhesion molecule-1 compared with that for the control (83.0 ± 0.7, 34.8 ± 1.2, and 5.4 ± 0.0 ng/mL, respectively), whereas other progestogens or 17β-estradiol additive to progestogens did not significantly change expression. MPA significantly increased U937 monocytoid cell adherence compared with the control (56.0 ± 1.5 vs 46.5 ± 3.5 adherent cells per 10 fields) but did not increase adherence to HUVECs with knocked down intercellular adhesion molecule-1. MPA increases cell adhesion molecule expression on HUVECs, causing increased numbers of monocytoid cells to adhere to HUVECs. These MPA effects may be a risk factor for atherogenesis on endothelial cells in postmenopausal women receiving hormone replacement therapy.

Hormone replacement therapy leads to increased plasma levels of platelet derived microparticles in postmenopausal women

Whereas prevention of cardiovascular diseases by hormonal replacement therapy is still part of an ongoing debate, well-defined data are available relating hormonal replacement therapy to an elevated risk of venous thrombosis and embolism. Although it seems that venous thrombosis in patients treated with hormonal replacement therapy is linked to changes in plasmatic coagulation, less is known about the role of platelet-derived microparticles, as well as endothelial cell-derived microparticles. In this prospective case-control study, levels of microparticles were investigated in postmenopausal women receiving hormone replacement therapy (n = 15) and compared to age-matched controls (n = 15). Total count of microparticles and the subgroup of microparticles derived from endothelial cells did not differ in the investigated groups. In contrast, median levels of microparticles derived from platelet/megacaryocyte were higher in women taking hormonal replacement therapy (5,244 × 10(6)/l) than in controls (2,803 × 10(6)/l; p = 0.040). Furthermore, hormonal replacement therapy led to a higher plasma level of microparticles derived from activated platelets, exposing P-selectin (136 × 10(6)/l vs. 58 × 10(6)/l; p = 0.011), or exposing CD63 (171 × 10(6) vs. 91 × 10(6)/l; p = 0.011) compared to the control group. Higher concentrations of microparticles derived from (activated) platelets/megacaryocytes were present in postmenopausal women taking hormonal replacement therapy. This finding indicates a procoagulant state in these women and might play a role in the development of venous side effects. In contrast, levels of endothelial cell-derived microparticles did not differ.

Influence of Sex and Hormone Status on Circulating Natriuretic Peptides

The aim of this study was to assess the relationship between sex hormones and natriuretic peptide levels in community-based adults. Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear. Experimental studies suggest that androgens may suppress natriuretic peptide secretion. We measured N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone-binding globulin plasma levels in 4,056 men and women (mean age 40 ± 9 years) from the Framingham Heart Study Third-Generation cohort. Sex/hormone status was grouped as: 1) men; 2) post-menopausal women not receiving hormone replacement therapy; 3) pre-menopausal women not receiving hormonal contraceptives; 4) post-menopausal women receiving hormone replacement therapy; and 5) pre-menopausal women receiving hormonal contraceptives. Circulating NT-proBNP levels were associated with sex/hormone status (overall p < 0.0001). Men had lower NT-proBNP levels than women of all menopause or hormone groups, and women receiving hormonal contraceptives had higher NT-proBNP levels than women who were not receiving hormone therapy (all p < 0.0001). These relationships remained significant after adjusting for age, body mass index, and cardiovascular risk factors. Across sex/hormone status groups, free testosterone (FT) levels decreased and sex hormone-binding globulin levels increased in tandem with increasing NT-proBNP levels. In sex-specific analyses, NT-proBNP levels decreased across increasing quartiles of FT in men (p for trend <0.01) and women (p for trend <0.0001). Adjustment for FT markedly attenuated the association between sex/hormone status and NT-proBNP concentrations. These findings suggest that lower levels of circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP concentrations in women.

Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure

Postmenopausal women receiving hormone replacement therapy (HRT) have been reported to have more adverse outcomes after vascular reconstructions, including increased intimal hyperplasia development and bypass graft failure. HRT may be affecting the pathway contributing to intimal hyperplasia. An important component of this pathway involves matrix metalloproteinases (MMPs), implicated in vascular remodeling due to their ability to degrade components of the extracellular matrix. We hypothesize that estrogen (Est) and progesterone (Prog) upregulate the MMP pathway in vascular smooth muscle cells (VSMCs) thereby increasing MMP activity and function. VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est + Prog combination (Est/Prog), and/or doxycycline (40 microg/mL; Doxy). Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis we have previously shown membrane type 1-MMP (MT1-MMP) messenger ribonucleic acid (mRNA) levels are significantly increased by Est. Here, Western blot analyses indicated MT1-MMP and MMP-2 protein levels, not tissue inhibitor of MMP-2 (TIMP-2), were increased in response to Est and Est/Prog (P < .05 vs control). In-gel zymography revealed that Est and Est/Prog resulted in increased MMP-2 activity (hormone groups, P < .05 vs control) with no significant difference among the hormone groups. VSMC migration was increased by 45 +/- 14% in response to Est (P < .05 vs control), as measured using a modified Boyden chamber assay. Doxycycline significantly inhibited basal and Est/Prog-stimulated increases in MMP-2 activity (P < .05 vs control; P < .05 vs hormone groups), and partially blocked basal and hormonally stimulated migration (P < .05 vs control and Est). Estrogen and progesterone affects the MMP pathway by increasing MMP-2 enzymatic activity, possibly via the upregulation of MT1-MMP expression without a corresponding increase in TIMP expression. This increased collagenase activity increases VSMC motility and their ability to migrate through a collagen type IV lattice. Est/Prog upregulation of MT1-MMP may contribute to the adverse effect of HRT on vascular interventions.

Genistein and phycocyanobilin may prevent hepatic fibrosis by suppressing proliferation and activation of hepatic stellate cells

Hepatic fibrosis reflects hepatotoxin-mediated activation of hepatic stellate cells, resulting in their proliferation and transformation to myofibroblasts that secrete collagen. This activation is suppressed by estrogen, an effect which explains the decreased risk for hepatic fibrosis enjoyed by premenopausal women and by postmenopausal women receiving hormone replacement therapy. Since stellate cells have been found to express the beta but not the alpha isoform of the estrogen receptor, it can be predicted that nutritional intakes of the soy isoflavone genistein - a selective agonist for ERbeta in the low nanomolar plasma concentrations achievable with these intakes - have potential for suppressing hepatic fibrosis, in both men and women. The antiproliferative impact of estrogen on stellate cells is mediated at least in part by suppression of NADPH oxidase activity; oxidant production by this enzyme complex plays a crucial role in stellate cell activation. Alternatively, it may be feasible to inhibit NADPH oxidase with phycocyanobilin (PCB), a biliverdin homolog found in spirulina that has recently been shown to inhibit the NADPH oxidase activity of human cell cultures in low micromolar concentrations. Joint administration of soy isoflavones and PCB in appropriate doses might have considerable potential for prevention of hepatic fibrosis in at-risk subjects.

Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells

Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on MMP gene expression in human VSMCs. VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1beta (100 U/mL; IL-1beta). Gene array analysis indicated Est+IL-1beta increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 mRNA levels were significantly increased by Est/Prog+IL-1beta treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of MMP (TIMP), were significantly increased by Est/Prog+IL-1beta, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone. Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1beta. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications.

Bone Fragility: Failure of Periosteal Apposition to Compensate for Increased Endocortical Resorption in Postmenopausal Women

The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength. Bone loss from the inner (endocortical) surface contributes to bone fragility, whereas deposition of bone on the outer (periosteal) surface is believed to be an adaptive response to maintain resistance to bending. To test this hypothesis, changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius, bone turnover markers, and fracture incidence were measured annually in 821 women 30-89 years of age for 7.1 +/- 2.5 years. The analyses were made in 151 premenopausal women, 33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women receiving hormone replacement therapy (HRT). In premenopausal women, periosteal apposition increased the radius width, partly offsetting endocortical resorption; therefore, the estimated cortical thickness decreased. Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength. Estimated endocortical resorption accelerated during perimenopause, whereas periosteal apposition decreased. Further cortical thinning occurred, but estimated bending strength was maintained by modest outward cortical displacement. Endocortical resorption accelerated further during the postmenopausal years, whereas periosteal apposition declined further; cortices thinned, but because outward displacement was minimal, estimated cortical area and bending strength now decreased. Women with highest remodeling had the greatest loss of bone mass and strength. Women with low remodeling lost less bone and maintained estimated bone strength. In HRT-treated women, loss of bone strength was partly prevented. These structural indices predicted incident fractures; a 1 SD lower section modulus doubled fracture risk. Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.

Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement Therapy

The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Teriparatide [rhPTH(1-34)], given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 microg/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400-1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar.

Angiotensin II Plays an Important Role in Maintaining Blood Pressure in Postmenopausal Women Receiving Hormone Replacement Therapy

We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.

Long-term hormone replacement therapy does not cause increased platelet activation

Observational studies have shown apparently lower ischemic coronary disease risk in postmenopausal women receiving hormone replacement therapy (HRT). However, several recent studies have shown an increase in ischemic cardiac events when HRT is initiated in postmenopausal women with known coronary artery disease. It is postulated that estrogen may result in increased platelet aggregation. We evaluated platelet activation, as measured by flow cytometric analysis using P selectin and PAC1 as activation markers, and aggregation, as measured by standard platelet aggregation using platelet-rich plasma, in 27 postmenopausal women (17 HRT, 10 placebo) who were participants in 2 placebo-controlled randomized angiographic trials evaluating the effect of HRT on coronary atherosclerosis or saphenous vein graft disease. All women had received HRT or placebo for >2 years and were on aspirin therapy. The estrogen component was either conjugated equine estrogen or 17beta-estradiol. Patients on HRT and those on placebo had comparable degrees of platelet aggregation when measured using various doses of agonists (adenosine diphosphate and epinephrine). There were no significant differences in levels of platelet activation measured by flow cytometry. We conclude that long-term HRT does not appear to cause increased platelet activation and aggregation in women with coronary artery disease. There may be increased platelet activation in the early period after HRT initiation; however, this was not assessed in this study.

Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy

Determining the benefits and/or drawbacks of hormone replacement therapy (HRT) on women's health is an imperative public health goal. Research in rodents suggests benefits of estrogen on neuronal growth and function. However, little research has investigated the effects of HRT on brain tissue in humans. We used high-resolution magnetic resonance imaging and an optimized voxel-based morphometric technique to examine the effects of HRT on brain volume in postmenopausal women. We report two main results: (a) HRT is associated with the sparing of grey matter in prefrontal, parietal, and temporal brain regions and white matter in medial temporal lobe regions, and (b) longer durations of therapy are associated with greater sparing of grey matter tissue. HRT should be considered a possible mediator of age-related neural decline in both grey and white matter tissues.

Plasma Adiponectin Levels in Post-menopausal Women Receiving Hormone Replacement Therapy

This study aimed to evaluate the correlation between plasma adiponectin levels and plasma lipid and lipoprotein levels in post-menopausal women (PMW) receiving hormone replacement therapy (HRT). Various clinical and biochemical parameters, including plasma lipid and lipoprotein concentrations and adiponectin levels, were measured in 54 healthy PMW before and after 3 and 6 months of HRT. Control groups consisted of women aged < 40 years (n = 20) or > 60 years (n = 17). PMW had significantly lower baseline adiponectin levels compared with the younger or older control groups, but adiponectin concentrations were not significantly altered after 3 or 6 months of HRT. Adiponectin levels in PMW were positively correlated with plasma high-density lipoprotein-cholesterol levels and were negatively correlated with body mass index and triglyceride levels. Our data suggest that circulating adiponectin may contribute to lipid homeostasis in PMW. Further studies are needed to elucidate the effects of HRT and oestrogen on adiponectin levels.

Laboratory pain perception and clinical pain in post-menopausal women and age-matched men with osteoarthritis: relationship to pain coping and hormonal status

The present study examined relationships between pain coping, hormone replacement therapy, and laboratory and clinical pain reports in post-menopausal women and age-matched men with osteoarthritis. Assessment of nociceptive flexion reflex threshold was followed by an assessment of electrocutaneous pain threshold and tolerance. Participants rated their arthritis pain using the Arthritis Impact Measurement Scales. To assess pain coping, participants completed measures of emotion-focused coping, problem-focused coping, and pain catastrophizing. Results indicated that women were more likely than men to report using emotion-focused pain strategies, and that emotion-focused coping was associated with more arthritic pain and lower electrocutaneous pain tolerance. Correlations between coping measures and pain reports revealed that catastrophizing was associated with greater arthritis pain and lower pain threshold and tolerance levels. However, catastrophizing was not related to nociceptive flexion reflex threshold, suggesting that the observed relationship between catastrophizing and subjective pain does not rely on elevated nociceptive input. A comparison of men ( n=58), post-menopausal women receiving hormone replacement therapy ( n=32), and post-menopausal women not receiving hormone replacement therapy ( n=42) revealed no significant group differences in arthritis pain, electrocutaneous pain threshold or tolerance, or nociceptive flexion reflex threshold. Thus, older adults with osteoarthritis do not exhibit the pattern of sex differences in response to experimental pain procedures observed in prior studies, possibly due to the development of disease-related changes in pain coping strategies. Accordingly, individual differences in clinical and experimental pain may be better predicted by pain coping than by sex or hormonal differences.

Alterations in gallbladder emptying and bile retention in the absence of changes in bile lithogenicity in postmenopausal women on hormone replacement therapy.

The role of female sex hormones in the pathogenesis of gallstones is well established. Pregnancy, contraceptive use, estrogen replacement therapy in postmenopausal women, and estrogen therapy in men for the treatment of prostatic carcinoma have been found to be associated with increased risk of cholesterol gallstones. Alterations in gallbladder emptying and in bile lithogenicity in postmenopausal women receiving hormone replacement therapy (HRT) have not been studied to date. The present study was undertaken to study the effect of HRT on gallbladder emptying and bile lithogenicity. Sixteen postmenopausal women were included in the study. None of the patients had gallstone disease and none had received prokinetic drugs, such as, erythromycin, metoclopramide, domperidone or cisapride, aspirin, and nonsteroidal antiinflammatory drugs. Gallbladder emptying (n = 16), bile microscopy (n = 7), cholesterol saturation index (CSI) (n = 7), and nucleation time (n = 7) were studied before and 3 months after HRT (conjugated estrogen, 0.625 mg, + medroxyprogesterone acetate, 2.5 mg, everyday). Fasting and residual volumes increased (fasting volume, 18.2 +/- 2.2 mL pre-HRT vs 27.6 +/- 3.2 mL post-HRT, P = 0.0003; residual volume, 3.9 +/- 0.6 mL pre-HRT vs 10.3 +/- 2.0 mL post-HRT, P = 0.00009) and ejection fraction decreased (78.2 +/- 2.5% pre-HRT vs 62.2 +/- 3.8% post-HRT; P = 0.0017) after 3 months of HRT. There was no change in CSI (2.32 +/- 0.36 pre-HRT vs 2.60 +/- 0.51 post-HRT; P = NS) or in nucleation time (19.0 +/- 1.2 days pre-HRT vs 17.6 +/- 1.3 days post-HRT; P = NS). None of the bile samples either pre-HRT or post-HRT showed cholesterol monohydrate crystals. Though impairment of gallbladder emptying occurs in the short term with HRT in postmenopausal women, there is no change in CSI and nucleation time.

Changes in Hemostasis and Lipid Metabolism in Postmenopausal Women Receiving Hormone Replacement Therapy: Effects of Natural and Synthetic Progestogens

Summary Objective In this study, we evaluated hemostatic factors related to cardiovascular disease in postmenopausal women receiving estrogen or combined progestogen replacement therapy. We further compared the effects of natural and synthetic progestogens on lipid profiles and hemostatic factors. Materials and Methods Of the 60 subjects, 20 who had undergone a hysterectomy used conjugated equine estrogen (CEE; 0.625 mg/day) alone (group I); the other 40 used CEE (0.625 mg/day for 21 days) plus either micronized progesterone (200 mg/day; group II; n = 20) or medroxyprogesterone acetate (10 mg/day; group III; n = 20) for the final 10 days. The effects on lipid profiles and hemostatic parameters were evaluated at baseline and after 6 and 12 months of treatment. Results Only group I patients showed a significant reduction in low-density lipoprotein cholesterol (LDL-C) and the atherogenic ratios of total cholesterol/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C, as well as an increase in triglycerides. Tissue plasminogen activator levels decreased significantly in group I but did not change in groups II or III. Antithrombin III and protein S levels decreased significantly in group I but increased in groups II and III. Group I patients showed a stronger increase in protein C than those in either group II or III. There were no significant differences in hemostatic parameters between groups II and III. Conclusion Estrogen replacement therapy may have beneficial effects on lipid profile and fibrinolytic factors in postmenopausal women. Both natural and synthetic progestogens attenuated the effects of estrogen. The 1-year effects of hormone replacement therapy on factors related to venous thromboembolism were positive. Micronized progesterone was not superior to medroxyprogesterone acetate.