Hormone Replacement Therapy In Postmenopausal Women Research Articles

Association of periodontitis with menopause and hormone replacement therapy: a hospital cohort study using a common data model.

The present study was designed to compare the incidence of periodontitis according to menopausal status and to investigate the possible effect of hormone replacement therapy (HRT) on periodontitis in postmenopausal women using a common data model (CDM) at a single institution. This study involved retrospective cohort data of 950,751 patients from a 20-year database (2001 to 2020) of Ewha Womans University Mokdong Hospital converted to the Observational Medical Outcomes Partnership CDM. One-way analysis of variance models and the χ² test were used to analyze the statistical differences in patient characteristics among groups. A time-dependent Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals, and P values less than 0.05 were considered to indicate statistical significance. Of the 29,729 patients, 1,307 patients were diagnosed with periodontitis and 28,422 patients were not. Periodontitis was significantly more common among postmenopausal patients regardless of HRT status than among the non-menopausal group (P<0.05). Time-dependent Cox regression analysis showed that the postmenopausal patients had a significantly higher chance of having periodontitis than non-menopausal patients (P<0.05), but after adjustment for age, body mass index, and smoking status, the difference between the non-menopausal and post-menopausal HRT-treated groups was insignificant (P=0.140). Postmenopausal women had a significantly greater risk of periodontitis than non-menopausal women. Additionally, the use of HRT in postmenopausal women could reduce the incidence of periodontitis.

Hormone Replacement Therapy and Psoriasis Risk: A Nationwide Population-Based Cohort Study.

Hormone replacement therapy (HRT) is used to relieve menopause symptoms, but has been reported to be associated with coronary heart disease and cancers in women. However, a link between HRT and psoriasis has yet to be established. The aim of this study was to determine the association between HRT and the risk of psoriasis. We executed a nationwide population-based study. A total of 1,130,741 post-menopause women were enrolled in the national health care insurance database based on the enrollment criteria. The study population was classified into four groups based on the duration of the HRT, and the risk of psoriasis was analyzed. The incidence rates of psoriasis per 1,000 person-years were 3.36 and 4.09 in the no history of HRT and ≥ 5 years of HRT, respectively. After adjustment for age, smoking, alcohol intake, regular exercise, body mass index, diabetes mellitus, hypertension, and dyslipidemia, the most prolonged duration of the HRT group (≥ 5 years) exhibited significantly increased risk of developing psoriasis (hazard ratio, 1.22; 95% confidence interval, 1.16-1.29). We propose that HRT in post-menopausal women is associated with an increased likelihood of psoriasis development.

Effect of Hormonal Replacement Therapy on Gastroesophageal Reflux Disease and its Complications in Postmenopausal Women

Female hormones and hormone replacement therapy (HRT) are thought to play a role in gastroesophageal reflux disease (GERD). Pregnancy, menopause, and HRT have all been reported as risk factors for GERD.1-6 It has been suggested that estrogen and progesterone confer their effect on the gastrointestinal tract by increasing nitric oxide synthesis, a muscle relaxant which decreases smooth muscle tone of the lower esophageal sphincter and esophageal body predisposing patients to gastroesophageal reflux.6-8 However, the exact mechanism that these hormones play in GERD remains to be elucidated because menopause, which is a risk factor for GERD, is associated with a decrease in estrogen and progesterone levels. Thus the exact relationship between the different hormonal therapies and GERD remains unclear. The aim of this study was to determine the role and possible risk that estrogen and progesterone HRT pose for the development of GERD in postmenopausal women. In addition, we aimed to assess the relationship between HRT in postmenopausal women and GERD complications, such as esophageal stricture and Barrett's esophagus.

Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI).

Premature ovarian insufficiency (POI) occurs in at least 1% of all women and causes life-long health problems and psychological stress. Infertility caused by POI used to be considered absolute, with infertility treatment having little or no value. Generally, it has been thought that medicine can provide little service to these patients. The etiology of POI has been found to be genetic, chromosomal, and autoimmune. In addition, the increasing numbers of cancer survivors are candidates for iatrogenic POI, along with patients who have undergone ovarian surgery, especially laparoscopic surgery. Over 50 genes are known to be causally related to POI, and the disease course of some cases has been clarified, but in most cases, the genetic background remains unexplained, suggesting that more genes associated with the etiology of POI need to be discovered. Thus, in most cases, the genetic background of POI has not been clarified. Monosomy X is well known to manifest as Turner’s syndrome and is associated with primary amenorrhea, but recent studies have shown that some women with numerical abnormalities of the X chromosome can have spontaneous menstruation up to their twenties and thirties, and some even conceive. Hormone replacement therapy (HRT) is recommended for women with POI from many perspectives. It alleviates vasomotor and genitourinary symptoms and prevents bone loss and cardiovascular disease. POI has been reported to reduce quality of life and life expectancy, and HRT may help improve both. Most of the problems that may occur with HRT in postmenopausal women do not apply to women with POI; thus, in POI, HRT should be considered physiological replacement of estrogen (+progesterone). This review describes some new approaches to infertility treatment in POI patients that may lead to new treatments for POI, along with the development of more sensitive markers of secondary/preantral follicles and genetic diagnosis.

Controversies Regarding Postmenopausal Hormone Replacement Therapy for Primary Cardiovascular Disease Prevention in Women.

The debate over the safety and benefit of hormone replacement therapy (HRT) in postmenopausal women for primary prevention of cardiovascular disease (CVD) has been ongoing for the past several decades. Observational trials in the 1980s suggested a benefit of HRT for primary CVD prevention. However, randomized controlled trials in the 1990s suggested potential harm. Because of these discrepancies, recommendations from authorities on the usage of postmenopausal HRT have fluctuated. Many believed that the timing of HRT initiation relative to the onset of menopause, also known as the "timing hypothesis," was the factor that could explain the differences among these studies. Some recent investigations have concluded that HRT initiated in postmenopausal women near the onset of menopause confers a cardioprotective benefit, while others simply showed that HRT does not cause harm. Research has expanded to evaluate alternative doses, preparations, routes, and formulations, including selective estrogen receptor modulators, to demonstrate their suitability for this purpose. This article is a review of the major research studies of HRT in postmenopausal women with respect to its safety and efficacy for the primary prevention of CVD.

Does hormone replacement therapy benefit post-menopausal women? – a scoping review

Post-menopausal women experience symptoms such as irregular periods, lower fertility, vaginal dryness, hot flashes and night sweats. Hormone replacement therapy (HRT) relieves menopausal symptoms. The aim of this review was to assess the benefits and risks of HRT in post-menopausal women. A scoping review was conducted for original peer-reviewed English language papers using the electronic databases of PUBMED, JAMA, BMC and TRIP. The papers were subjected to a three-stage screening process. The type of study, year of study, age, participants, type of therapy and the aim of the study defined the inclusion and exclusion criteria. HRT was associated with reduced risk and prevalence of end-stage kidney disease, gastric esophageal reflex disease (GORD) symptoms, periodontal disease and associated with the increased risk of overall cancers. The benefits of HRT depend on the duration of therapy, formulation, route of administration, time of initiating therapy (age &lt;60 years) and type of therapy. Post-menopausal symptomatic women mostly benefited with hormone replacement therapy. To reduce risks of adverse events, HRT should be initiated with appropriate monitoring.

Sex hormone replacement therapy in periodontology-A systematic review.

To analyse whether sex hormone replacement therapy (HRT) improves periodontal parameters and dental implants osseointegration in humans. Electronic databases and hand searches were performed from June to August 2018 in SciELO, LILACS and PubMed/MEDLINE. Human observational and interventional studies that evaluated the following parameters were included: clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), radiographic bone loss (RBL) or osseointegration. Initial search retrieved 1,282 non-duplicated articles. Fifteen studies were selected after inclusion criteria were applied. All studies were performed in postmenopausal women. Mean differences for PPD reduction ranged from 0.02 to 0.2mm in HRT-positive patients; mean CAL gain -0.18 to 0.54mm; mean RBL reduction -0.87 to 0.15mm; and mean BOP reduction 9%-30.3%. Failure rate of dental implants increased -5.5% to 11.21% when HRT was used. Very low but consistent evidence suggests a reduction in BOP and no impact on RBL in postmenopausal women receiving HRT. There are inconsistent reports that suggest that HRT in postmenopausal women: (a) improves or does not impact PPD reduction and CAL gain; and (b) does not impact or increase implant loss. In summary, there is no evidence to support HRT prescription for either men or women for periodontal/implant placement purposes.

In This Issue

HomeCirculation ResearchVol. 122, No. 1In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published5 Jan 2018https://doi.org/10.1161/RES.0000000000000192Circulation Research. 2018;122:2Altered Mitochondrial Dynamics in Lipotoxic Hearts (p 58)Excess lipids meddle with mitochondrial function in the heart, report Tsushima et al.Download figureDownload PowerPointObesity and diabetes are 2 major risk factors for heart disease and can lead to myocardial lipotoxicity—cardiac dysfunction caused by excessive fatty acid accumulation. At a pathological level, lipotoxicity has been associated with mitochondrial dysfunction, but exactly how excess lipids affect mitochondria is unclear. To find out, Tsushima and colleagues studied mice that were genetically engineered to accumulate excess fatty acids specifically in their cardiac myocytes. These animals ultimately developed heart failure, but not until they are ≈4 months old, giving the team the opportunity to study pathological progression of lipotoxicity. In early weeks of life, excess lipids were associated with an increase in mitochondrial activity. Prolonged excess, however, caused the mitochondria to produce high levels of reactive oxygen species, which in turn led to post-translational modifications of proteins involved in mitochondrial fusion and fission. Indeed, the team also observed that cardiac mitochondria in these mice were abnormally thin and fragmented. On the basis of these findings, the authors suggest that lipid-induced perturbation of mitochondrial dynamics could be an important pathological mechanism in lipotoxic cardiomypathies.Cell Cycle Activity and Cardiac Cell Therapy (p 88)Boosting proliferation in stem cell-derived cardiomyocytes could improve their regenerative potential, say Zhu et al.Download figureDownload PowerPointCardiac cells have limited capacity to divide. Most adult cardiac myocytes are postmitotic, and while cardiac progenitors are present and able to divide, they are unable to restore sufficient muscle to fully repair a heart after a myocardial infarction. The efficacy of exogenous cells to repair the damage has been tested in animals and patients, but regardless of the cell type used, regeneration is often limited by poor retention of the cells in the myocardium. Zhu and colleagues hypothesized that if the transplanted cells could be prompted to proliferate, those that do engraft may multiply and provide a better chance of repair. To test this, the team over-expressed the cell cycle promoter CCND2 in human induced pluripotent stem cells (hiPSCs) and then differentiated these cells into cardiac myocytes (CM). The hiPSC-CMs proliferated more in culture than their wild-type counterparts and, when injected into mice with injured hearts, were more effective at reducing infarct size and at restoring heart function. The results suggest that promoting proliferation of therapeutic cells, whether genetically or pharmacologically, might be a way to improve cell-based therapies for heart regeneration.Sex Hormones, Carotid Plaque Composition, and Stroke (p 97)Glisic et al investigate the effects of sex hormones on stroke risk and atherosclerosis.Women with atherosclerosis tend to exhibit plaques with more stable compositions than men. Women are also less likely to suffer strokes. But 10 years after menopause, a women’s risk of stroke almost doubles. These sex- and menopause-associated differences led Glisic and colleagues to investigate the role of sex hormones. Indeed, both estradiol and testosterone are known to affect the vascular system in a variety of ways. The team studied 645 postmenopausal women (average age, 65) and 835 similarly aged men with atherosclerosis. Testosterone and estradiol levels were assessed, along with plaque composition and stroke risk in a 10-year follow up. They found that women with detectable estradiol had both an increased risk of stroke and an increased likelihood of having unstable plaques (intraplaque hemorrhages) than women with undetectable estradiol. This association was not observed in men, and testosterone levels showed no associations. These results are consistent with previous studies suggesting that hormone replacement therapy could have harmful vascular effects in elderly women compared with women closer to menopause age. The study, thus, raises further concerns about the use of hormone-replacement therapy in postmenopausal women, say the authors. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Jain P, Jayappa S, Sairam T, Mittal A, Paul S, Rao V, Chittora H, Kashyap D, Palakodeti D, Thangaraj K, Shenthar J, Koranchery R, Rajendran R, Alireza H, Mohanan K, Rathinavel A and Dhandapany P (2021) Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy, Journal of Medical Genetics, 10.1136/jmedgenet-2021-107866, (jmedgenet-2021-107866) January 5, 2018Vol 122, Issue 1 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000192 Originally publishedJanuary 5, 2018 PDF download Advertisement

O16 Phyto-oestrogenic property of mimosine: A phenylalanine alkaloid

Hormone replacement therapy (HRT) has been generally used in postmenopausal symptoms in women caused by a lack of endogenous oestrogen. However, due to the increased concern around the potential associated risks of breast and endometrial cancer there is an increased demand for natural oestrogenic agents with lesser side effects. Mimosine is a phenylalanine class of alkaloid. It has been reported that, another phenylalanine alkaloid capsaicine and its analogues possess oestrogenic activity. Therefore, this study was designed to investigate the oestrogen like activity of mimosine by using in vitro assays with the ER positive MCF-7 cell line and in silico models. Cell viability by cellular count and MTT cell proliferation assays were performed using the oestrogen-dependent MCF-7 breast cancer cells. The regulation of oestrogen marker TFF1 and PGR gene expression were also studied. The binding ability of mimosine to ER α was predicted by in silico docking method. The results indicated that mimosine caused significant cell proliferation ( P P P P α binding site as compared to estradiol. The results indicate the oestrogenicity of mimosine for the first time and suggest that, it can be further studied and developed as an alternative to HRT for postmenopausal women.

HRT for women with premature ovarian insufficiency: a comprehensive review.

BACKGROUNDPremature ovarian insufficiency (POI), often and misleadingly referred to as ‘premature menopause’, is defined as a loss of ovarian activity before the age of 40 years and is characterized by irregular or absent periods and reduced fertility. Symptoms include those associated with the natural menopause (night sweats and vaginal dryness), and with the long-term adverse effects of estrogen deficiency (osteoporosis and cardiovascular disease): the latter is believed to explain the shorter life expectancy associated with POI.OBJECTIVE AND RATIONALEThe objective of the current review was to collect all relevant studies supporting recommendations on the indications, treatment options, and risks of hormone replacement therapy (HRT) (estrogen, progestogens and androgens) for women with POI.SEARCH METHODSThe current review was written based on the best available evidence on the topic collected for the recently published ESHRE guideline on the management of women with POI. PUBMED/MEDLINE and the Cochrane library were searched in a stepwise approach. Relevant references were summarized in evidence tables, with assessment of the quality.OUTCOMESHRT is strongly recommended for women with POI, mainly for vasomotor and genito-urinary symptom relief. In addition, HRT has been shown to have a role in bone protection and probably also in primary prevention of cardiovascular disease. There is little evidence on the optimal type, regimen and dose of HRT; patient preference for route and method of administration of each component of HRT must be considered when prescribing, as should contraceptive needs. In women with POI, physiological replacement of estrogen (and progesterone) is essential for their health, and the controversies that surround the use of HRT in postmenopausal women do not apply.LIMITATIONS, REASONS FOR CAUTIONN/A.WIDER IMPLICATIONSNew areas of study on HRT for women with POI should focus on life expectancy, quality of life and neurological function. Furthermore, randomized controlled trials comparing transdermal estradiol with oral estrogens with regard to efficacy, patient satisfaction and side effects are urgently needed.STUDY FUNDING/COMPETING INTERESTSThe authors received no funding for the review. The costs for the development of the ESHRE guideline were covered by ESHRE. The authors have no conflicts of interest to disclose.

Hormone Replacement Therapy for Surgical Menopause: Is there an Ideal Drug? A Comparative Study of Conjugated Equine Estrogens and Tibolone

ABSTRACT Objective To compare the effects of continuous combined conjugated equine estrogens (CEE) with those of tibolone on symptom control, lipid profile, and tolerability in women with surgical menopause. Materials and methods This was a randomized controlled trial study conducted in the Department of Obstetrics and Gynaecology of Global Rainbow Hospital Pvt. Ltd., Agra (2014–2016) comprising 150 women. Generally, healthy postmenopausal women having undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy irrespective of age and indication of surgery and no absolute contraindications to hormone replacement therapy (HRT) or tibolone were enrolled. Fifty subjects did not receive any HRT, 50 were treated with CEE 0.625 mg, and 50 were given tibolone 2.5 mg for 13 treatment cycles, each of 28 days. Results were statistically analyzed regarding drug efficacy in amelioration of menopausal symptoms and side effects at follow-up periods of 1, 6, and 12 months. Results A total of 150 subjects were enrolled and received at least one dose of the study medication, of which 134 (89.4%) subjects completed the study (n = 40 in CEE and n = 44 in tibolone). The incidence of postmenopausal symptoms decreased significantly over time in the treatment groups, compared with baseline, including significant decreases in the incidence of urogenital and sexual health symptoms, with p-values 0.001 and 0.004 in cases that received CEE and tibolone respectively. Significant differences in symptom control (other than hot flashes) were observed between treatment groups in a few different cycles for different symptoms, but no consistent or clinically significant trends were observed. Significant decreases in total cholesterol (5.6%) and low-density lipoprotein cholesterol (7.5%) were observed at cycle 13, compared with baseline, in the CEE group, and significant decreases in high-density lipoprotein cholesterol (8.5%) and triglycerides (13.7%) were observed at cycle 13, compared with baseline, in the tibolone group. Significant weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared with the CEE group (0.96 kg). The incidences of adverse events were similar in both treatment groups. Conclusion Women treated with CEE and tibolone showed significant improvement of climacteric symptoms, including urogenital and sexual health symptoms. Treatment with either preparation significantly improved subjective wellbeing, vasomotor symptoms, and vaginal dryness. The CEE and tibolone each induced a different mix of beneficial changes in the lipid profile. It is seen that tibolone seems to be effective on estrogen withdrawal symptoms and with its acceptable androgenic side effects can be an appropriate selection for HRT in postmenopausal women with decreased sexual desire. How to cite this article Gupta N. Hormone Replacement Therapy for Surgical Menopause: Is there an Ideal Drug? A Comparative Study of Conjugated Equine Estrogens and Tibolone. J South Asian Feder Menopause Soc 2017;5(1):11-15.

ETA Receptor Antagonism and Estrogen Replacement Prevent Ang II Hypertension in Menopausal Mice

Cardiovascular disease, including hypertension, increases dramatically in women after menopause, however the efficacy of hormone replacement therapy (HRT) in preventing such diseases has produced controversial results. Endothelin receptor antagonists have been tested as anti‐hypertensive agents in clinical trials and may represent a promising alternative to HRT in postmenopausal women. Therefore, we sought to directly compare the anti‐hypertensive capacity of estrogen replacement (17‐b estradiol pellet, 0.1mg) vs. the ETA receptor antagonist ABT‐627 (5mg/kg, i.p., daily) in the VCD mouse model of menopause (4‐vinylcyclohexene diepoxide, VCD). Ang II (800ng/kg/min, 14d) was infused into VCD‐treated menopausal female mice alone (Meno), or with either concurrent 17‐b estradiol replacement (E2) or ETA receptor antagonism (ETAA). Premenopausal mice received sesame oil vehicle with and without subsequent Ang II (Con, Con/Ang). Ang II infusion induced a significant increase in systolic blood pressure in VCD‐treated menopausal mice compared to Ang II infusion in premenopausal mice (Con Δ2 ± 2 mmHg, Con/Ang Δ15 ± 2* mmHg, Meno/Ang Δ37 ± 6*# mmHg, *P&lt;0.05 vs Con, #P&lt;0.05 vs Con/Ang). Both 17‐b estradiol replacement and ETA receptor antagonism prevented the increased blood pressure response in Ang II‐infused menopausal mice (E2 Δ10 ± 6* mmHg, ETAA Δ14 ± 3* mmHg, *P&lt;0.05 vs Meno/Ang). Splenic and renal T cell profiles were assessed via flow cytometry. 17‐b estradiol replacement increased the percentage of Foxp3+ T regulatory cells in the spleen compared to all other groups (Con 17 ± 1%, Con/Ang 18 ± 1%, Meno/Ang 18 ± 1%, E2 23 ± 1%*, ETAA 18 ± 1%, *P&lt;0.05 vs all groups). However, no changes in T cell profiles occurred with any treatment in the kidney. Quantitative real‐time PCR demonstrated that Ang II‐induced expression of whole kidney collagen type IV in VCD‐treated menopausal mice was significantly reduced by ETA receptor antagonism, but not 17‐b estradiol replacement (ETAA 0.68 ± 0.08 fold*, E2 1.25 ± 0.05 fold*, *P&lt;0.05 vs Meno). These data suggest that ETA receptor antagonism may be an effective treatment strategy for preventing hypertension in postmenopausal women.Support or Funding InformationAmerican Heart Association Predoctoral Fellowship (DPP), NIH DK073611 (HLB), Sarver Heart Center (DPP), ARCS Foundation (DPP)

Molecular Pathways: Estrogen Pathway in Colorectal Cancer

Worldwide, colorectal cancer has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data support a role for estrogen and its receptors in the initiation and progression of colorectal cancer and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of colorectal cancer. In the Women's Health Initiative trial, use of HRT in postmenopausal women reduced the risk of colon cancer by 56% [95% confidence interval (CI), 0.38-0.81; P = 0.003]. A recent meta-analysis showed that in women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03-0.35; P = 0.026). In this review, using the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of colorectal cancer. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT, or soy products, exerts its effects through preventing this loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of colorectal cancer depends on identification of susceptible colorectal cancer population(s). Thus, research to better understand the estrogen pathway is fundamental for clinical delivery of these agents.

A Modest Proposal for a Clinical Trial on Single-Bundle Versus Double-Bundle Anterior Cruciate Ligament Reconstruction

A Modest Proposal for a Clinical Trial on Single-Bundle Versus Double-Bundle Anterior Cruciate Ligament Reconstruction

Hormone Replacement Therapy is Associated With a Decreased Prevalence of Peripheral Arterial Disease in Postmenopausal Women

The effect of hormone replacement therapy (HRT) in postmenopausal women on the development of peripheral atherosclerosis remains in question. The goal of this study was to analyze the use of HRT in a large population of postmenopausal women and to determine its association with the prevalence of peripheral arterial disease (PAD). A prospective database of patients who underwent voluntary vascular screening was used. Identification of patients as postmenopausal, and their use of HRT, was based on patient questionnaires. PAD was defined to be present if either lower extremity ankle-brachial index was ≤0.9. Analysis was performed on data from 847,982 postmenopausal women; 433,178 (51.1%) reported having used HRT. HRT subjects were slightly older than patients who had not used HRT (64.5 years vs. 63.6 years). Caucasian women were significantly more likely to have used HRT than non-Caucasian women (52.4% vs. 47.6%). HRT subjects were significantly more likely to have smoked cigarettes (42.8% vs. 40.6%), to have hypertension (47.9% vs. 45.1%), and to have hypercholesterolemia (55% vs. 51.5%) than women who had not used HRT (all P < 0.001). However, HRT subjects were significantly less likely to have diabetes mellitus (8.6% vs. 10.2%, P < 0.001). Despite the increased prevalence of several atherosclerotic risk factors among women who used HRT, they were significantly less likely to have PAD (3.3% vs. 4.1%, P < 0.001). Multivariate analysis adjusting for age, race, and medical comorbidities that predispose toward the development of atherosclerosis confirmed that HRT was independently associated with a decreased risk of PAD (odds ratio: 0.8, 95% confidence interval: 0.78-0.82). In subsets of postmenopausal women with known atherosclerotic risk factors, the significant effect of HRT on the prevalence of PAD was maintained; in women with either a smoking history, hypertension, hypercholesterolemia, diabetes, or age of ≥70 years, the odds ratio of HRT use with regard to PAD remained approximately 0.8. The use of HRT in postmenopausal women appears to be associated with a significant reduction in the prevalence of PAD in this population-based study. This association appeared to be significant even in postmenopausal women with known atherosclerotic risk factors. These observational data may suggest a relationship between HRT and the prevalence of PAD that has not been the specific subject of previous randomized prospective studies.

Risk-Benefit Analysis of Combination Versus Unopposed HRT in Post-Menopausal Women

Many trials on the use of hormone replacement therapy (HRT) have provided contradictory results on its risks and benefits in post-menopausal women. The use of HRT declined globally following publication of the first data from the Women’s Health Initiative (WHI) trial in 2002, with the revelation that there was an increased risk of breast cancer and coronary heart disease (CHD) in postmenopausal women taking HRT. Following this, other leading studies published results that were consistent with these findings, which reduced enthusiasm for HRT use. However, recent publications from the International Menopause Society indicate that HRT is the first-line and most effective treatment for menopausal symptoms. Moreover, when the full results of the WHI trial were subsequently published, it appeared that HRT may confer benefits for CHD prevention below age 60. The statements from the British Menopause Society and the International Menopause Society (IMS) published in 2008 also supported this opinion. These revelations renew interest in HRT use. This paper analyzes the effects of combination versus unopposed HRT on osteoporosis, breast and CHD, endometrial cancer induction, venous thromboembolic disease, lipids and lipoproteins, neuroprotection, and cognitive function in post-menopausal women.

Effects of long-term hormone replacement therapy: Results from a cohort study

The positive effects of hormonal replacement therapy (HRT) in protecting the cardiovascular system in women have been supported by several observational studies, while also being questioned by other randomized controlled trials. Today, it is unclear whether HRT plays a crucial role, or even whether there is any role at all, for this therapy in preventing or in lowering cardiovascular disease (CVD). In the present study, we have evaluated the effectiveness of long-term HRT in post-menopausal women on the incidence of cardiovascular events and arterial remodeling, as well as on some metabolic factors. Eighty-four post-menopausal women (mean age: 46.3 ± 5.2; age range: 42-66 yr) underwent HRT for 10.9 ± 1.2 yr (range: 8-12 yr). None of these subjects showed new cardiovascular events, and we found a reduction of the intima-media thickness (baseline: 1.39 ± 0.2, 1.35 ± 0.2, 1.31 ± 0.2 mm) and total cholesterol, LDL and antithrombin III levels were lower, while HDL and fibrinogen levels increased. The study highlights a number of positive effects both on vascular conditions and metabolic and coagulative markers that are usually considered as generic and crucial risk factors for CVD. The relatively low number of patients is perhaps a limitation of this study, however, the long-term period of followup should be considered an interesting and important factor. Furthermore, this study underlines the real-life clinical experience of a Menopause Center.

Effect of hormone replacement therapy on total serum anti-oxidant potential and oxidized LDL/.BETA.2-glycoprotein I complexes in postmenopausal women

Oxidative stress and consequent oxidized lipoprotein production is thought to play a central role in both the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (oxLDL)/β2-glycoprotein I (β2GPI) complexes are etiologically important in the development of atherosclerosis. The aim of the present study was to investigate whether long-term treatment with conventional hormone replacement therapy (HRT) in postmenopausal women could affect total serum antioxidant capacity (TAC) and serum levels of oxLDL/β2GPI complexes. A total of 60 normolipidemic postmenopausal women treated with oral estrogen together with progestin therapy for 3 months were selected. TAC and serum levels of oxLDL/β2GPI complexes were measured at the beginning and end of the HRT. HRT led to a significant increase in TAC (15%, P=0.02) and a minor but statistically nonsignificant decrease of oxLDL/β2GPI complexes (3%, P=0.30) when compared with the baseline control levels. There was also no significant association between TAC and oxLDL/β2GPI complexes changes related to HRT. This study indicates that, HRT in postmenopausal women leads to an increase in TAC without an equivalent change in serum levels of oxLDL/β2GPI complexes. It is concluded that beneficial effects of HRT could be explained, at least in part, by improving antioxidant status, but may not be directly associated with a change in oxidized lipoprotein production.

Hormone replacement therapy: the risks and benefits of treatment

Several recent large studies have provoked concern among both health professionals and the general public regarding the safety of hormone replacement therapy (HRT). This article provides a review of the current literature surrounding the risks and benefits of HRT in postmenopausal women, and how the data can be applied safely in everyday clinical practice.

Effects of methanolic extract of Cuminum cyminum on total serum cholesterol in ovariectomized rats

Sir, Estrogens have a protective role in lipid metabolism[1] and postmenopausal women are at high risk for developing cardiovascular disorders due to estrogen deficiency. As suggested by many epidemiological studies, hormone replacement therapy (HRT) in postmenopausal women appears to be associated with reduction in the risks of coronary heart disease.[2] Protection against cardiovascular disorders is an attractive side of HRT in postmenopausal women, but at the same time it is associated with serious side effects like breast and endometrial cancers and is also associated with patient incompatibility which presents many limitations in long-term use. Phytoestrogens, polyphenolic non-steroidal plant compounds with estrogen-like biological activity are currently offering an effective and safe alternative to hormone replacement therapy. Owing to the estrogen-like property they are effective in a variety of aliments such as menopausal symptoms and postmenopausal disorders, such as osteoporosis and cardiovascular disorders.[3] Ample evidence from epidemiological studies and clinical trials suggests the plausibility of a causal, inverse relationship between phytoestrogens and cardiovascular disease. The well established low rates of cardiovascular disease and high intake of dietary phytoestrogens in Asian populations are consistent with a potential cardioprotective effect of phytoestrogens.[2] Fruits of Cuminum cyminum (Apiaceae), commonly known as jeera are consumed as condiment across the globe. Fruits of Cuminum cyminum (CC) are rich in estrogenic isoflavonoids luteolin and apigenin.[4] CC extract is included as one of the major components in some polyherbal formulations because of its estrogenic nature. The estrogenic activity of acetone extract of CC has been reported earlier in immature ovariectomized rats.[5] It has been reported to reduce plasma cholesterol levels in diabetic rats.[6] The present study was undertaken to evaluate hypocholesterolemic effect of methanolic extract of Cuminum cyminum (MCC) as a part of anti-osteoporotic evaluation of MCC in ovariectomized (OVX) rats. Methanol was the solvent of choice owing to its excellent penetration and extraction ability. Forty adult Sprague Dawley female rats of 3 months age, weighing 200-250 gm were divided into four groups with N = 10 per group. Three groups were bilaterally ovariectomized while one was sham operated (SH control). MCC 1000 mg/kg and estradiol benzoate equivalent to 0.15 mg/kg of estradiol were administered to OVX rats per orally for 10 weeks. MCC was administered in two divided doses with 2 ml/kg dose volume. SH control and OVX control groups were administered with vehicle 0.5% sodium carboxy methyl cellulose. The treatment was started the day after ovariectomy. At the termination of study, blood was collected from overnight fasted animals; serum was harvested and preserved at 4°C until the analysis. Total serum cholesterol was determined colorimetrically using standard cholesterol estimation kit (Erba). Results were analyzed by one-way ANOVA at P < 0.05. OVX rats showed significantly elevated levels of serum total cholesterol at the end of 10 weeks as compared to SH control. Treatment with estradiol and MCC both significantly decreased total cholesterol levels in serum. The decrease in total serum cholesterol caused by MCC was significantly greater than that caused by standard drug estradiol. It was observed that total cholesterol levels in MCC treated rats were lower but not significantly than SH control rats. The results indicated that estradiol as well as MCC protected OVX rats against increased cholesterol levels due to ovariectomy while MCC was better than estradiol [Table 1]. Table 1 Effects of oral treatment of estradiol and MCC (methanolic extract of Cuminum cyminum) on total serum cholesterol in ovariectomized (OVX) rats It is likely that the hypocholesterolemic effect of MCC may be due to its phytoestrogenic content but to validate the claims comprehensive and detailed investigation has to be undertaken. Thus methanolic extract of Cuminum cyminum can be a potential candidate to be explored for the treatment of menopausal disorders, especially cardiovascular disorders in postmenopausal women.