Hormone Replacement Therapy Therapy Research Articles

(072) PRESCRIBING PATTERNS AND COST OF HORMONE THERAPIES AMONGST ISSWSH PROVIDERS

Abstract Introduction Vaginal estrogen is commonly used to treat vulvovaginal disorders and genitourinary syndrome of menopause (GSM). Systemic hormone replacement therapy (HRT) is an evidence-based treatment for menopause and female sexual dysfunction. Insurance coverage for topical estrogen and HRT is highly variable and remains inaccessible for many patients. Compounded medications are an alternative that some prescribers turn to, despite inconsistency in quality, safety, and prices. Objective This study aims to examine prescribing patterns of ISSWSH providers of various hormonal and non-hormonal topical therapies, HRT, and cost of these medications. Methods A fourteen-item survey was distributed to ISSWSH providers via online platforms including social media. Participants were asked about medical education background and specialty, practice location, topical vaginal HRT (i.e., estrogen, estrogen and testosterone) and non-hormonal therapy (i.e., capsaicin, gabapentin) prescription practices, the most common diagnoses for which they prescribe these medications, systemic hormone therapy prescription practices, and counseling on cost-saving programs. Pharmacies used by respondents were surveyed regarding monthly cost of the compounded medications mentioned above. All data was de-identified prior to analysis. Descriptive statistics were performed in SPSS. Results Of the fifty-five responses collected, a majority of participants (51%) are ob-gyn providers and 22% are urology providers. The remaining participants are providers of internal medicine, family medicine, midwifery, urogynecology, and functional medicine. A majority are designated MD, DO, or equivalent (49%), and 45.5% are advanced practice providers (NP or PA). Notably, 100% of participating family medicine providers (n = 8) report prescribing estrogen-containing systemic therapies, compared to ob-gyns (89%) and urologists (58%). Systemic testosterone is prescribed most often by urologists. Numerous providers report prescribing topical estrogen and testosterone: 50% being family medicine, 67% urologists, 67% midwives, 71% ob-gyns, and 100% of urogynecologists. Prescribing patterns for non-hormonal topicals vary. Gabapentin and valium appear to be most common in ob-gyn practices (43% each). Valium is also commonly prescribed by urologists, family medicine providers, and urogynecologists. According to the results, internal medicine providers rarely prescribe non-hormonal options. From the 37 pharmacies we contacted, the median monthly cost of compounded vaginal hormone therapy was $55.00. The median monthly costs of non-hormonal topicals, including topical gabapentin, diazepam suppository, topical diazepam, topical capsaicin, and baclofen, are $55.00, $56.00, $73.00, $58.50, $62.00, and $56.00, respectively. Our data reveals that 91% of participants report counseling patients on cost-saving programs such as GoodRx, Mark Cuban Cost Plus Drugs. Conclusions Hormone therapies are prescribed at high rates by providers within the ISSWSH community; however, the types of therapies prescribed and prescription frequency vary greatly. Counseling regarding cost-saving methods shows to be promising; however, patients do not usually expect to pay cash. Atorvastatin is the most commonly taken medication in the US, and the average monthly copay is $2.48, which is drastically different from the median $60.00 monthly cost we found for hormonal and non-hormonal therapies aimed at vulvovaginal disorders and GSM. Future directions for this project include correlating prices with zip codes to examine geographical trends in medication cost. Disclosure No.

Hormone Replacement Therapy Is Associated with Disease Activity Improvement among Post-Menopausal Women with Inflammatory Bowel Disease.

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case-control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There was a significant reduction in the frequency of PGA scores ≥2 post HRT treatment (p < 0.01). HRT treatment was associated with a 5.6× increase in the odds of post-HRT PGA score improvement compared to controls (OR 5.6; 95% CL 1.6, 19.7) in our univariate logistic regression analysis. (4) Conclusion: Post-menopausal IBD women who underwent HRT therapy showed an improvement in their disease symptoms following HRT compared to post-menopausal women without HRT therapy, who showed no change.

S886 Hormone Replacement Therapy Is Associated With Disease Activity Improvement Among Post-Menopausal Women With Inflammatory Bowel Disease

Introduction: There have been limited data on the impact of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize the population of post-menopausal women with IBD and to determine the effect of HRT on disease activity. Methods: A retrospective cohort study of postmenopausal women with IBD at the University of Minnesota and Jefferson University Hospital was conducted from 1/1/2000-1/1/2020. Electronic health records were manually reviewed for demographics, menopause history, IBD history including disease activity, surgeries, hospitalizations, and medications pre- and post-HRT. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. Patients were matched by age at menopause onset (+/- 5 years) and IBD type. McNemar’s test was used to compare outcomes pre- and post-HRT given the paired nature of the data. Pearson's chi-squared test was used to compare patients and controls. Results: Of the 249 patients recognized from the initial search, we identified 37 women who were menopausal and started on HRT. Mean age of menopause onset in the HRT patients was 46 years, 59% had Crohn’s disease (CD) and 41% had ulcerative colitis (UC). 31 matched controls that were within a 5-year range of menopause of the HRT patients were selected (61% CD, 39% UC). Based on PGA score, there was greater disease severity in the HRT cohort pre-menopause (p=0.03) and trend towards greater frequency of PGA score ≥2 (p=0.11). There was a significant reduction in frequency of PGA ≥2 post-HRT treatment (p< 0.01). HRT treatment was associated with a 5.6x increase in odds of post-HRT PGA score improvement compared to controls (OR 5.6; 95% CL 1.6, 19.7) in univariate logistic regression analysis. (Table) Conclusion: Post-menopausal IBD women who underwent HRT therapy had a significant improvement in their disease activity following HRT compared to post-menopausal women without HRT therapy, who showed no change in disease activity. Pre-HRT disease activity seemed to be higher in patients who underwent HRT compared to the controls. While we found more women with active disease underwent HRT, further study in a larger cohort of patients is needed to confirm this finding. Table 1. - Outcomes pre and post hormone replacement therapy Pre-HRT Post-HRT P-value Hospitalized (n=25) 10 (40%) 8 (32%) 0.32 Surgery 17 (46%) 5 (14%) < 0.01 PGA scores < 0.05 Remission 9 (24%) 17 (46%) Mild 16 (43%) 17 (46%) Moderate 7 (19%) 1 (3%) Severe 5 (14%) 2 (5%) Moderate to severe disease 12 (32%) 3 (8%) < 0.01

AMBULATORY BLOOD PRESSURE IN POSTMENOPAUSAL WOMEN ON ESTROGEN, ANDROGEN OR PROGESTERONE THERAPY

Objective: Objective of this study was to evaluate different hormone replacement therapy (HRT) combinations on ambulatory blood pressure (ABPM) and body mass index (BMI) in postmenopausal women. Design and method: One hundred and fifty women 47–62 y’s of age were first on estrogen/androgen therapy, then they were without HRT therapy for three months and later on estradiol and drospirenone combined therapy. Validated, Meditech ABPM 05 was used to obtain 24-h blood pressure (BP) after each regime. All women did not change antihypertensive treatment during the study. Wilcoxon Signed Rank Test was used to examine whether there was a statistically significant difference in blood pressure and body mass index values at different hormone therapy regimens. Results: There were no significant differences in BP parameters and BMI between different therapy regimes but lowest BP and BMI values were recorded while women were on estradiol and drospirenone combined therapy. The affinity of progesterone for the mineralocorticoid receptor is about five times that of aldosterone and may well antagonize the salt-retaining effect of estrogens, and thus lowering of blood pressure. Conclusions: We may conclude that estradiol and drospirenone combined therapy lowers blood pressure and maintains a stable body weight in postmenopausal women.

Clinical observation and study of hormone replacement therapy on postoperative cervical squamous cell carcinoma

Objective To observe the clinical effect of hormone replacement therapy(HRT) on patients with cervical squamous cell carcinoma after operation and its effect on sex hormone, blood fat, bone content and tumor markers, and to evaluate the clinical significance of HRT therapy. Methods From January 2016 to January 2019, a total of 100 patients with cervical squamous cell carcinoma admitted to Zhuhai Maternal and Child Health Hospital were analyzed retrospectively.After surgical treatment, 50 patients were willing to receive hormone replacement therapy as the experimental group and 50 patients received routine treatment as the control group, Kupperma score was used to evaluate the severity of perimenopausal symptoms, and the serum levels of sex hormones, blood fat, bone content and tumor markers in the two groups before and after treatment were detected and the occurrence of adverse reactions were evaluated. Results Before treatment, there was no significant difference in kupperma score, estradiol, follicle-stimulating hormone, luteinizing hormone level, lipid level, bone content and tumor marker level between the two groups(all P>0.05). After HRT treatment, kupperma score in the experimental group was significantly lower than that before treatment((11.47±5.12) vs.(20.46±7.52), t=7.262). In the detection of sex hormones, the levels of estradiol in the experimental group was significantly increased((39.26±7.43) ng/L vs.(13.78±7.52) ng/L, t=12.345), and the levels of follicle stimulating hormone((34.25±7.61) U/L vs.(62.18±19.12) U/L, t=8.245)and luteinizing hormone((20.31±6.25) U/L vs.(35.08±6.27) U/L, t=5.452, P=0.004) in the experimental group were significantly decreased.In the detection of blood lipid level, bone content and tumor markers, high-density lipoprotein((1.62±0.33) mmol/L vs(1.34±0.26) mmol/L, t=4.592, P=0.008) and alkaline phosphatase levels((66.21±25.75) U/L vs.(46.88±9.06) U/L, t=5.912, P=0.001)was significantly increased, the low density lipoprotein((2.78±0.43) mmol/L vs.(2.87±0.78) mmol/L, t=4.265, P=0.012)and total cholestenone((4.02±0.45) mmol/L vs.(4.23±0.91) mmol/L, t=5.761, P=0.002) levels were significantly decreased in the experimental group, with statistically significant differences(all P 0.05); there was no significant difference in the above indicators between the experimental group and the control group before and after treatment (P> 0.05); there was no significant increase in adverse reactions such as breast swelling and pain (3 cases), body mass increase (2 cases), bleeding (1 case), body pain (4 cases), vomiting (4 cases), etc. between the experimental group and the control group (2, 1, 2, 3, 1 case) There was no statistical significance (P> 0.05). Conclusion HRT treatment of cervical squamous cell carcinoma patients after surgery can significantly improve the peri menstrual syndrome caused by low estrogen level, and did not significantly increase the risk of recurrence of cervical cancer patients and adverse reactions. Key words: Hormone replacement therapy; Cervical squamous cell carcinoma; Clinical observation

Abstract WMP57: Worsening Migraines in Current Hormone Replacement Therapy Users Predicts Higher Risk of Stroke

Background: There has been a long-standing debate in the role of hormone replacement therapy (HRT) and migraines as risk factors for ischemic stroke. HRT are considered a risk factor for migraines. The risk of ischemic stroke may increase as the severity of migraines increases in patients that are currently using HRT. Methods: We analyzed the data for 82,208 women aged 50 - 79 years who were enrolled in the observational arm of the Women’s Health Initiative Study. We determined the risk of ischemic stroke in participants with migraines who had current Hormone replacement therapy (HRT) (unopposed estrogen and/or estrogen plus progesterone), past HRT, and no HRT. We further dichotomized participants with migraines into participants who experienced an increase in migraine severity of one grade or more from baseline on the third-year follow up visit and participants who experienced no change or a decrease in migraine severity from baseline on the third-year follow up visit. The relative risk of developing ischemic stroke was compared between participants who were currently on HRT and participants who were either previously on HRT or never had HRT. Results: Out of the 82,208 women, 37680 (45.8%) were currently using HRT and 44528 (54.2%) were either past users or had never used HRT therapy. Compared with never or past users of HRT, rate of increase in severity of migraines was significantly higher among those who were currently on HRT therapy (17.3% versus 18.7% versus 20.6%, respectively, p&lt;0.0001). Odds ratio (OR) of ischemic stroke for patients who never used HRT or used HRT only in the past compared to those who were current users and experienced no change or a decrease in migraine severity was 0.91 [confidence interval (CI) 0.88 - 0.94] versus 1.1 [CI 1.1 - 1.2], (p&lt;.0001). OR of ischemic stroke for patients who never used HRT or used HRT only in the past compared to those who were current users and experienced an increase in severity of migraines was 0.81 [CI 0.74 - 0.88] versus 1.3 [CI 1.1 - 1.5] (p&lt;.0001). Conclusions: Patients that are current users of HRT that have an increase in severity of one grade or more of migraines are shown to have an increased risk of ischemic strokes. Future studies are required to further investigate these correlations.

Periodontal treatment outcomes in post menopausal women receiving hormone replacement therapy.

To evaluate the effect of hormone replacement therapy(HRT) on periodontal treatment outcomes in a group of postmenopausal women with periodontitis. 23 post-menopausal chronic periodontitis patients were included in this study. The test group(n=11) consisted of women who started HRT with this study and received conjugated estrogen and medroxyprogesteron. The control group(n=12) was women not taking any HRT or supplement therapy. Study groups received the same periodontal treatment. All subjects examiend by recording the following: plaque index (PI), sulcus bleeding index (SBI), periodontal pocket depth (PD) and relative attachment level (RAL) from 6 sites in each tooth. Measurements were recorded at the baseline, 1 month, 3 months, and 6 months following periodontal treatment. Serum estrogene level and bone mineral density was recorded at baseline and 6 months following periodontal treatment. The GI change was greater in the control group. There wasn't significant difference by means of PD, the attachment gain was significantly greater in the HRT receiving group. HRT seems to have a positive effect on periodontal treatment outcomes.

The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

Soluble CD163 (sCD163) is a novel marker linked to states of low-grade inflammation such as diabetes, obesity, liver disease, and atherosclerosis, all prevalent in subjects with Turner syndrome (TS) and Klinefelter syndrome (KS). We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards to treatment with sex hormone therapy in males with and without KS and females with and without TS. Males with KS (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study. Females with TS (n=8) and healthy age-matched controls (n=8) participating in a randomized crossover trial. The intervention comprised of treatment with sex steroids. Males with KS had higher levels of sCD163 compared with controls (1.75 (0.47–6.90) and 1.36 (0.77–3.11) respectively, P<0.001) and the levels correlated to plasma testosterone (r=−0.31, P<0.01), BMI (r=0.42, P<0.001), and homeostasis model of assessment insulin resistance (r=0.46, P<0.001). Treatment with testosterone did not significantly lower sCD163. Females with TS not receiving hormone replacement therapy (HRT) had higher levels of sCD163 than those of their age-matched healthy controls (1.38±0.44 vs 0.91±0.40, P=0.04). HRT and oral contraceptive therapy decreased sCD163 in TS by 22% (1.07±0.30) and in controls by 39% (0.55±0.36), with significance in both groups (P=0.01 and P=0.04). We conclude that levels of sCD163 correlate with endogenous testosterone in KS and are higher in KS subjects compared with controls, but treatment did not significantly lower levels. Both endogenous and exogenous estradiol in TS was associated with lower levels of sCD163.

Hormone replacement therapy increases the risk of cranial meningioma

AimWe investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting. MethodsWe conducted a nationwide case–control study in Denmark based on population-based administrative and health registries. The study included all female patients aged 55–84years with a first time diagnosis of meningioma during 2000–2009. The cases were matched on birth year with female population controls. Ever use of HRT since 1995 was defined as ⩾2 HRT prescriptions and categorised according to HRT type (oestrogen only, combined oestrogen–progestagen, and progestagen only) and cumulated duration of use (<1, ⩾1 to <5, ⩾5 to <10, ⩾10years). We used conditional logistic regression to compute odds ratios (ORs), with 95% confidence intervals (CIs), for meningioma associated with HRT use, and adjusting for potential confounders. ResultsWe identified 924 cases and 6122 controls. Ever use of HRT was associated with an increased risk of meningioma (OR, 1.3; 95%CI, 1.1–1.5) compared with non-use (0–1 prescriptions). The risk increased with increasing duration of HRT use, reaching an OR of 1.7 (95% CI, 1.2–2.3) after more than 10years of use. The risk of meningioma associated with long-term (⩾10years) HRT use was most pronounced for combined oestrogen–progestagen therapy (OR, 2.2; 95% CI, 1.4–3.3), especially when this regimen constituted the sole HRT therapy (OR, 2.7; 95% CI, 0.9–7.5), although the latter estimate was based on small numbers. ConclusionsLong-term HRT use, particularly of combined oestrogen–progestagen therapy, may increase the risk of meningioma.

NSAIDs and Hormone Replacement Therapy in Geriatric Crohnʼs Disease

Purpose: The US population is aging and the burden of patients with geriatric Crohn's disease (CD) is increasing. Studies have suggested that inflammatory bowel disease (IBD) including CD in elderly patients is different from the disease in young patients, arguing for two variant disease phenotypes. Treatment patterns may differ between geriatric and young IBD, with elderly patients receiving medications for concomitant illness and prophylaxis of cardiac, vascular and bone health. Nonsteroidal antiinflammatory drugs (NSAIDs) and hormone replacement therapy (HRT) have been associated with initial onset of IBD and reactivation of quiescent disease in IBD. Data describing NSAIDs and HRT treatment in elderly CD is limited. Methods: We performed a comprehensive analysis of CD patients age ≥ 65 followed in a tertiary care center. We determined patterns of CD activity over an 18 month time period and its relationship with treatment patterns of NSAIDs and HRT therapy. CD activity was categorized by retrospective chart review, with active disease defined by physician global assessment, clinical impression, symptoms of diarrhea and abdominal pain, and endoscopic and/or radiographic evidence of activity. Patients were labeled as active disease if they had ≥ 1 relapse during the study period and inactive patients remained in remission the entire time. Results: There were 90 geriatric CD patients, with 35.6% (n = 32) showing evidence of active CD during the study time period. The mean age for active CD was 71.4 ± 6.4 (years ± S.D.) and for inactive CD was 72.8 ± 6.8 (years ± SD). Among geriatric patients with active CD, 9.4% were on NSAIDs while the inactive CD cohort had 15.5% receiving NSAIDs. Female constituted 54% of the geriatric CD patients (n=49) and HRT was identified in only 7 patients (8% of the total and 14% of the female geriatric cohort). Among female CD patients with active disease 19% were on HRT, while 11% of inactive CD geriatric females were on HRT (p=NS). Conclusion: Our study of geriatric CD patients suggests that use of NSAIDs and HRT did not correlate with increased rates of disease activity during an 18 month time period. Further prospective studies evaluating the use of NSAIDs and HRT in geriatric CD are warranted.

Decline in prolonged hormone replacement therapy in women aged 45 years or more, and impact of a centralised database tool

Abstract Objective Evaluation of discontinuation in prolonged use of menopausal and post-menopausal hormone replacement therapy (HRT) in The Netherlands after the publication of the Million Women Study in The Lancet of August 9, 2003. Furthermore estimation of the contribution of a centralised database tool on this decline, supplying community pharmacists with their patients on prolonged HRT therapy. Setting Dispensing data of more than 90% of Dutch community pharmacies were collected in a centralised database. Shortly after the publication of the Million Women Study, this database was used to offer community pharmacists online access to a listing of their patients with prolonged HRT use. Methods In August 2003 all women who had used HRT for at least one year were selected as long-term users. This cohort was followed until April 2004. The proportion of patients who had stopped their prolonged HRT in this cohort was calculated. This decline was also measured according to the use of a database tool. For this purpose community pharmacies were divided into pharmacies who had repeatedly consulted the centralised database tool (T pharmacies; n = 343) and control pharmacies who had evidently not consulted the tool (C pharmacies; n =490). The two groups of pharmacies were compared according to characteristics of the pharmacy on which information was available in the centralised database. They were also compared for patient characteristics that were routinely collected in the database. Differences between the two groups for averages of these parameters were tested with a chi square test and with a chi square test for trend for ordinal variables with more categories. The proportion of patients who stopped their prolonged HRT was calculated for each of the two groups of pharmacies. These proportions were compared with a Z test for proportions. The two groups of pharmacies were compared for cessation of HRT treatment and for ceasing treatment earlier by a Kaplan-Meier survival curve. Cox survival analyses was used to estimate the chances for discontinuation of HRT for patients within the two pharmacy groups with the possibility to adjust for possible confounders such as patient's age and type of HRT medication. Key findings After publication of the Million Women Study in The Lancet of August 9, 2003, 63% of the women in The Netherlands who had used HRT for more than one year in August 2003 had stopped their prolonged use in April 2004. A centralised database tool supplying community pharmacists with a list of their patients on prolonged HRT therapy caused a significantly higher proportion of cessation in the T group of pharmacies than in the C group (65% versus 62%; P &amp;lt; 0.05). Furthermore, the time needed for halving the number of patients on prolonged HRT was significantly shorter in T pharmacies than in C pharmacies (187 days versus 202 days; P &amp;lt; 0.05). Patients in T pharmacies had a significantly increased chance of 7.6% (95% confidence interval: 1.05–1.10) of discontinuing their HRT and of doing so earlier. Conclusions The results of the Million Women Study had a major impact on prolonged HRT use in The Netherlands. A centralised database tool for prolonged use of HRT could have a modest but significant impact on dispensing patterns.

Submaximal exercise coronary artery flow increases in postmenopausal women without coronary artery disease after estrogen and atorvastatin

The aim of this study was to determine the effect of statins and hormone therapy on submaximal exercise-induced coronary artery blood flow in postmenopausal women without a history of coronary artery disease. Hormone therapy or statin therapy in early postmenopausal women without coronary artery disease has been shown to enhance arterial endothelial function; we hypothesized that these agents would improve submaximal exercise-induced coronary artery blood flow. Sixty-four postmenopausal women, aged 50 to 65 years without documented coronary artery disease, were randomized in a double-blind, crossover fashion to receive 8 weeks of hormone therapy versus placebo, with or without 80 mg/day of atorvastatin. Before receipt of any therapy and after each treatment period, each woman underwent measures of coronary artery blood flow at rest and stress. The combination of hormone therapy and atorvastatin increased submaximal exercise-induced coronary artery blood flow (P = 0.04). In the subgroups of women compliant with treatment, resting coronary artery blood flow increased in those receiving hormone therapy (P = 0.03) or statin therapy (P = 0.02). In postmenopausal women aged 50 to 65 years without documented coronary artery disease, resting and submaximal exercise-induced coronary artery blood flow improves after receipt of high-dose atorvastatin and conjugated estrogens therapy.

Multidisciplinary working: the need for competence

Historically it was the gynaecologist in the UK, who offered support to women at the time of the menopause, usually in the form of a prescription for hormone replacement therapy (HRT) and often primarily for treatment of short and intermediate term symptoms. Women were seen in the general Gynaecology Clinic and consultations were often brief. In the past 10 years however, as more and varied treatments have become available and as the professional roles of other colleagues have evolved, it is now increasingly common to see the primary care doctor, nurses including the practice nurse or indeed other health-care professionals such as pharmacists, counsellors and dieticians seeing and advising women, alongside the development of specialist menopause clinics led by gynaecologists. The multidisciplinary approach can enhance the quality of care, while at the same time taking into account other aspects such as service efficiency, safety, continuity and timeliness of care. As we increasingly recognize the menopausal years as a crucial time for health promotion, advice has become broader and now encompasses all aspects of healthy living including dietary advice, lifestyle management and disease prevention as well as symptom control, medication management and prevention of longer term sequelae of estrogen deficiency. Following a comprehensive holistic health history, the menopause consultation has become a time to discuss a variety of health issues, not just relief of troublesome menopausal symptoms. In addition, we have seen the popularity of HRT use among women fluctuate alongside media coverage which is often negative. One positive effect of this, however, is that women are increasingly seeking a more in depth discussion about the safety of HRT on an individual basis. In addition, many women are turning initially to therapies other than HRT with little professional advice. Today’s patient tends to be more knowledgeable with information from peers, the Internet and media but unfortunately the information is often either superficial or too complex to be of value to an individual patient. There is room for professionals of all groups to better educate women about menopause, HRT and other therapy options. This knowledge empowers women to make informed choices about how best to manage their own menopause and the years beyond. Formal doctors’ training programmes have been developed, such as the RCOG Special Skills module for gynaecologists and the Faculty of Sexual and Reproductive Health courses for other doctors, but the needs of other health professionals have gone broadly unmet, except for ad hoc study days and journal articles. There has been a paucity of accredited post-registration, education programmes and a lack of accountability in terms of competence for non-medical practitioners working in menopause. The role of nurses in particular has developed over a long period of time and a ‘nurse’ working in menopause might be a health-care support worker, welcoming women and assisting a doctor with examinations, such as pelvic and vaginal examinations, or a Nurse Consultant assessing and advising women independently, prescribing where appropriate and investigating abnormal pathology, with many levels of expertise in between. With this wide spectrum of responsibility, there is a need for nurses to be professionally accountable for their practice and competent in the work they choose to do. Similarly, medical and other colleagues need to have confidence that nurses have the necessary attitudes, skills and knowledge to work at a given level of responsibility. The Royal College of Nursing Competence Framework for nurses and health-care support workers working in menopause is a step towards the profession themselves taking responsibility for clinical practice within this field and enables nurses and employers to identify an appropriate level of practice for a particular nurse, given their knowledge and clinical skills. It offers nurses a pathway towards expert practice and guidance within the specialist field of menopause. The Royal College of Obstetricians and Gynaecologist Standards for Gynaecology support multidisciplinary working and recognize the need for non-medical health professionals to be ‘appropriately trained’ (p. 35). For nurses, education programmes, which are both professionally and academically accredited, are now available at both a foundation level and a more advanced level. However in the current climate, there are issues relating to funding and availability of study leave for those nurses wanting to complete such courses. Menopause International 2009; 15: 140–141. DOI: 10.1258/mi.2009.009038

Influence Of Hormone Replacement Therapy With Maximal Eccentric Exercise On Estrogen Receptor Coregulators And Skeletal Muscle Damage In Postmenopausal Women

The use of hormone replacement therapy (HRT) is a potential treatment to relieve symptoms of menopause and prevent the onset of disease such as osteoporosis in postmenopausal women. Although estrogen has a possible protective effect against exercise-induced skeletal muscle damage, it is unclear if HRT therapy enhances estrogen receptor (ER) activity in skeletal muscle at rest and following resistance exercise. PURPOSE: To evaluate changes in the mRNA gene expression of ER coregulators (SRC and SMRT) and markers of skeletal muscle damage (CK, LDH, and TNF-a) in postmenopausal women following a high-intensity resistance exercise bout. METHODS: Fourteen postmenopausal women were divided into two groups: Control, women not using HRT (n=6, 59±2 yr, 63±7 kg), or HRT, women using traditional HRT (n=8, 59±1 yr, 89.5±8.4 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on the Cybex dynamometer at 60°/s with 20 second rest periods between sets. Two muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 hours after the exercise bout. mRNA gene expression was determined using RT-PCR for SRC, SMRT, and TNF-a. Blood draws were performed at baseline and 3 days post-exercise to measure CK and LDH. Independent t-tests were performed to test group differences (Control vs HRT). A probability level of p≤0.05 was used to determine statistical significance with Bonferroni adjustments. RESULTS: We observed significantly greater changes in mRNA expression of SRC and SMRT (p≤0.01) and significantly lower changes in mRNA expression of TNF-a (p≤0.01) in the HRT group compared to controls following the exercise bout. mRNA expression of SRC significantly increased (p≤0.01) and mRNA expression of SMRT significantly decreased (p≤0.01) following the exercise bout in both groups. CK and LDH levels were significantly greater post-exercise (p≤0.01) in the Control group. CONCLUSIONS: These data suggest a single bout of maximal eccentric exercise significantly enhances ER activity with greater response present in postmenopausal women using HRT. Postmenopausal women not using HRT experienced greater muscle damage after exercise indicating a possible protective effect of HRT against exercise-induced skeletal muscle damage. Keywords: SRC, SMRT, muscle damage

Hormone replacement therapy diminishes hearing in peri-menopausal mice

We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. – PNAS 103, 14246–14249]. To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen + progestin) and estrogen alone on hearing in peri-menopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion-product otoacoustic emissions (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, subcutaneous implanted pellet of estrogen + progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen + progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen + progestin treatment group in the high and middle frequency ranges (15–29 and 30–45 kHz) after as early as 2 months of treatment ( p < 0.01 and p < 0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen + progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen + progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

Effect of hormone replacement therapy on serum complement (C3, C4) and immunoglobulin (IgG, IgM) levels in post-menopausal women

Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy (HRT) regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed in 54 women receiving HRT therapy (CEE 0.625 mg+MPA 2.5 mg/day), and in 54 control women not receiving HRT. The results showed that the mean serum C3 and C4 levels were significantly higher in women receiving HRT than those untreated women (P<0.01). There was significant difference in IgG and IgM levels between two groups. It was concluded that HRT might be involved in the development of cardiovascular diseases through inflammatory mechanisms, as suggested by increased serum levels of C3 and C4.

Combined hormone replacement therapy improves lipids but may increase leucocytes

Dear Sir, Recent clinical trial data have cast doubt on the efficacy of oral hormone replacement therapy (HRT) for decreasing cardiovascular events. One of the postulated mechanisms is the upregulation of inflammation leading to accelerated atherosclerosis, plaque instability or thrombosis. Thus, plasma C-reactive protein levels increase during HRT, an effect that is attenuated with statin therapy [1]. On the other hand, some markers of inflammation may be reduced with HRT therapy, including levels of cell adhesion molecules [2], whilst other markers seem not to be influenced by HRT [3]. In a randomized, double-blind, controlled study, we evaluated the efficacy of continuous combined HRT with 1 mg oestradiol and 0.5 mg norethisterone acetate (Activelle®, Novo Nordisk A/S, Bagsvaerd, Denmark) compared with placebo in lowering total and LDL cholesterol levels in women at high risk for cardiovascular disease (CVD). The subjects were postmenopausal women aged 40–75 years (mean 64 years) with LDL cholesterol levels ≥4.1 mmol L−1. All had at least one other CVD risk factor. Major exclusions were the standard ones for the use of HRT. All provided written informed consent and the study was approved by the regional ethics committee. Subjects (n = 113) were treated with a cholesterol-lowering diet for 14 weeks and continued the diet throughout. If LDL cholesterol levels remained ≥4.1 mmol L−1 at week 5, they started therapy with cerivastatin 300 μg at week 6. At week 14, subjects were randomized to HRT or matching placebo. Combined oestrogen and progestin was provided in one daily tablet containing oestradiol 1 mg and norethisterone acetate 0.5 mg. HRT or placebo was planned to continue for 36 weeks. However, due to withdrawal of cerivastatin in August 2000, the study was stopped prematurely. At that time 23 subjects had received HRT or placebo for 12 weeks or more. Laboratory samples were obtained after an overnight fast. Total cholesterol and triglyceride concentrations were measured using automated analyser equipments (Hitachi 911; Hitachi Limited, Tokyo, Japan) and reagents from Boehringer Mannheim (Mannheim, Germany). HDL cholesterol concentrations were measured on a Hitachi 911 analyzer using the direct, enzymatic inhibition assay of Boehringer Mannheim. LDL cholesterol was calculated using the Friedewald formula. Standard methods were used to determine liver transaminase, creatinine, erythrocyte, platelet and leucocyte counts. Analyses were performed at the Department of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway. For statistical analyses, an analysis of covariance model was used with the change from randomization to week 12 as response, group as fixed factor and the values at randomization as covariate. The mean difference between groups over the randomized period, P-values for the between-group comparison and 95% confidence intervals were calculated using the Statistical Analysis System version 6.12 (SASTM; SAS, Cary, NC, USA). Continuous combined HRT reduced total cholesterol by 0.7 mmol L−1 (95% CI, −1.1, −0.3) or 14% and LDL cholesterol levels by 0.6 mmol L−1 (95% CI, −1.0, −0.1) or 20% (Table 1). Levels of HDL cholesterol were also reduced by 0.3 mmol L−1 (95% CI, −0.4, −0.1) or 14%. Levels of glucose, liver transaminases, creatinine, erythrocytes and platelets did not differ between the groups (data not shown). However, levels of leucocytes increased in the HRT group compared with placebo after adjustment for baseline levels (mean difference 0.7 × 109 L−1, 95% CI, 0.3–1.2). In this study HRT resulted in a further reduction in total and LDL cholesterol levels, in addition to the reduction due to the combination of diet and cerivastatin. However, HDL cholesterol levels were reduced and the leucocyte count increased. The effects of HRT on lipid levels are in accordance with earlier data. Whilst therapy with oestrogen alone reduces total and LDL cholesterol and increases HDL cholesterol, the addition of a gestagen, in particular when the gestagen is taken continuously, has a deleterious effect on HDL cholesterol. However, the leucocyte count increased. In a previous study conducted amongst women with diabetes, the leucocyte count did not change during treatment with conjugated equine oestrogen plus medroxyprogesterone acetate for 6 months [2]. Differences between trials may be due to the type of HRT that is used, subject characteristics or other variables. Our finding may be the result of chance as the number of participants was low. However, the relationship between HRT use and leucocyte count warrants further investigation. No conflict of interest was declared. This study was supported by a research grant from Novo Nordisk.

Effects of hormone replacement therapy and tıbolone on skın thıckness and bone ın postmenopausal women

Effects of hormone replacement therapy and tıbolone on skın thıckness and bone ın postmenopausal women

Vitamin D and its binding protein Gc: Long‐term variability in peri‐ and postmenopausal women with and without hormone replacement therapy

Objective. Measurement of plasma 25‐hydroxyvitamin D (25OHD) level is often used to evaluate a patient's vitamin D status. The purpose of this study was to investigate the variability in individual plasma 25OHD‐ and vitamin D‐binding protein‐ (Gc) levels over a 5‐year period in postmenopausal women with and without hormone replacement therapy (HRT). Material and methods. A total of 187 women were followed‐up for 5 years. At baseline, 89 women were allocated to treatment with HRT, given orally. Measurements were performed at baseline and after 1, 2 and 5 years of follow‐up. Results. At baseline, 25OHD levels were positively associated with sunbathing and use of vitamin D supplements, and inversely associated with smoking. HRT therapy increased plasma levels of Gc (+8 %) but did not affect 25OHD levels or the free 25OHD index (molar ratio of 25OHD‐ to Gc levels). Among those classified in the lowest 25OHD tertile at baseline, 40 % remained in the lowest tertile during all subsequent measurement time‐points. Similarly, 32 % of those classified in the highest baseline tertile remained in the highest tertile during all subsequent measurements. Use of the free 25OHD index showed similar results. No independent predictors of changes in vitamin D tertiles during follow‐up were identified, which suggests that the observed variation was caused by the intra‐individual variation in measured parameters. For all participants, the within‐patient variability in 25OHD measurements was between 13 % and 19 %. Conclusions. In healthy postmenopausal women, HRT increases Gc levels. Owing to the high intra‐individual variation in plasma 25OHD, it seems questionable to use a single estimate as a predictor of individual vitamin D status.

Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women

Hepatic lipase (HL) is a lipolytic enzyme that hydrolyzes triglycerides and phospholipids in almost all major classes of lipoproteins. The HL gene has a functional promoter polymorphism at position -480, which affects transcription and leads to CC, CT, and TT genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up observational study of 88 postmenopausal women with different HL genotypes (CC, n = 49; CT, n = 34; TT, n = 5). These women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 26) used sequential estradiol valerate (EV) plus progestin (levonorgestrel), the HRT-EV group used EV alone (n = 32), and the control group (n = 30) used no HRT. The HRT-EV and HRT-EVP groups started estrogen at menopause for estrogen-deficiency symptoms, whereas the control group took no estrogen due to either the absence of such symptoms or a dislike of estrogen therapy. In addition to serum lipid concentration and HL genotype, the atherosclerosis severity score (ASC) for the abdominal aorta and carotid arteries was determined by ultrasonography. There was a significant interaction between HRT therapy and HL genotypes on the increase in ASC (P = 0.046) after adjustment for age, body mass index, changes in high-density lipoprotein cholesterol and baseline ASC. In subjects with the T allele, the progression of ASC was significantly faster in the control group than the HRT group (P = 0.0006), whereas in the CC genotype, there were no significant differences in ASC progression between the control and HRT groups. Our results suggest that the beneficial effect of HRT on atherosclerosis progression was restricted to women with the T allele, in whom the progression of ASC was slower by half. These results may help us understand in greater detail the benefits and possible risks associated with HRT in atherosclerotic diseases.