Administration Of Hormone Replacement Therapy Research Articles

Premature ovarian insufficiency in patients with galactosemia

Background. Galactosemia is a congenital disorder of carbohydrate metabolism caused by a defect in any of the enzymes of galactose metabolism. One of the long-term complications is premature ovarian insufficiency (POI), which is more common in patients with the c.563A>G (Q188R) mutation in the homozygous state in the galactose-1-phosphate uridylyltransferase (GALT) gene. At the same time, fertility factors may be higher in patients with POI caused by classical galactosemia (CG) compared with other causes of POI, which makes it difficult to resolve the issue of the need to use fertility preservation methods for this group of patients in the prepubescent period. Case report. This article describes two clinical observations of patients with CG who were diagnosed with hypergonadotropic hypogonadism. Patient A. was initiated hormone replacement therapy (HRT) at the age of 11, and according to the results of osteodensitometry, there is currently no decrease in bone mineral density. In patient C. at the age of 14, before the start of HRT, ovaries without pronounced follicular apparatus, osteopenia and osteoporosis were detected. The issue of the necessity and timing of the use of fertility preservation methods is being considered. Conclusion. Patients with CG are recommended to monitor hormonal profile indicators for timely administration of HRT. Cryopreservation of ovarian tissue should be considered as one of the options for maintaining fertility in patients with CG, taking into account that some of them still have the possibility of spontaneous pregnancy, despite the POI.

Analysis of options for prescribing hormone replacement therapy after thyroid organ-sparing surgery

Background. Performing thyroid organ-sparing surgery primarily aims to preserve the quality of life. Organ-sparing surgery should be understood as hemithyroidectomy with mandatory removal of the isthmus and pyramidal lobe of the thyroid (if present). The choice of one or another concept of prescribing hormone replacement therapy remains debatable. The purpose of the study is to determine the proportion of patients who do not need replacement therapy with levothyroxine after organ-sparing surgery on the thyroid gland, among those who were prescribed replacement therapy immediately and one month after discharge from the hospital, as well as to analyze the factors causing hypothyroidism in people with hemithyroidectomy. Materials and methods. The first group included 82 patients with hemithyroidectomy who were prescribed replacement therapy immediately after discharge from the hospital. The second group included 61 patients with hemithyroidectomy. The administration of replacement therapy was postponed for one month. A month after the operation, clinical examinations and monitoring of thyroid-stimulating hormone and free thyroxine indicators were performed. Results. After one month of observation, 72 (87.8%) of 82 patients in the first group continued to take levothyroxine, and 8 (13.1%) of 61 persons in the second group began to take it. In the first group, there was a moderate direct correlation between thyroid-stimulating hormone level before surgery and levothyroxine dose one month after (Spearman’s correlation coefficient 0.304, p=0.009). It was found that the chances of continuing taking levothyroxine after one month in the first group were 47 times higher than the chances of prescribing levothyroxine after one month in the second group. The proportion of patients in the first group who continued to take levothyroxine after one month was significantly higher than the proportion of patients in the second group who started taking levothyroxine after one month (87.8±3.6% vs. 13.1±3.5%, p<0.0001, Fisher’s exact test). Conclusions. Among patients who were prescribed hormone replacement therapy immediately after hemithyroidectomy, 12.2% did not need to continue taking levothyroxine after one month. Among persons in whom the administration of hormone replacement therapy was postponed for one month after hemithyroidectomy, 86.9% of patients did not require the use of levothyroxine in the future. The volume of the thyroid remnant ≤ 3.67 cm3 can be considered a predictor for hypothyroidism occurrence in the future, with a high risk of prescribing hormone replacement therapy. The study of such a factor as the ratio of the remnant thyroid volume to the body weight did not provide statistically reliable data for its use as a predictor of hypothyroidism occurrence in the postoperative period.

Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone replacement therapy (HRT). Full-text articles published up to April 30, 2021, were searched through PUBMED, EMBASE, the Cochrane library and Web of Science (WOS) databases and were screened strictly according to inclusion criteria. Randomized clinical trials and case control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. Data are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random effect models were used for the meta-analysis. HRT administration increases estradiol (E2) and reduces follicle stimulating hormone (FSH) serum levels compared with pre-treatment. Their changes are evident when oral and transdermal HRT are administered, while vaginal HRT not. No significant effect on E2 and FSH was found between 6 and 12 months, as well as between 12 and 24 months. No significant effect on E2 and FSH was shown between different regimes. No difference was observed between different HRT regarding their effect on lipid profiles, breast pain and vaginal bleeding, but oral estrogen combined synthetic progestin caused a reduction in sex hormone-binding globulin (SHGB). The review suggested oral and transdermal HRT could lead to a rise in E2 serum levels and a decrease in FSH. The types and doses of HRT did not seem to modify the E2 and FSH level. Also, oral estrogen combined synthetic progestin could cause a reduction in SHGB. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

Effective Image Communication of Hormone Replacement Therapy Risks and Benefits.

This article focuses on the value of a unique graphic/image designed to communicate health risks and benefits related to the administration of hormone replacement therapy. It will demonstrate why equations, technical terms, and confusing rhetoric need not be used for communication to patients and others. The use of a "familiar" theater graphic (given the name Benefit/Risk Characterization Theater) will allow physicians and patients to share decision-making by visualizing tradeoffs through the use of a clearer format: example Benefit/Risk Characterization Theaters: breast cancer risks associated with hormone replacement therapy, effectiveness of estrogen in treating menopausal symptoms, and thromboembolic risk of taking estrogen for postmenopausal women. The article describes a practical, simple methodology that can be used in many countries to facilitate doctor-patient communication.

Sociodemographics of Patient Populations Undergoing Gender-Affirming Surgery: A Systematic Review of All Cohort Studies.

Sociodemographic and health characteristics of patients undergoing gender-affirming surgery (GAS) are currently unknown. Understanding these patient characteristics is vital to optimizing patient-centered care for transgender patients. To determine sociodemographic characteristics for the transgender population undergoing GAS. Collected sociodemographic information included the following: age, race/ethnicity, body metrics, hormone replacement therapy administration and duration, substance use, psychiatric comorbidities, and medical comorbidities. A search of seven electronic databases (PubMed, PsycINFO, Embase, CINAHL, Web of Science, Cochrane, and Gender Studies) was used to find all articles on GAS from inception through May 2019. The 15,190 articles were then subjected to two levels of screening, and articles unrelated to gender-affirming care, unavailable in English, n<5, and with no outcomes reporting were excluded. Textbook chapters and letters were also excluded. A total of 406 studies were fully extracted, with 307 studies reporting age (n=22,727 patients), 19 reporting race/ethnicity (n=1184), 74 reporting body metrics (body mass index [BMI] n=6852, height n=416, and weight n=475), 58 reporting hormone therapies (n=5104), 56 reporting substance use (n=1146), 44 reporting psychiatric comorbidities (n=574), and 47 reporting medical comorbidities (n=573). From the 406 studies, 80 were done in the United States. Regarding U.S. studies, 59 studies reported age (n=5365), 10 reported race/ethnicity (n=709), 22 reported body metrics (BMI n=2519), 18 reported hormone therapies (n=3285), 15 reported substance use (n=478), 44 reported psychiatric comorbidities (n=394), and 47 reported medical comorbidities (n=293). Age was the most reported characteristic, reported in 75.62% of studies (73.75% of U.S. studies). Race/ethnicity was the least commonly reported data, reported in 4.68% of studies (12.50% of U.S. studies). The type of sociodemographic information reported by GAS studies is inconsistently reported. To improve patient-centered care for transgender patients, further work is needed to create a standardization of collected sociodemographic information.

Effects of Contraception Pills and Hormone Replacement Therapy on Tissue Plasminogen Activator -1 and Plasminogen Activator Inhibitor-1 in Per and Postmenopausal Women

Contraception is a program employed to avoid pregnancy during premenopausal period where as hormonereplacement therapy (HRT) is a medical option to ameliorate menopausal complications. The present studywas designed to evaluate the effects of contraceptions and HRT on estradiol hormone ,tissue plasminogenactivator-1 (TPA-1),and plasminogen activator in hibitor-1(PAI-1).One hundred (120) women were recruited ;30 women with contraception; 30 women with HRT ,and60women contraception ; with HRT , and 60 women as a control group. All ages of women were rangedbetween 31-70 years old and subdivided into four groups(31-40,41-50, 51-60, 61-70 years old ).Data obtained from this study indicated a significant elevation (p&lt;0.05) in the levels of estradiol hormone inall tested groups of women compared to control women (without contraception and HRT).It was establisheda significant drop (p&lt;0.05) in the concentration of TPA-1 in women taking contraception and those intakeHRT in a comparison with control groups. About levels of PAI-1,they were significantly higher (p&lt;0.05)in both women with contraception and HRT than of control women .From these observations the availableconclusion may be administration of contraception and HRT influence fibrinolytic system and increaseincidence of thrombotic events .

The role of bilateral ovariectomy in the impairments of prooxidant-antioxidant balance and renal concentrating capacity in rats in the period of late manifestations of the traumatic disease and the efficacy of hormone replacement therapy

Introduction. Traumatic events are currently considered to be one of the topical issues. The progression of renal failure plays an important role in the pathogenesis of traumatic disease. It is essential to evaluate the ability of renal tubular epithelium to the urine osmotic concentration in order to indicate the direct renal tubular damage. A sodium-free water clearance (S-CH2O) is a sensitive indicator reflecting the kidneys ability to concentrate the urine. It is established that the renal functional state, the resistance of the kidneys to the development of various disorders depends on the estrogen concentration. The key mechanism of the indirect effect of estrogens on the kidneys is via their direct antioxidant action. However, the role of estrogens in the pathogenesis of oxidative and functional impairments of the kidneys in the presence of cranioskeletal trauma is insufficiently studied. There is no data available on the efficacy of hormone replacement therapy under those circumstances.The objective of research: to determine the pro-oxidant-antioxidant balance and renal concentrating capacity following the cranioskeletal trauma model in rats with bilateral ovariectomy in the period of late manifestations of the traumatic disease and evaluate the efficacy of hormone replacement therapy.Material and methods: The experimental studies were conducted on 64 white non-linear female rats weighing 200-220g. The experimental model of hypoestrogenism was performed through the surgical removal of gonads. The rats were subjected to the cranioskeletal model one month after removal of the gonads. Hormone replacement therapy (HRT) was used as a corrective treatment in the separate subgroup of gonadectomized rats subjected to the cranioskeletal trauma. The control groups consisted of intact animals and rats 1 month after removal of the gonads that were not injured. The renal functional state was determined via a water loading test in the control groups of animals and after 1 and 2 months of postrraumatic period. The sodium concentration, as well as the S-CH2O value was measured in serum and urine. The content of thiobarbituric acid reactive substances (TBARs) and catalase activity were determined in renal cortex and medulla. The prooxidant/antioxidant ratio (ProAntidex) was calculated based on the above data.The results and discussion. The conducted studies indicated the considerable decrease in ProAntidex value in renal cortex and medulla in the group of gonadectomized rats compared to the animals without gonadectomy after 1 month of the posttraumatic period, confirming the protective antioxidant role of estrogens in adequate renal function. The cranioskeletal trauma model led to the declined parameter value in renal cortex and medulla in both experimental groups after 1 month of the posttraumatic period. The prooxidant/antioxidant ratio was significantly decreased in the first month following the trauma in the gonadectomized rats as compared to the rats without the gonadectomy, and remained at the same level up to the 2nd month of the posttraumatic period. The identified abnormal value of ProAntidex in the posttraumatic period clearly affected the dynamics of S-CH2O. This parameter was reported as decreased in both experimental groups compared to the control. However, the parameter was substantially decreased 1 and 2 months after trauma under conditions of the gonadectomy. The administration of hexestrol and progesterone to the gonadectomized rats with trauma model resulted in the considerable increase in value of ProAntidex in renal cortex and medulla starting from the 1st day of the posttraumatic period compared to the animals without corrective medication. Moreover, it was accompanied by a statistically significant increase in S-CH2O rate, indicating the enhancement in the functional capacity of the renal tubules.Conclusions. The value of ProAntidex decreases in renal cortex and medulla in the group of gonadectomized female rats after 1 month of the posttraumatic period, and is significantly lower compared to the animals without removal of the gonads. The cranioskeletal trauma model leads to the substantially declined prooxidant/antioxidant ratio value in renal cortex and medulla, which is reported as considerably greater in the group of gonadectomized animals after 1 month of the posttraumatic period, showing no tendency to enhance after 2 months of the experiment. The administration of hormone replacement therapy to the gonadectomized rats is accompanied by the increase in ProAntidex value and S-CH2O rate compared to the animals without corrective medication.

Hormone replacement therapy after surgery for epithelial ovarian cancer.

Women who have undergone surgical treatment for epithelial ovarian cancer (EOC) may develop menopausal symptoms due to immediate loss of ovarian function following surgery and chemotherapy. Women may experience vasomotor symptoms, sleep disturbance, difficulty concentrating, sexual dysfunction, vaginal symptoms and accelerated osteoporosis. Although hormone replacement therapy (HRT) is the most effective treatment to relieve these symptoms, its safety has been questioned for women with EOC. To assess the safety and efficacy of HRT for menopausal symptoms in women surgically treated for EOC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), MEDLINE via Ovid (1946 to 12 June 2019) and Embase via Ovid (1980 to 2019, week 23). We also handsearched conference reports and trial registries. There was no language restriction. We included randomized controlled trials (RCTs) with participants of any age and menopausal status who had undergone surgery for EOC and, after diagnosis and treatment, used any regimen and duration of HRT compared with placebo or no hormone therapy. We also included trials comparing different regimens or duration of administration of HRT. Two review authors independently identified studies that met the inclusion criteria. They used Covidence to extract study characteristics, outcome data and to assess methodological quality of the included studies. Our search strategy identified 2617 titles, of which 2614 titles were excluded. Three studies, involving 350 women, met our inclusion criteria. Two of the studies included pre and postmenopausal women, and the third only included premenopausal women. The overall age range of those women included in the studies was 20 to 89.6 years old, with a median follow-up ranging from 31.4 months to 19.1 years. The geographical distribution of participants included Europe, South Africa and China. All stages and histological subtypes were included in two of the studies, but stage IV disease had been excluded in the third. The three included studies used a variety of HRT regimens (conjugated oestrogen with or without medroxyprogesterone and with or without nylestriol) and HRT administrations (oral, patch and implant), In all studies, the comparisons were made versus women who had not received HRT. The studies were at low or unclear risk of selection and reporting bias, and at high risk of performance, detection and attrition bias. The certainty of the evidence was low for overall survival and progression-free survival, and very low for quality-of-life assessment, incidence of breast cancer, transient ischaemic attack (TIA), cerebrovascular accident (CVA) and myocardial infarction (MI). Meta-analysis of these studies showed that HRT may improve overall survival (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.54 to 0.93; 350 participants, 3 studies; low-certainty evidence). Quality-of-life assessment by use of the EORTC-C30 questionnaire was performed only in one study. We are uncertain whether HRT improves or reduces quality of life as the certainty of the evidence was assessed as very low (mean difference (MD) 13.67 points higher, 95% CI 9.26 higher to 18.08 higher; 1 study; 75 participants; very low-certainty evidence). Likewise, HRT may make little or no difference to progression-free survival (HR 0.76, 95% CI 0.57 to 1.01; 275 participants, 2 studies; low-certainty evidence). We are uncertain whether HRT improves or reduces the incidence of breast cancer (risk ratio (RR) 2.00, 95% CI 0.19 to 21.59; 225 participants, 2 studies; very low-certainty evidence); TIA (RR 5.00, 95% CI 0.24 to 102.42; 150 participants, 1 study; very low-certainty evidence); CVA (RR 0.67, 95% CI 0.11 to 3.88; 150 participants, 1 study; very low-certainty evidence); and MI (RR 0.20, 95% CI 0.01 to 4.10; 150 participants, 1 study; very low-certainty evidence). The incidence of gallstones was not reported in the included studies. Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC, but the certainty of the evidence is low. HRT may make little or no difference to quality of life, incidence of breast cancer, TIA, CVA and MI as the certainty of the evidence has been assessed as very low. There may be little or no effect of HRT use on progression-free survival. The evidence in this review is limited by imprecision and incompleteness of reported relevant outcomes and therefore the results should be interpreted with caution. Future well-designed RCTs are required as this is an important area to women experiencing menopausal symptoms following surgical treatment for ovarian cancer, especially as doctors are often reluctant to prescribe HRT in this scenario. The evidence in this review is too limited to support or refute that HRT is very harmful in this population.

The Contribution of Hormone Replacement Therapy in Postmenopausal Women to Prevent Periodontal Disease

Aim: We investigated the possible association of hormone replacement therapy (HRT) administration and periodontitis in postmenopausal women by testing of systematic inflammatory parameters. Participants and Methods: 169 postmenopausal women participated in a prospective clinical study. They were divided into two groups: Group HRT (n=69) received HRT and Group no-HRT (n=100) did not receive HRT, but continued with body exercise and daily suitable natural food diet. We measured in the serum: Interleukin-1a (IL-1a); Interleukin-1b (IL-1b); Interleukin-6 (IL-6); Τumor necrosis factor (TNF-α); C-reactive protein of serum (CRP); Alkaline phosphatase (ALP); and Activin A. We also examined: oropharyngeal cavity microbial cultures; use of periodontal probe; depth of pocket; and bone mineral density. Results: The laboratory analyses showed statistical significant decrease of TNF-a (p<0.001), IL-6 (p<0.001), IL-1a (p<0.001), IL-1b (p<0.001), alkaline phosphatase (p<0.001) and CRP (p<0.001) in Group HRT compared to no-HRT. Activin A was also reduced but not statistically significantly (p=0.549). Oropharyngeal cavity cultures were all negative in Group HRT. Conclusion: We conclude that post-menopausal women after administration of HRT are protected of oral cavity health problems periodontitis and other local symptoms,

The Association between Female Reproductive Factors and Open-Angle Glaucoma in Korean Women: The Korean National Health and Nutrition Examination Survey V.

Purpose We investigated associations between female reproductive factors and open-angle glaucoma (OAG) in Korean females using the Korea National Health and Nutrition Examination Survey (KNHANES). Methods A nationwide, population-based, cross-sectional study was conducted. We enrolled 23,376 participants from the KNHANES who had undergone ophthalmologic exams from 2010 through 2012. Associations between undiagnosed OAG and female reproductive factors such as age at menarche and menopause, parity, history of lactation, and administration of oral contraceptives (OC) or hormone replacement therapy (HRT) were determined using stepwise logistic regression analyses. Results Of the enrolled participants, 6,860 participants (397 with OAG and 6,463 without OAG) met our study criteria and were included in the analyses. In the multivariate logistic regression analysis after adjusting for all potential confounding factors, only early menopause (younger than 45 years) was significantly associated with OAG in participants with natural menopause (OR 2.28, 95% CI 1.17–4.46). Age at menarche, parity, history of lactation, and administration of OC or HRT were not significantly associated with OAG. Conclusions Only early menopause was associated with an increased risk of OAG in our study, in contrast to previous Western studies reporting both early menopause and late menarche as associated factors.

Endocrinopathy-induced euvolemic hyponatremia.

Euvolemic hyponatremia results from either the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency. Furthermore, the criteria for diagnosis of SIADH entail the exclusion of hypothyroidism and hypoadrenalism. We aim to assess the yield of euvolemic hyponatremia workup focusing on underlying endocrinopathies in a real-world setting. A single-center retrospective study includes all patients diagnosed with euvolemic hyponatremia in a tertiary hospital between 1.1.2007 and 1.1.2013. Demographic, clinical, and laboratory data were collected from medical charts. Euvolemic hyponatremia was detected in 564 patients. Thyroid function was tested in 69% (391/564) and adrenal function was assessed in 29% (164/564) of cases. Endocrinopathy-induced euvolemic hyponatremia was diagnosed in nine (1.6%) patients: three patients were diagnosed with hypothyroidism-induced hyponatremia, three with adrenal insufficiency as an underlying cause, and three with central hypothyroidism and central hypoadrenalism. All nine had medical history and symptoms suggestive of endocrine deficiencies other than the hyponatremia, which resolved within 1-3days after administration of hormone replacement therapy. Yield of performed workup for hypothyroidism and hypoadrenalism in euvolemic hyponatremia was low. However, in this real-world study, only a limited number of patients underwent a full ascertainment of hypoadrenalism and hypothyroidism, which was diagnosed only in patients with additional findings supportive of these endocrinopathies; a higher rate of undiagnosed endocrinopathies cannot be ruled out. As both hypoadrenalism and hypothyroidism are easily treatable, potentially life-threatening conditions, there are insufficient data to change current recommendation for their universal evaluation in patients with euvolemic hyponatremia.

Gynecological Care and Prevention of Gynecological Malignancies in BRCA1 and BRCA2 Mutation Carriers

This paper summarizes the current knowledge of gynecological care aspects in women with inherited predisposition to breast and ovarian cancer, i.e. BRCA1 and BRCA2 mutation carriers, and proposes guidelines for furher management of these women, addressing follow-up recommendations, prophylactic surgery indications and preimplantation genetic conseling. It evaluates cancer risk and severity of ovarian cancer in particular with regards to its high mortality resulting from aggressive biological behavior of the tumor and late detection rates. BRCA-positive women should be enrolled in prevention programs including carefull surveillance, prophylactic surgery or pre-implantation genetic counseling. Follow-up care consists of gynecological examination, expert oncogynecological ultrasound and tumor marker CA125 examination every six months. However, the most effective strategy for mortality reduction in ovarian cancer is prophylactic surgery--salpingo-oophorectomy (and hysterectomy). The optimal age for surgery is between 35 to 40 years. Prophylactic salpingo-oophorectomy performed in premenopausal women was proved to reduce the risk of ovarian as well as breast cancer. Symptoms of estrogen deficiency after prophylactic surgery can be suppressed by administration of hormone replacement therapy without increasing the risk of breast cancer. Preimplantation genetic diagnosis is an effective way to prevent the trans--mission of hereditary predisposition to the next generation. The management of patients with hereditary suspceptibility to ovarian cancer should be confined to specialized centres.

Impact of obesity on the health of women in midlife

Key content Obesity is a major public health issue worldwide and lifestyle factors affecting weight should be addressed at every opportunity. Weight gain is not affected by the menopause or administration of hormone replacement therapy. Menopause favours the development of central adiposity. Obesity is a risk factor for menopausal symptoms and depression. Increased adiposity affects the hypothalamic‐pituitary‐gonadal function, which may manifest as menstrual dysfunction and late onset of menopause. Learning objectives To understand the impact of obesity on both general and reproductive health in women in midlife. To understand the pathophysiology underlying these changes. To understand the significance of fat distribution on metabolism and disease. Ethical issues While there is evidence that there is a genetic predisposition towards obesity, lifestyle is also recognised as a significant risk factor. The cost of obesity to the UK National Health Service is huge and it is a potentially avoidable problem.

Hormonal correction of atrophic changes in women with urogenital prolapse

In order to determine the hormonal homeostasis in women with urogenital prolapse after hysterectomy surgery the study of vaginal microbiota in 51 patients was conducted. It has been proved that mainstay of treatment for improving clinical effect and partial restoration of own microflora is administration of hormone replacement therapy with low-active estrogen fractions (Estrone, Estriol). Cyclic use of Ovestin vaginal cream or suppositories helps prevent urinary incontinence and recurrences of vaginal prolapse after vaginal hysterectomy

Routes of administration of hormone replacement therapy and cardiovascular effects in postmenopausal women

Earlier results of observational data showed beneficial effects with hormone therapy in women after menopause but the large clinical trials such as the Women’s Health Initiative (WHI), Heart and Estrogen/progestin Replacement Study (HERS) failed to demonstrate protective cardiovascular effects. However, re-analysis of WHI results recommended that the adverse outcomes maybe influenced by several factors such as age, time of initiation, dose, route of hormone therapy and pre-existing cardiovascular disease. In recent times, the use of hormone therapy in postmenopausal women is still limited to climacteric symptoms, probably due to insufficient data to support its use in chronic conditions such as cardiovascular disease. However, results from The Kronos Early Estrogen Prevention Study (KEEPS), has been expected to provide a definite answer to reduce cardiovascular disease with hormone therapy in postmenopausal women. Based on the results from recent studies, re-analysis of WHI results, and WHI /HERS reports, this article highlights the cardiovascular effects of hormone replacement therapy with different routes of administration in postmenopausal women.

Trends in organ donor management: 2002 to 2012.

Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p < 0.001). Incidence of traumatic brain injury donors decreased (42.1% to 33.9%; p < 0.001) relative to an increased number of expanded criteria donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p < 0.001) and organs (5,857 to 6,945; p < 0.001). There has been an increase in organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p < 0.001) for a thoracic transplant recipient. The marked increase in the use of HRT in the management of brain-dead donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors.

Sex hormone replacement in disorders of sex development.

People with disorders of sex development (DSD) may have impaired sex steroid production or their gonads removed before, during or after adolescence, thus requiring hormone replacement therapy (HRT) to induce puberty and/or maintain secondary sexual characteristics, to optimize bone health, and to promote physical and social well-being. Oestrogens are usually used for this purpose in persons reared as females (eventually combined with progestins if a uterus is present) and androgens in those reared as males. An alternative therapy for women with ascertained complete androgen insensitivity syndrome could be testosterone, because this is the main sex steroid hormone secreted by their gonads, but this approach remains to be better explored. Few sound evidence-based data are available to guide HRT administration at puberty and in adulthood in individuals with DSD, but recent data and new formulations may give better perspectives for the future.

HRT prescribing post WHI and MWS: What did you do? Would you do it again?

As we write the editorial for this edition, a very public row has broken out over the principal findings of the Million Women Study (MWS). It was this study, in combination with the principal findings of the Women’s Health Initiative (WHI), that completely transformed the opinion of professionals and patients worldwide with regard to almost any hormone therapy. Various estimates of the quantitative effect on hormone-replacement therapy (HRT) prescribing exist depending on the markets examined but it is clear that the overall effect is a halving in the use of HRT globally. It is highly likely that most HRT prescribers reduced the numbers of prescriptions immediately after the publication of these studies. Thus, was what many of us did right? Before we changed our prescribing habits or advice to patients, did we look at the data with the same level of scrutiny we would apply were we personally to be the ones about to start or continue therapy? Did we follow the investigators’ conclusions, or worse the conclusions from the media to influence our actions? Most of us recall the frenzy of sensationalism that accompanied these publications. Newspaper front pages screamed about the dangers of HRT and interviews with lead investigators promulgated their conclusions further. It was all too easy to take the path of least resistance and accept the indirect recommendations from investigators and press and the more direct guidance from some regulatory authorities. What we all should have done right from the start is to make our own minds up, either sit down, read the papers in detail or discuss them in a practice or multiprofessional meeting. Following the herd may have been the safest thing to do from a purely professional point of view but did we do the right thing for our patients? Without a doubt there may have been patients taking HRT who were not being regularly assessed and having their risk profiles assessed yearly who should have considered stopping. The worrying thing is the number of patients who had their treatment stopped suddenly without an option to discuss things further. With this probably well-intentioned risk-reducing manoeuvre, many women were plunged suddenly into a hormone-free hell. Many women suffered a significant and sudden reduction in quality of life, seeking out alternatives such as phytoestrogens and other drugs that are largely less well researched than HRT. It was easy to see the immediate effects on quality of life but other unwanted effects of cessation such as bone loss, vulvovaginal atrophy and short-term cognitive effects would take longer to present. Thus, what should we do with the reawakened debate about the validity of the MWS? Firstly, it should be considered that the recent publication does not actually provide new factual challenge to the MWS, it provides challenges to the methodological processes that lead to the main conclusion that HRT causes breast cancer. This conclusion has been challenged in several publications since the MWS was published and now adds further concern that the validity of the data and subsequent recommendations from regulatory authorities may need urgent review. Professionals new to the area of menopause are right to be confused. Have we been practising proper evidencebased medicine? Has there been a formal revision of the advice that arose from the main conclusions of the WHI and MWS? Whether a revision is needed or not we should all be practising an individualized approach to HRT prescribing, known risks and benefits should be carefully discussed prior to the decision to prescribe with effectiveness, tolerance and both shortand long-term effects monitored to facilitate continued prescription. What is urgently required is a formal expert group reappraisal resulting in a balanced assessment of whether women can feel safer on HRT and whether prescribers can have a greater degree of professional support from a regulatory body. In the meantime, please encourage colleagues to be aware of the debate, keep their professional ears to the ground and remain open to the possibility that HRT administration to the right woman at the right time in her life might actually be good for her.

Hormone replacement therapy and incidence of central nervous system tumours in the Million Women Study.

We examined the relation between the use of hormone replacement therapy (HRT) and the incidence of central nervous system (CNS) tumours in a large prospective study of 1,147,894 postmenopausal women. Women were aged 56.6 years on average at entry, and HRT use was recorded at recruitment and updated, where possible, about 3 years later. During a mean follow-up of 5.3 years per woman, 1,266 CNS tumours were diagnosed, including 557 gliomas, 311 meningiomas and 117 acoustic neuromas. Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). In past users of HRT the relative risk was 1.07 (95% CI: 0.93-1.24) for all CNS tumours. Among current users of HRT, there was significant heterogeneity by the type of HRT with the users of oestrogen-only HRT at higher risk of all CNS tumours than users of oestrogen-progestagen HRT (RR = 1.42, 95% CI: 1.21-1.67 versus RR = 0.97, 95% CI: 0.82-1.16) (heterogeneity p < 0.001). Among current users of oestrogen-only and oestrogen-progestagen HRT, there was no significant heterogeneity by duration of use, hormonal constituent or mode of administration of HRT.

The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy.

The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P<0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R=0.451, P<0.001) in women using oral HRT, but there was no correlation in women using the transdermal route. Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first-pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.