Initiation Of Hormone Replacement Therapy Research Articles

Plasma Homocysteine Levels as Cardiovascular Disease Risk vis-a-vis Estrogen Levels in Pre and Postmenopausal Women

Objectives: The objective of the study is to evaluate plasma homocysteine level and its relation with serum estrogen in pre and postmenopausal women as a risk factor in coronary artery disease (CAD). Materials and Methods: A cross-sectional study was conducted among premenopausal (n = 50) and postmenopausal women (n = 50) with an estimation of plasma homocysteine (Hcy) and serum estradiol (E2). Postmenopausal women based on their angiographic status were sub-grouped into A (with normal coronaries) and B (with CAD). Results: The levels of Hcy, 21.98 (20.89–24.05) μmol/L, increased significantly (P < 0.0001) and that of E2, 3.05 (2.32–3.6) pg/mL, decreased significantly (P = 0.0001) in the postmenopausal group when compared to Hcy, 6.11 (4.94–8.27) μmol/L and E2, 26.37 (25.3–29) pg/mL in premenopausal group. The levels of Hcy were elevated (24.7 ± 3.92 μmol/L) in postmenopausal Group B in comparison with postmenopausal Group A (21.37 ± 3.31 μmol/L), P = 0.002. Logistic regression analysis showed Hcy and body mass index to be independent predictors of CAD. Plasma Hcy showed an area under curve (AUC) of 1.00 with sensitivity and specificity of 100% at cutoff >12.6 μmol/L between pre and postmenopausal groups and AUC of 0.722 with 60% sensitivity and 84% specificity at cutoff >23.7 μmol/L between postmenopausal Groups A and B. Conclusion: We observed low E2 and high Hcy levels in postmenopausal women in comparison with premenopausal women. Among postmenopausal women, those with CAD had higher Hcy levels. Assessing Hcy levels routinely in postmenopausal women will help in better risk prediction of CAD and may also help in conjunction with other risk factors to decide the initiation of hormone replacement therapy.

Effects of Hormone Replacement Therapy on Autoimmune Markers and Clinical Outcomes in Pediatric Patients with Hashimoto's Thyroiditis

Objective: Hashimoto’s Thyroiditis (HT), a chronic autoimmune thyroiditis, is the predominant cause of hypothyroidism in regions without iodine deficiency. HT is characterized by the loss of immunological tolerance of the thyroid gland, leading to autoimmune attacks. This study aimed to compare the autoantibody profiles, along with clinical and laboratory findings, of patients diagnosed with Hashimoto’s disease who were either receiving treatment or followed without treatment. Material and Methods: Clinical manifestations, laboratory data, and thyroid ultrasonography (USG) findings of patients diagnosed with Hashimoto’s thyroiditis receiving hormone therapy and those followed without treatment were compared in our clinic. Results: Among a total of 249 patients, 116 received hormone replacement therapy, while 133 were followed without treatment. The mean age of all patients was 13.91±3.71 years, with a mean age at diagnosis of 11.51±3.79 years. After twelve months of follow-up, the untreated group showed an increase in serum fT4 and antiTPO levels (p=0.012 and p=0.001), with no significant difference found in serum TSH, fT3, and antiTG levels. Those receiving treatment exhibited a significant decrease in serum TSH levels and a significant increase in serum fT4 levels (p=0.002 and p<0.001, respectively). Although there was an increase in serum antiTPO and antiTG levels over time, no change was detected in serum fT3 levels. Clinical improvement was significantly greater in the treatment group (p=0.044). Conclusion: It has been concluded that early initiation of hormone replacement therapy in Hashimoto’s thyroiditis can mitigate negative clinical effects during follow-up, contributing to patient comfort and alleviating clinical complaints.

Estrogen-induced phenotype in hiPSC-derived cardiomyocytes of a woman affected by both Long QT Syndrome Type 2 and Polycystic Ovary Syndrome

Abstract Introduction Long QT Syndrome (LQTS) is an arrhythmogenic disorder caused either by genetic alteration or by exogenous factors. Polycystic Ovary Syndrome (PCOS) is a disease associated with high levels of testosterone and low levels of estrogen (E2). It has been suggested that hormones can influence the occurrence of malignant cardiac events in LQTS type 2 (LQT2) women, carriers of mutations on the potassium channel (hERG). However, the precise mechanisms governing this process still need to be clarified. Purpose We studied a patient affected by both LQT2 and PCOS who started experiencing cardiac symptoms after initiation of hormonal replacement therapy. We observed a correlation with the occurrence of arrhythmic events and the irregular assumption of the hormonal replacement therapy, thus we aim to dissect the underlying mechanism in patient-in-a-dish cardiac cellular model. Methods Induced Pluripotent Stem Cells (hiPSC) were generated from a woman affected by both LQT2 and PCOS and from a healthy donor, and then differentiated into cardiomyocytes (hiPSC-CMs). hiPSC-CMs were stimulated with E2 10nM for five time points (1, 5, 10, 15 and 30 minutes). The expression of potassium channel hERG, and of the G-coupled estrogen receptor (GPER) regulating the fast non-genomic pathway, were quantified after E2 stimulation at different time points by In Cell Western (ICW). The Unstimulated sample were used to normalize GPER and hERG expression to 100%. Electrophysiological experiments were performed using the whole-cell patch-clamp technique in current-clamp mode to record spontaneous action potentials (APs). AP duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90) was quantified. During spontaneous activity, AP duration values were rate-corrected with Bazett’s formula, thus obtaining cAPD. Results LQT2 hiPSC-CMs express higher levels of GPER (p<0.05) and hERG (p<0.01) than healthy hiPSC-CMs. A significant decrease in GPER expression was detected during 10nM E2 stimulation in healthy cardiomyocytes at the five time points (p<0.0001), while any difference was detected in hERG expression levels. E2 stimulation at different time points did not affect neither GPER nor hERG expression in LQT2 hiPSC-CMs. In LQT2 hiPSC-CMs, APDC values were significantly increased (p<0.0001) compared to healthy cells; pre-incubation with E2 for 10 minutes significantly shortened cAPD50 and increased spontaneous firing rate. In healthy hiPSC-CMs, E2 had no effect. Conclusions The hiPSC-CM model reproduces the LQT2 clinical phenotype. cAPD50 shortening by E2 was unexpected based on the proarrhythmic effect in the patient. The mechanism of LQT2-specific effects of E2 are under investigation.

Identification and Management of Radiation-Induced Premature Ovarian Failure

Premature ovarian failure (POF) is the dysfunction of ovarian follicles resulting in amenorrhea before the natural age of menopause. For women with locally advanced cervical cancer (LACC), POF is caused by chemoradiation due to the cytotoxic effects of radiation on the ovary. The diagnosis is confirmed with an FSH level in the postmenopausal range. The recommendation is for all patients with POF to take hormone replacement therapy (HRT) through the average age of natural menopause (age 50-51). The goal of this study is to determine how POF was managed in a large cohort of premenopausal women with LACC receiving pelvic RT. We retrospectively reviewed medical charts of premenopausal patients who underwent RT for LACC at an academic hospital from 2010 to 2020. Data regarding the type and duration of RT, demographics, and survival was obtained. The following data points were obtained from clinic notes documented after radiation treatment started: FSH levels, estradiol levels, menstrual history, menopausal symptoms. Additionally, data regarding HRT initiation was extracted, including the type of HRT and the department of the prescribing provider. Descriptive analysis was performed to determine the frequency of each variable of interest including patient characteristics, receipt hormone therapy, type of hormone therapy and menopausal symptoms. A total of 45 premenopausal patients treated for locally advanced cervical cancer with a median age of 39 (range 22- 50 years) were included. 51% (n = 23) of the patients were started on hormone therapy either during or post radiation treatment. 20 patients had documented menopausal symptoms. Most frequently reported symptoms included hot flashes (80%), fatigue (25%) and anxiety (15%). Most (78%) women received combination oral contraceptive pills (OCP) and some also received an estrogen patch/cream. 38% (n = 7) of patients started the HRT post RT while 61% (11) patients started during RT treatment. Of the available data, HRT was prescribed by a radiation oncologist 39% of the time and a gynecologic oncologist 35% of the time. The onset of POF was identified clinically by the onset of hypo-estrogen vasomotor symptoms. FSH levels were not routinely checked prior to prescribing HRT. The most commonly prescribed HRT was the combination oral contraceptive pill, which was prescribed and managed by both radiation oncologists and gynecologic oncologists. Our study illustrates the need for a standardized method to routinely assess the onset of POF while undergoing radiation treatment. With frequent follow-ups, radiation oncologists have the opportunity to identify early signs POF and provide adequate treatment. Additional studies are needed to evaluate if patients initiated and maintained HRT for the recommended length of time.

Hormone Therapy, Suicidal Risk, and Transgender Youth in the United States

This study uses the 2015 US Transgender Survey to test how initiation of hormone replacement therapy (HRT) affects the risk of attempting suicide among transgender individuals. We constructed a retrospective panel and employed a stacked event study design to demonstrate that HRT is associated with a substantially lower risk of suicide attempt. The average treatment effect on the treated is a decrease of 5.7 percentage points in the risk of ever attempting suicide if HRT is started between the ages of 14 and 17, which amounts to a 14.4 percent reduction in the risk of attempting suicide relative to the pretreatment mean.

Long-Term Non-Cancer Risks in People with BRCA Mutations following Risk-Reducing Bilateral Salpingo-Oophorectomy and the Role of Hormone Replacement Therapy: A Review.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35-45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population.

A Study of Cardiovascular Manifestations in Hypothyroidism

Aim and Objective: To study cardiovascular manifestations in hypothyroidism. Materials and Methods: An observational study was carried out in Parul Sevashram Hospital, Vadodara, Gujarat, India. 150 patients, both men, and women, diagnosed with hypothyroidism attending the Parul Sevashram Hospital were recruited from the outpatient and in-patient departments of medicine. Clinical profiles, history, complications, and all required data were collected. All patients were regularly called for follow-up based on their visits. As per the investigator’s discretion, laboratory tests, i.e., thyroid function tests, CBC, electrocardiogram (ECG), and 2D echocardiography were performed as and when required, and medication was prescribed. All physical examinations and all vitals were recorded at every visit till the end of the study. Results: A total of 150 patients were included in this study. Male:female: 57:93; age: 28–76 years. Patients were examined in a prospective manner and results were compared with the control group to evaluate the effect of hypothyroidism, subclinical and overt, on the cardiac status by echocardiography. Variables of heart structure and function were assessed by cross-sectional and Doppler echocardiography. Interventricular septum (IVS) dimensions were significantly raised in moderate subclinical and severe overt hypothyroidism (mean 0.9 +/- 0.03 and 0.9 +/- 0.2 cm). Left ventricular posterior wall (LVPW) thickness was significantly increased only in overt hypothyroidism (mean 1.3 +/- 0.2). However, RVW and LVID showed no definite pattern of change. Pericardial effusion and diastolic dysfunction were seen in 72 cases only in overt hypothyroidism. Diastolic dysfunction with pericardial effusion was found in 74 (49.3%) cases followed by diastolic dysfunction in 49 (32.6%), systolic dysfunction in 15 (10.0 %), and increased interventricular septum spectrum thickness in 12 (8.6%) patients. The majority of the diastolic dysfunction was mild dysfunction associated with females. No cases were found to have severe diastolic dysfunction. Discussion: On the basis of a case history, the clinical and para-clinical manifestations of hypothyroidism are reviewed. Exertion dyspnea without signs of cardiac insufficiency occurs frequently. The minute and stroke volume and heart rate are reduced. The blood pressure may rise (reversible) and hypertension may occur. The function of the left ventricle is reversibly reduced. X-ray of the thorax may reveal massive relatively asymptomatic pleural effusion and cardiomegaly. Pericardial exudate occurs frequently and is demonstrated best by echocardiography. The plasma concentrations of several different enzymes (including creatine kinase (CK), CK-MB, and LDH) may be raised in myxedema. The reason for this is perhaps compromised membrane function in the skeletal muscle cells. Conclusion: Hypothyroidism, both subclinical and overt, is associated with cardiovascular alteration, both structural and functional. IVS and LVPW thickness are markedly affected, and there is an impairment in left ventricular function in diastole. Furthermore, hypothyroidism is more common in females, between the age group of 20–50 years. The majority of the patients have cardiovascular changes such as ECG abnormalities, pericardial effusion, diastolic dysfunction, and diastolic hypertension. We strongly suggest early detection and initiation of hormone replacement therapy can minimize the associated cardiovascular changes. Recommendation: To study inter-and intracellular deposits, infiltrations, and fibrosis in the myocardium and these probably contribute to some of the on-specific, reversible ECG changes (low voltage, flattening/inversion of T waves, sinus bradycardia). To study hypothyroidism present can increase atheroma formation. The patients can be grouped into overt and subclinical hypothyroid.

Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort

BackgroundThe risk of dementia is higher in women than men. The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) in the prevention of cognitive decline has shown conflicting results. Here we investigate the modulating role of APOE genotype and age at HRT initiation on the heterogeneity in cognitive response to HRT.MethodsThe analysis used baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort (total n= 1906, women= 1178, 61.8%). Analysis of covariate (ANCOVA) models were employed to test the independent and interactive impact of APOE genotype and HRT on select cognitive tests, such as MMSE, RBANS, dot counting, Four Mountain Test (FMT), and the supermarket trolley test (SMT), together with volumes of the medial temporal lobe (MTL) regions by MRI. Multiple linear regression models were used to examine the impact of age of HRT initiation according to APOE4 carrier status on these cognitive and MRI outcomes.ResultsAPOE4 HRT users had the highest RBANS delayed memory index score (P-APOE*HRT interaction = 0.009) compared to APOE4 non-users and to non-APOE4 carriers, with 6–10% larger entorhinal (left) and amygdala (right and left) volumes (P-interaction= 0.002, 0.003, and 0.005 respectively). Earlier introduction of HRT was associated with larger right (standardized β= −0.555, p=0.035) and left hippocampal volumes (standardized β= −0.577, p=0.028) only in APOE4 carriers.ConclusionHRT introduction is associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher life-time risk of AD in this large at-risk population subgroup. Confirmation of findings in a fit for purpose RCT with prospective recruitment based on APOE genotype is needed to establish causality.

Hipotireoza - dijagnostički izazov kod dece - prikaz slučaja

Hypothyroidism is an endocrine disorder with a wide range of symptoms and multi-organ involvement. Almost all cells of the body have receptors for thyroid hormones, and the clinical picture of hypothyroidism is a result of the reduced effect of thyroid hormones on target organs and can be nonspecific, especially in children and adolescents, and thus may remain unrecognized for a longer period of time. Pericardial effusion, which occurs with a frequency of 10%-30% in adult patients with hypothyroidism, is very rare in children. Pericardial effusion, as well as all other symptoms of hypothyroidism, is reversible after the initiation of hormone replacement therapy. This is a report of a girl in whom pericardial effusion was the most significant manifestation of autoimmune thyroiditis, and in whom, at the time of diagnosis, other disorders due to the prolonged effect of low levels of thyroid hormones on target organs were also observed.

A Single-Center 10-Year Experience of 180 Transmasculine Patients Undergoing Gender-Affirming Mastectomy While Continuing Masculinizing Hormone Replacement Therapy.

Gender-affirming mastectomy is a fundamental step in the transition process of transmasculine patients following the initiation of hormone replacement therapy. Its perioperative management, however, remains underreported and controversial. In this study, a large series of mastectomies in transmen maintaining hormonal therapy is presented. Over a 10-year study period, a consecutive series of 180 transmasculine patients undergoing chest masculinizing surgery was evaluated. Demographical and surgical data were collected and analyzed for potential factors influencing outcome. The overall rate of complications was 15.5%. Patients who underwent periareolar incision mastectomy were significantly more likely to develop any type of complication than patients with a sub-mammary incision (28.6% vs. 13.2%, p = 0.045). Hematoma was the most common reason for surgical revision. It occurred significantly more often among the periareolar group (21.4% vs. 7.9%, p = 0.041). Duration and type of hormonal therapy did not differ between patients with or without complications. In a multivariate regression analysis, smoking and type of incision were identified as significant predictors of the all-cause complication rate, whereas the influence of BMI and resection weight diminished after adjusting for confounding factors. There is scarcity of information concerning the influence of perioperative hormonal therapy in patients undergoing chest wall masculinization. The observed complication rates-with special regard to hematoma-were comparable to current reports; yet further research is needed to profoundly evaluate this topic and provide evidence-based recommendations for the perioperative management of HRT of transmasculine patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Cancer immunotherapy associated hypophysitis: Pathophysiology and management

Immune checkpoints are small molecules produced by immune cells that play crucial role in maintaining homeostasis of immune system. Targeting the immune checkpoint molecule, specifically, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1) with inhibitory monoclonal antibodies has been reported to have antitumor activity. The US Food and Drug Administration (FDA) has been recognized several immune checkpoint inhibitors (ICIs) for the treatment of several types of cancer, mainly two types of ICIs that target CTLA-4 and PD1, have been approved as immunotherapeutic agent for cancer treatment. Autoimmune side effects results from immune checkpoint blockade, termed as immune related adverse events (irAEs) are frequent and usually mild, can include multiple endocrinopathies. The unique characteristic of irAEs is their non-reversibility, with incidence and prevalence expected to be increased in the upcoming years. Immune-related hypophysitis (IRH) is one of the most frequently reported irAEs after thyroid dysfunction. Hypophysitis, specifically associated with anti-CTLA-4 therapy, primary adrenal insufficiency (PAI) and diabetes mellitus are rare irAEs but can be fatal if not diagnosed and treated in early stage. Combinatorial therapy using anti- CTLA-4 and anti-PD1 drug is associated with increasing prevalence of IRH. The exact mechanism behind the development of irAEs remain to be elucidated. Most ICI associated endocrinopathies are manifested within 8-12 weeks after the initiation of ICI therapy. Management of ICI associated hypophysitis requires withdrawal of the ICI therapy, initiation of steroids and finally initiation of hormone replacement therapy and usually includes long-term management and care for controlling the irreversible side effects. In this review, we try to summarize the current scenario regarding the epidemiology, mechanism pathophysiology and management procedure for IRH in cancer patients receiving immunotherapy.

Premature ovarian insufficiency.

Premature ovarian insufficiency is a complex condition with a heterogenous aetiology, and is defined as loss of ovarian function before the age of 40. Early diagnosis and initiation of hormone replacement therapy is essential to alleviate symptoms and prevent later complications as a result of premature oestrogen deficiency. In this clinical review article we present an update on the diagnostics and treatment of the condition.

Relationship between the type of hormone replacement therapy and incidence of breast cancer in Korea

Objective This study aimed to investigate the relationship between hormone replacement therapy (HRT) types and breast cancer (BC) incidence in postmenopausal women in Korea. Methods The nested case–control study used data from the National Health Insurance Service database. Among the women aged ≥50 years who menopaused between 2004 and 2007, BC incidence up to 2017 was analyzed in 36,446 women using or having used HRT for >1 year and in 36,446 women who did not use any HRT for more than 1 year. HRT types and duration were classified into three categories. Results BC risk (BCR) decreased with tibolone use for all ages. With HRT initiation in women aged ≥50 years, BCR was lower with tibolone and estrogen–progestogen therapy. HRT for <3 years showed lower BCR with tibolone, while higher BCR was observed with estrogen-only therapy. BCR was lower in women of all ages on HRT for >5 years than in the control group. Conclusions For women in their 50s, tibolone use lowers BCR; for all ages, the use of any HRT for >5 years showed lower BCR in Korea. These divergent results from western countries could be associated with the specific characteristics of BC in Korea.

Quality of life assessment in women with spontaneous premature insufficiency: A comparative cross-sectional study

ObjectivePremature ovarian insufficiency is cessation of ovarian function prior to 40 years of age. It is known to have varied short and long-term implications on the health of the women. The quality of life is affected in various domanins. The objective of this study is to evaluate QOL of women with POI and the factors associated with it, using WHO QOL-BREF scale. MethodsThis is a cross sectional comparative study. Women with premature ovarian insufficiency with normal karyotype were included before initiation of hormone replacement therapy as cases and age matched women without any menstrual irregularity, infertility or any chronic illness were included as controls. Written informed consent was obtained from all patients. The pre-validated Tamil version of the WHOQOL-BREF (26 items, 4 domains) was filled through face-to-face interview. The score of each domain was transformed into 0–100 as per the guideline provided by WHOQOL-BREF. Statistical analysis was done using SPSS version 19. ResultsA total of 100 (50 women with POI and 50 control women) completed the WHOQOL-BREF questionnaire. The mean age of the women who participated in the study was 29.6 ± 6.5 years. Among the cases, 72% were nulliparous. There was statistically significant difference in the median scores of overall QOL, physical, psychological and social domains between the two groups. Univariate analysis showed that nulliparity and infertility were the factors responsible for poor QOL, however, these were not independently associated with poor QOL after applying bivariate linear regression analysis. ConclusionThe scores of overall QOL, physical, psychological and social domains were poorer in women with POI as compared to healthy controls.

Incidence and familial risk of premature ovarian insufficiency in the Finnish female population.

STUDY QUESTIONWhat is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women?SUMMARY ANSWERThe incidence of POI increased among females aged 15–19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased.WHAT IS KNOWN ALREADYSo far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause.STUDY DESIGN, SIZE, DURATIONPopulation-based study with 5011 women diagnosed with POI in 1988–2017. The data were collected from national registries and covers POI subjects in entire Finland.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model.MAIN RESULTS AND THE ROLE OF CHANCEThe incidence was highest in the 35–39 age group, ranging from 73.8/100 000 women-years in 1993–1997 to 39.9/100 000 women-years in 2013–2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015–2017. Cumulative incidence of POI for women under 40 years in 1988–2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3–6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls.LIMITATIONS, REASONS FOR CAUTIONFor some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria.WIDER IMPLICATIONS OF THE FINDINGSThe risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis.STUDY FUNDING/COMPETING INTEREST(S)This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare.TRIAL REGISTRATION NUMBERN/A.

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence.

Menopause, probably the most important natural change in a woman’s life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1β, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.

Clinicohormonal Parameters as a Primary Step to Differentiate Normosmic Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome in a Tertiary Care Hospital in Eastern India

Introduction: Idiopathic hypogonadotropic hypogonadism is a rare gonadal dysgenesis in which puberty does not take place naturally. It occurs due to insufficient pulsatile secretion of Gonadotrophin-Releasing Hormone (GnRH) and the resulting Follicle-Stimulating Hormone (FSH) and Luteinising Hormone (LH) deficiency leads to absence of or delayed sexual maturation. Kallmann syndrome is an uncommon genetic disorder characterised by hypogonadotropic hypogonadism associated with anosmia or hyposmia. When anosmia is absent, the same is referred as normosmic Idiopathic Hypogonadotropic hypogonadism (nIHH). Aim: To find out the significant differences between Kallmann syndrome and nIHH based on clinical features and biochemical assessment as a primary measure to initiate the treatment early. Materials and Methods: This hospital based cross-sectional observational cohort study was conducted in Department of Endocrinology, Nilratan Sircar Medical College and Hospital, Kolkata, India. The study was done on 55 cases of IHH presenting to the department with delayed secondary sexual characteristics. Results: Out of these 55 cases, 45 (81.8%) were of nIHH and only 10 (18.2%) cases were of Kallmann Syndrome. It was found that both the conditions show male predominance. Smell abnormalities were present only in Kallmann group. The level of serum testosterone was significantly higher (p&lt;0.05) in nIHH subjects (mean-35.59 ng/dL) than patients with Kallmann Syndrome (mean-14.90 ng/dL). Patients with Kallmann syndrome showed significantly reduced pubic and axillary hair development and absence of gonadal development. Conclusion: Absence of puberty with anosmia/hyposmia with low serum FSH and LH, drastically reduced serum testosterone, are factors that point towards the diagnosis of Kallmann syndrome even in absence of genetic study, which is helpful for initiation of hormone replacement therapy for treatment.

Risk of cardiovascular changes in hypothyroidism in North-west Punjab population

Background: This study was done with an objective to study the cardiovascular involvement associated with newly detected overt and subclinical hypothyroidism. Methods: A total number of 150 newly detected hypothyroid patients, diagnosed by the clinical evaluation, confirmed by thyroid hormone assay, were subjected to electrocardiograph and echocardiography. It was a cross-sectional study design based on the random sampling method, which was conducted for 2 years in the Central Laboratory of Adesh Institute of Medical Sciences and Research and Center for Interdisciplinary Biomedical Research, Adesh University. Results: Of 150 patients studied, 62 were overt hypothyroid and 88 were subclinical hypothyroid. Forty-one were male and 109 were female. Hypothyroidism was newly diagnosed more in females and maximum in the age group of 41–70 years (69.9%). Of 150 patients, 63.3% had symptoms <2-month duration. Cardiovascular symptoms were present in 68.0% of patients. Bradycardia was observed in 44.0% of patients. Stage 1 hypertension was noticed in 30.7% (systolic high blood pressure). Low-voltage complexes in electrocardiogram (ECG) were present in 34.0% study group. Pericardial effusion was present in 32.7% of patients. Diastolic dysfunction was noticed in 20.0% study group. Altered lipid profile was present in 74.0% (total cholesterol) and 65.3% (total triglycerides). Conclusions: Hypothyroidism is common in female, maximum between the age group of 17 and 47 years. Majority of the patients have cardiovascular changes such as ECG abnormalities, pericardial effusion, diastolic hypertension, and diastolic dysfunction. Systematic study was done to know the early effects of hypothyroidism on cardiovascular system. The identification of patients with hypothyroidism is an important individual as well as public health issue. Hence, early detection and initiation of hormone replacement therapy can minimize the associated cardiovascular changes.

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.

Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.