Need For Hormone Replacement Therapy Research Articles

Long-Term Effects on Gonadal Function After Treatment of Colorectal Cancer: A Systematic Review and Meta-Analysis

Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies.

First successful ovarian cortex allotransplant to a Turner syndrome patient requiring immunosuppression: wide implications

ObjectiveTo determine whether we can safely and successfully transplant an ovary tissue allograft from a non-identical donor to her Turner syndrome sister. DesignTransplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However there have not yet been any ovary transplants between non-identical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available. SubjectsA 20 year old amenorrheic woman with non-mosaic 45-XO Turner syndrome requested ovary tissue transplantation from her fertile 22 year old 46-XX sister. They were an HLA match but were ABO incompatible, a well known contra-indication to solid tissue or organ transplantation. The Turner syndrome sister strongly preferred to be able to become pregnant naturally without donor egg IVF, and to avoid HRT (hormone replacement therapy). In her religious group, that would also be important for finding a marital match. Despite the poor prognosis associated with ABO incompatibility, an ovary from her 22 year old non-identical fertile sister was transplanted to her employing the immunosuppression protocol now used for kidney transplant patients in our centers at Washington University and Johns Hopkins. Main Outcome MeasuresPost-operatively at 5 months she developed normal monthly menstrual ovarian function, and she became spontaneously pregnant with a normal baby girl. The relation between her post-op FSH and AMH levels continues to support the theory that tissue pressure controls primordial follicle recruitment. The fact that ABO incompatibility did not prevent success suggests that diffusion and not revascularization may be all that is required for successful long term ovarian cortex transplant survival with spontaneous pregnancy. ResultsOvary allotransplantation with safe immunosuppression allows natural conception, and also normal hormone function obviates the need for HRT. Orthotopic placement of the graft and surgical technique is critical for natural conception and a higher pregnancy rate. ConclusionAllotransplantation requiring safe immunosuppression, if successful, may be a much more commonly used indication for ovary transplantation in the future than frozen ovary grafts or grafts between identical twins.

P-364 Impact on fertility outcomes in survivors after hematopoietic stem cell transplantation for benign and malignant hematologic disorders: a systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility after hematopoietic stem cell transplantation (HSCT) in females and males up to the age of 1 year? Summary answer The overall prevalence of infertility (95% CI) in women treated with HSTC is 64% (0.58-0.70) and in men 39% (0.31-0.47). What is known already HSCT is a well-established treatment that has significantly increased survival in haematological malignancies and also benign diseases since its introduction in the 1980s. The use of high-dose chemotherapy and radiotherapy, myeloablative conditioning, combined with HSCT exposes serious long-term complications, including gonadal dysfunction and infertility. The risk of ovarian and testicular damage seems to be very high. Therefore, the European Society for Blood and Marrow Transplantation (EBMT) had recommended in 2015 to consider fertility preservation measures in children and adolescents requiring HSCT. However, the data on which this recommendation was based was limited and heterogeneous. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane in November 2023, considering papers published since 2000. Participants/materials, setting, methods A total of 1632 records were identified for abstract screening. Only females and males without recurrent disease and follow up of more than one year were considered. For the systematic review, 68 studies fulfilled the criteria. For the meta-analysis, studies with < 10 patients were excluded. Infertility was defined in females as very low AMH, hypergonadotropic hypogonadism, amenorrhoea and/or need for hormone replacement therapy and in males as low inhibin B and/or azoospermia. Main results and the role of chance In total, 68 out of 1632 studies were included in the final analysis. Malignant diseases were mainly acute myeloid / lymphoblastic leukemia, chronic myeloid leukemia/ lymphocytic leukemia and non-hodgkin’s and hodgkin’s lymphoma. Benign diseases were sickle cell disease, Fanconi anaemia, and β-thalassemia major. In the meta-analysis, 56 studies were included, comprising 1853 female malignant cases, 241 female benign cases, 1871 male malignant cases, and 226 male benign cases. The analysis, employing a random-effects model for estimating prevalence and its 95% confidence interval, revealed that the overall pooled prevalence of infertility exceeded 30% in all groups. The prevalence of infertility was highest in female malignant cases (65%, 95% CI: 0.58-0.71). In women with benign diseases it was 61% (95% CI: 0.48-0.73). In males with malignant diseases it reached 41% (95% CI: 0.32 to 0.51) and with benign diseases 31% (95% CI: 0.19 to 0.46). Heterogeneity of data was high as shown by female as shown by the malignant cases of 83% and benign cases of 65% in women and the malignant cases of 91% and benign cases of 74% in males. Limitations, reasons for caution The heterogeneity of the included studies due to treatment variations and diverse characteristics of the study populations with large age ranges, did not allow further subgroup analyses. Thus, an individual and reliable fertility prognosis is still difficult to give. Wider implications of the findings The results of this meta-analysis support the clinical necessity of fertility preservation counselling in females and males undergoing HSCT treatment. Further prospective studies addressing the individual impact of the HSCT treatment on gonadal function are needed Trial registration number The study protocol was registered at the international Prospective Register of Systematic Reviews, PROSPERO (Registry number CRD42023486928).

Breaking barriers: How transwomen meet their healthcare needs.

Transgender women - individuals assigned male at birth but who identify as female - are disproportionately affected by, among others, human immunodeficiency virus (HIV), other sexually transmitted diseases (STIs) and mental health issues. Studies show that transgender women often encounter discrimination and stigma when seeking healthcare from health facilities. This study assessed the healthcare needs of transgender women, their experiences of the mainstream healthcare system and alternative strategies for navigating the healthcare system. The study was carried out in the City of Ekurhuleni Metropolitan Council in South Africa's Gauteng province. A case study design was followed. Participants were purposively selected and included 10 transgender women aged 26-50. Individual semi-structured interviews were conducted over 2 months. Participants expressed a need for hormone replacement therapy, HIV treatment and prevention and treatment for STIs. Experiences of participants within the healthcare system were predominantly negative, with instances of discrimination, stigma and privacy violations being commonplace. Alternative strategies to meet their healthcare needs included the use of self-medication, consulting traditional healers and utilising non-governmental organisations. There is an urgent need for equitable and inclusive health management of transgender women in South Africa.Contribution:This study provided a first look in a South African context into how and to what extent transwomen employ alternative healthcare strategies such as self-medication and utilising non-governmental organisations when faced with mainstream healthcare access barriers. The use of traditional doctors was identified as a novel, alternative strategy used by transwomen to access healthcare and treatment.

Factors That Inform Individual Decision Making Between Active Surveillance, Hemithyroidectomy and Total Thyroidectomy for Low-Risk Thyroid Cancer: A Scoping Review.

Background: Due to the excellent prognosis and relatively high incidence of small low-risk thyroid cancers, more conservative management strategies such as active surveillance (AS) or hemithyroidectomy (HT) may be preferable to total thyroidectomy (TT) for patients seeking to balance long-term survival rates with the potential adverse effects of overtreatment. The aim of this review was to synthesize key factors or variables that inform patient decision making about treatment for low-risk thyroid cancer, from current primary investigations that presented participants with information facilitating this choice. Methods: Studies were identified from the Medline, Cochrane, and Embase databases up until March 2022. Study characteristics were extracted into a pre-piloted form. Factors were hypothesized to include treatment-related risks and possible outcomes and identified from a review of studies with consensus by discussion. Results: The search identified 444 unique studies: 397 were excluded on review of abstract and title with 47 studies undergoing a full text review and 6 studies identified to be eligible. Four were cross-sectional: one a prospective cohort study and one a mixed-methods study with both a prospective observational and qualitative component. The decisions addressed included: the choice between AS versus surgery (HT and/or TT) and HT versus TT and enrolled participants ranging from healthy volunteers to thyroid cancer patients. Treatment choice was the primary outcome in five studies. Across the studies, participants who were given the option of AS or surgery predominately chose the more conservative pathway, with a range of 70-84%. The major factors represented by information provision in the studies were risk of cancer recurrence or spread, need for hormone replacement therapy, and voice change. Conclusions: A framework of key factors informing patient treatment choice may be derived from current studies involving information provision for low-risk thyroid cancer management. Further research evaluating the efficacy and optimal timing for decision support interventions would help inform the design and clinical use of these tools to promote shared decision making.

Bone Mineral Density Changes Within and Outside of RT Fields Used to Treat Cervical Cancer

Pelvic insufficiency fractures and decreased bone mineral density (BMD) can occur in women treated with radiotherapy (RT) for gynecologic cancers. The purpose of this study was to compare the magnitude of BMD changes inside and outside of the radiation field in patients treated with radiation +/- chemotherapy for cervical cancer.In an IRB-approved prospective study, women (N = 78) with cervical cancer were assessed with serial tomographic scans and dual-energy x-ray absorptiometry (DXA) scans to evaluate the incidence of pelvic fractures (previously reported) and post-treatment BMD changes. Patients were treated with definitive RT or chemoradiation (CRT) at a single institution between 09/2008 and 07/2015. DXA scans were obtained at baseline (before CRT), 3 months, 1 year, and 2 years after completion of therapy. Serial BMD values at L1, L2, L3 and L4 were extracted from DXA reports. Patients with a pre-treatment history of pelvic fractures, bone metastases, or pelvic RT were excluded. The current analysis focused on a subset of 78 patients whose RT fields had upper borders below L1 and above L4, permitting a comparison of BMD changes in the field (L4) with those in a vertebral body outside the field (L1). Linear mixed models (LMM) were performed to examine the impact of radiotherapy on BMD change over time, and were adjusted for covariates (age, menopausal status, BMI, number of chemotherapy cycles).The median age of 78 patients was 45.5 years (range 23-88); all received RT and 76/78 (97.5%) received concurrent CRT. Treatment was associated with a significant decline in BMD in all 4 lumbar vertebral bodies over time, P < 0.05 with nadir at 3 months (L4) and 1 year (L1). By pairwise comparisons at 3 months and 2 years after treatment, BMD in L4 (inside RT field, P = 0.037) significantly improved while BMD in L1 (outside RT field) did not significantly change. After controlling for covariates noted above, there was no significant difference in BMD between 3 months and 2 years. Levels of C-terminal telopeptide of type I collagen (P = 0.018), bone alkaline phosphatase (P < 0.001), and number of chemotherapy cycles (P = 0.031) were significant predictors of L1 BMD loss. A trend of higher BMD at all time points was found for patients who were premenopausal versus postmenopausal at study entry. At 1- and 2-years of follow-up, trends towards BMD at levels higher than baseline were seen for patients who received hormone replacement therapy (HRT) after RT.Significant BMD loss following radiation treatment in all lumbar vertebrae (both in and out of field) was observed. On multivariate analysis, in-field vertebral bodies experienced no additional significant BMD decline earlier than those out-of-field, suggesting multifactorial contributors to bone density loss. HRT may improve BMD recovery and emphasizes the need for HRT after radiotherapy in appropriate premenopausal women.J. Wu: None. D.S. Lakomy: None. B. Fellman: None. M.P. Salcedo: IGCS-International Gynecologic Cancer Society, Brazilian Federation of Gynecology and Obstetricians (FEBRASGO)/BRAZIL (Federação Brasileira de Ginecologia e Obstetricia, FEBRASGO). A. Sood: Consultant; Kiyatec, Astra Zeneca. Stock; BioPath. sponsored research; M-Trap. A. Jhingran: American Board of Radiology. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. R.B. Iyer: None. C. Jimenez: None. L. Colbert: None. K. Schmeler: None. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca.

Clinical Implications

Clinical Implications

Pathophysiology and management of classic galactosemic primary ovarian insufficiency.

Classic galactosemia is an inborn error of carbohydrate metabolism associated with early-onset primary ovarian insufficiency (POI) in young women. Our understanding of the consequences of galactosemia upon fertility and fecundity of affected women is expanding, but there are important remaining gaps in our knowledge and tools for its management, and a need for continued dialog so that the special features of the condition can be better managed. Here, we review galactosemic POI and its reproductive endocrinological clinical sequelae and summarize current best clinical practices for its management. Special consideration is given to the very early-onset nature of the condition in the pediatric/adolescent patient. Afterward, we summarize our current understanding of the reproductive pathophysiology of galactosemia, including the potential action of toxic galactose metabolites upon the ovary. Our work establishing that ovarian cellular stress reminiscent of endoplasmic reticulum (ER) stress is present in a mouse model of galactosemia, as well as work by other groups, are summarized.Lay summaryPatients with the condition of classic galactosemia need to maintain a strict lifelong diet that excludes the sugar galactose. This is due to having mutations in enzymes that process galactose, resulting in the buildup of toxic metabolic by-products of the sugar. Young women with classic galactosemia often lose the function of their ovaries very early in life (termed 'primary ovarian insufficiency'), despite adherence to a galactose-restricted diet. This means that in addition to the consequences of the disease, these women also face infertility and the potential need for hormone replacement therapy. This article summarizes current strategies for managing the care of galactosemic girls and women and also what is known of how the condition leads to early primary ovarian insufficiency.

LARGE, RECURRENT PLEURAL EFFUSION FROM IATROGENIC METHIMAZOLE-INDUCED HYPOTHYROIDISM

SESSION TITLE: Medical Student/Resident Disorders of the Pleura Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pleural effusion is a recognized but uncommon manifestation of hypothyroidism. We describe a large, recurrent unilateral effusion attributed to iatrogenic hypothyroidism from methimazole. The effusion resolved with methimazole discontinuation and without the need for hormone replacement therapy. CASE PRESENTATION: An 84 year-old female with remote history of hyperthyroidism treated with methimazole and partial thyroidectomy presented with three days of dyspnea. Evaluation revealed a large unilateral pleural effusion. Diagnostic and therapeutic thoracentesis removed a 1.4L collection that was borderline exudative by Light’s criteria. Her dyspnea transiently resolved but recurred within 5 days. Repeat thoracentesis removed an additional 1.2 liters of exudative fluid. Cytologic and microbiologic studies were unremarkable. However, serum TSH and free T4 were noted to be 56.9 and 0.6, respectively, consistent with hypothyroidism. It was discovered that her primary provider had started methimazole 3 months prior, after misinterpreting routine results as recurrence of her hyperthyroidism when they were actually indicative of subclinical hypothyroidism (TSH/FT4 4.25/0.9, respectively). Methimazole was discontinued upon this discovery. In follow up visits, her thyroid function tests normalized without the need for hormone replacement therapy, and the pleural effusion never recurred. DISCUSSION: Hypothyroidism is rare but recognized cause of pleural effusions (1). Case studies have documented pleural effusions directly related to hypothyroidism, including some attributable to methimazole, which in turn has been theorized to be mediated by a drug-induced ANCA-vasculitis mechanism (2). Our patient developed a large, recurrent, unilateral pleural effusion when methimazole was erroneously prescribed for subclinical hypothyroidism. Her subsequent hospitalization with dyspnea that led to the recognition of iatrogenic hypothyroidism. After repeated diagnostic and therapeutic thoracenteses, her clinical course finally improved after discontinuation of the offending agent and without the need for hormone replacement therapy. Our case reinforced the connection between hypothyroidism and pleural effusions, including those from methimazole-induced hypothyroidism. It also re-emphasizes the importance of appropriate outpatient monitoring and interpretation of thyroid function labs (3). CONCLUSIONS: Pleural effusions can arise due to hypothyroidism, including iatrogenic hypothyroidism secondary to methimazole. The fluid collection may be massive and lead to significant symptoms, but the clinical course appears to be self-limited once the offending agent is removed. Thyroid function tests should be appropriately monitored after the initiation of anti-thyroid drugs like methimazole to avoid complications. Reference #1: Gottehrer A, Roa J, Standford GG, Chernow B, Sahn SA. Hypothyroidism and Pleural Effusions. Chest. 1999;98(5):1130-1132. Reference #2: Gaspar-da-Costa P, Duarte Silva F, Henriques J, do Vale S, Braz S, Meneses J, et al. Methimazole associated eosinophilic pleural effusion: a case report. BMC Pharmacol Toxicol. 2017 Mar 21;18(16). Reference #3: Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014 Dec 1;24(12):1670-1751. DISCLOSURES: No relevant relationships by Tydus Thai, source=Web Response No relevant relationships by Kenneth Wei, source=Web Response

Endocrine Outcomes of Transsphenoidal Surgery for Pituitary Apoplexy Versus Elective Surgery for Pituitary Adenoma

Objective: To determine the rate of hormone replacement therapy (HRT) after transsphenoidal surgery (TSS) for pituitary apoplexy (PA) versus elective resection of a null cell (NC) macroadenoma. Methods: A retrospective cohort study was performed. Data was collected on all consecutive patients who underwent TSS from December 31, 2000 to December 31, 2016. Patients were split into two groups: (1) patients that presented with PA, and (2) patients that underwent elective TSS for NC macroadenoma. Postoperative pituitary function was determined by examining HRT, hormone lab values, and an evaluation by an endocrinologist for each patient. The odds ratio (OR) was calculated to determine if there was an association between PA and the need for HRT after surgery when compared to elective resection of a NC macroadenoma. Results: The need for HRT was significantly higher following surgery for PA compared to resection of a NC macroadenoma (14.7% versus 2.9%, OR = 5.690; 95% confidence interval (CI) = 1.439 to 22.500; P = .013). Conclusion: There is an increased need for hormone replacement therapy after surgery in patients with PA versus patients undergoing elective resection of a NC macroadenoma. Further studies are warranted to strengthen this data and help determine further predictors of the need for HRT. Abbreviations: BNP = brain natriuretic peptide; CI = confidence interval; DDAVP = desmopressin acetate; GH = growth hormone; HRT = hormone replacement therapy; MRI = magnetic resonance imaging; NC = null cell (adenoma); OR = odds ratio; PA = pituitary apoplexy; TSS = transsphenoidal surgery.

The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage.

Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH) in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1) patients with lowered basal laboratory values; (2) patients with lowered basal laboratory values or the need for hormone replacement therapy; (3) diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients), lowered estradiol (14.3% of female patients) and lowered insulin-like growth factor I (IGF-I) values (12.1%) were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians’ diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery) were predominantly observed for the somatotropic axis (12.5%), the gonadotropic axis in women (11.1%) and the corticotropic axis (10.6%). Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004). In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4) values) to 94.6% (prolactin values).

Human Chorionic Gonadotropin Stimulation Test in Prepubertal Children with Micropenis Can Accurately Predict Leydig Cell Function in Pubertal or Postpubertal Adolescents

Background/Aim: To evaluate the accuracy of the human chorionic gonadotropin (hCG) stimulation test in children with micropenis in predicting later Leydig cell function. Methods: We conducted a retrospective investigation of testosterone response to a 3-day hCG test (3,000 IU/m²/day) in prepuberty to indicate the need for hormone replacement therapy (HRT) in adolescence. Results: Fifty Japanese boys (range, 0.8-15.4 years of age; median, 8.9) with micropenis were enrolled. Thirty-four spontaneously developed puberty and preserved the ability of testosterone production (group 1), while 16 did not develop any pubertal signs without HRT (group 2). Serum testosterone levels after the hCG test (post-hCG T) in group 2 (range, <0.05-1.1 ng/ml; median, 0.24) were significantly lower than in group 1 (range, 0.5-8.7 ng/ml; median, 2.4; p < 0.0001). Based on true positives who required continuous HRT, the area under the receiver-operating characteristics curve for post-hCG T was 0.983 [95% confidence interval (CI), 0.90-1.00]. The post-hCG T cut-off level corresponding to the Youden index was 1.1 ng/ml (95% CI, 1.0-1.1), with a sensitivity of 100.0% (95% CI, 79.4-100.0) and a specificity of 94.1% (95% CI, 80.3-99.3). Conclusions: The hCG test in prepubertal children with micropenis can be useful for predicting Leydig cell function in pubertal or postpubertal adolescents. The post-hCG T cut-off level of 1.1 ng/ml is recommended to screen for those who will likely require HRT for pubertal development.

Riesgos y beneficios a largo plazo de la terapia mediante substitución de hormonas

Existe un consenso en cuanto a que las consecuencias a largo plazo de la deprivación ovárica pueden ser prevenidas o reducidas mediante una terapia del hueso trabecular que en uno de cada dos casos resulta en riesgos de por vida de fracturas osteoporósicas. La terapia de substitución hormonal (TSH) previene esta pérdida del hueso y disminuye la incidencia de fracturas. Se recomienda un mínimo de 5 años de tratamiento para lograr beneficios significativos. La evidencia epidemiológica viene acumulándose en cuanto a que la terapia de estrógenos postmenopausia reduce el riesgo de enfermedades cardiovasculares y de apoplejías en cerca de 30% y 70%, aún en presencia de factores de riesgo establecidos. Dada la frecuencia de enfermedades cardiovasculares, ésta viene a ser probablemente una de las ventajas originales de la terapia mediante substitución de hormonas en la próxima década. Las inquietudes acerca de la seguridad a largo plazo de la TSH se han concentrado en el cáncer endometrial y de mama. El incremento del riesgo de cáncer de endometrio asociado con la terapia única con estrógenos es disminuida con la adición secuencia de progesterona por 10 a 12 días de cada ciclo. El posible efecto de la terapia (TSH) en cuanto a riesgos de cáncer de mama debe ser considerada frente a experiencias que indican que uno de cada 12 desarrollan esta enfermedad. Los estudios epidemiológicos que investigan esta relación son revisados en este trabajo. Existe un gran consenso en que la terapia mediante substitución de hormonas (TSH) con una duración de 5 a 6 años no incrementa los riesgos de cáncer de mama. Terapias de mayor duración (10-15 años) se han reportado, que incrementan este riesgo, pese a que no toda la información es conforme. Otros factores, tales como la historia familiar y las enfermedades benignas de mama, también podrían influir en los riesgos de cáncer. Los beneficios potenciales de la terapia de substitución de hormonas frente a la mortalidad y morbilidad son enormes. Frente a esto existe un posible pequeño incremento del riesgo de cáncer de mama con un tratamiento a largo plazo. Debe buscarse un mayor conocimiento de las consecuencias a largo plazo de la menopausia y de beneficios potenciales de la TSH, de manera que las mujeres puedan tomar decisiones informadas acerca de la necesidad de la terapia mediante substitución de hormonas.

Long-term outcome of loss-of-function mutations in thyrotropin receptor gene.

Loss-of-function mutations in the thyrotropin receptor (TSHR) gene lead to resistance to TSH (RTSH) presenting with either congenital hypothyroidism (CH) or subclinical hypothyroidism (SCH). Despite several reports of patients with TSHR mutations, data on the long-term outcome of this condition are limited, and no consensus exists on the need for hormone replacement therapy. The aim of the present study was to assess the long-term outcome in children and adolescents with RTSH due to TSHR mutations. The TSHR gene was sequenced in 94 subjects (aged 3 days-21 years) with either nonautoimmune SCH or CH with RTSH. Twenty-seven subjects (29%) carried mutations in TSHR. Fifteen infants were identified by neonatal screening, and the other 79 patients were detected in the process of testing for various other conditions or because of family occurrence of thyroid test abnormalities. Six different mutations were identified: c.484C>G (p.P162A), c.202C>T (p.P68S), c.790C>T (p.P264S), c.269A>C (p.Q90P), c.1957C>G (p.L653V), and c.1347C>T (p.R450C). Twelve subjects were homozygous, three were compound heterozygous, and 12 were heterozygous. Mean serum TSH levels at diagnosis and at last visit were significantly higher in patients with TSHR mutations than in those without mutations (29.04 vs. 14.15, p=0.002; 31.73 vs. 6.19, p<0.0001, respectively). Homozygous patients had a more severe phenotype (TSH 53.6 vs. 9.24, p<0.0001). Mean serum free thyroxine (fT4) levels at the last visit were significantly lower than at the first visit in the homozygous individuals (p=0.05) for a follow-up period of as long as 11 years. Heterozygous subjects had only mild hyperthyrotropinemia with stable TSH levels. However, homozygous subjects showed a trend toward increased TSH and decreased fT4 with time. SCH in heterozygotes with TSHR mutations is a stable compensated condition with an appropriately adjusted set point for pituitary-thyroid feedback that does not require replacement therapy. However, homozygous subjects, with incompletely compensated SCH, show reduced fT4 levels over time and may require levothyroxine treatment. Replacement therapy should be considered on an individual basis, and long-term follow up is recommended.

Hemithyroidectomy: A Meta-Analysis of Postoperative Need for Hormone Replacement and Complications

Background: We sought to determine certain factors predicting postoperative need for hormone replacement therapy (HRT) after hemithyroidectomy. Methods: A PubMed search was conducted to identify articles with separate cohorts for total and hemithyroidectomy. Outcomes of interest included hypothyroidism and complications. Results: Of 50,445 patients, 15,412 (30.6%) underwent hemithyroidectomy. The reported incidence rate of postoperative hypothyroidism was 10.9-48.8%. The pooled mean preoperative thyroid-stimulating hormone (TSH) level was 1.06 µIU/l (0.83-1.29) higher in hypothyroid patients. A preoperative TSH level >2.5 µIU/l was associated with a relative risk (RR, 95% CI) of 3.16 (2.03-4.90) for postoperative hypothyroidism. There was a significant pooled RR of 3.52 (2.55-4.86) for thyroid antibodies and 3.30 (2.49-4.36) for thyroiditis on pathology for postoperative HRT. The pooled RR for postoperative complications was 10.67 (5.75-19.31) for temporary hypocalcemia, 3.17 (1.72-5.83) for permanent hypocalcemia, 1.69 (1.30-2.20) for temporary injury to the recurrent laryngeal nerve (RLN), 1.85 (1.28-2.69) for permanent RLN injury and 2.58 (1.69-3.93) for hemorrhage in patients who underwent total thyroidectomy compared to hemithyroidectomy. Conclusion: Higher preoperative TSH levels, presence of anti-thyroid antibodies and thyroiditis predict postoperative need for HRT. It is imperative to counsel patients with these findings regarding their higher risk of developing postoperative hypothyroidism and need for HRT after hemithyroidectomy.

Hemithyroidectomy: a meta-analysis of postoperative need for hormone replacement and complications

Background: We sought to determine certain factors predicting postoperative need for hormone replacement therapy (HRT) after hemithyroidectomy. Methods: A PubMed search was conducted to identify articles with separate cohorts for total and hemithyroidectomy. Outcomes of interest included hypothyroidism and complications. Results: Of 50,445 patients, 15,412 (30.6%) underwent hemithyroidectomy. The reported incidence rate of postoperative hypothyroidism was 10.9–48.8%. The pooled mean preoperative thyroid-stimulating hormone (TSH) level was 1.06 μIU/l (0.83–1.29) higher in hypothyroid patients. A preoperative TSH level >2.5 μIU/l was associated with a relative risk (RR, 95% CI) of 3.16 (2.03–4.90) for postoperative hypothyroidism. There was a significant pooled RR of 3.52 (2.55–4.86) for thyroid antibodies and 3.30 (2.49–4.36) for thyroiditis on pathology for postoperative HRT. The pooled RR for postoperative complications was 10.67 (5.75–19.31) for temporary hypocalcemia, 3.17 (1.72–5.83) for permanent hypocalcemia, 1.69 (1.30–2.20) for temporary injury to the recurrent laryngeal nerve (RLN), 1.85 (1.28–2.69) for permanent RLN injury and 2.58 (1.69–

Pituitary Function Following Gamma Knife Radiosurgery for Pituitary Adenomas

To investigate the relationship between dosimetric characteristics of treatment plans and the need for hormone replacement therapy after Gamma Knife radiosurgery (GKRS) for the treatment of pituitary adenomas.

Advances in hormone replacement therapy: making the menopause manageable

The importance of the results of some large, randomized controlled trials (RCTs) on Hormone Replacement Therapy (HRT) has modified the risk/benefit perception of HRT. Recent literature review supports a different management.The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch.The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.

Do Finnish women using hormone replacement therapy need more information about risks

In 1998, the Women's Health Initiative (WHI) in 2002 and the Million Women Study (MWS) in 2003 have shown a need for re-evaluation of the benefits and adverse reactions of hormone replacement therapy (HRT). Consequently the authorities in Europe and USA have issued new recommendations against the use of HRT. The aim of this study was to examine women's perceptions of HRT since the publication of the Women's Health Initiative study and the Million Women Study, and the kind of sources women use to obtain information about HRT. The data was collected with questionnaire survey in the autumn 2003 among 315 women using HRT. One third of the respondents (35%) had experienced fears concerning HRT use, and more than half (52%) reported that the debate in the media had markedly influenced them; they have experienced fears or worries, considered discontinuation or discussed with the physician. Whereas the most common source of information concerning the benefits of HRT was the physician (74%), the most common source of information concerning the risks of HRT was the media (78%). This study shows that women using HRT should get more information about the risks from health care professionals. Physicians and pharmacists have an opportunity to alleviate fears and to help women to critically evaluate the information they get from the media. Such discussions are also important to women who have been using HRT for years.

Evaluation of the Accuracy of Height Assessment of Premenopausal and Menopausal Women

To assess the accuracy of linear measurement of premenopausal and menopausal women. Observational. OB/GYN practice in a university setting. OB/GYN staff responsible for obtaining linear measurements. Equipment utilized, technique for obtaining linear measurement, accuracy of linear measurement. A research assistant observed six measurers measuring 64 women. Ninety four percent of measurements were inaccurate (p<.001) when compared to those of the research assistant. Measurements differed by as much as 18 cm from the research assistant (M=6.4 cm). Measurements obtained by measurers with more than 10 years of experience were significantly closer to the research assistant measurements than those obtained by less experienced measurers. Inaccurate equipment, incorrect technique, and staff inexperience all contributed significantly to inaccuracy of linear measurement in a GYN practice. Correct equipment and staff education are needed. Accurate linear measurements must be obtained to allow for valid clinical decisions regarding the need for hormone replacement therapy based on loss of stature of menopausal women.