Thyroid Hormone Supplementation and All-Cause Mortality in Community-Dwelling Older Adults: Results from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful. OBJECTIVES: Determine the association between all-cause mortality and levothyroxine use among older adults. DESIGN: Longitudinal observational study. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up. MEASUREMENTS: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638). RESULTS: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98). CONCLUSION: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults.

Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality.

CONTEXT: The long-term effects of female hormone replacement therapy (HRT) in Turner syndrome (TS) are unknown. OBJECTIVE: To examine morbidity, mortality and medicinal use in TS and the impact of HRT in 45,X women. DESIGN AND SETTING: National cohort study, following all TS individuals ever diagnosed in Denmark from 1977 to 2014. PATIENTS AND METHODS: In the Danish Cytogenetic Central Registry, we identified 1156 females diagnosed with TS from 1960 to 2014, and, subsequently, Statistics Denmark randomly identified 115 577 age-matched female controls. TS women and their matched controls were linked with person-level data from the National Patient Registry and the Medication Statistics Registry, and they were compared concerning mortality, hospitalizations, and medical prescriptions. Among 329 45,X women, 44 had never been HRT treated, and 285 had been treated at some point. HRT treated women were compared with untreated concerning mortality, hospitalizations, and medical prescriptions. RESULTS: Endocrine and cardiovascular mortality and morbidity were significantly increased in TS compared with the matched controls. Comparing HRT treated with nontreated 45,X women, we found a similar mortality (hazard ratio 0.83, 95% confidence interval 0.38-1.79). Among the HRT-treated 45,X women, we found a significantly lower use of antihypertensives, antidiabetics, and thyroid hormones and significantly reduced hospitalization rates for stroke and osteoporotic fractures. CONCLUSION: Women with TS have an increased overall mortality and morbidity. HRT seems to have a beneficial effect on endocrine conditions, hypertension, and stroke in women with 45,X karyotype, with no clear impact on mortality.

Thyroid Hormone (Triiodothyronine) Therapy in Children After Congenital Heart Surgery: A Meta-Analysis.

Thyroid hormone modifies metabolic, immune and cardiovascular functions and has been administered perioperatively to treat a relative reduction of thyroid function in children following cardiopulmonary bypass (CPB) for correction of congenital heart disease. However, it remains unclear whether its use is associated with improved outcomes. We performed a meta-analysis of studies that evaluated the impact of thyroid hormone supplementation on clinical outcomes in children undergoing repair of congenital heart disease using CPB. A systematic review of published trials was conducted to identify studies of children randomized to thyroid hormone supplementation or placebo undergoing congenital heart surgery. A meta-analysis was then conducted to determine the clinical impact of thyroid hormone replacement on cardiac function and postoperative characteristics. The following outcomes were included for the study: duration of mechanical ventilation, duration of intensive care unit (ICU) stay, duration of postoperative hospital stay, inotrope score, cardiac index at 24 hours postoperatively, and inpatient mortality. A total of 9 studies with 711 patients were included in the analyses. All included studies were prospective and patients were randomized to either thyroid hormone or placebo. There was wide variation in thyroid hormone dosing, ranging from 0.4 µg/kg up to 5 µg/kg over a 24-hour period, and duration of therapy, ranging from a single dose after cessation of CPB to continued thyroid hormone for the duration of the ICU stay. There was a significant difference in the mean inotrope score between the 2 groups of -1.249 (95% confidence interval -1.570 to -0.929, P < 0.001), with the inotrope score being significantly lower in the thyroid group. There was no difference in duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, cardiac index, and mortality between groups. In this meta-analysis, routine thyroid hormone replacement with approximately 1-5 µg/kg administered over 24 hours does not significantly alter the postoperative course in children following CPB. However, given a clinically small but significant difference in respect to lower inotrope score and shorter duration of ICU and hospital stays with higher thyroid replacement additional studies are warranted.

Pattern of mortality after menopausal hormone therapy: long-term follow up in a population-based cohort.

OBJECTIVE: To investigate long-term pattern of mortality in menopausal women according to different modalities of hormone therapy. DESIGN: Population-based prospective cohort study. SETTING: Denmark 1993-2013. POPULATION: A total of 29 243 women aged 50-64 years at entry into the Diet, Cancer and Health Cohort, enrolled 1993-97 and followed through 31 December 2013. METHODS: Cox' proportional hazards models for increasingly longer periods of follow-up time were used to estimate mortality pattern according to baseline hormone use adjusted for relevant potential confounders. MAIN OUTCOME(S): All-cause and cause-specific mortality. Outcome information was obtained from the Danish Register of Causes of Death (linkage 99.6%). RESULTS: A total of 4098 women died during a median follow up of 17.6 years. After adjustment for relevant lifestyle risk factors, hormone use had no impact on all-cause mortality, regardless of modality. Among baseline users, lower cardiovascluar disease mortality was only evident after 5 years [hazard ratio (HR) 0.54; 95% CI 0.32-0.92], but dissipated with additional follow up. Conversely, lower colorectal cancer mortality (HR 0.64; 95% CI 0.46-0.89) and higher breast cancer mortality (HR 1.34; 95% CI 1.05-1.72) only became evident after 15 years of follow up. There were no significant associations for mortality from other types of cancer or from stroke. CONCLUSIONS: In this long-term follow-up study, taking hormones during menopause was not associated with overall mortality among middle-aged women. Investigating cause-specific mortality revealed significant, albeit weak, differential associations according to both causes of death and over time, underlining the importance of carefully considering individual risks and duration of treatment when making decisions on hormone therapy. TWEETABLE ABSTRACT: Long-term follow-up study confirms no association between menopausal hormone therapy and overall mortality.

Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

INTRODUCTION: Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer. PATIENTS AND METHODS: We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects' use of hormone replacement therapy at the time of randomization: never, current, or former users. RESULTS: A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and < 10% had not completed high school. The never-user group was slightly older than the current or former user groups (average, 63.8 vs. 61.4 vs. 63.3 years; P < .001). Almost one-half (47.1%) of the current users had undergone hysterectomy, compared with 21.6% of never-users and 34.0% of former users (P < .001). Adjusted colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P < .001). CONCLUSIONS: Hormone replacement therapy is associated with a reduced risk of colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality.

Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients.

OBJECTIVE: To study the clinical characteristics, treatment, and prognosis of thyroid cancer in children and adolescents. METHODS: We performed a retrospective analysis of clinical data from 83 cases of thyroid cancer in children and adolescents from January 1990 to December 2010. We compared extra-thyroid extension, lymph node metastasis, distant metastasis, and prognosis between pediatric patients ≤12 years of age (27 cases) and those >12 years of age (56 cases). All the patients agreed to undergo thyroidectomy and endocrine therapy, and the consent was obtained from parents or guardians. RESULTS: Histopathology included papillary carcinoma in 67 cases, papillary carcinoma with partial follicular growth pattern in 1 case, papillary carcinoma with squamous metaplasia in 4 cases, follicular carcinoma in 7 cases, medullary carcinoma in 3 cases, and poorly differentiated carcinoma in 1 case. The total lymph node metastasis rate was 78.31%. Patients ≤12 years of age showed a higher rate of lymph node metastasis than the older group (92.59% vs. 71.43%, P=0.028). The incidence rate in females in the older group was higher than that in the younger group (80.36% vs. 59.26%, P=0.041). There were no significant differences in extra-thyroid extension, distant metastasis, survival rate, or recurrent disease between the two groups. CONCLUSIONS: The lymph node metastasis of thyroid cancer is higher in patients ≤12 years of age than in those >12 years of age; the incidence rate is higher in females than in males. Childhood thyroid cancer has a good prognosis, surgery being the most effective treatment. Choosing a reasonable surgery method and comprehensive postoperative treatment can achieve a cure and satisfactory survival rate.

Epidemiologic factors that predict long-term survival following a diagnosis of epithelial ovarian cancer.

BACKGROUND: Various epidemiologic factors have been shown to influence the risk of ovarian cancer development. Given the high fatality associated with this disease, it is of interest to evaluate the association of prediagnostic hormonal, reproductive, and lifestyle exposures with ovarian cancer-specific survival. METHODS: We included 1421 patients with invasive epithelial ovarian cancer diagnosed in Ontario, Canada. Clinical information was obtained from medical records and prediagnostic exposure information was collected by telephone interview. Survival status was determined by linkage to the Ontario Cancer Registry. Proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer-specific mortality associated with each exposure. Analyses were stratified by histologic subtype to further investigate the associations of risk factors on ovarian cancer-specific mortality. RESULTS: After a mean follow-up of 9.48 years (range 0.59-20.32 years), 655 (46%) women had died of ovarian cancer. Parity (ever) was associated with a significant 29% decreased mortality risk compared with nulliparity (HR=0.71; 95% CI 0.54-0.93; P=0.01). There was a borderline significant association between ever use of oestrogen-containing hormone replacement therapy (HRT) and mortality (HR=0.79; 95% CI 0.62-1.01; P=0.06). A history of cigarette smoking was associated with a significant 25% increased risk of death compared with never smoking (HR=1.25; 95% CI 1.01-1.54; P=0.04). Women with a greater cumulative number of ovulatory cycles had a significantly decreased risk of ovarian cancer-specific death (HR=0.63; 95% CI 0.43-0.94; P=0.02). Increasing BMI (kg m-2) 5 years before diagnosis was associated with an increased risk of death (HR=1.17; 95% CI 1.07-1.28; P=0.0007). Other hormonal or lifestyle factors were not significantly associated with ovarian cancer-specific mortality. CONCLUSIONS: Parity, ovulatory cycles, smoking, and BMI may affect survival following the diagnosis of ovarian cancer. Whether or not oestrogen-containing HRT use is beneficial for survival requires further evaluation.

Testosterone therapy in men with testosterone deficiency: are the benefits and cardiovascular risks real or imagined?

In the adult male, testosterone (T) deficiency (TD) also known as male hypogonadism, is a well-established medical condition, which has been recognized for more than a century. T therapy in men with TD was introduced as early as 1940s and was reported to improve overall health with no concomitant serious adverse effects. A wealth of recent studies demonstrated that T therapy in men with TD is associated with increased lean body mass, reduced fat mass and waist circumference, improvement in glycemic control, and reduced obesity. T therapy is also associated with improvements in lipid profiles, amelioration of metabolic syndrome (Met S) components, reduced inflammatory biomarkers, reduced systolic and diastolic blood pressure, and improvements in sexual function. More importantly, T therapy is associated with amelioration of diabetes and reduced mortality. However, few studies, marred with serious methodological and analytical flaws reported between 2010 and 2014, suggested that T therapy is associated with increased cardiovascular (CV) risk. As summarized in this review, a thorough and critical analysis of these studies showed that the risks purported are unsubstantiated and such studies lacked credible scientific and clinical evidence. Moreover, recent observational, registry studies, clinical trials, and meta-analyses, all revealed no increase in CV risks in men receiving T therapy. In this review, the benefits of T therapy in adult men with TD and the lack of credible evidence suggesting that T therapy is linked to increased CV risks are discussed. It should be noted that the literature is replete with studies demonstrating beneficial effects of T therapy on CV and overall health.

Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study.

BACKGROUND: Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events. The US Food and Drug Administration recently cautioned that testosterone replacement therapy might increase risk of heart attack and stroke, based on evidence from studies with short treatment duration and follow-up. No previous study has assessed the effect of duration of testosterone treatment on these outcomes. We aimed to assess the association between long-term use of testosterone replacement therapy and mortality, cardiovascular events, and prostate cancer diagnoses, using a time-varying exposure analysis. METHODS: We did a population-based matched cohort study of men aged 66 years or older newly treated with testosterone replacement therapy and controls matched for age, region of residence, comorbidity, diabetes status, and index year from 2007-12 in Ontario, Canada, using data from the Ontario Drug Benefit database, the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, the CIHI National Ambulatory Care Reporting System, the Ontario Health Insurance Plan database, the Ontario Myocardial Infarction Database, the Ontario Diabetes Database, the Ontario Cancer Registry, and the Registered Persons database. We assessed the association between cumulative testosterone replacement therapy exposure and mortality, cardiovascular events, and prostate cancer using marginal models with a time-varying testosterone exposure. FINDINGS: We included 10 311 men treated with testosterone replacement therapy and 28 029 controls between Jan 1, 2007, and June 30, 2012. Over a median follow-up of 5·3 years (IQR 3·6-7·5) in the testosterone replacement therapy group and 5·1 years (3·4-7·4) in the control group, patients treated with testosterone replacement therapy had lower mortality than did controls (hazard ratio [HR] 0·88, 95% CI 0·84-0·93). Patients in the lowest tertile of testosterone exposure had increased risk of mortality (HR 1·11, 95% CI 1·03-1·20) and cardiovascular events (HR 1·26, 95% CI 1·09-1·46) compared with controls. By contrast, those in the highest tertile of testosterone exposure had decreased risk of mortality (HR 0·67, 95% CI 0·62-0·73) and cardiovascular events (HR 0·84, 95% CI 0·72-0·98), with a significant trend across tertiles (p<0·0001). Risk of prostate cancer diagnosis was decreased for those with the highest tertile of exposure (HR 0·60, 95% CI 0·45-0·80) compared with controls, but not for those with the shortest exposure. INTERPRETATION: Long-term exposure to testosterone replacement therapy was associated with reduced risks of mortality, cardiovascular events, and prostate cancer. However, testosterone replacement therapy increased the risk of mortality and cardiovascular events with short durations of therapy. In view of the limitations of observational data and the potential for selection bias, these results warrant confirmation in a randomised trial. FUNDING: Physicians' Services Incorporated Foundation and Ajmera Family Chair in Urologic Oncology.

Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.

AIMS: There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke. METHODS AND RESULTS: We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3. CONCLUSION: In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

Survival in women with NSCLC: the role of reproductive history and hormone use.

INTRODUCTION: Although lung cancer is the leading cause of cancer death in women, few studies have investigated the hormonal influence on survival after a lung cancer diagnosis and results have been inconsistent. We evaluated the role of reproductive and hormonal factors in predicting overall survival in women with non-small-cell lung cancer (NSCLC). METHODS: Population-based lung cancer cases diagnosed between November 1, 2001 and October 31, 2005 were identified through the Metropolitan Detroit Surveillance, Epidemiology, and End Results Registry. Interview and follow-up data were collected for 485 women. Cox proportional hazard regression models were used to determine hazard ratios (HRs) for death after an NSCLC diagnosis associated with reproductive and hormonal variables. RESULTS: Use of hormone therapy (HT) was associated with improved survival (HR, 0.69; 95% confidence interval, 0.54-0.89), adjusting for stage, surgery, radiation, education level, pack-years of smoking, age at diagnosis, race, and a multiplicative interaction between stage and radiation. No other reproductive or hormonal factor was associated with survival after an NSCLC diagnosis. Increased duration of HT use before the lung cancer diagnosis (132 months or longer) was associated with improved survival (HR, 0.54; 95% confidence interval, 0.37-0.78), and this finding remained significant in women taking either estrogen alone or progesterone plus estrogen, never smokers, and smokers. CONCLUSION: These findings suggest that HT use, in particular use of estrogen plus progesterone, and long-term HT use are associated with improved survival of NSCLC.

Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends.

INTRODUCTION: Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population. AIM: The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer. METHODS: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality. MAIN OUTCOME MEASURES: We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy. RESULTS: Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy. CONCLUSIONS: In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed.

Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial.

OBJECTIVE: To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women. DESIGN: Open label, randomised controlled trial. SETTING: Denmark, 1990-93. PARTICIPANTS: 1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone. INTERVENTIONS: In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years. MAIN OUTCOME MEASURE: The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction. RESULTS: At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer. CONCLUSIONS: After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT00252408.

[Individual factors and mortality associated with hormone replacement therapy in a French cohort of women from 60 to 69 years of age]. / Caractéristiques individuelles et mortalité associées au traitement hormonal substitutif de la ménopause: étude d'une cohorte française de femmes d'âge compris entre 60 et 69 ans.

OBJECTIVES: Given the specificity of French postmenopausal hormonal replacement therapy, we study the link with overall mortality. MATERIALS AND METHODS: A cohort of 1200 women from 60 to 69 years of age was followed up from 2001 to 2009. We computerized from the health care repayment database the current reimbursement of behind-the-counter hormonal therapy. We sent a questionnaire to identify their lifetime history of hormone use. We test whether current and former users have higher risk of death from all cause combined. We adjusted the survival analysis on the individuals factors associated to the hormone use. The statistical methods Kaplan-Meier curves in univariate analysis and Cox Regression Model in multivariate analysis were used. RESULTS: Current users present a reduced all-cause mortality rate while former users have a higher all-cause mortality rate. This trend suggests a "healthy estrogen user survivor effect" bias. After adjustment on confounding factors, hormonal users do not have a statistically significant increased risk of overall mortality. CONCLUSION: Postmenopausal hormone replacement therapy is not linked with mortality for women from 60 to 69 years of age covered by the self-employed workers health and retirement French insurance fund.