Psycho-organizational and medical factors in burnout in French medical and surgery residents.

Hospital residency is stressful, with a risk of burnout. To assess the prevalence of burnout in medical and surgical residents and identify psycho-organizational and medical risk factors with a view to prevention. A transverse study was conducted in France between September 2018 and November 2018, targeting 633 hospital residents. A self-administered questionnaire was delivered by e-mail. Burnout was assessed on the Maslach Burnout Inventory, anxiety/depression on the Hospital Anxiety and Depression Scale (HAD) and stress on a visual analogue scale (VAS). Two-hundred and sixteen of the targeted residents (34%) responded. Twenty-three (12%) showed severe burnout in all three dimensions, severe loss of empathy being the most frequent. Almost one-third showed symptoms of anxiety. Residents exposed to psycho-organizational constraints (stress, time pressure, intense work rhythm) and/or with symptoms of anxiety/depression more frequently showed burnout. Prevention of burnout requires reinforced medical monitoring and reduced psycho-organizational constraints.

Medical and socio-occupational predictive factors of psychological distress 5 years after a road accident: a prospective study.

PURPOSE: Psychosocial consequences of road accidents are a major clinical problem that incurs significant social, occupational, and economic costs. The purpose of our study was to assess medical and socio-occupational factors of psychological distress in the severely injured 5 years after a road accident. METHODS: A total of 691 of the 1168 subjects enrolled in a prospective cohort of road accident casualties (ESPARR cohort) responded to both standardized follow-up questionnaires at 1 and 5 years, assessing socio-occupational characteristics, physical and psychological sequelae, pain and perceived quality of life. RESULTS: One quarter of participants exhibited psychological distress 5 years after the road accident; most of whom are women, with low educational level, and suffering from spinal lesions. After adjusting for several factors, psychological distress at 5 years was predicted by female gender and low educational level, and by several other factors observed 1 year after the road accident: poor self-reported quality of life, attention deficit and symptoms of anxiety. CONCLUSIONS: Early-stage improvement in the screening and care of mental disorders in road accident casualties should help to reduce long-term psychological distress.

Implementation of a self-administered questionnaire to detect lung carcinogens.

BACKGROUND: Between 10 and 20% of lung cancers are of occupational origin. Screening for occupational risk factors is part of the diagnostic workup. A self-administered questionnaire to detect lung carcinogens of occupational origin, the RECAP questionnaire, was drawn up and validated with a view to limiting under-declaration of lung cancer as an occupational disease (OD). AIMS: Optimal administration conditions were investigated, to facilitate systematic use in the management of patients admitted to hospital with lung cancer. METHODS: The various care pathways of lung cancer patients were first studied in two centres, to identify the health-care professionals involved in medical management, the various care sites and the stages of treatment. A focus group of health-care professionals was set up, and semi-directive interviews were conducted with 24 patients. RESULTS: Caregivers tended to suggest that a physician or nurse should present the RECAP questionnaire, whereas patients rather chose non-caregiver staff, seeing the undertaking as being 'administrative' in nature. Some caregivers and patients thought the questionnaire should not be administered at the outset of treatment, due to the psychological trauma entailed by diagnosis. Administration during chemotherapy was recommended by patients, as they are more freely available at that time, and by caregivers, who thought patients better able to pay attention then. CONCLUSIONS: The study highlighted patients' lack of information on how lung cancer can be recognized as an OD. Implementing the RECAP questionnaire should facilitate patients' claims for insurance cover for lung cancer as an OD.

Design and validation of a self-administered questionnaire as an aid to detection of occupational exposure to lung carcinogens.

OBJECTIVE: Ten to thirty percent of lung cancer is thought to be of occupational origin. Lung cancer is under-declared as an occupational disease in Europe, and most declarations of occupational disease concern asbestos. The purpose of this study was to design and validate a short, sensitive self-administered questionnaire, as an aid for physicians in detecting occupational exposure to asbestos and other lung carcinogens in order to remedy occupational lung cancer under-declaration. STUDY DESIGN: Cross-sectional study. METHODS: A short (30-question) self-administered questionnaire was drawn up by oncologist-pneumologists and occupational physicians, covering situations of exposure to proven and probable lung carcinogens. Understanding and acceptability were assessed on 15 lung cancer patients. Validity and reliability were assessed on 70 lung cancer patients by comparison against a semi-directive questionnaire considered as gold standard. Sensitivity and specificity were assessed by comparing responses to items on the two questionnaires. Reliability was assessed by analysing the kappa concordance coefficient for items on the two questionnaires. RESULTS: Sensitivity was 0.85 and specificity 0.875. Concordance between responses on the two questionnaires was 85.7%, with a kappa coefficient of 0.695 [0.52-0.87]. Mean self-administration time was 3.1 min (versus 8.12 min to administer the gold-standard questionnaire). In 16 patients, the self-administered questionnaire detected lung carcinogen exposure meeting the criteria for occupational disease. CONCLUSION: The present short, easy-to-use self-administered questionnaire should facilitate detection of occupational exposure to lung carcinogens. It could be used in occupational lung cancer screening and increase the presently low rate of application for recognition of lung cancer as an occupational disease.

Factors influencing return to work after illness in France.

BACKGROUND: Few studies have been published about the factors influencing return to work after sickness absence. AIMS: To identify medical and occupational factors influencing the type of fitness certificate given by occupational physicians before employees return to work after sickness absence. METHODS: A cross-sectional study was undertaken over 3 months in several health services in France. Workers undergoing a medical examination before returning to work after a period of sickness absence of at least 3 weeks were included. Medical and occupational factors were collected using a questionnaire. The relationship between different factors and certification of fitness was assessed by univariate and multivariate analyses. RESULTS: Among the 402 workers included, 64% were considered fit to return to work. Being older, strenuous work, prolonged sick leave and fear of returning to work appeared to be negative factors influencing the return to a previous job. In contrast, having an education level higher than secondary school, being satisfied at work, perception of very good health and benefitting from satisfactory professional relationships appeared to favour return to work. We developed a predictive score of not being fit to return to work after illness. CONCLUSIONS: Our study highlighted the relationship between medical and occupational factors with problems returning to work. The predictive score may be used by occupational physicians as a screening tool to identify those who are likely to have difficulties returning to work after illness, so that their working conditions can be modified to take this into consideration.

[Systematic analysis of evaluations of Objective Structured Clinical Exam (OSCE) multiple circuits: Explanatory variables and inter-rater correlations]. / Analyse systématique des évaluations de circuits multiples d'examen clinique objectif structuré (ECOS) : variables explicatives et corrélations inter-évaluateurs.

INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) assess professional performance in a simulated environment. Following their integration into the reform of the 2nd cycle of medical studies (R2C), this pedagogical modality was implemented in France. This study investigates the variability of students' OSCE scores, as well as their inter-rater reproducibility. METHODS: This single-center retrospective study covered several sessions of evaluative OSCE circuits conducted between January 2022 and June 2023. Variables collected were: baseline situation family, competency domain, presence of a standardized participant for stations; gender and professional status for evaluators; scores (global, clinical and communication skills), number of previously completed OSCE circuits and faculty scores for students. RESULTS: The variability of the overall score was explained mainly (79.7%, CI95% [77.4; 82.0]) by the station factor. The student factor and the circuit factor explained 7.5% [12.9; 20.2] and<0.01% [2.10-13; 2.10-9] respectively. The inter-rater intra-class correlation coefficient was 87.2% [86.4; 87.9] for the global score. Station characteristics (starting situation, domain) and evaluator characteristics (gender, status) were significantly associated with score variations. CONCLUSION: This first study on the variability of OSCE circuit scores in France shows good reproducibility with influence of station characteristics. In order to standardize circuits, variability linked to the domain competency should be considered as well.

Did the introduction of maize into Europe provide enemy-free space to Ostrinia nubilalis? Parasitism differences between two sibling species of the genus Ostrinia.

We examined whether maize offers enemy-free space (EFS) to its pest Ostrinia nubilalis, and may thereby have contributed to its divergence from the sibling species, Ostrinia scapulalis, feeding mainly on mugwort, when introduced into Europe five centuries ago. We collected Ostrinia larvae on maize (70 populations, 8425 individuals) and mugwort (10 populations, 1184 individuals) and recorded parasitism using both traditional (counting emerging parasitoids) and molecular methods (detection by specific polymerase chain reaction). The main parasitoid was Macrocentrus cingulum (Braconidae). On mugwort, parasitism was twice that on maize, and parasitoid-related mortality was 8 times higher. This suggests that maize affords substantial EFS to Ostrinia feeding on it. The lower Mortality:Infestation ratio in maize suggests that O. nubilalis' immune response might be stronger than that of O. scapulalis. If so, adapting to maize and diverging from O. scapulalis would decrease the impact of parasitism on O. nubilalis at both ecological and evolutionary levels.

SARS-CoV-2 infection: advocacy for training and social distancing in healthcare settings.

This article reports the observed rate of infection with severe acute respiratory syndrome coronavirus-2 in healthcare workers (HCWs) who worked on wards dedicated to care of patients with coronavirus disease 2019 (COVID-19) compared with HCWs who worked on non-COVID-19 wards. The infection rate was significantly higher among HCWs who worked on non-COVID-19 wards (odds ratio 2.3, P=0.005), illustrating the need to strengthen social distancing measures and training.

Working conditions and risk exposure of employees whose occupations require driving on public roads - Factorial analysis and classification.

INTRODUCTION: Several studies of the working conditions of drivers, and in particular on their pace of work, have enabled a better understanding of the risk factors for road accidents that occur during work. However, few studies are available on the risk exposure and working conditions of employees whose occupations involve driving. The purpose of this paper is to identify the different groups of employees occupationally exposed to road risk and to classify them according to working conditions. METHODOLOGY: A Multiple Correspondence Analysis (MCA) was implemented on the 41,727 individuals from the SUMER 2010 survey (Medical Monitoring of Occupational Risk Exposure: SUrveillance Médicale des Expositions aux Risques professionnels) and for 45 variables about working conditions. The analysis used 5 categories of weekly driving exposure as a supplementary variable (variable which is not used to perform the MCA): Non-exposure; Exposed <2 h; Exposed 2-10 hours; Exposed 10-20 hours; and Exposed >20 h. The results of the MCA were used to construct an ascending hierarchical classification. RESULTS: The first factorial axis differentiates between conventional and unconventional work schedules. Axis 2 differentiates modalities corresponding to the working hours of the most recent working week. The third axis chiefly contrasts persons who have rules to follow with those who have none. An ascending hierarchical classification distinguishes 10 clusters of individuals according to working conditions. Four clusters of employees were excessively exposed to occupational driving. Clusters also have distinct demographic, occupational and psychosocial characteristics. CONCLUSION: Analysis of data from the SUMER survey confirms that employees exposed to road risk are particularly affected by atypical work time characteristics, but can be found in all activity sectors and in all types of job.

A lipid-parameter-based index for estimating insulin sensitivity and identifying insulin resistance in a healthy population.

AIM: Insulin resistance needs to be identified as early as possible in its development to allow targeted prevention programmes. Therefore, we compared various fasting surrogate indices for insulin sensitivity using the euglycaemic insulin clamp in an attempt to develop the most appropriate method for assessing insulin resistance in a healthy population. METHODS: Glucose, insulin, proinsulin, glucagon, glucose tolerance, fasting lipids, liver enzymes, blood pressure, anthropometric parameters and insulin sensitivity (Mffm/I) using the euglycaemic insulin clamp were obtained for 70 normoglycaemic non-obese individuals. Spearman's rank correlations were used to examine the association between Mffm/I and various fasting surrogate indices of insulin sensitivity. A regression model was used to determine the weighting for each variable and to derive a formula for estimating insulin resistance. The clinical value of the surrogate indices and the new formula for identifying insulin-resistant individuals was evaluated by the use of receiver operating characteristic (ROC) curves. RESULTS: The variables that best predicted insulin sensitivity were the HDL-to-total cholesterol ratio, the fasting NEFA and fasting insulin. The use of the lipid-parameter-based formula Mffm/I=12x[2.5x(HDL-c/total cholesterol)-NEFA] - fasting insulin appeared to have high clinical value in predicting insulin resistance. The correlation coefficient between Mffm/I and the new fasting index was higher than those with the most commonly used fasting surrogate indices for insulin sensitivity. CONCLUSION: A lipid-parameter-based index using fasting samples provides a simple means of screening for insulin resistance in the healthy population.

Road casualties in work-related and private contexts: occupational medical impact. Results from the ESPARR cohort.

BACKGROUND: Road accidents may impact victims' physical and/or mental health and socio-occupational life, notably including return to work. OBJECTIVES: To assess whether the occupational medical consequences sustained by subjects injured in road accidents occurring in a work-related context differ from those associated with private accidents. METHODS: 778 adults who were in work or occupational training at the time of their accident were included. Two groups were distinguished: 354 (45.5%) injured in road accidents occurring in a work-related context (commuting or on duty) and 424 (54.5%) injured in a private accident. The groups were compared on medical and occupational factors assessed on prospective follow-up at 6 months and 1 and 3 years. Multivariate analysis explored for factors associated at 6 months and 1 year with sick leave following the accident and duration of sick leave. RESULTS: There were no significant differences between groups for demographic data apart from a slightly higher injury severity in private accidents (32.5% of private accidents with MAIS3+(Maximum Abbreviated Injury Scale greater or equal to 3) vs. 23.7% for work-related accidents, p = 0.007). Victims of work-related accidents were more often on sick leave (OR = 1.8; 95% CI, 1.1-2.9). Although the length of sick leave is higher for work-related accidents that for private accidents, multivariate analysis showed that the injury severity and the post-traumatic stress disorder (PTSD) are significant factors to explain the time to return to work. There were no significant differences according to occupational impact during follow-up, notably including sick-leave duration, number of victims returning to work within 3 years and number of victims out of work due to incapacity. CONCLUSIONS: In the ESPARR (follow-up study of a road-accident population in the Rhône administrative county: Etude de Suivi d'une Population d'Accidentés de la Route dans le Rhône) cohort, the fact that a road accident occurred in a work-related context did not affect the occupational consequences.

Factors associated with non-return to work in the severely injured victims 3 years after a road accident: A prospective study.

Road accidents may impact victims' physical and/or mental health and socio-occupational life, particularly the capacity to return to work. The purpose of our study is to assess modifiable medical and socio-occupational factors of non-return to work in the severely injured 3 years after a road accident. Among1,168 road accidents casualties in the Rhône administrative Département of France followed for five years, 141 of the 222 severely injured (Maximal Abbreviated Injury Scale ≥ 3) aged more than 16 years who were in work at the time of the accident, reported whether they had returned to work in the 3 years following the accident. The subgroups of those who had (n=113) and had not returned to work (n=28) were compared for socio-occupational (gender, age, educational level, marital status, socio-occupational group) accident-related medical factors (type of road user, type of journey, responsibility in the accident, initial care) and post-accident medical factors (pain intensity, post-traumatic stress disorder, physical sequelae, quality of life) by using standardized tools. Severity of initial head, face and lower-limb injury, intense persistent pain, post-traumatic stress disorder, poor self-assessed quality of life and health status at 3 years were associated with non-return to work on univariate analysis. On multivariate analysis, severity of initial head and lower-limb injury, intense persistent pain at 3 years and post-traumatic stress disorder were significantly associated with non-return to work 3 years following severe road-accident injury. Post-traumatic stress disorder and chronic pain were essential modifiable medical determinants of non-return to work in the severely injured after a road accident: early adapted management could promote return to work in the severely injured. Improve early adapted treatment of pain and PTSD in the rehabilitation team should help the severely injured return to work following a road accident.

Lupus nephropathy and pregnancy. Report of 104 cases in 36 patients.

The reciprocal influence of lupus nephropathy on the outcome of pregnancy and of pregnancy on the course of renal involvement was studied retrospectively in a series of 106 pregnancies observed during the past two decades in 36 patients with lupus nephropathy. The overall incidence of live births, corrected for induced abortions, was 54 (84%) in 64 pregnancies that began before clinical onset of systemic lupus erythematosus (SLE), 20 (87%) in 23 pregnancies that began after onset of SLE, and only four (57%) in seven cases where SLE was first manifested during or after gestation. Relapse or exacerbation of disease activity occurred in 12 (46%) of 26 pregnancies antedated by clinical onset of SLE, more frequently during gestation than post partum, with two cases (8%) of irreversible deterioration of renal function; clinical exacerbation of lupus disease was observed in 11 (66%) of 15 cases where SLE was clinically active at the time of conception, and in only one (9%) of 11 cases where SLE nephritis was in stable clinical remission for at least five months before conception. The data indicate that successful outcome of pregnancy may be expected even in the more severe forms of lupus nephritis if gestation begins after a sustained, complete clinical remission.

Impaired mental well-being and psychosocial risk: a cross-sectional study in female nursing home direct staff.

OBJECTIVES: The present study sought to quantify the impaired mental well-being and psychosocial stress experienced by nursing home staff and to determine the relationship between impaired mental well-being assessed on the 12-item General Health Questionnaire (GHQ-12) and exposure to psychosocial stress assessed on Siegrist's effort/reward and overcommitment model. METHODS: A transverse study was conducted in France on 2471 female employees in 105 nursing homes for the elderly. Personal and occupational data were collected by questionnaire for 668 housekeepers, 1454 nursing assistants and 349 nurses. RESULTS: 36.8% of participants (n=896) showed impaired mental well-being, 42.7% (n=1039) overcommitment and 9% (n=224) effort/reward imbalance. Overcommitment (prevalence ratio (PR)=1.27; 95% CI (1.21 to 1.34)) and effort-reward imbalance (PR=1.19; 95% CI (1.12 to 1.27)) were significantly associated with presence of impaired mental well-being after adjustment for personal factors (age and private life events). Taking effort and reward levels into account, the frequency of impaired mental well-being was highest in case of exposure to great extrinsic effort and low rewards of any type: esteem, PR=3.53, 95% CI (3.06 to 4.08); earnings, PR=3.48, 95% CI (2.99 to 4.06); or job security, PR=3.30, 95% CI (2.88 to 3.78). Participants in situations of overcommitment and of effort/reward imbalance were at the highest risk of impaired mental well-being: PR=3.86, 95% CI (3.42 to 4.35). CONCLUSIONS: Several changes in nursing home organisation can be suggested to reduce staff exposure to factors of psychosocial stress. Qualitative studies of the relation between impaired mental well-being and psychosocial stress in nursing home staff could guide prevention of impaired mental well-being at work.

Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women.

Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17beta-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (<5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400 microg/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 microg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P<0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P<0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (-29% and -32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P<0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300 microg/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months. We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels.

Full-term pregnancy with embryos from donated oocytes in a 36-year-old woman allografted for chronic myeloid leukemia.

We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.

Fibrinogen and plasminogen modifications during oral estradiol replacement therapy.

OBJECTIVE: To assess the effects of oral E2 replacement therapy on various hemostatic parameters and cardiovascular risk factors in healthy, postmenopausal women. DESIGN: A double-blind, randomized, prospective study comparing the effect of a placebo and of oral micronized E2 (2 mg daily) during a 6-month period. Evaluations were performed before treatment and after 3 and 6 months. SETTING: Departments of Gynecology, Hemostasis, and Nutrition, Hôtel-Dieu, Paris, France. PATIENT(S): Thirty-six healthy women with natural or surgical menopause. RESULT(S): Compared with placebo, oral E2 replacement therapy resulted in a significant decrease in fibrinogen and apo B and a significant increase in plasminogen. CONCLUSION(S): Besides the effects on lipoproteins, oral estrogen replacement therapy modifies parameters involved in coagulation and fibrinolysis.

Dose-ranging studies of a novel intranasal estrogen replacement therapy.

OBJECTIVE: To study the efficacy and tolerability of Aerodiol, a novel intranasal estradiol spray, and to determine an appropriate dose range. METHODS: An exploratory, parallel-group, dose-finding study was followed by a large-scale, double-blind, placebo-controlled study. In the exploratory study, 134 postmenopausal women were allocated to receive a daily dose of 100--900 microg of Aerodiol for 12 weeks. Efficacy was determined by an overall assessment of estrogenization. In the placebo-controlled study, 420 postmenopausal women were randomized to receive 100, 200, 300, or 400 microg of Aerodiol, or oral estradiol 1 or 2 mg, or placebo, daily for 12 weeks. Efficacy was assessed by the Kupperman Index and the number of hot flushes per day after 12 weeks. RESULTS: In the exploratory study, the level of estrogenization was sufficient for 23% of women in the 100 microg/day group, excessive for 36% of the 900 microg/day group, and good for more than 80% of women receiving 200--600 microg/day. In the placebo-controlled study, the Kupperman Index at week 12 was significantly lower than placebo (P<0.01) for all Aerodiol groups except the 100 microg/day group. The efficacy of Aerodiol 300 microg/day was similar to oral estradiol 2 mg/day. The variability in exposure to estradiol was lower with Aerodiol than with oral estradiol. Aerodiol therapy was well tolerated in both studies. Premature withdrawals were approximately equally distributed among treatment groups in the placebo-controlled study. CONCLUSIONS: Aerodiol was effective in reducing climateric symptoms at doses between 100 and 600 microg/day. Treatment was well tolerated and well accepted. A dose of 300 microg/day is recommended for initiating hormone replacement therapy.

Chlormadinone acetate versus micronized progesterone in the sequential combined hormone replacement therapy of the menopause.

OBJECTIVE: The efficacy and safety of chlormadinone acetate (CA) versus micronized progesterone (P) were assessed in non-hysterectomized postmenopausal women. MATERIALS AND METHODS: This was a multicenter, randomized, parallel group study with a 6-month double-blind period followed by a 12-month open period. Patients were randomized to receive every month during 18 months percutaneous 17 beta-estradiol (E(2)) 1.5 mg/day from Day 1 to 24 of treatment cycle, combined from Day 11 to 24 to either CA 10 mg/day (n=167) or P 200 mg/day (n=169). Endometrial biopsy (EB, main analysis criterion) was performed at baseline, and at Day 18-24 of the 6th and 18th cycles. RESULTS: At Month 6, EB did not evidence any hyperplasia. EB were inadequate for assessment in 24.5% and 47.5% of patients in the CA and MP groups, respectively. CA was found to be as protective as P (96.3% and 92.0% of success). However, the hormonal status of the endometrium differed (P<0.001): a secretory endometrium was found in 81.5% of the CA patients, compared to 50.7% in the P group. These transformations resulted in predictable, cyclic bleeding in 94.5% of the CA patients, compared to only 62.3% of the P patients (P=0.0001). Unscheduled bleeding, spotting and/or metrorrhagia, were more frequent under P than under CA (17.9% and 13.7%, respectively). The beneficial effects on hot flushes were more important in the CA group than in the P (P<0.001). At Month 18, the biopsy and clinical results were similar to those obtained at Month 6. The safety profile, particularly the lipid one, was similar in both groups, except for drowsiness and dizziness, which were significantly more frequent under P than under CA. CONCLUSION: The progestative effects of CA on the endometrium and on menopause-related symptoms were at least as good as those of P. Moreover, CA resulted more often than P in secretory effects, and in satisfying bleeding patterns.

Comparative endometrial histology in postmenopausal women with sequential hormone replacement therapy of estradiol and, either chlormadinone acetate or micronized progesterone.

OBJECTIVES: To determine the endometrial response in postmenopausal women treated with a sequential hormone replacement therapy (HRT) of estradiol and, either chlormadinone acetate (CA) or micronized progesterone (MP). METHODS: Three hundred and thirty-six postmenopausal women with a normal endometrium were randomized in the double-blind study. All patients received percutaneous estradiol 1.5 mg/day from day 1 to day 24 and either CA 10 mg/day or oral MP 200 mg/day from day 10 to day 24. The total duration of treatment was 18 months. Endometrial biopsies were performed before treatment and between day 18 and day 24 of the 18th month of HRT. RESULTS: Of the 336 patients selected, 317 had a biopsy at inclusion. Of them, 244 patients (124 in the CA group and 120 in the P group) were suitable for evaluation for analysis at the 18th month. Insufficient sampling occurred in 33.9% in the CA group and 60% in the MP group (probably atrophic). No case of hyperplasia could be reported in both groups. The endometrium was atrophic in 19.5 versus 27.1%, proliferative in 3.7 versus 8.3% and secretory in 76.8 versus 62.5% in CA and MP groups, respectively. It was possible to see histological differences induced by the two progestins. The CA endometria showed fewer glands lined by a cubo-cylindrical epithelium, with an edematous stroma, compared to the MP endometria which had more glands lined by a cylindrical epithelium, stroma being poorly edematous. These figures varied in intensity due to the length of progestative impregnation, predecidualization occurring later in the CA group, with distended capillaries. CONCLUSIONS: These results show that CA 10 mg/day is a powerful progestin compared to MP 200 mg/day, on weakly estradiol-primed endometria, giving a molecule-specific histological aspect with a good endometrial safety.