Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding (i.e. pharmaceutical or medical device companies). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last guidelines from the Collège National des Gynécologues et Obstétriciens Français on the management of women with AUB were published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescents; idiopathic AUB; endometrial hyperplasia and polyps; type 0-2 fibroids; type 3 or higher fibroids; and adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and evidence profiles were compiled. The GRADE® methodology was applied to the literature review and the formulation of recommendations. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 are strong and 17 weak. No response was found in the literature for 14 questions. We chose to abstain from recommendations rather than providing advice based solely on expert clinical experience. CONCLUSIONS: The 36 recommendations make it possible to specify the diagnostic and therapeutic strategies for various clinical situations practitioners encounter, from the simplest to the most complex.

[Women with a very high risk of breast cancer: Contraceptives, hormonal replacement therapy use and personalized screening]. / Femmes à très haut risque de cancer du sein : contraception, traitement hormonal substitutif et dépistage personnalisé.

Women with a high family risk of breast cancer are those with an identified genetic predisposition or those who have a suggestive family history without an identified germinal mutation, particularly for BRCA1 and BRCA2. Among these women with a very high risk of breast cancer, the fear of a potentially increased risk of breast cancer linked to some hormonal contraceptives and to the use of hormone replacement therapy, in connection with the general population data collected in literature, has led to certain reluctance to prescribe them to these women. Moreover, confusion often sets due to poor knowledge of the literature. Furthermore, the monitoring procedures consist of breast screening and strategies of risk reduction, based on recent recommendations. In order to improve the gynaecological monitoring throughout their lives, we offer here a review based on an analysis of recent literature and of the recommendations concerning personalized screening, contraception and hormone replacement therapy among women with a very high risk of breast cancer free from this illness.

Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.

AIM: The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT). MATERIALS AND METHODS: Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence. SUMMARY RECOMMENDATIONS: The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).

Quality of life of patients with bilateral oophorectomy before the age of 45 for the treatment of endometriosis.

INTRODUCTION: The study aimed to evaluate the quality of life and associated factors among women who underwent bilateral oophorectomy (BO) before the age of 45 for the treatment of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: This cross-sectional study was carried out in 52 women who were treated from January 2014 to December 2019 in 2 public and private DIE surgical centers in Toulouse. All women answered the Menopausal Quality of Life questionnaire (MenQOL). Mean MenQOL scores were compared according to age at BO, smoking, BMI, level of education, delay between BO and the survey and post-BO hormone replacement therapy (HRT) using Mann-Whitney and Anova tests. Spearman's correlation coefficient was used to analyze the correlations between all the MEnQOL domain scores and clinical variables. The variables associated with the outcomes in univariate analyses with p < 0.2 were jointly evaluated using multiple linear regression. RESULTS: The mean age at the time of the survey was 43.4 ± 3.4 years while the mean age at BO was 40.5 ± 3.4 years. The mean MenQOL score was 3.96 (± 1.45), with the highest scores in the sexual (4.77) and vasomotor (4.01) domains. BMI and smoking were independently and significantly associated with the mean total MenQOL score, all domain scores being significantly higher in overweight/obese women. A trend towards worse MenQOL scores was found in patients who had BO before the age of 41. We did not find any difference according to whether or not they were taking HRT. CONCLUSION: This is a first study evaluating quality of life in a specific population of oophorectomized women under the age of 45 using MenQOL for DIE. While BO is effective in relieving pain in women with severe DIE, the induced premature menopause is associated with a poor quality of life, which deserves further attention.

[Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynecologists and Obstetricians (CNGOF)]. / Prise en charge des ménorragies : recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, or medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last guidelines from the Collège national des gynécologues et obstétriciens français (CNGOF) on the management of women with AUB was published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescent; idiopathic AUB; endometrial hyperplasia and polyps; fibroids type 0 to 2; fibroids type 3 and more; adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 present a strong agreement and 17 a weak agreement. Fourteen questions did not find any response in the literature. We preferred to abstain from recommending instead of providing expert advice. CONCLUSIONS: The 36 recommendations made it possible to specify the diagnostic and therapeutic strategies of various clinical situations managed by the practitioner, from the simplest to the most complex.

[Menopause hormone treatment in practice. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Le traitement hormonal de la ménopause en pratique. RPC Les femmes ménopausées du CNGOF et du GEMVi.

Menopause Hormonal Treatment (MHT) was initially developed to correct the climacteric symptoms induced by postmenopausal estrogen deficiency. In non-hysterectomized women, MHT combines estrogens and a progestogen, the latter opposing the negative impact of estrogen on endometrial proliferation. In France, and contrary to the USA and Northern European countries, MHT mainly combines 17ß-estradiol, which is the physiological estrogen produced by the ovary, and progesterone or its derivative, dihydrogesterone. France has been a pioneer in the development of cutaneous administration routes (gel or transdermal patch) for estradiol, allowing better metabolic tolerance and a reduction of the risk of venous thromboembolism compared to the oral route. The choice of the doses as well as the treatment regimen is underpinned by tolerance as well as acceptance and compliance. The risk of breast cancer, which is one of the main risks of MHT, is higher with estro-progestogen combinations than with estrogens alone ; the preferential use of progesterone or dihydrogesterone being likely to limit the excess risk of breast cancer associated with MHT at least for duration of treatment of less than 5 to 7 years. The question of the optimal duration of MHT remains an issue and must take into account the initial indication of treatment as well as the benefit-risk balance, which is specific to each woman. Continuation of MHT is conditioned by the benefit-risk balance, which must be evaluated regularly, but also by the evolution of symptoms when MHT is stopped as well as menopause-related health risks or induced by MHT. After stopping MHT, it is necessary to maintain a medical follow-up to be adapted to the clinical situation of each woman and in particular, her cardiovascular and gynecological risk factors.

[Menopause, menopause hormone therapy and osteoporosis. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Ménopause, traitement hormonal de ménopause et ostéoporose. RPC Les femmes ménopausées du CNGOF et du GEMVi.

Postmenopausal osteoporosis is a frequent clinical condition, which affects nearly 1 in 3 women. Estrogen deficiency leads to rapid bone loss, which is maximal within the first years after the menopause transition and can be prevented by menopause hormone therapy (MHT). Assessment of the individual risk of osteoporosis is primarily based on the measurement of bone mineral density (BMD) at the spine and femur by DXA. Clinical risk factors (CRFs) for fractures taken either alone or in combination in the FRAX score were shown not to reliably predict fractures and/or osteoporosis (as defined by a T-score<-2.5) in early postmenopausal women. If DXA measurement is indicated in all women with CRFs for fractures, it can be proposed on a case-by-case basis, when knowledge of BMD is likely to condition the management of women at the beginning of menopause, particularly the benefit-risk balance of MHT. MHT prevents both bone loss and degradation of the bone microarchitecture in early menopause. It significantly reduces the risk of fracture at all bone sites by 20 to 40% regardless of basal level of risk with an estrogen-dependent dose-effect. Given the inter-individual variability in bone response, individual monitoring of the bone effect of MHT is warranted when prescribed for the prevention of osteoporosis. This monitoring is based on repeated measurement of lumbar and femoral BMD (on the same DXA measurement system) after 2years of MHT, the response criterion being no significant bone loss. Discontinuation of treatment is associated with a resumption of transient bone loss although there is a large variability in the rate of bone loss among women. Basically, there is a return to the level of fracture risk comparable to that of in untreated woman of the same age within 2 to 5years. Therefore, when MHT is prescribed for the prevention of osteoporosis in women with an increased risk at the beginning of menopause, measurement of BMD is recommended when MHT is stopped in order to consider further management of the risk of fracture whenever necessary (with possibly another anti-osteoporotic treatment).

[Regional state-of-the-art of the access to oncofertility consultation for young women with breast cancer]. / État des lieux régional de l'accès à une consultation d'oncofertilité chez les femmes jeunes ayant un cancer du sein.

OBJECTIVES: According to the 2004 Bioethics Act, oncofertility counselling must be systematically offered to all women of childbearing age before they are exposed to potentially gonadotoxic treatment. The main objective of this study was to evaluate the proportion of women under 40 years of age treated with chemotherapy for breast cancer in Midi-Pyrénées who have received an oncofertility consultation. A secondary objective was to assess practitioners' knowledge on the subject. METHODS: A cross-reference was made between the databases of the oncology network in Midi-Pyrénées and the two approved centres for the preservation of fertility in the region. A computerized practitioner questionnaire was sent to all surgeons and oncologists who could manage these patients. RESULTS: From 2012 and 2017, 667 women aged≤40 years received (neo)adjuvant chemotherapy treatment: only 156 (23.4%) had access to an oncofertility consultation and 58 (8.7%) received preservation. This rate (23.4%) varied according to the age of the patients, ranging from 56.9% for those aged 25-29 to 13.4% for those aged 35-39 and the managing institution. Of the 85 practitioners surveyed, 45 (55%) responded to the questionnaire, and of these 20 (44%) knew that ovarian stimulation treatment could be used even in hormone-dependent breast cancer situations and 13 (29%) of practitioners believed that the time required to preserve fertility was more than 1 month. CONCLUSION: Our study revealed a significant disparity in access to oncofertility consultation. It is essential to set up information and awareness-raising actions on the subject.

[Cognition disorders and parkinsonian syndrome: diffuse Lewy body disease?]. / Troubles cognitifs et syndrome parkinsonien: maladie a corps de Lewy diffus?.

A 68 year old man developed progressive cognitive impairment with an akinetic-rigid syndrome which was atypically responsive to levodopa. The patient died after 18 months and the postmortem examination showed typical Lewy bodies in the substantia nigra and pale bodies in the cortex which were unlabelled by ubiquitin antibodies. This case is particular by the neuropathological examination (no immunoreactivity to antibodies against ubiquitin) and by the abnormal response to treatment (dystonia). These two aspects are discussed.

Kufs' disease presenting as progressive dementia with late-onset generalized seizures: a clinicopathological and electrophysiological study.

A 32-year-old woman presented with increasing motor difficulties and memory disturbances. Neurological examination only showed mild cerebellar and extrapyramidal symptoms, whereas neuropsychological evaluation disclosed severe cognitive changes consistent with dementia. Her motor and mental status progressively deteriorated until death, which occurred 5 years after the first admission. One year before death, while she was almost bedridden, symptoms of myoclonic epilepsy first appeared, with frequent generalized seizures and generalized myoclonus, occurring especially upon sensory stimulation or passive joint movements. Pathological examination showed neuronal inclusions typical of Kufs' disease. This case, with primary progressive dementia and late-onset myoclonic epilepsy, differs from previously reported cases. Three special electrophysiological features were abnormal, "giant", evoked potentials; unusually marked photosensitivity; and seizure induction by any sensory stimulation.

[Behavior and mental activity disorders after carbon monoxide poisoning. Bilateral pallidal lesions]. / Troubles du comportement et de l'activité mentale après intoxication oxycarbonée. Lésions pallidales bilatérales.

Two patients who had suffered severe carbon monoxide intoxication showed lasting neuropsychologic sequelae: 1) deep inertia involving the whole behaviour and expressed by an almost complete lack of activity if not induced by someone else; a mental gap when the patients were left to themselves and a tendency to give up the mental activity when stimuli ceased; an apparent affective indifference connected with a lack of spontaneous expression of the affects; 2) pseudo-obsessionnal activities: coprolalia with sexual themes in one patient, obsessive collecting and tidying up activities in the other one. Neurologic examination was normal, particularly no parkinsonian syndrome was present. CT scans showed bilateral pallidal low density areas. Both patients had moderate intellectual impairment in psychometric tests and amnestic disorders. There is a possible relationship between memory and cognitive impairment and mental inertia. The onset of pseudo-obsessional signs following basal ganglia lesions is emphasized. The central semeiological fact seems to be a disorder of the initiation and the carrying on of any external action as well as mental activity itself. This may be related with the activity disorders represented at a more elementary level by motion impairment in parkinsonian akinesia.

[Striatonigral degeneration associated with olivopontocerebellar atrophy. Anatomo-clinical study of 3 cases. Nosologic discussion]. / Dégénérescence striato-nigrique associée à une atrophie olivo-ponto-cérébelleuse. Etude anatomo-clinique de trois cas. Discussion nosologique.

Results of a clinicopathologic study in 3 cases of nigrostriatal degeneration associated with olivopontocerebellar atrophy are reported. The clinical picture was primarily that of parkinsonism but associated disorders were atypical: sphincter and deglutition disorders, pyramidal signs and action myoclonia; paralysis of vertical gaze (with a deficit of convergence in 1 case) and a cerebellar syndrome in 2 cases; postural hypotension with an invariable pulse, amyotrophy of the hands and a paradoxical response to Dopa: worsening of akineto-hypertonic symptomatology and deglutition disorders in 1 case. Pathologic examination showed similar lesions in the 3 cases: atrophy with pigmentation of the putamen and changes in the substantia nigra, associated with evidence of olivopontocerebellar degeneration. There was marked loss of neurones in the intermediolateral tract in the cord of the patient with the Shy and Drager's syndrome. All cases reported of this abiotrophic association have been of a sporadic nature. The predominance of females, the age of onset and duration of the disease are features that do not differ much from those of pure nigrostriatal degenerative disorders. These cases cannot therefore be considered as a pathological entity but as a particular form of degeneration affecting multiple systems.

[Tardive spino-cerebellar degeneration with amyotrophia, complicating a severe case of pallido-luysian degeneration and diffuse histological lesions of senility. (Anatomo-clinical study of a case with nosographic discussion)]. / Dégénérescence spino-cérébelleuse tardive avec amyotrophies, comportant une atteinte pallido-luysienne sévère et des lésions histologiques diffuses de sénilité. (Etude anatomo-clinique d'un cas avec discussion nosographique)

Anatomo-clinical findings are reported in a case of central nervous system degeneration which began at age 47 and progressed over a three year period. Information obtained prior to the patient's death suggested probable spinocerebellar degeneration with amyotrophies. Postmortem anatomical examination confirmed this diagnosis but also revealed the existence of unsuspected lesions. These clinically non-manifested lesions involved severe pallido-luysian degeneration as well as numerous and diffuse senile plaques. The nosological implications of this case are discussed.