The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17β-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.

The diagnosis of menopause is sometimes difficult. The objective of this chapter is to describe the process of diagnosing menopause in a physiological situation, then in different clinical situations: women using hormonal contraception (per os, implant or intrauterine device), women with a history of hysterectomy, women previously treated for cancer. A review of the literature was carried out via Pubmed, Medline and Cochrane Library. The recommendations of international societies were also taken into account: International Menopause Society (IMS) https://www.imsociety.org, European Menopause and Andropause Society (EMAS) https://www.emas-online.org. In a classic situation, the diagnosis of menopause is a clinical diagnosis, made retrospectively, based on a 12-month period of consecutive amenorrhoea in a compatible age group (after 45 years of age). No hormonal dosage or imaging is indicated to make a diagnosis of menopause in a classic situation. In women using oestroprogestogen or progestative-only-pill contraception, implant, or Levonorgestrel-intrauterine device (LNG IUD), hormonal assays or pelvic ultrasound are neither recommended to make a diagnosis of menopause (grade C), nor to decide to stop contraception (grade C). The proposed strategy is the discontinuation of oral contraception, removal of the implant or LNG-IUD, and clinical follow-up (occurrence of amenorrhea) (expert opinion). In women with a history of hysterectomy, in the absence of evaluable clinical symptoms (amenorrhea), a repeat FSH≥40 combined with low estradiol (<20pg/ml) at least 3 months after the procedure could be a diagnostic orientation towards menopausal status. After cancer, in women who have received gonadotoxic treatment, the classic clinical criteria of 12 months of amenorrhea cannot be used to make a diagnosis of menopause with certainty (expert opinion). No further examination can be recommended to make a definite diagnosis of menopause (expert opinion). In breast cancer, the hormonal status to be taken into account when choosing initial hormone therapy is the one found before starting any treatment. If at the time of diagnosis of breast cancer the menopausal status is not known due to hormonal contraception, it is preferable to consider the patient as non-menopausal by default for the choice of hormone therapy for the cancer.

The results of the WHI, which reported a doubling of the risk of Alzheimer\'s disease (AD) and a decline in cognitive function in women who were given menopause hormone therapy (MHT), have raised concerns on the deleterious impact of MHT on the central nervous system. Such as for the cardiovascular system, the very late age of initiation of treatment and the nature of the molecules have led to conclusions that cannot be extended to women in their fifties, at the onset of their menopause which is the usual age of MHT initiation. The molecules, which are used in France, 17-beta estradiol and natural progesterone (or its isomer, dydrogesterone) are very different from the equine conjugated estrogens and medroxyprogesterone acetate used in the WHI. It can now be stated that if MHT is started within the window of opportunity (i.e. before the age of 60 or within the first 10years after the beginning of menopause) no deleterious effect on cognition is observed. Moreover, cognition remains relatively stable at the beginning of menopause since the cognitive reserve as well as the different compensation circuits allow compensation for estrogen deficiency. This does not in any way prejudge a possible positive effect of MHT on AD, which is very difficult to demonstrate, as the age of onset of this dementia is very late, 20 or 30years after the initiation of treatment.

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 17β-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.

BACKGROUND: Verification of new reagent lots is a part of the crucial tasks in clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) EP26-A guideline provides laboratories with an evaluation method for reagent verification. The purpose of this study was to compare the performance of EP26-A with our laboratory reagent lot verification protocol and get the final scheme.
METHODS: 16 chemiluminescence analytes including estradiol (E2), progesterone (P), ferritin (FER), cortisol (COR),carbohydrate antigen 153 (CA153), and free prostate-specific antigen (FPSA). were prospectively evaluated in two reagent lots. The laboratory\'s lot verification process included evaluating 5 patient samples with the current and new lots and acceptability according to a predefined criteria. For EP26-A, method imprecision data and critical differences at medical decision points were important factors affecting the sample size requirements and rejection limits.
RESULTS: The number of samples required for EP26-A was 3 to 12, of which P, CA153, and FPSA had increased by more than 5 samples compared with the current protocol. Of the 16 chemiluminescence analytes, 11 had higher rejection limits when using EP26-A than the current laboratory scheme. Our current protocol and EP26-A were in agreement in 32 of the 32 (100%) paired verifications.
CONCLUSIONS: The EP26-A protocol is an important tool to find the differences between reagent lots, and it makes up for the loopholes in the statistical efficiency, sample concentration and quantity, and the selection of rejection limits in the current protocol.

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BACKGROUND: Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK, and are severe in 25%.
OBJECTIVE: To identify which treatments are most clinically effective for the relief of VMSs for women in natural menopause without hysterectomy.
METHODS: English publications in MEDLINE, Embase, and The Cochrane Library up to 13 January 2015 were searched.
METHODS: Randomised controlled trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMSs (up to 26 weeks), vaginal bleeding, and discontinuation.
METHODS: Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs).
RESULTS: Across the three networks, 47 RCTs of 16 treatment classes (n = 8326 women) were included. When compared with placebo, transdermal estradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%; MR 0.23; 95% credible interval, 95% CrI 0.09-0.57), whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR 2.23; 95% CrI 0.7-7.1). Isoflavones and black cohosh were more effective than placebo, although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) found to be ineffective in relieving VMSs, but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding, therefore no conclusions could be made.
CONCLUSIONS: For women who have not undergone hysterectomy, transdermal O+P was the most effective treatment for VMS relief.
CONCLUSIONS: Which treatment best relieves menopause flushes? Results from the #NICE guideline network meta-analysis.

Ovarian reserve markers have been documented to perform very well in the clinical practice. While this is widely recognized, still now there is no consensus on how to use new biomarkers in the clinical practice. This study was conducted among Italian IVF centres using the Delphi technique, a validated consensus-building process. Briefly three consecutive questionnaires were developed for clinicians in charge of IVF centres. In the first rounds, participants were asked to rate the importance of a list of statements regarding the categorization of ovarian response and the diagnostic role of biomarkers. In round 3, participants were asked to rate their agreement and consensus on the list of statements derived from the first two rounds. There were 120 respondents. Consensus was achieved for many points: (a) poor ovarian response is predicted on the basis of the following: AMH < 1 ng/ml or AFC < 7, FSH ≥ 10 IU/l, age ≥ 40 yrs; (b) hyper-response is predicted on the basis of the following: AMH > 3 ng/ml or AFC > 14; (c) day 3 FSH measurement should always be associated to estradiol; (d) AMH can be measured on a random basis; (e) the measurement of the AFC with the 2D technology may be considered adequate and (f) the AFC should be measured in the early follicular phase and consists in the total number of 2-9 mm follicles in both the ovaries. The present study suggests that extensive consensus on the importance and use of new ovarian reserve markers to improve IVF safety and performance is already present among clinicians.

OBJECTIVE: Establishment of guidelines for post-partum contraception.
METHODS: Systematic review of publications between 1960 and 2015 from database Medline, Embase, Cochrane Library and recommendations of international societies.
RESULTS: The most recent French data show that approximately 2% of women with induced abortion have deliver within 6 months before this abortion and 4% had a child six to twelve months earlier (Evidence Level [EL] 3). A contraceptive counseling is ideally recommended after delivery to avoid unplanned pregnancies (grade C). Among non-breastfeeding women, the shorter median delay for recovery ovulation is 39 days after delivery (EL4). Starting effective contraception later 21 days after delivery in women who does not want closely spaced pregnancy is recommended (grade B), and to prescribe it at the maternity (Professional consensus). In breastfeeding women, the recovery of ovarian activity is dependent on breastfeeding characteristics. Only exclusive breastfeeding with very specific conditions can be used for contraception over a six months period (EL2). For all other breastfeeding conditions, contraceptive strategies are the same than without breastfeeding (grade B). According to the post-partum risk of venous thromboembolism, the combined hormonal contraceptive use before six post-partum weeks is not recommended (grade B). In women with vascular risk factors, the evaluation of benefit risk balance of this use between 6th and 12th post-partum weeks is recommended (Professional consensus). Progestin only contraceptives with low dose are allowed in earlier post-partum (grade B), except at the acute phase of severe thromboembolic event (Professional consensus). In women who want intra-uterine device (IUD) as contraception, it is recommended to prescribe IUD at the hospital and to insert the IUD during the postnatal consultation (grade B). In breastfeeding women, progestin contraception\'s (oral or subcutaneous) are permitted immediately after delivery (grade B). For women at short interpregnancy interval risk, long acting reversible contraceptives (implant or IUD) started at the hospital is suggested (grade B).
CONCLUSIONS: The wide contraceptive choice permits to find the best strategy for each woman while respecting post-partum period specificities.

Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) α and β differ from that used by 17β-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17β-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor γ and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.