Menopausal Hormone Replacement Research Articles

The most prominent terminological problems in reproductive medicine

Constant improvement of professional skills and competence are essential components of modern post diploma medical education in the 21st century. Despite of world-wide spread of evidence-based medicine many physicians from such areas as obstetrics, gynecology, andrology, endocrinology, cardiology. gerontology etc. still use outdated and incorrect terminology from reproductive medicine. The such unfavourable trend leads to serious increasement of insufficient/overdiagnosis, treatment mistakes and poor outcomes such as sexual dysfunction, infertility and comorbidity. The present article presents actual interpretations and characterization of gynecological and andrological terms such us menopausal hormonal therapy (MHT) and hormone replacement therapy (HRT) among females and male hypogonadism.

Transcriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer's disease.

The hippocampus, vital for memory and learning, is among the first brain regions affected in Alzheimer's Disease (AD) and exhibits adult neurogenesis. Women face twice the risk of developing AD compare to men, making it crucial to understand sex differences in hippocampal function for comprehending AD susceptibility. We conducted a comprehensive analysis of bulk mRNA postmortem samples from the whole hippocampus (GSE48350, GSE5281) and its CA1 and CA3 subfields (GSE29378). Our aim was to perform a comparative molecular signatures analysis, investigating sex-specific differences and similarities in the hippocampus and its subfields in AD. This involved comparing the gene expression profiles among: (a) male controls (M-controls) vs. female controls (F-controls), (b) females with AD (F-AD) vs. F-controls, (c) males with AD (M-AD) vs. M-controls, and (d) M-AD vs. F-AD. Furthermore, we identified AD susceptibility genes interacting with key targets of menopause hormone replacement drugs, specifically the ESR1 and ESR2 genes, along with GPER1. The hippocampal analysis revealed contrasting patterns between M-AD vs. M-controls and F-AD vs. F-controls, as well as M-controls vs. F-controls. Notably, BACE1, a key enzyme linked to amyloid-beta production in AD pathology, was found to be upregulated in M-controls compared to F-controls in both CA1 and CA3 hippocampal subfields. In M-AD vs. M-controls, the GABAergic synapse was downregulated, and the Estrogen signaling pathway was upregulated in both subfields, unlike in F-AD vs. F-controls. Analysis of the whole hippocampus also revealed upregulation of the GABAergic synapse in F-AD vs. F-controls. While direct comparison of M-AD vs. F-AD, revealed a small upregulation of the ESR1 gene in the CA1 subfield of males. Conversely, F-AD vs. F-controls exhibited downregulation of the Dopaminergic synapse in both subfields, while the Calcium signaling pathway showed mixed regulation, being upregulated in CA1 but downregulated in CA3, unlike in M-AD vs. M-controls. The upregulated Estrogen signaling pathway in M-AD, suggests a compensatory response to neurodegenerative specifically in males with AD. Our results also identified potential susceptibility genes interacting with ESR1 and ESR2, including MAPK1, IGF1, AKT1, TP53 and CD44. These findings underscore the importance of sex-specific disease mechanisms in AD pathogenesis. Region-specific analysis offers a more detailed examination of localized changes in the hippocampus, enabling to capture sex-specific molecular patterns in AD susceptibility and progression.

Sexual and reproductive health of baby boomers.

Early baby boomers constitute a cohort that was the first to benefit from numerous innovative interventions in sexual and reproductive health services as exemplified by hormonal contraception, legal abortion, invitro fertilisation, screening mammography and menopausal hormone replacement besides medication for male erectile dysfunction. The quest for a youth elixir continues to be a challenge for sexual health sciences.

The Exciting Potential for ChatGPT in Obstetrics and Gynecology

ABSTRACT In November 2022, AI Lab OpenAI launched the online chatbot ChatGPT (Chat Generative Pre-Trained Transformer), an accessible language model that uses the artificial intelligence (AI) branch of natural language processing (NLP) to answer prompts based on a library of 175 billion parameters from the “internet, books and other sources.” Because of its ability to answer clinical questions in plain English that can be understood by providers and patients alike, the potential for ChatGPT to be used as a clinical tool is obvious. Despite its impressive fund of source knowledge, these data are potentially biased and unreliable and may not reflect current stances. In addition, ChatGPT does not list sources for its information, and its current capability to answer clinical questions correctly is not well understood. This study aimed to assess answers given by ChatGPT in response to a spectrum of questions about obstetrics and gynecology including systems-level questions, ethical questions, and treatment-related decision making. A total of 14 questions were asked. The first question asked why US preterm birth rates are so high. The second question asked for a list of the most important interventions physicians can do to monitor, prevent, and treat premature births. The third question asked whether vaginal progesterone was effective and safe for preventing preterm birth in women with a short cervix in the midtrimester, and the fourth question asked the same question but in women with a history of preterm birth and no short cervix. The fifth question asked why maternal mortality rates in the United States are so high. The sixth question asked for a list of what obstetricians can do to prevent preeclampsia. The seventh question asked about the safety of hospital births when compared with planned home births in the United States. The eighth question asked whether it is ethically acceptable for an obstetrician to provide emergency cesarean delivery without a woman's informed consent to save the fetus or the mother. The ninth question asked how obstetricians should screen for domestic abuse and intimate partner violence in pregnancy. The 10th question asked if women should freeze their eggs and at what age. The 11th question asked about the risks and benefits of menopause hormone replacement therapy. The 12th question asked how abortion bans in the United States affect women's health and lives. The 13th question asked whether complex hyperplasia atypia surgery should be performed only by a gynecologist-oncologist. The final question asked whether we should continue using the term “pregnant woman” versus alternative including “pregnant person.” Overall, ChatGPT provided nuanced and informed answers to question on virtually any topic in obstetrics and gynecology, but occasionally revealed an apparent lack of insight into the questions being asked. ChatGPT can provide preliminary information about a wide range of topics and can be valuable to both providers and patients and will continue to improve as training data are updated, and the model learns from user prompts.

European trends in ovarian cancer mortality, 1990–2020 and predictions to 2025

IntroductionOver the last decades, ovarian cancer mortality in Europe has been decreasing, but disparities in trends were observed. In this paper, we analysed ovarian cancer mortality trends in Europe over the period 1990–2020 and predicted the number of deaths and rates by 2025. MethodsWe extracted population and death certification data from ovarian cancer in women for 31 European countries, between 1990 and 2020 from the World Health Organization database. We computed age-standardised mortality rates (ASMR) per 100,000 women-years, based on the world standard population. We also obtained predictions for 2025 using a joinpoint regression model and calculated the number of avoided deaths over the period 1994–2025. ResultsOver the observed period, mortality from ovarian cancer showed a favourable pattern in most countries. In the EU-27, rates declined by 5.9% from 2010–2014 to 2015–2019, reaching an ASMR of 4.66/100,000. During the same period, the decline in ovarian cancer mortality was more pronounced in the EU-14 countries (−7.0%) compared to Transitional countries (−2.1%). Declines were also observed in the United Kingdom, to reach an ASMR of 5.29. Decreases in mortality from ovarian cancer are predicted until 2025, to 4.17/100,000 for the EU-27. ConclusionsFavourable trends in ovarian cancer mortality are expected to persist in Europe and can be mainly attributed to the increased use of oral contraceptives in subsequent generations of European women. Decreased use of menopausal Hormone Replacement Therapy and improved diagnosis and management may also have played a role.

Hormones and dry eye disease

The endocrine system influences all tissues and cells in the human body. The ocular surface is constantly exposed to circulating hormones and expresses their specific receptors. Dry eye disease (DED) is a disorder with multifactorial etiology, and endocrine anomalies are one of the inciting factors. The endocrine anomalies that cause DED include physiological conditions such as menopause, menstrual cycle variations, pathologies such as polycystic ovarian syndrome, androgen resistance, iatrogenic conditions such as contraceptive use, and antiandrogen treatment. This review highlights the status of these hormones in DED along with the mechanism of action of different hormones on the ocular surface structures and the clinical implications of these effects. The influence of androgens, estrogens, and progesterone on the ocular surface tissues, and the implications of androgen-deficient states in DED are also discussed. The physiological and pathological effects of menopause and sex hormone replacement therapy are discussed. The effects of insulin and insulin resistance on the ocular surface and DED, and the growing potential of topical insulin therapeutics for DED are mentioned. Thyroid-associated ophthalmopathy, its impact on the ocular surface, and the tissue effects of thyroid hormone in the context of DED are reviewed. Finally, the potential role of hormonal therapeutics in the management of DED has also been discussed. The compelling evidence suggests that it would be clinically beneficial to consider the possibility of hormonal imbalances and their impact while treating patients with DED.

Re-Evaluating the Association Between Hormonal Contraception and Breast Cancer Risk.

This review aims to summarize and assess key studies investigating the relationship between hormonal contraception and breast cancer risk. Approximately two-thirds of breast cancers express the estrogen receptor, and long-term exposure to estrogen is a debated risk factor for breast cancer development. This hypothesis is based on prior studies looking at reproductive risk factors (endogenous estrogen exposure) along with hormone replacement therapy (exogenous hormone exposure). Historically accepted reproductive risk factors include age at menarche, age at first delivery, and parity. Exogenous hormone exposure encompasses both receipt of hormonal contraception and menopausal hormone replacement therapy. This review highlights the reported risks associated with the most common hormonal contraception methods including oral, transdermal, and transvaginal routes. Large observational studies of the past and more recent works are summarized highlighting gaps in knowledge. Several themes emerge: difficulty accounting for well-established risk factors in analyses of epidemiologic studies, challenges determining whether associations between hormonal contraception and breast cancer are due to the exogenous hormones themselves or to increased engagement with the medical system, and discrepancies between statistically significant and clinically significant risk, odds, and hazard ratios. Understanding the strengths and limitations of these studies will help providers in and outside of oncology support women making decisions regarding both cancer risk-reduction and family planning.

Association of sleep characteristics with renal function in menopausal women without recognized chronic kidney disease.

To delineate the association between sleep characteristics and renal function in peri-post menopause free of Chronic kidney disease (CKD) as well as cardiometabolic and hormone indicators. Cross-sectional data from a total of 823 Han-Chinese women aged 40-67 years who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from November 2011 to November 2020 were analyzed through the Pittsburgh Sleep Quality Index (PSQI) and serum cystatin C (Cys-C). Logistic regression models were used to assess the association between cumulative/each sleep parameter and renal function after adjusting for cardiometabolic variables. After confounding factors, we identified that poor perceived sleep quality, shorter sleep duration (<6 h), low sleep efficiency (<75%), delayed sleep latency and worse sleep disturbance elevated more than doubled the odds ratio for declining renal function (≥0.91 mg/dL, the highest Cys-C) in postmenopause in a graded fashion. Meanwhile, multiple logistic regression analysis revealed that sleep disorder (PSQI ≥ 8), late postmenopause, highest quartile independently increased the odds ratio for declining renal function (OR 2.007, 95% CI: 1.408-2.861, OR = 3.287, 95%CI: 3.425-8.889, OR = 2.345, 95% CI: 1.310-4.199, respectively), while participants with menopausal hormone replacement (MHT) lower the odds of declining renal function (OR = 0.486, 95% CI: 0.324-0.728). The findings proposed that maintaining good sleep quality should be attached great importance to postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as MHT of renal disease progression in postmenopausal women.

Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing.

The totality of evidence indicates menopausal hormone replacement therapy (HRT) effects are determined by timing of initiation according to age and/or time since menopause, underlying health of target tissue, and duration of therapy. Initiated in women at younger than 60 years and/or at or near menopause, HRT significantly reduces all-cause mortality and cardiovascular disease (CVD), whereas other primary CVD prevention therapies such as lipid-lowering fail to do so. The magnitude and type of HRT-associated risks, including breast cancer, stroke, and venous thromboembolism, are rare (<10 events/10,000 women), not unique to HRT, and comparable with other medications. Hormone replacement therapy is a sex-specific and time-dependent primary CVD prevention therapy that concomitantly reduces all-cause mortality, as well as other aging-related diseases with an excellent risk profile. Keeping in mind that prevention strategies must be personalized, health care providers and patients can use cumulated HRT data in making clinical decisions concerning chronic disease prevention including CVD and mortality reduction.

Preliminary cost variance modeling to compare autologous intraovarian platelet-rich plasma vs. standard hormone replacement therapy for menopause management

Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will use HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of HRT risks from extended use has piqued interest in safer options. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. Mean ± SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about $576 ± 246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean ± SD cost for OPRP at $8,710 ± 4,911/yr ( P < 0.0001 vs. HRT, by T-test). Upper-bound estimates for annual HRT and OPRP costs were $1,341 and $22,232, respectively. While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT options that are currently marketed.

Abstract P1-10-01: Results from the breast cancer - anti progestin prevention study 1 (BC-APPS1) trial - a novel approach in breast cancer prevention

Abstract Background The luminal progenitor (LP) population in the normal breast is under the control of paracrine progesterone signalling and likely represents the cell of origin of estrogen receptor negative (ER-) BC. Exogenous progestins, as contraception or menopausal hormone replacement therapy (HRT), increase the risk of ER- and ER+ BC. We sought to examine the effect antagonism of progesterone signalling on the tissue composition and cellular hierarchy of normal human breast and thus the potential for progesterone receptor antagonism in breast cancer prevention. Methods BC-APPS1 is a single arm phase 2 pilot study in which premenopausal women at increased familial BC risk underwent vacuum assisted biopsy (VAB) in the luteal phase of the menstrual cycle prior to commencing a 12 week course of the selective progesterone receptor modulator (SPRM) ulipristal acetate (UA; 5mg daily). VAB was repeated in the final week of therapy. The primary endpoint of BC-APPS1 was change in epithelial Ki67 assessed by immunohistochemistry. Secondary endpoints included toxicity and additional tissue endpoints including immunofluorescence (IF) staining of LP markers, 2D mixed luminal/basal and 3D (mammosphere) colony formation assays, LP fraction by FACS (CD49f+/EPCAM+ cells), single cell and bulk RNAseq, epithelium/stromal laser capture microdissection-based proteomics and tissue stiffness analyses. Baseline samples were compared to a historic cohort of normal risk (n=25) and high risk (n=41) samples for IF analyses. Results Between 03/2016 and 03/2019 26 women were recruited to BC-APPS1 and 24 underwent paired biopsies. The trial met its primary endpoint with a significant reduction in median Ki67 between baseline (4.89%; IQR 4.36-10.42) and 12 weeks (2.41%; IQR 1.57-3.24; p&amp;lt;0.0001). Study procedures were well tolerated with minimal drug toxicity (all G1/2). 2 women discontinued UA due to anxiety: 1 drug induced and 1 induced following development of a small haematoma following VAB1. FACS analysis (n=17) demonstrated significant reduction in the LP proportion with UA treatment (median baseline 44.7% IQR 28.1-55.2 and 12 weeks 25.4% IQR 17.2-37.8; p&amp;lt;0.01). Breast tissue from high-risk women had increased expression of PR+ (10.8% vs 4.5%; p&amp;lt;0.01) and dual Sox9+Ki67+ cells (4.8% vs 0.8%, p&amp;lt;0.01). The Sox9+Ki67+ population reduced significantly with UA therapy in BC-APPS1 (4.4% vs 1.3%, p&amp;lt;0.05). In functional analyses both mammosphere and mixed luminal/basal colony formation reduced with UA treatment and single cell RNAseq (n=8 pairs) and epithelium/stromal laser capture microdissection-based proteomics (n=5 pairs) identified stromal components and remodelling as key pathways perturbed by UA treatment. Tissue stiffness, assessed by atomic force microscopy and previously shown to be positively associated with %mammographic density, was significantly reduced with UA treatment. Conclusions: High risk women have increased surrogate markers of BC risk including proliferating luminal progenitor cells which can be reduced by short term SPRM treatment with UA. Treatment is generally well tolerated and SPRM therapy is an attractive candidate for BC prevention. Longer term studies are warranted and stromal remodelling and breast tissue stiffness data suggest that mammographic density should be investigated as a potential surrogate biomarker of activity. Citation Format: Sacha Howell, Alice Greenhalgh, Robert Pedley, Suad Alghamdi, Amanda Caruso, Mujtaba Ansari, Tiago Moreira, Sue Astlet, Anthony Maxwell, Yit Lim, Hayley Brookes, Faiza Idries, Anthony Howell, D Gareth Evans, Michael Sherratt, Andrew Gilmore, Elaine Harkness, Walid Khaled, Alecia-Jane Twigger, Matt Roberts, Robert Clarke, Bruno Simoes. Results from the breast cancer - anti progestin prevention study 1 (BC-APPS1) trial - a novel approach in breast cancer prevention [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-01.

The Reactivity of Human and Equine Estrogen Quinones towards Purine Nucleosides

Conjugated estrogen medicines, which are produced from the urine of pregnant mares for the purpose of menopausal hormone replacement therapy (HRT), contain the sulfate conjugates of estrone, equilin, and equilenin in varying proportions. The latter three steroid sex hormones are highly similar in molecular structure as they only differ in the degree of unsaturation of the sterane ring “B”: the cyclohexene ring in estrone (which is naturally present in both humans and horses) is replaced by more symmetrical cyclohexadiene and benzene rings in the horse-specific (“equine”) hormones equilin and equilenin, respectively. Though the structure of ring “B” has only moderate influence on the estrogenic activity desired in HRT, it might still significantly affect the reactivity in potential carcinogenic pathways. In the present theoretical study, we focus on the interaction of estrogen orthoquinones, formed upon metabolic oxidation of estrogens in breast cells with purine nucleosides. This multistep process results in a purine base loss in the DNA chain (depurination) and the formation of a “depurinating adduct” from the quinone and the base. The point mutations induced in this manner are suggested to manifest in breast cancer development in the long run. We examine six reactions between deoxyadenosine and deoxyguanosine as nucleosides and estrone-3,4-quinone, equilin-3,4-quinone, and equilenin-3,4-quinone as mutagens. We performed DFT calculations to determine the reaction mechanisms and establish a structure–reactivity relationship between the degree of unsaturation of ring “B” and the expected rate of DNA depurination. As quinones might be present in the cytosol in various protonated forms, we introduce the concept of “effective barriers” to account for the different reactivity and different concentrations of quinone derivatives. According to our results, both equine estrogens have the potential to facilitate depurination as the activation barrier of one of the elementary steps (the initial Michael addition in the case of equilenin and the rearomatization step in the case of equilin) significantly decreases compared to that of estrone. We conclude that the appearance of exogenous equine estrogen quinones due to HRT might increase the risk of depurination-induced breast cancer development compared to the exposure to endogenous estrone metabolites. Still, further studies are required to identify the rate-limiting step of depurination under intracellular conditions to reveal whether the decrease in the barriers affects the overall rate of carcinogenesis.

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Primary Ovarian Insufficiency in Women With Addison's Disease.

ContextPrimary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison’s disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied.ObjectiveTo assess the prevalence of POI in a large cohort of women with AAD and describe clinical, immunological, and genetic characteristics.MethodsAn observational population-based cohort study of the Norwegian National Addison Registry. The Norwegian Prescription Database was used to assess prescription of menopausal hormone replacement therapy (HRT). A total of 461 women with AAD were studied. The primary outcome measure was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism variation.ResultsThe prevalence of POI was 10.2% (47/461) and one-third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%).ConclusionOne in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD <40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC.

Evaluation of a tertiary and district general hospital menopause service.

Requests for management of menopausal symptoms and hormone replacement are increasing in the UK. Referrals to specialist clinics have to be balanced with increasing recommendations within the NHS to improve efficiency and patient care. Retrospective evaluation of clinic records over two months at a district general (Poole Hospital) and tertiary (Guy's Hospital) menopause service. Data on referral origin, reason for referral, interval from referral to review and outcome were collected and compared between trusts. To evaluate and compare referrals and outcomes in a tertiary and district general menopause service and provide recommendations for improving efficiency. Most referrals are from primary care but up to 25% are from other specialties. Half of the appointments are new referrals and 95% of women attend. Of the new referrals, 50% have multiple medical comorbidities, 25% a personal or family history of cancer and 25% treatment resistance; 30% have premature ovarian insufficiency. At Guy's Hospital, 30% are reviewed more than 18 weeks after referral, at Poole Hospital this is 6%. Treatment resistance is reported in half of the women reviewed at follow-up. Menopause services review a complex patient population and the majority of referred women have more than one co-morbidity; they require time, specialist knowledge of current treatment options and a multidisciplinary approach. The main barrier to service efficiency is capacity, particularly in population dense areas; cognitive behavioural therapy and non-hormonal methods appear under-utilised in primary care, as do alternative methods of follow-up within the clinics such as telephone and patient-initiated appointments.

Drug–Drug Cocrystals Provide Significant Improvements of Drug Properties in Treatment with Progesterone

Progesterone (Prog), a natural steroid hormone, is widely used in birth control pills and menopausal hormone replacement therapies. Phloroglucinol (SPF) and resveratrol (RSV) are also two kinds of active products that can be used during pregnancy. Drug–drug cocrystals of Prog with SPF and RSV were designed and successfully synthesized for purpose of bringing improvements of drug properties, including solubility, hydroscopic stability, and color stability. The cocrystals and their hydrate structures were systematically characterized by X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. In addition, powder dissolution experiments of Prog, Prog-SPF, and Prog-RSV were conducted in aqueous solutions with the presence of different surfactants, and the result revealed that the Prog-SPF cocrystal exhibits a superior solubility compared with Prog and Prog-RSV. Furthermore, the Prog-SPF cocrystal also enhances the hydroscopic stability and color stability of SPF. Those findings may provide a promising formulation to overcome some weaknesses of the parent drugs.

Breast Density of Mammography is Correlated with Reproductive Risk Factors Regardless of Menopausal Status: A Cross-Sectional Study of the Korean National Screening Program.

Objective:To clarify the limitations of mammography screening for women with dense breasts, we examined breast density and its effects on screening results. Patients and Methods:We performed a cross-sectional, observational study on women who underwent mammography. Data from the National Cancer Screening Program(NCSP) from 2009 to 2013 were used. The study population consisted of participants with high breast density. We used a logistic regression analysis to evaluate the relationships between breast density and reproductive factors and screening results according to menopause status. Results:High breast density was reported for 57.5% of all participants (3,417,319 participants). Screening results indicated breast density of <25%, 25-50%, 51-75%, and ≥76% for 16.4%, 26.3%, 37.8%, and 19.5%, respectively, of participants. According to the screening results, high breast density was correlated with high deferment and recall rates. Reproductive factors, especially parity, breastfeeding, and use of oral contraceptives, had consistent effects on screening results of premenopausal and postmenopausal women. Regardless of menopausal status, age, early onset of menarche (15 years or younger), fewer live births (≤1 birth), and previous benign breast disease were correlated with increased breast density. In postmenopausal women, early-onset menopause and longer-term hormone replacement therapy (≥2 years) also independently increased breast density.Conclusion:Breast density influenced screening results, which could increase the rate of recall. Breast density was also influenced by reproductive factors, with patterns similar to those of breast cancer risk, regardless of menopausal status. We need to identify high-risk women with high density who would probably benefit from supplemental breast cancer screening.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

Recommendations on menopausal hormone replacement therapy.

Recommendations on menopausal hormone replacement therapy.