A Case of Pyocolpos in a Postmenopausal Woman With a History of Lichen Sclerosus and Postmenopausal Bleeding.

Pyocolpos refers to the buildup of pus within the vaginal cavity. Pyocolpos in the background of lichen sclerosis and postmenopausal bleeding (PMB) has not been previously described. A 69-year-old para 3 patient presented with a history of PMB with a long-standing history of lichen sclerosis. The vaginal examination was impossible due to vaginal adhesions. Vulval appearances revealed the loss of the clitoral architecture. Further imaging revealed an endometrial thickness of 4-5 mm, a focal abnormality within the posterior ectocervix compatible with a hemorrhagic cystic lesion distending the posterior fornix, and some free fluid within the pelvis. A hysteroscopy was abandoned as the vagina was completely obliterated. After a multidisciplinary assessment, the patient had a total abdominal hysterectomy, and the presence of a pyocolpos was noticed at the opening into the vault. We could not find any previous case reports of pyocolpos that are associated with lichen sclerosus. The long-standing history of lichen sclerosus may have caused an obstruction of the outflow tract, which was secondarily infected and slowly progressed into the formation of pyocolpos. Other management options could have been explored if the diagnosis of pyocolpos had been made preoperatively. Pyocolpos should be considered in patients with a history of a long-standing lichen sclerosus who present with abdominal pain and a pelvic mass on imaging.

Dihydrotanshinone I targets ESR1 to induce DNA double-strand breaks and proliferation inhibition in hepatocellular carcinoma.

BACKGROUND: Due to its high incidence and elevated mortality, hepatocellular carcinoma (HCC) has emerged as a formidable global healthcare challenge. The intricate interplay between gender-specific disparities in both incidence and clinical outcomes has prompted a progressive recognition of the substantial influence exerted by estrogen and its corresponding receptors (ERs) upon HCC pathogenesis. Estrogen replacement therapy (ERT) emerged for the treatment of HCC by administering exogenous estrogen. However, the powerful side effects of estrogen, including the promotion of breast cancer and infertility, hinder the further application of ERT. Identifying effective therapeutic targets for estrogen and screening bioactive ingredients without E2-like side effects is of great significance for optimizing HCC ERT. METHODS: In this study, we employed an integrative approach, harnessing data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, clinical paraffin sections, adenoviral constructs as well as in vivo studies, to unveil the association between estrogen, estrogen receptor α (ESR1) and HCC. Leveraging methodologies encompassing molecular dynamics simulation and cellular thermal shift assay (CETSA) were used to confirm whether ESR1 is a molecular target of DHT. Multiple in vitro and in vivo experiments were used to identify whether i) ESR1 is a crucial gene that promotes DNA double-strand breaks (DSBs) and proliferation inhibition in HCC, ii) Dihydrotanshinone I (DHT), a quinonoid monomeric constituent derived from Salvia miltiorrhiza (Dan shen) exerts anti-HCC effects by regulating ESR1 and subsequent DSBs, iii) DHT has the potential to replace E2. RESULTS: DHT could target ESR1 and upregulate its expression in a concentration-dependent manner. This, in turn, leads to the downregulation of breast cancer type 1 susceptibility protein (BRCA1), a pivotal protein involved in the homologous recombination repair (HRR) process. The consequence of this downregulation is manifested through the induction of DSBs in HCC, subsequently precipitating a cascade of downstream events, including apoptosis and cell cycle arrest. Of particular significance is the comparative assessment of DHT and isodose estradiol treatments, which underscores DHT's excellent HCC-suppressive efficacy without concomitant perturbation of endogenous sex hormone homeostasis. CONCLUSION: Our findings not only confirm ESR1 as a therapeutic target in HCC management but also underscores DHT's role in upregulating ESR1 expression, thereby impeding the proliferation and invasive tendencies of HCC. In addition, we preliminarily identified DHT has the potential to emerge as an agent in optimizing HCC ERT through the substitution of E2.

Hypogonadism as a consequence of craniopharyngioma in female patients: comparison of childhood and adult onset and effects of estrogen replacement therapy.

PURPOSE: (1) to compare clinical, biochemical features in female patients with hypoestrogenism due to childhood- and adult-onset CP; (2) to reveal effects of estrogen replacement therapy in female patients with childhood-onset CP. METHODS: Thirty-seven women that received specific treatment for CP in the period from 1980 to 2019 were recruited: 21 with childhood-onset and 16 with adult-onset CP. Clinical and hormonal characteristics were evaluated. Seventeen-beta-estradiol 2 mg and dydrogesterone 10 mg in sequential regiment was used in 18 childhood-onset cases. Mean follow-up was 31 months. RESULTS: Amenorrheic women with childhood- and adult-onset CP presented with the same complaints except for lack of genital hair and breast hypoplasia, which were common in patients with childhood-onset CP. BMI was lower in childhood-onset CP group, as was the proportion of overweight patients. They had more favorable lipid profile. The levels of estradiol, testosterone and DHEA-S were low and did not differ. Uterine and ovary volumes were reduced in all patients, but the decline was noticeable in the childhood-onset group. Mineral bone density of lumbar vertebrae was diminished in childhood-onset group. Estrogen therapy in these patients led to clinical improvement: increase in BMD in lumbar spine without negative changes in BMI and/or lipid profile. CONCLUSIONS: Study showed that women with childhood-onset CP had less negative metabolic changes. However, they have more pronounced breast and uterus hypoplasia and lower BMD in lumbar spine. The estrogen replacement therapy led to clinical improvement and BMD increase in lumbar spine without increase of BMI and/or lipid profile changes.

Association between estrogen replacement therapy and heart failure in postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Based on past epidemiological investigations, the cardiovascular role of estrogen replacement therapy (ERT) in postmenopausal women has always been controversial. The real efficacy of ERT for heart failure (HF) among postmenopausal women remains to be further investigated. This article is based on research into European and American populations. PURPOSE: To determine the impact of estrogen replacement therapy on HF using meta-analysis. METHODS AND MATERIAL: Electronic literature was searched on Web of Science, PubMed, and Embase databases to identify randomized controlled trials (RCTs) comparing the hospitalization for heart failure between ERT users and non-users among postmenopausal women. Pairs of reviewers screened eligible articles independently, extracted data, and evaluated the risk of bias. Summary relative risks were estimated for the composite endpoint of first hospitalized heart failure and admission to the hospital for heart failure. RESULTS: A pooled study of five randomized controlled trials found that estrogen replacement therapy had no significant effect on the composite endpoint in postmenopausal women, with a relative risk of 1.02 (95% CI 0.94-1.10). CONCLUSION: This systematic review demonstrated that estrogen replacement therapy did not significantly change the risk of first hospitalized heart failure and admission to the hospital for heart failure in postmenopausal women.

Prolame produces anxiolytic- and antidepressant-like effects in middle-aged female rats with less uterotrophic effects than 17ß-estradiol.

Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17ß-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 µg/kg), 17ß-estradiol (E2, 40 or 80 µg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

Correlating estrogen replacement therapy and temporomandibular disorders: a comprehensive review following PRISMA principles and cochrane handbook for systematic reviews of interventions.

BACKGROUND: Estrogen replacement therapy (ERT) is a common hormonal treatment for postmenopausal women, aimed at alleviating menopausal symptoms and reducing the health risks associated with estrogen deficiency. However, the impact of ERT on temporomandibular disorders (TMDs) remains unclear. This systematic review aims to evaluate the relationship between ERT and TMDs, including TMD occurence, pain, and associated symptoms. METHODS: A comprehensive search of seven electronic databases was conducted using predefined search terms and Boolean operators. Inclusion criteria encompassed studies examining the association between ERT and TMDs. Two independent reviewers screened the identified articles, extracted data, and assessed the risk of bias using the RoB -2 tool. RESULTS: Search strategy identified a total of 3 articles which met the inclusion criteria. The included studies investigated the impact of ERT on TMD occurrence and its related symptoms. The analysis revealed no significant association between ERT and TMD occurrence. A significant dose relationship was noted in one of the studies while another mentioned the possible relationship of TMD with educational status. Risk of bias among the studies was low, and the overall quality of evidence was deemed to be high. CONCLUSION: This systematic review suggests that there is no conclusive evidence supporting an increased risk of TMDs among women receiving ERT. The findings indicate that ERT is unlikely to have a noticeable impact on TMDs. However, due to the limited number of studies available, further research is warranted to strengthen these conclusions and explore potential factors that may influence the relationship between ERT and TMDs.

Menopause and accelerated aortic stiffness.

BACKGROUND: The menopausal transition is widely believed to increase the risk of cardiovascular disease, based on the notion that estrogen is cardioprotective in women. While aortic stiffness is an independent predictor of cardiovascular disease, it has been unclear whether this risk increases during menopause. OBJECTIVE: This study aimed to determine the association between changes in menopausal status and aortic stiffness. MAIN OUTCOME MEASURES: Menopausal status was classified using the Stages of Reproductive Aging in Women criteria in a stratified random sample of Australian women aged 40-80 years, at three time-points over 14 years (n = 469 in 2001-02 and 2005, and n = 323 in 2014). Aortic stiffness was measured non-invasively via carotid-femoral pulse wave velocity at each time point. Mixed modeling was employed to determine the independent associations between menopausal status and aortic stiffness accounting for multiple covariates including age, systolic blood pressure, heart rate, medications, cholesterol, waist circumference, smoking and diabetes status. RESULTS: There was no evidence to support an association between the menopausal transition and an acceleration of aortic stiffness. However, there was an acceleration of aortic stiffness in the late (8+ years) postmenopause phase, after accounting for age and traditional cardiovascular risk factors (0.122 [95%CI: 0.106, 0.139] m/s/year; p < 0.001). CONCLUSIONS: The menopausal transition is not associated with major changes in aortic stiffness beyond normal age-related effects. However, the clinically significant acceleration in aortic stiffness observed in late postmenopause may contribute to greater cardiovascular risk in this later life phase. Study registered in the Australian and New Zealand Clinical Trials Registry, reference ACTRN12618000005257.

Supraphysiologic doses of 17ß-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism.

BACKGROUND: 17ß-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. METHODS: In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. RESULTS: sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. CONCLUSION: These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.

Effect of Growth Hormone and Estrogen Replacement Therapy on Bone Mineral Density in Women with Turner Syndrome: A Meta-Analysis and Systematic Review.

Osteoporosis is a serious implication of Turner syndrome (TS). Common methods for the treatment of TS are growth hormone (GHT) and estrogen replacement therapy (ERT). We examined the relationship between the treatment of TS and bone mineral density (BMD) of the lumbar spine. The purpose of our study was to show the currency of BMD states among patients with TS for treatment with GHT and ERT. We searched databases for studies published from inception to April 2023. The articles were related to TS, osteoporosis, ERT, GHT, BMD and treatment patients with TS. We applied the selection criteria: lumbar spine values at L1-L4; dual-energy X-ray absorptiometry (DXA); treatment which was applied: one group of articles: ERT and two group of articles: GHT; results performed as means ± SD. In total, 79 articles were analyzed, of which 20 studies were included and 5 were considered for meta-analysis. The total number of women in the articles selected was 71. Based on the results of the meta-analysis, the effect of ERT on BMD demonstrated a significant increase in BMD (the standardized mean difference in the random model was 0.593 g/cm2, 95% CI: 0.0705 to 1.116; p = 0.026), which showed that treatment with estrogen particularly increases bone mass during treatment, which contributes to reducing the risk of fractures. The effect of GHT on BMD demonstrated a non-significant decrease in BMD in patients with TS. The results for growth hormone show that this therapy does not improve bone density. However, our review emphasizes the beneficial effect of supplementing growth hormone (GH) on the clinical presentation of TS.

Advantages and limitations of estrogen replacement therapy on hypogonadal survivors of childhood cancer.

BACKGROUND: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. METHODS: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. RESULTS: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = - 0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = - 0.769) or bone density (p = 0.18, R = - 0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. CONCLUSION: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment.

Comparison of the duration of estradiol administration and the effect on pregnancy outcome of day 3 vitrified-warmed embryo transfer cycle: a randomized controlled trial.

Based on the fact that the follicular phase in the menstrual cycle has length variation, it has been assumed that the duration of oestrogen (E2) administration could also be variable; therefore, for the first time, this randomized clinical trial study was conducted to investigate and compare the duration of estradiol administration and the effect on pregnancy outcomes in the cleavage-stage frozen embryo transfer (FET) cycle. We included women aged 20-40 with a normal uterus on hysteroscopy between September and December 2022 and who were divided randomly into three groups: group A [n = 79; 8-11 days of oestrogen before progesterone (P4) supplementation], group B (n = 78; 12-14 days of oestrogen before P4 supplementation), and group C (n = 76; 15-18 days of estrogen before P4 supplementation). Serum levels for E2 on the initial progesterone day and P4 on the transfer day were measured. The effect of the duration of E2 administration on clinical pregnancy and pregnancy loss was investigated. We found no significant differences between the three groups in the clinical pregnancy rate (P = 0.696) and clinical abortion rate (P = 0.925) according to the duration of the E2. There was no significant difference in the E2, P4 levels, and endometrial thickness in pregnant vs. non-pregnant women. The mean of the E2 and P4 levels was 300.03 ± 22.21 and 25.36 ± 5.78, respectively. Our findings suggest that variation in the length of E2 administration (8-18 days) before progesterone initiation in day 3 FET cycles does not affect pregnancy outcome and transfer time can be flexibly arranged.

Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia.

For post-menopausal women, stroke is complicated by the variable effects of estrogen therapy and the age-related therapeutic consequences involved. Estrogen therapy has been shown to have an age-dimorphic effect, which is neuroprotective in young females, but non-neuroprotective, even neurotoxic in acyclic females. We hypothesized that arterial baroreflex (ABR) and its downstream acetylcholine-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammatory pathways are involved in estrogen efficacy toward cerebral ischemic damage. Our data showed that estrogen supplements contributed to ABR improvement and neuroprotection in adult, not aged, ovariectomized (OVX) rats. In adult rats, OVX-induced estrogen deficiency aggravated middle cerebral artery occlusion (MCAO), which induced brain infarction and reduced ABR function, with decreased α7nAChR expression of the brain and exaggerated inflammation following MCAO; these effects were significantly prevented by supplementation with estrogen. ABR impairment by sinoaortic denervation partly attenuated the estrogen effect on baroreflex sensitivity (BRS) and ischemic damage in adult rats, as well as α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR anti-inflammatory pathways are involved in the neuroprotection of estrogen in adult OVX rats. In contrast, aged rats exhibited more severe ischemic damage and inflammatory response than adult rats, as well as poorer baroreflex function and lower α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR and post-ischemic inflammation. Most importantly, ketanserin restored ABR function and significantly postponed the onset of stroke in aged female strokeprone spontaneously hypertensive rats, whereas estrogen treatment failed to delay the development of stroke. Our findings reveal that estrogen is protective against ischemic stroke (IS) in adult female rats and that ABR played a role in this beneficial action. Dysfunction of ABR and unresponsiveness to estrogen in aged female rats may contribute to a reduced estrogen efficacy against cerebral ischemia.

Role of Phytoestrogen in Menopausal Women With Depressive Symptoms: A Consecutive Case Series Study.

Introduction During menopause, healthy women experience a diverse aggregate of clinical manifestations and symptoms that relate to hormonal and aging changes. These alterations are strictly associated with psychological disorders, mainly depression. Estrogen treatment may be effective for these mood variations caused by menopause. Aim To demonstrate the impact of phytoestrogen treatment in menopausal women with depressive symptoms. Methods The study is a consecutive case series study, with a six-month follow-up. It was conducted in a private consultant endocrinologist clinic in Trikala, Greece. A total of 108 eligible participants aged from 45 and above experiencing depressive symptoms were included. The Beck Depression Inventory-II (BDI-II) questionnaire for depressive symptoms was measured at three time points (t=0, t=3 months, t=6 months) and the means were analyzed and compared to each other. Results The overall mean BDI-II scores reveal that depressive symptoms constantly and gradually decreased over time, with the numbers of postmenopausal women experiencing minimal or mild depression and moderate depression, as tested at baseline and study completion (before and after phytoestrogen use), being inversely proportional. Conclusion Phytoestrogen administration to menopausal women is indicated to reduce depression symptoms. More research in the area is needed to reach definite conclusions.

Premature ovarian insufficiency and chance of pregnancy after childhood cancer: A population-based study (the Fex-Can study).

Endocrine complications are a common late effect after childhood cancer. Our study assessed the prevalence and predictors of premature ovarian insufficiency (POI) and prospects of pregnancy in young female survivors. This nationwide study combined registry and survey data for female childhood cancer survivors aged 19 to 40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Of 1989 approached young women, 1333 (67%) participated by completing a survey. Median age at diagnosis 1981 to 2017 was 6 (range 0-17) and at study 28 (19-40) years. There were two indicators of POI, induced puberty reported in 5.3% and estrogen replacement therapy (ERT) in 9.3% at assessment. In separate logistic regression analyses (P < .001), induced puberty and ERT were significantly predicted by hematopoietic stem cell transplantation (HSCT), abdominal irradiation, central nervous system irradiation and chemotherapy. ERT was also associated with older age at diagnosis. Of the 626 women (48% of responders) who had tried to become pregnant, 25% had undergone fertility investigations and 72% reported having a biological child. Treatment with HSCT was associated with 5.4 times the odds of needing fertility investigations (P < .001). Having a biological child was associated with non-HSCT treatment, but also with ever having had a partner and older age at the time of study (all P < .001). In conclusion, the majority of those female childhood cancer survivors who had tried to conceive were able to successfully give birth. However, a small identifiable group of female survivors are at risk of subfertility and early menopause.

Asociación entre el tratamiento hormonal y los eventos clínicos tempranos en mujeres con disección coronaria espontánea / Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection

Introducción y objetivos Los cambios hormonales se reconocen como un factor desencadenante de la disección coronaria espontánea (DCE). Sin embargo, se desconoce si la exposición al tratamiento con hormonas exógenas (TH) en el momento del diagnóstico tiene algún impacto clínico. Se estudió en mujeres con DCE la asociación entre la TH y los eventos clínicos a corto plazo. Método Se incluyó a mujeres con DCE del registro DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish). Se identificó a las mujeres en TH (estrógenos, progestágenos o gonadotropinas) al momento del diagnóstico y se comparó sus resultados a corto plazo con aquellas sin TH activa. El evento compuesto medido fue infarto de miocardio no fatal o intervención coronaria percutánea no planificada durante los primeros 28 días después del cateterismo índice. Resultados De 224 mujeres que sufrieron una DCE (media de edad, 52,0±10,0 años), 39 (17,4%) estaban en TH y 185 (82,6%) no. No se observaron diferencias significativas entre ambos grupos en la demografía, la presentación clínica, las características angiográficas o el tratamiento inicial. Todas las pacientes en TH sistémico (n=36, 92%) lo suspendieron al diagnóstico. El evento compuesto se produjo en 7 pacientes (17,9%) con TH en comparación con 14 (7,6%) sin TH (p=0,039). Tras un ajuste multivariable, el TH se mantuvo asociado con el evento compuesto registrado en los primeros 28 días de seguimiento (HR=3,53; IC95%, 1,30-9,61; p=0,013). Conclusiones En mujeres con DCE, la exposición al TH en el momento de la presentación clínica se asoció con eventos cardiovasculares recurrentes a corto plazo, como infarto de miocardio no fatal o revascularización percutánea no planificada (AU)

Introduction and objectives Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. Methods We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. Results of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). Conclusions In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization (AU)

Family building after diagnosis of premature ovarian insufficiency: a cross-sectional survey in 324 women.

OBJECTIVE: The diagnosis of premature ovarian insufficiency (POI) is a traumatic event for many patients that involves poor fertility prognosis. After such diagnosis, spontaneous pregnancies are rare. The alternatives for building a family are oocyte donation, embryo donation, and adoption. However, we have few information on how many women with POI finally built a family after the diagnosis and which alternative they chose. DESIGN: We performed a cross-sectional, descriptive study. METHODS: We conducted a survey of all the women who consulted for POI in the department of endocrinology and reproductive medicine at la Pitié Salpêtrière between May 31, 1991, and January 12, 2021. We included patients who continued to be followed up regularly by our department or were contacted by mail or phone between June and September 2021. We excluded patients with Turner syndrome and POI secondary to oncological treatment and patients under 18 at the time of the survey. RESULTS: 985 patients were referred to the department for POI, and 324 patients were finally analyzed. 41% of the women who wanted to build a family had children after the diagnosis: 53.9% by oocyte donation, 1 woman by embryo donation, 5.6% after ovarian stimulation, 13.5% by adoption, and 25.8% who had spontaneous pregnancy after a mean time of 2.5 years. Spontaneous pregnancy rate was 8.6% in the whole cohort. CONCLUSIONS: Having children after a diagnosis of POI is not uncommon but more often results from oocyte donation. This study will provide enlightened information for newly diagnosed women on the possibilities to build a family after POI diagnosis.

Cardio-Metabolic Health and HRT in Menopause: Novel Insights in Mitochondrial Biogenesis and RAAS.

Recent evidence shows the cardiometabolic effects of estrogen administration in postmenopausal women. Women have a cardiometabolic advantage during their reproductive years, which is lost at menopause due to declining estradiol (E2). E2, also known as 17-beta-estradiol, has diverse effects in its target tissues, including the cardiovascular (CV) system, through genomic and non-genomic signaling. Metabolic changes characteristic of menopause include a worsening lipid profile, changes in body fat distribution, epicardial and pericardial fat deposition, increased susceptibility to weight gain, and increased blood pressure, resulting in an increased risk of accelerated cardiovascular disease (CVD) development. E2 mediates its cardioprotective actions by increasing mitochondrial biogenesis, angiogenesis, and vasodilation, decreasing reactive oxygen species (ROS) and oxidative stress, and modulating the renin-angiotensin-aldosterone system (RAAS). In this review, we assess whether it is prudent to develop an approach to managing postmenopausal women based on modifying the patient's CV risk that includes human-identical hormone replacement therapy (HRT), modulation of RAAS, and stimulating mitochondrial biogenesis. Further research is needed to assess the safety and benefit of HRT to reduce cardiometabolic risk.

Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection.

INTRODUCTION AND OBJECTIVES: Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. METHODS: We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. RESULTS: Of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). CONCLUSIONS: In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization.