Hormone Replacement Therapy Research Articles (Page 1)

Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS.

Additional progesterone administration during the luteal phase enhances reproductive outcomes in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles in patients with low serum progesterone (P4). In this study we wanted to explore the use of urine P4 as a diagnostic tool during the luteal phase. This prospective observational cohort included a total of 464 HRT-FET cycles. The protocol entailed oral oestradiol (6 mg/24 h), followed by vaginal micronised progesterone (400 mg/12 h). On the day of blastocyst transfer, urine and serum samples were collected. Urine samples were analysed using an ARCHITECT automated immunoassay. A significant difference was found in median urine P4 between patients with serum P4 higher or lower than 11 ng/mL: 6400 ng/mL IQR [2528; 11,930] vs. 3408 ng/mL IQR [592; 6688], p < 0.001. The optimal cut-off to achieve live birth was a urine P4 ≥ 4000 ng/mL. The live birth rate was significantly higher in patients with urine P4 ≥ 4000 ng/mL, 48% (107/222) vs. 35% (45/130), respectively (p = 0.013). The odds ratio for live birth was 1.8 in patients with urine P4 ≥ 4000 ng/mL, 95% CI [1.067; 3.018], p = 0.028. The findings of the present study suggest that urine progesterone could be a valuable diagnostic tool to evaluate the need for additional progesterone in HRT-FET cycles.

Menopause often triggers a variety of physiological and psychological discomforts such as hot flashes, anxiety, insomnia, and mood swings, significantly impacting women's quality of life. Many women seek natural alternatives to hormone replacement therapy, leading to increased interest in aromatherapy and essential oils as complementary treatments. This study aimed to analyze and synthesize scientific evidence regarding the effectiveness of aromatherapy and essential oils in alleviating menopausal symptoms. Using a literature review method, this study systematically reviewed studies published between 2000 and 2025 through databases including PubMed, ScienceDirect, Scopus, and Google Scholar. The results revealed that essential oils, particularly lavender, clary sage, peppermint, and geranium, show significant potential in improving emotional stability, sleep quality, and vasomotor regulation. Thematic content analysis demonstrated that aromatherapy influences mood and hormonal balance through neurochemical and physiological mechanisms related to the limbic system and endocrine function. Despite variations in methodology, the findings consistently support aromatherapy as a safe, non-invasive, and effective complementary therapy for menopausal women. This study contributes to holistic healthcare by strengthening the integration of evidence-based aromatherapy into women's health strategies while emphasizing the need for further standardized, long-term clinical trials.

Background: Hormone replacement therapy (HRT) is commonly prescribed to alleviate menopausal symptoms, but its cardiovascular safety—especially its impact on arrhythmias and acute heart failure hospitalizations—remains debated. This study primarily evaluated the association of HRT use with arrhythmia risk, and secondarily with acute heart failure hospitalizations, in menopausal women. Methods: This retrospective study utilized TriNetX, a federated health research network including data from 91 healthcare organizations across the U.S. Two cohorts were defined: menopausal women with HRT use and those without HRT. Propensity score matching (1:1) was performed on age and sex to balance baseline characteristics. Outcomes assessed included atrial fibrillation (AF), atrial flutter, ventricular tachycardia (VTach), supraventricular tachycardia (SVT), and acute heart failure hospitalizations, evaluated up to 3 years after cohort entry. Statistical analyses included risk differences, odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). A p-value <0.05 was considered significant. Results: After matching, 172,086 patients (86,043 per group) were analyzed. HRT use was associated with significantly higher risks of AF (risk difference 0.018, 95% CI [0.016, 0.019], HR 2.74, 95% CI [2.55, 2.95]), atrial flutter (risk difference 0.002, 95% CI [0.001, 0.002], HR 2.79, 95% CI [2.16, 3.60]), VTach (risk difference 0.004, 95% CI [0.003, 0.004], HR 2.04, 95% CI [1.79, 2.32]), and SVT (risk difference 0.014, 95% CI [0.013, 0.016], HR 2.33, 95% CI [2.17, 2.51]), all p<0.001. Additionally, HRT use was associated with a higher risk of acute heart failure hospitalization (risk difference 0.003, 95% CI [0.003, 0.004], HR 2.19, 95% CI [1.90, 2.54], p<0.001). Survival probabilities at the end of follow-up were consistently lower in the HRT group across all outcomes. Conclusions: In this large, propensity-matched cohort study, HRT use in menopausal women was associated with a significantly increased risk of arrhythmias and acute heart failure hospitalizations. The elevated HRs highlight the potential impact of HRT on cardiac electrophysiology and heart failure risk. These findings underscore the need for careful risk-benefit discussions when considering HRT, particularly in women with underlying cardiovascular risk factors. Further research should focus on understanding the mechanisms driving these and identifying subgroups at highrisk for personalized decision-making.

Background: Heart failure with mildly reduced ejection fraction (HFmrEF), defined by a left ventricular ejection fraction (LVEF) of 41–49%, is a transitional state between preserved (HFpEF) and reduced (HFrEF) ejection fractions. Postmenopausal women are disproportionately affected, likely due to reduced cardioprotective estrogen. The impact of hormone replacement therapy (HRT) on HFmrEF remains ambiguous. Objective: To assess the effects of HRT on clinical outcomes, cardiac remodeling, and use of guideline-directed medical therapy (GDMT) in postmenopausal women with HFmrEF. Methods: A PRISMA-guided literature review was conducted across PubMed, Embase, Cochrane, Scopus, and SciSpace. Twenty studies—including systematic reviews, meta-analyses, and observational cohorts—met inclusion criteria, focusing on postmenopausal women aged 45–65 with heart failure. Due to limited HFmrEF-specific data, findings from HFrEF populations were included due to historical classification overlap. Primary outcomes included echocardiographic parameters, natriuretic peptides, hospitalizations, and GDMT use. Due to heterogeneity across studies, a narrative synthesis approach was used. Results: A meta-analysis of 25,047 women found no significant association between HRT and incident heart failure. However, in women with existing HF, HRT was linked to a 35% reduction in all-cause mortality (RR 0.65; 95% CI, 0.49–0.87; p = 0.003). Transdermal estradiol improved diastolic function, reducing E/e′ ratios and left atrial volume index. Conversely, a systematic review reported no significant effect on first HF hospitalization (RR 1.02; 95% CI, 0.94–1.10), suggesting limited preventative value. A meta-analysis of 33 trials (n = 44,639) found no mortality reduction overall, although early HRT use improved endothelial function. Women with HFmrEF or HFrEF were 23% less likely than men to receive GDMT (HR 0.77; 95% CI, 0.71–0.83), especially RAS inhibitors and β-blockers. Estrogen may enhance RAS inhibitor efficacy via nitric oxide and aldosterone modulation, though caution is advised due to potential hypotension and hyperkalemia. Conclusion: Transdermal HRT, particularly estradiol, may provide structural and clinical benefits for postmenopausal women with HFmrEF. Underuse of GDMT in this group highlights a persistent care gap. Further sex-specific research is needed to clarify HRT's role and optimize outcomes in women with HFmrEF.

Introduction: Artificial intelligence–enhanced electrocardiography (AI-ECG) models can accurately predict sex, and sex misclassification is associated with adverse cardiovascular (CV) outcomes and more male-like cardiac (e.g. greater left ventricular mass and chamber volumes) and non-cardiac phenotypes (e.g. higher muscle mass, lower body fat) in women. However, the underlying factors contributing to sex discordance besides traditional CV risk factors—such as sex-specific CV risk factors—remain unexplored. Objective: To evaluate whether elevated AI-ECG sex-discordance scores are associated with sex-specific risk factors in women, while accounting for social determinants of health (SDoH). Methods: In the community-based ELSA-Brasil cohort baseline (2008-2010), we evaluated whether sex-discordance scores in women—measured by an AI-ECG model—were associated with female-specific CV risk factors: early menarche (≤11 years), menopause status, non-spontaneous menopause, multiparity, infertility, polycystic ovary syndrome, hormone replacement therapy >60 years or >10 years post-menopause, menstrual cycle length, history of abortion, hormonal contraceptives, history of eclampsia, and pregnancy weight gain >30 kg. The sex-discordant score (absolute difference between AI-predicted and self-reported sex, with 0=men, 1=women) was treated as a continuous variable. Associations were tested using multivariable robust linear regression with an M-estimator at 95% efficiency, adjusted for age, race, education, and per capita income. Results: Among 13,730 participants (mean age=52 years,SD:9.1; 54% women; 45% Black), higher sex-discordance scores were significantly associated with menopause (β = 0.092; 95%CI: 0.025–0.159), hormone and chemotherapy induced menopause (β = 0.215; 95%CI: 0.007–0.423), and multiparity (≥4 live births) (β = 0.169; 95%CI: 0.086–0.252), history of eclampsia (β = 0.157; 95%CI: 0.052–0.260), pregnancy-related weight gain >30 kg (β = 0.234; 95% CI: 0.117–0.352), early menarche (β = 0.154; 95% CI: 0.073–0.235), and use of hormonal contraceptives (β = 0.104; 95%CI: 0.002–0.207). All associations remained significant after adjustment for SDoH (Table 1). Conclusions: Higher AI-ECG sex-discordance scores are associated with multiple female-specific CV risk factors. These findings suggest that the score may serve as a novel biomarker for identifying women at increased CV risk.

Health Implications of Inadequate Follow-Up for Women on Hormone Replacement Therapy in Primary Care: A Questionnaire-Based Cross-Sectional Study

Background Adrenal crisis, characterized by acute cortisol deficiency, is a rare, life-threatening condition that can precipitate cardiovascular collapse and heart failure (HF). Its role in HF with preserved ejection fraction (HFpEF) is underrecognized, particularly in cancer patients receiving therapies that impair adrenal function. This case series examines the clinical features, management, and outcomes of HFpEF induced by adrenal crisis, emphasizing early diagnosis and treatment. Methods We retrospectively analyzed four patients diagnosed with HFpEF secondary to adrenal crisis between January 2022 and January 2025 at Qingdao Central Hospital and Qingdao Municipal Hospital. Inclusion criteria included clinical evidence of adrenal crisis (low cortisol, hypotension, steroid responsiveness) and echocardiographic confirmation of HFpEF (EF ≥50%). Data on demographics, clinical presentation, laboratory findings, echocardiography, and outcomes were analyzed descriptively. Results The cohort comprised three males and one female (aged 41–77 years), all with HFpEF (EF 50%–60%). Two presented with myocardial infarction (one NSTEMI, one STEMI), and two had malignancy with adrenal metastasis (renal, lung). Three exhibited hypotension. Initial BNP levels ranged from 518.93–619.13 pg/mL, decreasing to 108.06–287.63 pg/mL pre-discharge after hormone replacement therapy and HF management. Mean EF improved by 1.75% (range: 0%–3%) at one-month follow-up, with BNP further declining to 20.36–177.24 pg/mL. All patients achieved symptom resolution with no recurrence reported. Conclusion Adrenal crisis is a rare, reversible etiology of HFpEF in patients with diverse underlying conditions, potentially including those with cancer-related adrenal dysfunction or prior therapies. Prompt steroid therapy appears to improve cardiac function and outcomes, suggesting a need for heightened awareness and consideration of adrenal screening in at-risk populations, such as those with malignancy, tuberculosis, or other causes of adrenal insufficiency. Larger studies are needed to confirm these preliminary findings and establish the prevalence of this etiology across different subpopulations.

Chronic pelvic pain syndrome (CPPS) in women is a debilitating condition with a high prevalence (5-25%), yet its etiology remains unclear. This prospective observational study aimed to identify clinical and medical history covariates associated with CPPS to elucidate potential pathophysiological mechanisms. A total of 225 women were evaluated in a gynecological pain clinic in Germany, including 41 patients with CPPS (≥ 6months of lower abdominal pain) and 184 control patients undergoing routine gynecological screening. Exclusion criteria included pregnancy, pelvic malignancy, acute pelvic inflammation, and abnormal uterine bleeding. Covariates were assessed through structured clinical history and physical examination. Significant associations with CPPS were observed for prior pelvic surgery (72% vs. 45%, p = 0.003), bowel constipation (37% vs. 11%, p = 0.002), history of endometriosis (33% vs. 10%, p = 0.043), and prior trauma (27% vs. 11%, p = 0.013). In contrast, there were no significant differences in rates of depression (p = 0.376), use of psychopharmaceuticals (p = 0.757), pelvic floor abnormalities (p = 0.503), uterine retroversion (p = 0.330), or pelvic congestion (p = 0.455). Dysmenorrhea (59% vs. 42%) and vulvar pain (31% vs. 8%) were more frequent in the CPPS group, though not statistically significant. No differences were found in delivery mode, use of intrauterine devices, analgesics, hormonal replacement therapy, and other medications, or comorbidities such as diabetes, thyroid disease, hypertension, other pain diseases, or musculoskeletal disorders. CPPS was not associated with several commonly suspected cofactors, including psychosomatic factors, pelvic congestion, or pelvic floor dysfunction. The findings suggest the existence of two subgroups of CPPS, the endometriosis-associated type and the neurovegetative type, associated with prior pelvic surgery, constipation, and trauma. This concept allows for the development of new targeted therapeutic strategies to successfully treat CPPS.

Female reproductive factors and metabolic dysfunction-associated steatotic liver disease: an integrated analysis of population cohort, liver imaging, and genetic data.

Serum levels of leucine-rich α-2 glycoprotein 1 (LRG1), pro-neurotensin (PNT), fatty acid-binding protein 4 (FABP4) and furin in pediatric growth hormone deficiency before and after 1-year growth hormone replacement therapy.

Characterization of Crinone®: progesterone vaginal gel.

Hormone Replacement Therapy (HRT) remains underutilised and under-researched in low- and middle-income countries (LMICs), despite its potential to alleviate menopausal symptoms. This study explored pharmacists’ perspectives on the use, cost, and availability of HRT across six LMICs. A cross-sectional survey was conducted from January 1 to March 31, 2025, as part of the Global Menopause Project. Pharmacists working in community, hospital, and private sector settings in Malaysia, Sri Lanka, Nepal, Nigeria, Ghana, and Tanzania were recruited. Participants completed an anonymous online questionnaire. The questionnaire was piloted prior to dissemination, assessed HRT availability, pricing, and perceived barriers to use. A total of 331 pharmacists responded: Ghana (18·4%), Sri Lanka (17·5%), Tanzania (16·9%), Nepal (16·6%), Malaysia (15·4%), and Nigeria (15·1%). The respondents were almost equally distributed between sexes (50·8% were female), and most were aged 26–35 years (49·0%). The majority worked in private community pharmacies (41·7%) or government hospitals (32·6%), and 57·4% were based in urban areas. From the sample, 68·9% of pharmacists reported that HRTs were available for dispensing in their respective countries (highest proportion was reported in Nepal, 92·7% and lowest in Nigeria, 42%). HRT costs varied widely, with Sri Lanka reporting the highest prices and Malaysia the lowest. Key barriers identified included low health literacy, economic constraints, and limited healthcare access. Significant disparities exist in HRT access, availability and affordability across LMICs, with urban-rural gaps further compounding inequities. Pharmacists’ insights underscore the urgent need for inclusive, equitable strategies in menopausal care and women’s health policy in resource-limited settings.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-18083-x.

Multiple endocrine neoplasia type 2A (MEN 2A) is a rare autosomal dominant disorder characterized by the co-existence of medullary thyroid carcinoma (MTC), pheochromocytoma, and, less commonly, primary hyperparathyroidism. Here we present a case of a 43-year-old female who presented with recurrent hyperadrenergic spells along with sustained hypertension, bilateral loin pain, and unintentional weight loss for 1 year. Physical examination revealed thyromegaly and hyperpigmented patches in the interscapular region. Laboratory investigations showed elevated 24-hour urinary fractionated metanephrine, raised serum calcitonin and carcinoembryonic antigen, along with a normal serum calcium profile. A CT scan of the adrenal gland was suggestive of bilateral adrenal pheochromocytoma. Ultrasound of the thyroid gland demonstrated bilateral neoplastic nodules in both lobes of the thyroid gland. A provisional diagnosis of MEN 2A was made. Bilateral adrenalectomy was done, followed by total thyroidectomy with prophylactic central lymph node dissection. Her postoperative evolution was favourable. She is currently maintained on appropriate hormone replacement therapy. Genetic counseling was done, and family screening was advised. This case highlights the importance of early detection and timely surgical intervention in MEN 2A, which are pivotal for improving outcomes and enabling preventive family screening. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S55]

BackgroundManaging donors after brain death (DBD) is a complex task, but intensivists are believed to play a crucial role in optimizing organ perfusion to enhance organ procurement. This survey aims to gather important data on the practical management of DBD in Italy and to identify areas for potential improvement.MethodsThis national survey was conducted online and distributed to all members of the Italian Society of Anesthesia, Analgesia, and Intensive Care (SIAARTI). The questionnaire consisted of 30 questions covering aspects such as the respondents' region of work, level of experience, and workplace characteristics. Clinical questions focused on hemodynamic monitoring and management in the ICU, fluid therapy, mechanical ventilation practices, nutritional habits, and management of endocrine disorders. Additionally, the survey examined practices during the brain death determination process and the organizational procedures involved in organ procurement in the operating room. The data collected were analyzed using descriptive statistics to provide a comprehensive overview of the current practices in DBD management in Italy.ResultsFrom May 4 to August 30, 2024, 364 valid responses have been considered. 63% of respondents reported that they have written guidelines or diagnostic and therapeutic care pathways (PDTA) for DBD, while 34.5% indicated that such pathways do not exist. Nearly 49% of the respondents rely exclusively on standard hemodynamic monitoring techniques. By contrast, 42% incorporate cardiac ultrasound along with both basic and advanced invasive hemodynamic monitoring methods. Norepinephrine was chosen as the preferred treatment by 64.5% of participants. 58% of respondents used balanced crystalloids, while both normal saline and human albumin were used by 20% of them. Most participants implemented protective mechanical ventilation strategies (tidal volume ≤ 6 mL/kg and PEEP ≤ 10cmH2O). Nutrition practices varied significantly among respondents. Additionally, 41% reported that they almost always administered hormonal replacement therapy, while 38% used it only in case of hemodynamic instability. In the assessment of brain death, 43% of physicians performed an apnea test using continuous positive airway pressure without disconnecting the ventilation circuit. The most commonly administered medications during surgery included neuromuscular blocking agents (43%), opioids (42%), inhaled anesthetics (25.5%), propofol (11.5%), and none of the above (3.8% ).ConclusionsThis survey reflects the current practices of SIAARTI members when managing DBD. It highlights several areas for improvement, particularly the need for written guidelines and PDTA to be readily accessible at every procurement site. Additionally, while protective mechanical ventilation is generally well understood, there is considerable variability in hemodynamic management, fluid strategies, and hormone replacement therapy (HRT). This emphasizes the importance of enhancing education and conducting more targeted research in these critical areas.Trial registrationNot applicable.Supplementary InformationThe online version contains supplementary material available at 10.1186/s44158-025-00292-5.

Objectives Menopausal Hormone Replacement Therapy (MHT) is widely used by peri- and post-menopausal women to alleviate menopause-related symptoms and preventing bone loss, but the underlying mechanisms remain inadequately elucidated. Accumulating evidence suggested that gut microbiota was involved in the regulation of bone metabolic processes. The aim of this study was to characterize the alterations in gut microbiota profiles by MHT treatment in postmenopausal women and explore the relationship between gut microbiota and bone metabolism. Methods Fecal samples collected from a total of 31 postmenopausal women with or without MHT were subjected to 16S ribosomal RNA (rRNA) gene sequencing and short-chain fatty acid (SCFAs) analysis in this study. The serum levels of bone metabolic markers were determined via chemiluminescent immunoassays. Spearman correlation coefficient was utilizes to assess the correlation between genera and bone metabolism indexes. Results Postmenopausal women undergoing MHT exhibited lower serum procollagen type I N propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1). Significant differences in alpha diversity and beta diversity were observed in the microbial compositions between two groups ( P < 0.05). Of the total 295 microbial taxa identified, 16 taxa displayed significant differential abundance, with Coprococcus, Eubacterium_ruminantium_group, Lachnospiraceae_UCG-010 being more enriched in MHT+, correlating with lower bone metabolic markers and higher estrogen level. Conversely, Escherichia-Shigella taxa was more abundant in MHT- group, positively correlating with high bone metabolic markers and lower estrogen level. SCFAs appeared to have a limited role in bone metabolism but were found to be associated with several genera, including Coprococcus, Adlercreutzia, Colidextribacter. Conclusions The findings of the study demonstrated that MHT has the potential to prevent osteoporosis through the alteration of the gut microbial composition in postmenopausal women and identified promising microbial taxonomic that may contribute to the protective effects of MHT on bone mass conservation. Comparing with most previous studies that focused on the gut microbiota profiles between individuals with different bone mass, our study emphasized the protective role of gut microbiota in MHT process while bone mineral content (BMC) has no significant difference.

Abstract Disclosure: A. Rothstein Costris: None. F. Manas: None. J. Patton: None. S.D. Rao: None. Introduction: Hormone replacement therapy (HRT) is currently approved only for the prevention of osteoporosis in postmenopausal women based on Women's Health Initiative (WHI) Trial results. Prior to 1995, HRT was the only effective therapy for prevention and treatment of OP. HRT has been shown to prevent post-menopausal bone loss, increase bone density, and reduce the risk of OP fractures. Thus, HRT can be an effective alternative therapy in selected patients, especially in the 10-15 years after menopause onset. Case presentation: We present the case of an 83y woman who has been on low-dose HRT (0.45 mg/1.5mg) with conjugated estrogen and medroxyprogesterone acetate for OP management for at least 20 years. She was unable to tolerate bisphosphonates and raloxifene due to side effects and hence preferred to continue HRT. She has been closely monitored with regular follow-ups. Due to the risks associated with prolonged HRT, an attempt to discontinue therapy was associated with vaginal dryness, dyspareunia, hot flashes and mood instability. Additionally, her CTX (ref. range 104-1,008 pg/mL) levels rose from 134 pg/mL to 575 pg/mL, indicating increase bone turnover. After further thorough discussion of the risks and benefits, a shared decision was made to continue HRT, reflecting the patient’s strong preference to maintain the therapy. Fortunately, she did not experience any complications besides occasional spotting. Never had blood clots, stroke, breast cancer, or heart attack. While on HRT, her bone density was well preserved and stable in the osteopenic range both at the lumbar spine and femoral neck. During her long-term treatment, she maintained a healthy intake of calcium and vitamin D, and regularly received mammograms and Pap smears as part of her routine care. Conclusions: The use of HRT beyond age 65 carries implications that depend on factors such as the type of therapy, the route of administration, and the dosage. Lower doses are generally associated with a reduced risk profile compared to medium or high doses, while vaginal or transdermal forms are often favored over oral preparations. Decisions about HRT should take into account the patient’s overall health, life expectancy, personal preferences, and symptom severity. Ongoing evaluations and collaborative decision-making are essential to ensure the therapy continues to be suitable and beneficial for the specific group of women who either cannot tolerate or prefer not to use bisphosphonates. Presentation: Saturday, July 12, 2025

Disclosure: H. Hodis: None. C. Dominguez-Bali: None. E.S. Johnson: None. H.A. Goraya: None. M.A. Syed: None. W.K. Massah: None. K. McCoy: None. M.A. Bencomo: None. E.S. Tsehaye: None. R. Polam: None. A. Dominguez-Bali: None.In our 2 medical centers, more than 50% of postmenopausal (PMP) women seeking care for their symptoms exceed the typical 10 year window protocol for the initiation of Hormonal Replacement Therapy (HRT) under current guidelines. To address this gap, we develop the protocol to treat a significant subset of these affected women with HRT beyond the 10 years window protocol. The purpose of this study is the evaluation of the utilization and safety of late HRT in symptomatic or asymptomatic PMP women using coronary calcium score (CCS). This retrospective analysis examines clinical outcomes for more than 100 patients (108) over the past 8 years. Women with a CCS of zero were eligible for full systemic HRT. With close follow up, considering individual comorbidities, preferences and responses, women with CCS above 50 were given local treatments, vaginal estradiol and testosterone without systemic HRT (vaginal estradiol and levonorgestrel transdermal patch) and patient outcomes were assessed using standardized questionnaires documenting symptom relief, hormone response, personal satisfaction and quality of life. Preliminary findings suggests that woman with a CCS of 0 experience symptom relief and therapeutic responses comparable to those initiating HRT within the recommended 10 year window protocol. Up to now, we have confirmed that CCS provides flexible treatment options. This study indicates that a significant number of late PMP women that go under the 10 year window protocol or are more than 60 years of age with a CCS of 0 can benefit from the delayed HRT achieving outcomes similar to early initiators of HRT. More studies need to be done that confirm that offering HRT in late menopause could be as secured and beneficial as those initiated in early menopause.Presentation: Monday, July 14, 2025

Disclosure: I. Murta: None. J. Bicca: None. N. Cardoso: None.Background: Endometriosis is an estrogen-dependent clinical syndrome traditionally regarded as a premenopausal condition that tends to regress after menopause. Contrary to this assumption, it can affect up to 4% of postmenopausal women. Hormone replacement therapy (HRT) in this population is challenging due to the potential reactivation of endometriotic lesions, reported in 16-22% of women aged 49-55 and a 1% risk of malignant transformation in those receiving combined HRT. Estrogen deprivation is often preferred out of concern for these complications, raising issues related to bone, cardiovascular, and metabolic health. The efficacy of HRT in this context depends on the dose, route of estrogen administration, and the type, metabolism, and progestogenic potency of the progestin used for symptom control. Clinical Case: A 54-year-old woman, SF, with no prior diagnosis of endometriosis but a long-standing history of deep dyspareunia, started presenting with hot flashes at age 47, followed by persistent pelvic pain and menorrhagia. Bone densitometry revealed osteopenia. Pelvic MRI with bowel preparation identified deep infiltrating endometriosis. Initial treatment with conventional oral progestin therapy failed to alleviate pelvic pain. She underwent surgical intervention, followed by oral progestin therapy, again with no clinical improvement. She started GnRH analog therapy with Goserelin (Zoladex), but experienced worsening vasomotor symptoms and vaginal atrophy, making the treatment poorly tolerated. After multiple failed approaches, the patient began treatment with a novel progestin (R2323) combined with low-dose transdermal estradiol (50 mcg, three times per week), which led to complete resolution of clinical symptoms and improved bone mineral density after two years of HRT. Conclusion: Although oral progestins are considered first-line therapy for endometriosis, they have a reported failure rate of 33%. GnRH agonists serve as an alternative but often induce hypoestrogenic side effects such as vasomotor symptoms and concerns regarding bone loss, particularly in menopausal patients. In this case, the progestin demonstrated antiestrogenic and antiprogestogenic activity with mild androgenic potential. Its therapeutic use led to a modest increase in bone mineral density, possibly due to this androgenic effect. Some evidence suggests that bone receptors may respond differently to this progestin's antiestrogenic action. The addition of low-dose estrogen supported metabolic and cardiovascular health. Combined HRT in patients with endometriosis should be assessed individually, considering dose, route, and type of progestin. Clinical guidelines and further clinical evidence are still needed to support decision-making regarding HRT in this population.Presentation: Monday, July 14, 2025

Abstract Disclosure: Z. Flores-Guerrero: None. O.A. Velasco-Espinosa: None. F. Martinez-Sanchez: None. F.J. Gomez-Perez: None. D. Cuevas-Ramos: None. Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of cells of the mononuclear phagocytic system. It is predominantly diagnosed in childhood (∼3 years), with 30% of cases occurring in adults. Its incidence in patients older than 15 years is 1-2 cases per million. Hypothalamic-pituitary region (HPR) infiltration occurs in 5-50% of cases, with arginine-vasopressin central deficiency (AVP-D) being the most common endocrine manifestation, reported in 15-50%.Here we present our case-series of patients with biopsy-confirmed LCH in any affected organ and clinical, biochemical, and/or radiological evidence of HPR infiltration. Demographic data, signs and symptoms, presentation, hormonal deficiencies, radiological findings, and treatments were analyzed. Continuous variables were described as medians with 25-75 percentiles, and categorical variables as frequencies.Nine patients (six men) were included, with a median follow-up of 2.4 years (1.5-5.7). Seven were diagnosed in childhood (2-5 years) and two in adulthood (27-30 years). The median age at diagnosis of HPR infiltration was 3 years (2-27). The most frequent symptoms were polydipsia-polyuria and skin lesions. All patients developed AVP-D; three had anterior pituitary deficiencies and one developed corticotropic insufficiency post-treatment. Skin (4/9) and bone (4/9) were the most affected organs. One patient had isolated pituitary involvement during recurrence. Five had pituitary involvement initially, none isolated. Although pituitary biopsies were not performed, HPR infiltration was confirmed by clinical, biochemical and therapeutic response criteria. One patient underwent a pituitary MRI, which showed hyperintensity and thickening of the infundibulum, hypothalamic involvement, and absence of the T1-sequence posterior lobe bright spot, typical findings of HPR infiltration. All patients received chemotherapy and hormonal replacement therapy (HRT); however, none recovered hormonal function. Follow-up MRIs in five cases showed resolution of the infiltration in four patients, with persistent but reduced involvement in one.HPR infiltration ​​secondary to LCH underlines the need to recognize this condition as a potential cause of pituitary dysfunction. It can occur at any stage of the disease, whether isolated or with multi-organ involvement. While AVP-D is the most frequent manifestation, present in all patients in this series, anterior pituitary deficiencies are also present in a significant number of cases (3/9), often overlooked due to lack of intentional investigation, particularly in adults. Despite the lack of hormonal recovery, it is crucial to assess all hormonal axes at diagnosis and follow-up, offering appropriate HRT in a timely manner. Although biopsy is the gold standard, diagnosis can be based on clinical, biochemical and radiological criteria. Presentation: Monday, July 14, 2025