Continuous Subcutaneous Delivery of rhPTH(1-84) and rhPTH(1-34) by Pump in Adults With Hypoparathyroidism.

Context: Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited. Case Descriptions: We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: -130 ± 222 mg/24 hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction. Conclusion: In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.

Effect of anti-Müllerian hormone on early pregnancy loss in hormone replacement therapy-frozen-thawed embryo transfer cycles: An analysis including 6597 pregnant patients undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycle.

OBJECTIVE: To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect. METHODS: A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 µg/L), group B (1-≤2 µg/L), group C (2-≤6 µg/L), and group D (>6 µg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in in vitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles. RESULTS: Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 µg/L. When the AMH concentration was less than 2.83 µg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 µg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383). CONCLUSION: For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 µg/L, the early pregnancy loss rate declined significantly with increasing AMH levels.

17ß-Estradiol protects female rats from bilateral oophorectomy-induced nonalcoholic fatty liver disease induced by improving linoleic acid metabolism alteration and gut microbiota disturbance.

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. Results: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. Conclusions: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Mid-luteal serum estradiol levels are associated with Live birth rates in Hormone Replacement Therapy Frozen Embryo Transfer (FET) cycles - a cohort study.

OBJECTIVE: To study whether mid-luteal serum estradiol (E2) levels are associated with the Live Birth Rate in Hormone Replacement Therapy FET cycles in patients with optimal mid-luteal serum progesterone (P4) levels. DESIGN: Observational prospective cohort study of 412 women having a Hormone Replacement Therapy FET single blastocyst transfer from January 2020 to November 2022. SUBJECTS: The Hormone Replacement Therapy FET priming regimen included oral estradiol (6mg/24h) administered in the evening, followed by vaginal progesterone (400mg/12h). Serum E2 and P4 levels were measured in a standardized manner, 2-4 hours after the latest progesterone administration and 9-14 hours after estradiol administration on the day of blastocyst transfer, day 6 of progesterone administration. Patients with serum P4 <11ng/mL (35nmol/l) on the day of transfer received additional rectal progesterone (400mg/12h). No additional estradiol was administered. MAIN OUTCOME MEASURES: The primary outcome was Live Birth Rate in relation to E2 levels at blastocyst transfer day. RESULTS: The optimal serum E2 range correlating with ongoing pregnancy was ≥292pg/ml <409pg/ml (≥1070pmol/l and <1500pmol/l). The Live Birth Rate was 59% (60/102) if E2 levels were within this range, whereas a significantly lower Live Birth Rate of 39% (101/260, p=0.001) was seen in patients if E2 levels were <292pg/ml (<1070pmol/l), and of 28% (14/50, p<0.001) if E2 levels were ≥409pg/ml (≥1500pg/mL). In a logistic regression analysis, adjusting for serum progesterone level ≥11ng/mL or <11ng/mL (≥35nmol or <35nmol/l) on the day of transfer, BMI, age at oocyte retrieval, day 5 or 6 vitrified blastocyst and blastocyst score, the adjusted risk difference (RD) of a live birth was -0.21 [-0.32; -0.10] when the E2 level was <292pg/mL (<1070pmol/l) and -0.31 [-0.45; -0.18] if the E2 level was ≥409pg/ml (≥1500pmol/l) compared to E2 levels ≥292pg/ml <409pg/ml (≥1070 <1500pmol/l). Importantly, only 25% of patents had optimal levels. CONCLUSION: The study shows a significant association between serum E2 levels and reproductive outcomes in a Hormone Replacement Therapy FET cohort in which optimal serum progesterone levels were secured. Mid-luteal serum E2 levels are associated with Live Birth Rate in Hormone Replacement Therapy FET cycles and E2 levels should neither be too high nor too low.

Hormone Replacement Therapy in Post-Menopause Hormone-Dependent Gynecological Cancer Patients: A Narrative Review.

BACKGROUND: Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause. METHODS: A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]). RESULTS: HRT can be prescribed to patients with early-stage, grade I-II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery. Caution should be exercised in administering HRT after serous borderline tumors and endometrioid OC, and HRT is not recommended in low-grade serous OC. HRT is not contraindicated in AC survivors. After surgery for EC, HRT can be prescribed in women with early-stage low-grade EC. There is not enough data to give indications to patients with advanced EC. CONCLUSIONS: HRT can be discussed with patients, evaluating the risks and benefits of hormone-dependent gynecological cancer. Counseling should be performed by gynecologic oncologists experienced in the management of these patients.

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences.

INTRODUCTION: Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. METHODS: In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. RESULTS: Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. DISCUSSION: Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.

Clinical Outcomes in Hormone Replacement Therapy (HRT)-Frozen Embryo Transfer (FET) Protocol Increased by Administering Gonadotropin-Releasing Hormone Agonist (GnRH) in the Initial Stage of the Luteal Phase: A Retrospective Analysis.

OBJECTIVE: The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH) administration supporting the luteal phase in frozen embryo transfer (FET) improves clinical outcomes Methods and materials This is a retrospective cohort study and we analyzed 3515 cycles of FET at the Department of Reproductive Medicine in our hospital from February 2018 through December 2021. Patients were divided into the GnRH (triptorelin+progesterone and human chorionic gonadotropin (hCG)) group and the non-GnRHa (existing treatment without triptorelin) group. There were 1033 and 2485 cases in the above groups, respectively. Live birth rates (LBR) and clinical pregnancy rates (CPR) were contrasted in the two groups. RESULTS: We found greater CPR (58.00% versus 48.40%, P-value = 0.003) and LBR (52.70% versus 45.60%, P-value = 0.001) for HRT-FET cycles, and found no clinical significance for natural cycle FET (NC-FET) (58.20% versus 52.90%, P-value = 0.364 and 54.40% versus 47.00%, P-value=0.211), GnRH+HRT-FET (53.00% versus 53.00%, P-value=0.176 and 46.20% versus 47.30%, P-value=0.794), and stimulation-FET (59.30% versus 52.90%, P-value=.00.566 and 59.30% versus 47.10%, P-value=.00.247) in terms of CPR and LBR in the two groups. There was a 47% increase in CPR in the GnRH group, and there was a 33% increase in LBR in the same group. CONCLUSION: During HRT-FET cycles, administering triptorelin three to four times in the existing luteal support can improve CPR and LBR, and administering triptorelin during the initial stage of the luteal phase can prove a new option for luteal support.

Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Introduction: Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. Methods: We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Results: Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. Discussion: These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

Is There a Special Role for Ovarian Hormones in the Pathogenesis of Lobular Carcinoma?

Lobular carcinoma represent the most common special histological subtype of breast cancer, with the majority classed as hormone receptor positive. Rates of invasive lobular carcinoma in postmenopausal women have been seen to increase globally, while other hormone receptor-positive breast cancers proportionally have not followed the same trend. This has been linked to exposure to exogenous ovarian hormones such as hormone replacement therapy. Reproductive factors resulting in increased lifetime exposure to endogenous ovarian hormones have also been linked to an increased risk of lobular breast cancer, and taken together, these data make a case for the role of ovarian hormones in the genesis and progression of the disease. In this review, we summarize current understanding of the epidemiological associations between ovarian hormones and lobular breast cancer and highlight mechanistic links that may underpin the etiology and biology.

The Association between Hormone Replacement Therapy and Gastroparesis in Post-Menopausal Women: A Worldwide Database Analysis.

Female sex hormones have been hypothesized to influence the higher prevalence of gastroparesis in females. This study investigated the effects of hormone replacement therapy (HRT) on gastroparesis and its related symptoms, medication use, and diagnostic testing in post-menopausal women. Utilizing the TriNetX platform, we conducted a population-based cohort study involving post-menopausal women aged 50 or older, with and without HRT. One-to-one propensity score matching was performed to adjust for age, race, ethnicity, diabetes, body mass index (BMI), and hemoglobin A1c. The exclusion criteria included functional dyspepsia, cyclic vomiting syndrome, and surgical procedures. After applying the exclusion criteria, we identified 78,192 post-menopausal women prescribed HRT and 1,604,822 not prescribed HRT. Post-propensity matching, each cohort comprised 67,874 patients. A total of 210 of the post-menopausal women prescribed HRT developed an ICD encounter diagnosis of gastroparesis at least 30 days after being prescribed HRT compared to post-menopausal women not prescribed HRT (OR = 1.23, 95% CI [1.01-1.51] p-value = 0.0395). These associations persisted in sensitivity analysis over 5 years (OR = 1.65, 95% CI [1.13-2.41] p-value = 0.0086). HRT was associated with increased GI symptoms, including early satiety (OR = 1.22, 95% CI [1.03-1.45] p-value = 0.0187), domperidone use (OR = 2.40, 95% CI [1.14-5.02] p-value = 0.0163), and undergoing gastric emptying studies (OR = 1.67, 95% CI [1.39-2.01] p-value < 0.0001). HRT is linked to an increased risk of developing an ICD encounter diagnosis of gastroparesis.

Frailty of Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Scoping Review.

PURPOSE: This study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT). MATERIALS AND METHODS: Database and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Four databases-PubMed, Cochrane Library, EMBASE, and CINAHL-were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches. RESULTS: A total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty. CONCLUSIONS: Further research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.

Association between menopausal hormone therapy and the risk of gastric cancer: A Korean nationwide population-based cohort study.

OBJECTIVE: Gastric cancer (GC) is more common in men than women, but also more common among postmenopausal than premenopausal women. The protective effect of reproductive hormones against GC remains unclear. Therefore, we evaluated the association between menopausal hormone therapy (MHT) and the risk of GC in women. METHODS: We investigated the national cohort data of women aged over 40 years who underwent health checkups by the Korean National Health Insurance Service in 2009. After excluding individuals with missing data and those previously diagnosed with cancer, 1,354,621 postmenopausal women were included and divided into groups according to their MHT history. We followed the study population until 2018 and analyzed the hazard ratios (HR) with 95 % confidence intervals (CIs) for the incidence rate of GC in a multivariate adjusted model. RESULTS: The number of women with and without a history of MHT was 214,723 (15.9 %) and 1,139,898 (84.1 %), respectively. During the mean 8.32 ± 0.8 years of follow-up, a total of 12,496 GC cases developed in the study population (10,962 MHT non-users; 1534 MHT users). In the adjusted model, MHT was associated with a 12 % decrease in the development of GC relative to non-use of MHT (HR 0.88; 95 % CI 0.83-0.93). Exposure to MHT for >2 years was linked to a reduction in GC risk, particularly when initiated before the age of 50, giving a 45 % risk reduction. CONCLUSIONS: According to our large-scale prospective national cohort study, exogenous MHT is associated with a decreased risk of GC in postmenopausal women.

Does hormone replacement therapy impact implant osseointegration in females- A systematic review and meta-analysis.

Background: This review aimed to comprehensively investigate the impact of Hormone Replacement Therapy (HRT) on implant osseointegration and bone loss. The study considered factors such as HRT type, osteoporosis, smoking, and diabetes mellitus, and analysed the available literature to provide insights into the association between HRT and implant outcomes. Methods: Multiple databases were utilized, and studies with diverse designs and methodologies were included that examined the relationship between HRT and implant osseointegration. The selected studies were analyzed and relevant data on implant success rates, bone loss, and other correlations was extracted. Results: The review findings indicate that HRT has a detrimental impact on implant osseointegration, as evidenced by lower implant success rates and increased bone loss in HRT-treated individuals. The odds ratio analysis further strengthens this association, with significant values of 0.59 (95% CI: 0.50-0.70) and 0.64 (95% CI: 0.54-0.76), indicating a higher likelihood of implant failure in HRT-treated patients., highlighting the need for caution when considering HRT as a treatment option in patients undergoing implant procedures. Smoking and diabetes mellitus were also found to significantly affect implant outcomes, emphasizing the importance of addressing these factors in patient management. Conclusion: The assessments demonstrate that HRT adversely affects implant osseointegration and increases bone loss. The results suggest the importance of considering the potential negative impact of HRT on implant outcomes and the need for thorough patient evaluation and management. Further research is warranted to explore the underlying mechanisms, assess the impact of specific HRT types and dosages, and evaluate preventive strategies to mitigate the detrimental effects of HRT on implant success.

Hormone replacement therapy and periodontitis progression in postmenopausal women: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. BACKGROUND: HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. METHODS: As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full-mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the gingival crevicular fluid were measured using enzyme-linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). RESULTS: In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL-6, and TNF-α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL-6, and TNF-α in the first year and with a decrease in CAL, SBI, BOP, IL-6, and ABH and an increase in BMD in the second year. CONCLUSIONS: In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss.

Hypogonadism and neurocognitive outcomes among childhood cancer survivors.

OBJECTIVE: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors. DESIGN: Cross-sectional study using retrospective cohort. METHODS: In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes. RESULTS: The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed. CONCLUSION: Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function.

A retrospective audit of general practitioner's referrals to Guys and St Thomas' specialist menopause clinic between 2021 and 2022.

Purpose: We performed a retrospective audit of General Practitioners' (GPs) referrals to the specialist Menopause Clinic at Guys and St Thomas's (GSTT) between 2021 and 2022. We aim to establish the indication for the referrals and whether they were compliant with the National Institute for Health and Care Excellence Guidance NICE.Background: GSTT is a teaching hospital in central London that educates gynaecologists in training as well as (GP) for specialist certification in Menopause. The menopause clinic receives approximately 580 GP referrals per month from South East London practices. The current waiting time for an initial appointment is up to 1 year. This delay reflects an increase in demand for menopause care and a deficit in service provision in many areas of the UK.NICE has recommended that GPs refer complicated cases to menopause specialists, with 11 specific criteria.Study Sample and Data Collection: We randomly selected 50 patients referred to the GSTT clinic by a GP between 2021 and 2022. Patient data were collected, including patient demographics, date of referral, indication for referral, date of consultation, waiting time, past medical history, investigations, and treatment instigated during the appointment.Results: The majority of referrals to the GSTT menopause Specialist clinic met the NICE guidelines (76%). One-sixth of the referrals could have been prevented or managed through alternative routes. Finally, although this is a small study, some patient unmet needs (PUNS) and GPs' educational needs have been identified.

Women at Altitude: Menstrual-Cycle Phase, Menopause, and Exogenous Progesterone Are Not Associated with Acute Mountain Sickness.

Gardner, Laurel, Linda E. Keyes, Caleb Phillips, Elan Small, Tejaswi Adhikari, Nathan Barott, Ken Zafren, Rony Maharjan, and James Marvel. Women at altitude: Menstrual-cycle phase, menopause, and exogenous progesterone are not associated with acute mountain sickness. High Alt Med Biol. 00:000-000, 2024. Background: Elevated progesterone levels in women may protect against acute mountain sickness (AMS). The impact of hormonal contraception (HC) on AMS is unknown. We examined the effect of natural and exogenous progesterone on the occurrence of AMS. Methods: We conducted a prospective observational convenience study of female trekkers in Lobuche (4,940 m) and Manang (3,519 m). We collected data on last menstrual period, use of exogenous hormones, and development of AMS. Results: There were 1,161 trekkers who met inclusion criteria, of whom 307 (26%) had AMS. There was no significant difference in occurrence of AMS between women in the follicular (28%) and the luteal (25%) phases of menstruation (p = 0.48). The proportion of premenopausal (25%) versus postmenopausal women (30%) with AMS did not differ (p = 0.33). The use of HC did not influence the occurrence of AMS (HC 23% vs. no HC 26%, p = 0.47), nor did hormonal replacement therapy (HRT) (HRT 11% vs. no HRT 31%, p = 0.13). Conclusion: We found no relationship between menstrual-cycle phase, menopausal status, or use of exogenous progesterone and the occurrence of AMS in trekkers and conclude that hormonal status is not a risk factor for AMS. Furthermore, women should not be excluded from future AMS studies based on hormonal status.