Estrogen Therapy Research Articles

THU554 Unconventional Estrogen Receptor Antagonists Reveal Cryptic Therapeutic Anti-breast Cancer Transcriptional Pathways

Abstract Disclosure: G. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: Advisory Board Member; Self; Olema Oncology. Grant Recipient; Self; Olema Oncology. Breast cancer is the most diagnosed cancer and 2nd leading cause of cancer-related death in women worldwide. The luminal subtype accounts for ∼70% of this heterogeneous disease. Standard of care for these estrogen receptor alpha (ERα) positive diseases includes 5 years of adjuvant endocrine therapy in the form of aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs). Despite therapeutic advances, approximately half of ERα+ patients develop resistance to these endocrine therapies. In this study, x-ray crystallography of SERMs and SERDs link structural characteristics to transcriptional activity in order to understand mechanisms of antiestrogen efficacy in ER+ drug resistant breast cancers. A new class of antiestrogen based on a tetrahydro-6-isoquinoline (T6I) scaffold was developed to antagonize ERα by adopting unique binding poses to inhibit coactivator binding to the ligand binding domain (LBD). Optimization of structure-activity relationships produced unique antiestrogenic activities and a lead compound that induces transcriptional programs similar to fulvestrant despite its SERM-like accumulation of ERα in the breast cancer cell. Like fulvestrant, this T6I uniquely induces the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to 17β-estradiol. Together, this study uses structurally unique antiestrogens to further the understanding of key functional components of estrogen therapies. Presentation: Thursday, June 15, 2023

FRI599 Quality Of Life In Girls With Turner Syndrome Using The Quality Of Life In Short Stature Youth Questionnaire (QoLISSY) - A Cross-sectional Study

Abstract Disclosure: N. Vijayakanthi: None. D.J. Marcus: None. S.P. Fritz: None. Y. Xiang: None. D.O. Fadoju: None. Background: Short Stature is a common finding in girls with Turner syndrome (TS). Its impact on Quality of life (QoL) in adolescents/adults with TS have been studied using generic QoL questionnaires. Short stature specific QoL questionnaires have not been used to study the impact of short stature and GH therapy in TS in previous studies. Methods: In this cross-sectional study, we aimed to evaluate QoL and the association between GH therapy and height on QoL of adolescents using the short stature specific questionnaire -Quality of Life in Short Stature Youth (QoLISSY). QoLISSY was designed specifically to assess QoL in short stature children with scales for both parents and children which assesses 3 core QOL dimensions: physical, social, emotional and 3 predictors of quality of life: Coping, Beliefs and Treatment (GH therapy). It has not been previously used in TS. Results: Of the 41 eligible patients, 37 patients were enrolled in the study. The mean age of our cohort was 16.3 ±1.3 years and the average final adult height was 145.03 ± 7.3 cm. About 70% of the patients received GH therapy and 80% received estrogen therapy. Compared to the reference short stature mean values, our TS cohort had comparable scores in all QoL subscales and total scores in both parent and patient reports apart from the parental report treatment subscale which was significantly lower than their respective reference short stature means [Mean ± SD: 47.43±27.13 vs 58.82±16.75; p=0.03]. Girls with height >-3SD had significantly lower score in the coping subscale, compared to the <-2SD height group [Mean ± SD: 42.14 ± 19.04 vs 62.25 ± 16.60; p= 0.024; multivariate analysis: p=0.012. In the parent report, the social subscale was significantly lower in the > -3SD height group compared to the <-2SD height group [Mean ± SD: 57.59 ± 22.25 vs 80.94 ± 11.26; p=0.022; multivariate analysis: p=0.024]. There was no statistically significant difference in the QOL between the GH vs no GH groups. Conclusion: We conclude that the QoL in girls with TS was comparable to the reference short stature population. GH therapy did not improve the QoL in girls with TS in our cohort. Height does not appear correlate with the overall QoL in girls with TS though they have some coping and social difficulties. We recommend psychological counseling and support for girls with TS especially to address their coping and social difficulties. Presentation: Friday, June 16, 2023

SAT403 Long-term Metabolic Effects Of Gonadotropin Releasing Hormone Agonist (GnRH) Therapy In Transgender Women Veterans

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. L. Gondin Hernandez: None. M. Mok: None. A. endoza: None. D. Tripathy: None. There is controversy regarding the effects of long-term GnRH agonist therapy on cardiovascular risk factors in older men with prostate cancer. GnRH agonists are used for gender affirming hormone therapy in adolescents and in adults who fail to suppress testosterone adequately. We examined the cardiometabolic effects of long-term GnRH agonist therapy in transwomen veterans. A retrospective chart review was performed on 74 transwomen veterans who were followed at the ALM VA Endocrinology clinic for at least 12 months and had detailed clinical, hormonal and biochemical profile (testosterone, estradiol, HbA1c, lipid profile) measured. Thirtytwo transwomen on GnRH agonist therapy (age 48 ± 2 yrs, BMI 28 ± 1 kg.m2) followed for 45 ± 5 months were compared with 22 transwomen (age 44 ± 3 yrs, BMI 28 ± 2 kg.m2) followed for 41 ± 7 months not on GnRH therapy. In the GnRH group, 14 were on oral E2, 12 on E2 patch and 6 were on E2 Injection. Similarly, in the non-GnRH group, the number of subjects on oral E2, E2 patch or E2 Injection were 17, 1, and 4 respectively. The average oral estrogen dose in both groups was 4 ± 0.4 mg. In the GnRH group, serum testosterone declined from 420 ± 36 ng/dl to 40 ± 5 ng/dL and serum estradiol before and after therapy was 39 ± 9 vs 89 ± 12 pg/mL. GnRH therapy led to increase in BMI (28 ± 1 vs 31 ± 2 kg.m2, p=0.006), though no difference was observed in SBP (126 ± 2 vs 120 ± 2 mmHg, p=ns), total Cholesterol (170 ± 7 vs 171 ± 8 mg/dL), HDL Cholesterol (45 ± 2 vs. 46 ± 2 mg/dL), LDL Cholesterol (98 ± 7 vs 99 ± 5 mg/dL) before and after treatment. There was no change in BMI (28 ± 2 vs 29 ± 1 kg.m2), SBP (121 ± 3 vs 125 ± 3, p=ns), total cholesterol (173 ± 5 vs. 170 ± 9 mg/dL), HDL chol (46 ± 2 vs. 49 ± 2 mg/dL), or LDL chol (97 ± 6 vs. 95 ± 7 mg/dL) in the control group. Plasma triglycerides increased in both the GnRH (134 ± 10 vs 168 ± 16 mg/dL, p<0.05) as well as in the control group (154 ± 30 vs 167 ± 20 mg/dL, p<0.05) after treatment. In conclusion, long-term estrogen therapy in transwomen increased plasma triglyceride. Concomitant GnRH agonist therapy was associated with greater weight gain, but did not affect other cardiovascular risk factors. Presentation: Saturday, June 17, 2023

SAT391 Supratherapeutic Estrogen Levels in Transgender Women Likely From Sublingual Estradiol

Abstract Disclosure: E. Jalal: None. C. Baldwin: None. Transgender medicine is typically managed in the outpatient setting. We report a case where the patient’s hospitalization provided unique insight into hormone management to achieve cis-female range estrogen and testosterone levels in a monitored environment.A 38-year-old transgender woman with HIV (on antiretroviral therapy) complicated by neurocognitive disorder, polysubstance use, mood disorder with previous suicidal ideation, and polytrauma (currently wheelchair bound) was admitted for respiratory failure from MRSA pneumonia. She completed 14 days of antibiotics with resolution of acute medical problems, but ability to secure a safe discharge plan prolonged her hospitalization. Endocrinology was consulted to aid in oral estradiol (E2) management.Prior to admission, patient reported taking 10mg of oral E2 daily. While hospitalized, she was given 6mg E2 daily, but requested resumption of her home dose. Initial total estrogen and testosterone levels were 913 pg/mL (56-213 pg/mL) and 105 ng/dL (264-916 ng/dL), respectively. She denied estrogen pellets, implants, or consumption of additional E2 beyond 6mg daily, nor did she have visitors who provided supplemental hormone; however, she admitted that she does not swallow the E2 pills immediately.Endocrinology initiated intramuscular leuprolide to suppress her total testosterone production to the female range of 0-50 ng/dL, allow for decreased dosing of E2 to maintain female range estrogen levels, and minimize venous thromboembolism (VTE) risk given reduced patient mobility. Her E2 was held for 5 days, with a subsequent total estrogen level of 398 pg/mL (56-213 pg/mL). She was restarted on oral E2 2mg, with total estrogen levels of 238 pg/mL and 517 pg/mL (56-213 pg/mL) at three and six days respectively. Oral E2 was again held for an additional four days, leading to total estrogen level of 119 pg/mL (56-213 pg/mL) and total testosterone of 18 ng/dL (264-916 ng/dL). Her final regimen is now oral E2 1mg daily. She did not develop VTE while hospitalized.Research into the pharmacokinetics of oral versus sublingual E2 is scarce. Differences in absorption explain this patient’s supratherapeutic estrogen level of 913 pg/mL and insufficiently suppressed total testosterone of 105 ng/dL. Sublingual E2 achieves higher peak levels but multi-daily dosing is required to fully suppress testosterone production when compared to its oral counterpart, which corresponds to this patient’s initial laboratory findings. Sublingual E2 also has a lower risk of VTE since it avoids first-pass metabolism. Future research should target alternative routes of estrogen therapy that may potentially be safer than current modalities. Presentation: Saturday, June 17, 2023

FRI268 Late Onset Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: M.S. Nicholson: None. A. Barnett: None. A 66-year old white female was admitted for weakness, acute kidney injury, and hypotension. This is her 3rd hospital or ER visit in the last 12 months for similar complaints. She has a 25 year history of type 2 diabetes on insulin and oral therapy and 30 year history of hypothyroidism on levothyroxine 75 mcg daily. She was on oral estrogen replacement therapy for post-menopausal symptoms with a hysterectomy in her early 50s. She has a sister with type 2 diabetes on oral meds and hypothyroidism. She has a brother with type 1 diabetes. Her serum sodium was 135 mmol/L (135-145), potassium was 5.4 mEq/L (3.5 -5.1), and calcium was 9.2 (8.5-10.1). Her Creatinine was 1.2 with a GFR of 48. A random cortisol in the ED was 9.2 (no ref range). Blood pressure was low and she was tachycardic and her weight was 68 kg. She was a well developed female with a a tanned complexion. Areas of vitiligo were noted on her arms. A cosyntropin stimulation test was done midday with a baseline, 30, and 60 minute cortisol levels of 9.2, 8.8, and 9.3 respectively. Baseline ACTH was 877.6 pg/mL (7.2-63.6). Her TSH was 4.09 mIU/mL (0.358-3.74) and free T4 was 1.29 ng/dL (0.76-1.46). DHEA-S was 14 mcg/dL (13-130). She was started on stress dose steroids with rapid improvement in BP, hyponatremia, and symptoms. GAD-65 antibodies were above 250 IU/mL and 21-hydroxylase antibodies were positive. Her TPO antibodies were negative. Non-insulin diabetes medications were stopped and she was discharged home after stabilization on prednisone 5 mg daily and fludrocortisone 0.1 mg daily. This patient has an atypical presentation of polyglandular autoimmune syndrome type 2 (PAS2). She presented with an Addisons crisis at the age of 66. She was already diagnosed with hypothyroidism and insulin requiring diabetes and evidence of vitiligo. A majority of patients with PAS2 are female and present in their 20s to 40s with primary adrenal insufficiency and primary hypothyroidism. Her initial manifestation was hypothyroidism and then diabetes and vitiligo with adrenal insufficiency many years later. Her random cortisol was not suppressed and this lead to a delay in her diagnosis. This was likely due to oral estrogen therapy raising cortisol-binding globulin. Her elevated baseline ACTH and lack of response to ACTH stimulation confirmed her diagnosis of primary adrenal insufficiency. An ACTH stimulation test was repeated as an outpatient with similar response. This case highlights the importance of provocative testing for adrenal disorders and testing for autoimmune causes of endocrine disorders when patients are not responding as expected. Presentation: Friday, June 16, 2023

Efficacy of a Diode Vaginal Laser in the Treatment of the Genitourinary Syndrome of Menopause.

Genitourinary syndrome of menopause (GSM) and vulvovaginal atrophy (VVA) are the most frequent menopause-related clinical entities and are consistently included in the definition of pelvic floor disorders (PFDs). Nonhormonal therapies, such as lubricants and moisturizers, are indicated as first-line treatments, while the "gold standard'' is represented by topical estrogen products; however, in cancer survivors hormonal treatment is not indicated. For this reason, energy-based therapeutic approaches-for instance, through laser technologies-may be employed as alternative options in this kind of patient; however, there are no studies evaluating the efficacy of a pure diode vaginal laser in the treatment of GSM. As a consequence, with our study, we aimed to evaluate outpatient nonablative diode laser treatment in sexually active women, with contraindications, no response, or refusal of local estrogenic therapy. This prospective study included patients with GSM, aged ≥ 18 years old, with contraindications, or refusal of local estrogen therapies. Women were evaluated via the use of their Vaginal Health Index (VHI) scores, which consists of five measures: elasticity, fluid volume, pH, epithelial integrity, and moisture. Moreover, the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria) was measured using a 10 cm visual analog scale (VAS), where the left extreme of the scale (score = 0) indicated "absence of symptom" and the right indicated "symptom as bad as it could be" (score = 100). Sexual function was evaluated with the Female Sexual Function Index (FSFI-19) questionnaire. The treatment was performed using a Leonardo Dual diode laser (Biolitec Italia Srl, Milano, Italy). The laser treatment consisted of three sessions, one per month. One month after the third session, the VHI, symptom VAS, and FSFI-19 were re-evaluated. In addition, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected. Our study enrolled a total of 26 consecutive patients. All patients were either in menopause or under treatment with gonadotropin-releasing hormone (GnRH). None of the patients reported adverse effects after laser treatment. In total, 19 (73.1%) patients referred improvements of their symptoms according to PGI-I scores. All domains of the FSFI-19 questionnaire, significantly improved after the diode laser treatment. The mean VHI score increased by 3.2 points, from 12.2 to 15.4 (p < 0.001). Additionally, we documented a significant improvement in symptoms affecting the VAS score, from 69.2 to 43.5 points (p < 0.001). A diode vaginal laser is an effective and easily tolerated ambulatory procedure for vaginal functional restoration in the treatment of GSM and VVA.

Induction of lactation in a patient with complete androgen insensitivity syndrome.

With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We describe the case of a woman with complete androgen insensitivity syndrome (CAIS) on conventional oestrogen therapy who was expecting a child via surrogacy and who wished to breastfeed. The woman was commenced on supplementary oestrogen therapy, domperidone and breast stimulation by mechanical breast pump 8 weeks prior to the delivery of her child. Following delivery, the patient produced a small, unquantified amount of milk, allowing her to suckle the infant for a short period of time. Induced lactation is possible in chromosomally XY individuals. It has been most successful in cis-women and transwomen, both of whom have had progesterone/progestogen exposure to the breast. We suggest that the addition of a progestogen to our patient's treatment regimen, either as part of her original hormone therapy or part of the lactation induction program, would have improved her changes of establishing successful lactation. Induced lactation is possible in chromosomally XY individuals with the use of pharmacological and non-pharmacological therapies. There are no standardised guidelines regarding the optimal regimen for induced lactation. Progesterone exposure to the breast is essential for ductal branching and alveolar maturation. In the published literature, induced lactation is more successful in transwomen and other XY individuals who have had prior progesterone exposure. The addition of progestogen to our patient's treatment regimen would have improved her chances of establishing successful lactation.

Terapia de estrógenos vaginales y riesgo de recurrencia en mujeres con antecedente de cáncer de mama

Breast cancer remains the most common malignant neoplasm and one of the leading causes of mortality in women, making it a significant target for global health efforts and a public health priority. Through the use of innovative therapies, survival rates have improved, leading to the emergence of associated conditions such as genitourinary menopausal syndrome. Hormonal therapy is employed for managing this condition, significantly alleviating its symptoms and, in some cases, serving as the sole solution. The most commonly utilized approach is vaginal estrogen therapy. Nevertheless, there have been reports of a potential risk of breast cancer recurrence associated with its use. In the Spanish-speaking context, there is limited evidence discussing this topic. A search was conducted across PubMed, ScienceDirect, and MEDLINE databases, using the terms "Vaginal Estrogen Therapy," "Recurrence," and "Breast Cancer." It was determined that, on a global scale, vaginal estrogen therapy is an effective and safe therapeutic option for managing genitourinary menopausal syndrome in women with a history of breast cancer. This therapy does not appear to increase the risk of recurrence, with the exception of those undergoing treatment with aromatase inhibitors. For these individuals, alternative therapies are recommended to mitigate this potential risk.

Estrogen Effects Differ Between Medium Maintenance and Replacement from Transcriptional and Clinical Perspectives in T47D Breast Cancer Cells.

Our most recent study revealed that the responsiveness of hormone receptor-positive breast cancer (HR+ BC) cells to estrogen or endocrine therapy can be altered by certain cell culture or ambient environmental conditions. Nevertheless, we were unable to investigate the relevant molecular mechanism and clinical relevance. Therefore, this study was planned as a follow-up. RNA sequencing was mainly used with T47D cells treated with or without 17β-estradiol (E2) under medium maintenance (MTN; conventional culture method) and medium exchange (EXC; daily replacing the existing medium with fresh medium). The role of E2 in transcription differed between MTN and EXC, and E2 played more important roles in transcription in terms of cancer development under EXC than under MTN, consistent with the previous functional effects of EXC. The novel concept of the "estrogen-responsive and proliferation-related gene (ERPG)" was introduced. The expression of ERPGs, which were distinguished from typical estrogen-responsive genes, was correlated with that of prognostic and predictive factors for HR+ BC. The transcriptional induction of ERPGs and typical estrogen-responsive genes regardless of E2 treatment under MTN was reminiscent of constitutive estrogen receptor (ER) activation. Additionally, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors were more effective under EXC than under MTN. This study, demonstrating the more important roles of estrogen in terms of cancer development under EXC than under MTN, supports the use of our research model in future studies to overcome endocrine resistance in HR+ BC.

The Relationship Between Myocardial Infarction and Estrogen Use: A Literature Review.

This thorough literature evaluation was prompted by significant research into the complex interactions between estrogen use and myocardial infarction (MI). Estrogenhas fascinated researchers because of its possible cardioprotective benefits and its impact on cardiovascular health. In order to clarify the connection between estrogen use and the risk of MI, this review critically examines the body of prior evidence. This review focuses on estrogen and its pivotal role in cardiovascular health, concentrating on lipid metabolism, vasodilation, inflammation, and endothelial function. It examines contentious data about estrogen therapy's heart-protective effects, taking into account age, initiation timing, dosage, and dosage of administration. Genetic and epigenetic influences on MI risk among estrogen users highlight intricate, personalized estrogen effects. The conclusion summarizes the main findings and emphasizes the need for an all-encompassing strategy for initiating and managing estrogen medication. It is crucial to consider patient-specific traits and risk factors to successfully customize treatment regimens. This review sheds vital light on the potential directions for better cardiovascular treatment for postmenopausal women by shedding light on the complex link between estrogen use and myocardial infarction. The review also identifies research gaps and future objectives in this area, highlighting the demand for novel medicines and individualized strategies to improve cardiovascular outcomes.

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity. Individuals with gender dysphoria and cisgender controls underwent 2 MRI measurements, with a median interval of 145 days (interquartile range [IQR] 128.25-169.75 d, mean 164.94 d) between the first and second MRI. Transgender women (TW) and transgender men (TM) underwent the first MRI before GHT and the second MRI after approximately 4.5 months of GHT, which comprised estrogen and anti-androgen therapy in TW or testosterone therapy in TM. Hypothalamic volumes were segmented using FreeSurfer, and effects of GHT were tested using repeated-measures analysis of covariance. The final sample included 106 participants: 38 TM, 15 TW, 32 cisgender women (CW) and 21 cisgender men (CM). Our analyses revealed group × time interaction effects for total, left and right hypothalamus volume, and for several subunits (left and right inferior tubular, left superior tubular, right anterior inferior, right anterior superior, all p corr < 0.01). In TW, volumes decreased between the first and second MRI in these regions (all p corr ≤ 0.01), and the change from the first to second MRI in TW differed significantly from that in CM and CW in several subunits (p corr < 0.05). We did not address the influence of transition-related psychological and behavioural changes. Our results suggest a subunit-specific effect of GHT on hypothalamus volumes in TW. This finding is in accordance with previous reports of positive and negative effects of androgens and estrogens, respectively, on cerebral volumes.

Real-world practice of estrogen and progestogen prescriptions in menopausal women in Japan: A descriptive study using a Japanese claims database.

This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women. Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed. In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021. This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women.

Effect of Postmenopausal Hormone Therapy on Glucose Regulation in Women With Type 1 or Type 2 Diabetes: A Systematic Review and Meta-analysis.

Blood glucose regulation in women with diabetes may change during and after menopause, which could be attributed, in part, to decreased estrogen levels. To determine the effect of postmenopausal hormone therapy (HT) on HbA1c, fasting glucose, postprandial glucose, and use of glucose-lowering drugs in women with type 1 and women with type 2 diabetes. We conducted a systematic search of MEDLINE, Embase, Scopus, the Cochrane Library, and the ClinicalTrials.gov registry to identify randomized controlled trials (RCTs). We selected RCTs on the effect of HT containing estrogen therapy in postmenopausal women (≥12 months since final menstrual period) with type 1 or type 2 diabetes. Data were extracted for the following outcomes: HbA1c, fasting glucose, postprandial glucose, and use of glucose-lowering medication. Nineteen RCTs were included (12 parallel-group trials and 7 crossover trials), with a total of 1,412 participants, of whom 4.0% had type 1 diabetes. HT reduced HbA1c (mean difference -0.56% [95% CI -0.80, -0.31], -6.08 mmol/mol [95% CI -8.80, -3.36]) and fasting glucose (mean difference -1.15 mmol/L [95% CI -1.78, -0.51]). Of included studies, 50% were at high risk of bias. When postmenopausal HT is considered for menopausal symptoms in women with type 2 diabetes, HT is expected to have a neutral-to-beneficial impact on glucose regulation. Evidence for the effect of postmenopausal HT in women with type 1 diabetes was limited.

The Correlation Between Progesterone and Mammographic Density in Postmenopausal Women: A Systematic Review of the Literature and Meta-Analysis.

Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.

Potential of Estradiol‐Functionalized Polyisocyanide Hydrogels for Stimulating Tissue Regeneration of the Pelvic Floor

AbstractThe high reoperation rate in pelvic organ prolapse (POP) surgery is probably due to impaired wound healing, and therefore, novel strategies that promote tissue regeneration are urgently needed. Estrogen therapy shows beneficial effects for vaginal wound healing: it reduces the inflammatory response and improves vaginal tissue strength and quality. Earlier, scaffolds that release the most potent estrogen, β‐estradiol (E2) have been described. This work describes the results of conjugating E2 covalently to the synthetic, but highly mimetic, polyisocyanide hydrogel (PIC‐E2). As adipose‐derived stem cells (ASCs) possess regenerative capabilities, the combination of PIC‐E2 and ASCs may have a synergistic effect on pelvic floor tissue regeneration. The results show that the PIC‐E2 bioactivity is not hampered upon covalent E2 conjugation and upregulates various extracellular matrix (ECM) genes in ASCs. Moreover, PIC‐E2 exerts similar effects regarding ECM metabolism compared to other E2‐releasing biomaterials, but at much lower doses, which is economically and therapeutically favorable. Based on these in vitro findings, the combination of the PIC‐E2 hydrogel and ASCs may have the potential to stimulate tissue regeneration in vivo, and therefore, feasibly improve the surgical outcomes for POP in the future.

Wealth of Knowledge and Passion: Patient Perspectives on Vaginal Estrogen as Expressed on Reddit

To qualitatively analyze the knowledge, attitudes, and beliefs of women regarding genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy as expressed on Reddit, a public, anonymous internet forum for discussion and information sharing. "r/menopause," a Subreddit with >30,000 subscribers, was queried for "vaginal estrogen" to collect postings related to vaginal estrogen in October 2022. Posts were analyzed qualitatively by 2 independent researchers. The principles of grounded theory were applied, and preliminary themes were generated. These themes were used to derive emergent concepts. Sixty-seven unique posts with 1101 responses were analyzed. Qualitative analysis revealed 5 preliminary themes: (1) questions regarding medication usage, (2) medication side effects, (3) medication alternatives, (4) frustration with the medical system, and (5) seeking validation for symptoms and experiences. Three emergent concepts were derived: (1) women experience bothersome side effects from menopause, and they desire compassionate and effective medical treatment; (2) women are engaged and active participants in their health and health care decisions; and (3) women perceive that their concerns are not taken seriously and seek validation for their medical conditions. Peri- and post-menopausal women have many questions and concerns about the condition of GSM and vaginal estrogen as treatment. They also have a broad range of frustrations including access to health care and questions about the usage of vaginal estrogen. By better understanding patient perspectives, physicians can better meet women's needs and improve care for GSM.

Chitosan/Solid-Lipid Nanoparticles Hybrid Gels for Vaginal Delivery of Estradiol for Management of Vaginal Menopausal Symptoms.

Hormonal replacement therapy is the mainstay treatment to improve quality of life and reduce mortality. With the increasing number of young women with early menopause, women now live longer (increased life expectancy). However, poor patient compliance with oral estrogen therapy has emerged. Intravaginal estrogen therapy can provide significant benefits with minimal risk for postmenopausal women with symptoms of the lower urinary tract and vaginal area but who do not want to take oral estrogen. In this study, estradiol-loaded solid lipid nanoparticles (SLPs) were prepared from compritol ATO 888 and precirol ATO 5, and two different stabilizers (Pluronic F127 and Tween 80) were studied. Selected SLPs (F3 and F6) were coated with different concentrations of the mucoadhesive and sustained-release polymer chitosan. Furthermore, gelation time, viscosity, mucoadhesion, ex vivo permeation, and in vitro irritation for vaginal irritation were studied. Particle sizes ranged between 450-850 nm, and EE% recorded 50-83% for the six SLPs depending on the type and amount of lipids used. Cumulative % drug release was significantly enhanced and was recorded at 51% to 83%, compared to that (less than 20%) for the control suspension of estradiol. Furthermore, extensive thermal gelation and mucoadhesion were recorded for chitosan-coated SLPs. Up to 2.2-fold increases in the permeation parameters for SLPs gels compared to the control suspension gel were recorded, revealing a slight to moderate irritation on Hela cell lines. These findings demonstrated chitosan-coated estradiol SLPs as novel and promising vaginal mucoadhesive hybrid nanogels.

P04.03.B VENOUS THROMBOEMBOLISM AND OTHER VASCULAR COMPLICATIONS IN PAEDIATRIC PATIENTS FOLLOWING CRANIOPHARYNGIOMA SURGERY: A SINGLE-CENTER, RETROSPECTIVE STUDY

Abstract BACKGROUND Craniopharyngioma (CP), although slow growing and histologically benign, carries considerable morbidity, particularly in the postoperative period: hypothalamus-pituitary dysfunction and electrolyte disorders represent common complications. Moreover, in these patients, the increased risk of deep venous thrombosis (DVT) and the possible development of fusiform intracranial aneurysms are well known. However, data are still poor, especially in the pediatric population. The aim of our study was to describe the occurrence and timing of DVT and other vascular alterations in neurosurgical operated CP patients and to evaluate the role of predisposing factors in the development of post-surgical and late vascular events. MATERIAL AND METHODS This was a single-center, retrospective study. We investigated 19 patients (11 males, 8 females, mean age 10.47±4.29) diagnosed with CP, who had been subjected to neurosurgery between December 2016 and August 2022 in Meyer Children’s Hospital IRCCS in Florence. Demographic and clinical characteristics and surgical data were recorded for each participant. RESULTS Five patients (26.3%, 3 females, 2 males, median age 15 years) presented vascular events, all during sodium imbalance. Calcium at lower limits was detected in four of them. Three DVT (two with associated pulmonary embolism, including one female patient’s death) developed after surgery, more frequently at 7-10 days (two patients were central catheter carriers, one obese patient showed hypercholesterolemia and hypertriglyceridemia). In a patient in hyponatraemic state a vascular parietal alteration compatible with pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting and prolonged intensive care. Superficial vein thrombophlebitis was a late complication in an overweight female patient on estrogenic replacement therapy. CONCLUSION Patients with CP undergoing neurosurgical brain tumor resection are at a higher risk of developing DVT and vascular alterations, thus careful follow-up should be done in these patients. In our study, we found that the phase of transition from central diabetes insipidus (CDI) to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is probably a significative time for developing this complication; so, we recommend careful monitoring of symptoms suggestive of vascular events in CP operated patients. However, we suggest the execution of a deep vein ultrasound examination in the post-neurosurgical two-four weeks for an early diagnosis of this problem for reducing the risk of severe complications.

Early-Stage Breast Cancer, EGFR-Mutated NSCLC, and High-Risk Melanoma: 2023 ASCO Annual Meeting Highlights for the Advanced Practitioner

Lisa Kottschade, APRN, MSN, CNP, FAPO, of Mayo Clinic, discusses encouraging results of a trial examining adjuvant ribociclib plus estrogen therapy in patients with stage II or III HR+/HER2− early breast cancer. She also discusses the use of the novel mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma. Finally, she analyzes the overall survival data reported in the ADAURA trial, which demonstrated a statistically significant disease-free and overall survival benefit for patients with EGFR-mutated stage IB to IIIA non–small cell lung cancer.

Trans-labial or introital ultrasounds for midurethral slings.

Stress urinary incontinence is common in adult women. The use of introital or trans-labial ultrasound can help the surgeon (urologist or gynecologist) to better assess the type of incontinence the patient presents in order to guide him in the management of the patient. Often, surgical treatment with a mid-urethral sling (MSU) placement can be chosen in case of failure of non-invasive therapies (such as local estrogen or physical therapy) and if the clinical examination shows an urethral hypermobility. The use of ultrasound can help in this choice. Although rare, complications of MSU can sometimes cause disabling symptoms and be difficult to diagnose. Introital or trans-labial ltrasound can help diagnose them. The objective of this work was to describe the realization of ultrasound of stress urinary incontinence before or after the placement of a MSU, in order to make their realization easier for young surgeons which can use them in current practice.