Estrogen Therapy Research Articles

A Pharmacovigilance Study on Steroid Induced Osteoporosis

Background: In elderly people, osteoporosis and low bone density are significant risk factors for morbidity and death. Low bone strength distinguishes these illnesses, which are correlated to an increased risk of fractures from even minor traumas. Objectives: To study pharmacovigilance on steroid induced osteoporosis. Methods: A total of 950 individual who were diagnosed with osteoporosis. These individuals were deemed to be at a high risk of osteoporosis. Patients were given information regarding the risks of steroid-induced osteoporosis, as well as a handout. The patient's steroid duration and any medicines used to control the risks of steroid-induced osteoporosis were the focus of the initial evaluation. Following that, evaluations of the pharmacological therapy being examined. Any problems found were discussed with the patient and/or the prescribing practitioner. Data was gathered at the start of the study and again after 6 months of observation. Results: Glucocorticoids (prednisolone) was the main prescription drug of the entire study sample. Family history of Osteoporosis was reported in 20% of the cases. The history of fracture was reported in 30% of the cases. Low calcium diet was reported in 35% of the cases. Osteoporosis was diagnosed in 17% of the cases, Osteopenia in 22% of the cases. In 88% of the cases the drug prescribed was >5mg daily. The duration of CS intake was high. This shows that the CS drug is being abused mostly in history of allergies and asthma as its easily available OTC leading to an increased risk of osteoporosis. Around 26% were prescribed antiosteoporosis treatment with Bisphosphonate. Estrogen therapy was prescribed in 16% of the cases. Calcium supplement consumption was increased by 17%. There was significant reduction in BMD, Glucocorticoid’s usage and daily dosage and result was statistically significant. Conclusion: Because all cells employ the same glucocorticoid receptor, corticosteroids' antiinflammatory effects cannot be distinguished from their metabolic effects; thus, precautions should be taken when corticosteroids are given. Clearly, the risk of serious adverse effects rises as the amount and duration of therapy increases, thus the smallest dose required to control the condition should be provided.

Venous Thrombo-Embolism Is Rare in Transgender and Gender Non-Binary Adolescents and Youth: A Multicenter Observational Study

Introduction An increasing number of adolescents and youth identify as transgender or gender non-binary (TNB). Gender-affirming hormone treatment (GAHT), including estrogen or testosterone therapy increase appearance congruence and psychological functioning, and decrease depression, anxiety and suicidal ideation. In adult TNB patients, estrogen therapy is associated with an increased risk of venous thromboembolism (VTE), while the thromboembolic risk of testosterone is less clear. A recent cross-sectional study conducted at Boston Children's Hospital (BCH) suggested that VTE is rare in TNB adolescents and youth and typically occurs in the setting of additional risk factors. Additionally, GAHT was not identified as a significant risk factor for thrombosis in this cohort. Herein, we sought to confirm our preliminary findings across 49 free-standing children's hospitals using an administrative database. Methods The study was deemed exempt by the Institutional Review Board at BCH. Administrative approval was obtained through the Children's Hospital Association. Data for this study were obtained from Pediatric Health Information System (PHIS), an administrative database that contains clinical and resource utilization data from inpatient, ambulatory surgery, emergency department, and observation encounters across 49 tertiary-care children's hospitals in the United States. Data quality and reliability are assured through a joint effort between CHA and participating institutions. International Classification of Disease, 9 th and 10 th Editions (ICD9/ICD10) codes were used to identify eligible subjects, defined as children (from birth to 21 years of age) hospitalized with VTE between 1/1/2012-12/31/2021 at one of 49-participating hospitals. ICD9/ICD10 codes for gender dysphoria were used to identify TNB adolescents and youth. Mean (SD) or median (range) were calculated for continuous data, and frequency with 95% confidence interval for categorical data. Results During the study period, 39,503 unique patients (birth-assigned females: 18,395 [47%]) were diagnosed with VTE. Mean age (SD) at VTE diagnosis was 7.7 (7.3) years. Only 23 (0.06%) patients had an ICD9/ICD10 diagnosis code for gender dysphoria. Of these 23 patients, six (26%) were birth-assigned males and 17 (74%) were birth-assigned females. Among these 23 patients, the median (range) age at VTE diagnosis was 16.2 (11.6, 20.5) years. VTE location for patients identified as TNB included: lower extremities (n=8), upper extremities (n=5), pulmonary embolism (n=5), cerebral sinus venous thrombosis (CSVT) (n=1), and other (n=4). Demographic data for the overall cohort and the subset of TNB patients are summarized in Table 1. 2,790 patients with a VTE diagnosis died prior to hospital discharge, while none of the 23 VTE patients identified as TNB died prior to hospital discharge. Only 2/23 (8.7%) TNB patients with VTE had a diagnosis code for hormone replacement therapy (HRT). One patient was a birth-assigned male, and one was a birth-assigned female. Among the 23 TNB patients with VTE, none had congenital heart disease, ten (43%) were obese, three (13%) had chronic renal disease, two (9%) had cancer and one (4%) had inflammatory bowel disease (Table 1). Discussion These data support our initial observation that VTE is extremely rare in TNB adolescents and youth and typically occurs in the setting of additional risk factors for VTE including cancer, renal disease, obesity, and inflammatory bowel disease. Only 2/23 TNB patients had a simultaneous code for HRT, suggesting that HRT may not be a significant risk factor for VTE in this cohort. A limitation of this investigation is the inability to estimate how many TNB patients received care at the participating centers during the study period.

Gallbladder disease in transgender individuals: associations with gender-affirming hormone therapy

Background Transgender individuals frequently undergo gender-affirming hormone therapy (GAHT) during their gender transition which plays a vital role in gender identity affirmation. Cholelithiasis, a common condition affecting 10-15% of the US population, has been linked to estrogen therapy in cisgender women. Despite the fact that hormonal profiles achieved after GAHT are not always identical to cisgender individuals, the effects of GAHT on gallbladder disease (GBD) risk have not been evaluated in transgender populations. This research aims to address this gap utilizing a large nationwide database. Methods The study analyzed medical records data from the TrinetX database from 52,847 trans men and 38,114 trans women. Four cohorts were created: trans women and men either receiving either hormone therapy or no intervention. Descriptive statistics were calculated before matching to estimate disease burden. The groups were then propensity score matched on known risk factors (age, race, BMI, etc.) and rates of GBD were compared. Results Before matching, trans women on hormone therapy (TWHT) had a significantly higher 10-year GBD probability than those naïve to therapy (TWNI) (4.69% vs 1.88%). For trans men, there was no significant difference in 10-year rates between those on therapy (TMHT) and those not (TMNI) (3.15% vs 3.87%). Cholecystectomy rates were significantly higher for TWHT than TWNI (1.10% vs. 0.57%), but similar between TMHT and TMNI (0.95% vs. 1.10%). After accounting for risk factors, TWHT had increased GBD risk (HR 1.832), while TMHT showed no significant change. Discussion This study suggests a link between estrogen GAHT and increased GBD risk in transgender women. Notably, testosterone GAHT did not offer protection against GBD in transgender men, contrary to expectations. This study is, to our knowledge, the first to describe the burden of GBD in the transgender population and to investigate the effects of GAHT on GBD risk.

Transgender Women on Estrogen Have a Lower Burden of Thrombotic Events Compared to Cisgender Men: A Nationwide Hospital-Based Survey

Due to public recognition and acceptance, more transgender women are being prescribed gender-affirming estrogen therapy. Traditionally, sexual dimorphism has been shown to play a significant role in the pathophysiology of thrombotic phenomena. While genetic factors remain the key players in the divergent male and female phenotypes, limited information is available regarding the thrombo-vascular effects of estrogen therapy in transgender women. Furthermore, available data has been conflicting with respect to vascular outcomes in this specific population. Therefore, more evidence is required to understand the long-term effects of gender-affirming estrogen therapy. In the current study, we investigated the thrombotic outcomes of estrogen therapy in transgender women (male sex assigned at birth), in comparison to cisgender men and cisgender women. We performed retrospective analyses using the TriNetX database that includes de-identified data for over 250 million patients across 76 certified healthcare organizations. We included all adults over the age of 18 years and excluded those with the presence of documented prothrombotic risk factors such as obesity, diabetes, hyperlipidemia, smoking, and cancer. Within the cohort of cisgender women, we excluded pregnancy and post-menopausal status. The thrombotic outcomes within the transgender cohort were recorded after the start of hormone replacement therapy. To account for thrombotic events, we used search terms such as acute myocardial infarction (MI), cerebral infarcts, pulmonary embolism (PE), and deep vein thrombosis (DVT). We found 12,369 transgender women, 29,746,302 cisgender men, and 32,591,972 cisgender women that were eligible for our study. The transgender women had lower incidences of MI (0.14% vs. 0.38%, P<0.0001), cerebral infarcts (0.21% vs. 0.49%, P<0.0001), and DVT (0.33% vs. 0.47%, P<0.022) compared to cisgender men. The incidence of PE was comparable in both these groups (P=0.85). Furthermore, we observed that transgender women also experienced significantly lower incidences of cerebral infarcts (0.21% vs. 0.42%, P=0.0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P=0.062) compared to cisgender women. The incidence of venous thrombosis was similar in these two groups. Overall, we observed a paradoxical decrease in rates of thrombotic events, suggesting that estrogen may play a protective role against the development of acute MI, cerebral infarction, and DVT in transgender women. Further investigation is required to understand the downstream targets that offer these cardioprotective effects. Importantly, our data may provide clinicians with reassurance that traditional vascular risks associated with estrogen may be less pronounced in males.

Venous Thromboembolism and Estrogen-Containing Gender-Affirming Hormone Therapy.

Gender-affirming therapy involves the use of hormones to develop the physical characteristics of the identified gender and suppressing endogenous sex hormone production. Venous thromboembolism (VTE) is a known risk of exogenous estrogen therapy, and while evidence of VTE risk among transgender women using modern gender-affirming hormone therapy (GAHT) is still emerging, it is thought to affect up to 5% of transgender women. Historically, GAHT was associated with a high risk of VTE; however, modern preparations are less thrombogenic mainly due to significantly lower doses used as well as different preparations. This review presents the available literature regarding the following four topics: (1) risk of VTE among transgender women receiving estradiol GAHT, (2) how the route of administration of estradiol affects the VTE risk, (3) perioperative management of GAHT, (4) VTE risk among adolescents on GAHT. There is a need for large, longitudinal studies of transgender women using GAHT to further characterize VTE risk and how this is affected by factors such as patient age, duration of GAHT use, tobacco use, body mass index, and comorbidities. Future studies in these areas could inform the development of clinical guidelines to improve the care of transgender people.

Genitourinary Syndrome of Menopause: A Narrative Review Focusing on Its Effects on the Sexual Health and Quality of Life of Women.

Genitourinary syndrome of menopause (GSM) is a progressive condition due to a hypoestrogenic state affecting perimenopausal and menopausal women. GSM was previously known as urogenital syndrome, vulvovaginal atrophy, or atrophic vaginitis. The term vulvovaginal atrophy did not encompass the symptoms of the urinary tract like incontinence, urgency, and discomfort, or allude that it is due to a hypoestrogenic state. Although a significant segment of the population is affected by GSM, it is very sparsely studied, detected, and treated. GSM affects the quality of life and sexual health of most menopausal women suffering from it. Only a few healthcare providers ask about the symptoms of GSM and a tiny percentage of women seek consultation for it. This may be because they are either embarrassed or believe it to be a part of the natural process of aging. As the life expectancy of women has increased in general, the prevalence of GSM has also risen, while it still remains underdiagnosed and untreated. Properly educating women so that they can seek consultation regarding symptoms of GSM, and training healthcare professionals about communicating with the patient, as well as correctly identifying, diagnosing, and managing the patient are all important to overcome this communication barrier.Once we cross the barrier of diagnosing patients with GSM, we still have to manage the patients with tailor-made prescriptions according to the severity of the symptoms and their preferences. While there are various treatment options, the most effective one is low-dose topical estrogen therapy. In this review, we intend to explore the existing knowledge about GSM and its effect on the quality of life and sexual health of women along with the treatment options for managing and reversing the effects of GSM.

Frequency and Characteristics of Postoperative Neuropathy in Individuals on Gender-Affirming Hormone Therapy Undergoing Gender Affirmation Surgery: A Retrospective Cohort Study.

Introduction Gender affirmation surgery includes procedures of the face, larynx, chest, reproductive system, external genitalia, and adipose tissue performed to ameliorate incongruence between gender identity and phenotype. The annual number of gender affirmation surgeries performed in the United States has increased significantly. There have been no investigations into the frequency of peripheral neuropathy after gender affirmation surgery, which is an important topic, given transgender individuals are at increased risk for delaying necessary medical care. After appreciating a number of cases of postoperative neuropathy in our clinical practice, we hypothesized that gender affirmation surgery is a high-risk procedure for postoperative neuropathy. Methods We conducted a one-year, monocentric, retrospective cohort study utilizing clinical data of individuals on gender-affirming hormone therapy undergoing gender-affirmation surgery under general anesthesia. The study included transgender women, assigned male at birth, receiving antiandrogen, progesterone, or estrogen therapy (target range plasma estradiol concentration 90-200 pg/ml) and transgender men, assigned female at birth, receiving antiestrogen or testosterone therapy (target range plasma testosterone concentration 320-1000 ng/dl). The primary objective was to estimate the incidence of postoperative peripheral neuropathy, defined as new numbness, paresthesia, neuropathic pain, or muscle weakness occurring in a peripheral innervation territory. Secondary objectives were to summarize the clinical presentation of neuropathy and investigate for associations between procedure characteristics and neuropathy. Results We identified nine cases of postoperative peripheral nerve injury in 232 consecutive gender affirmation procedures establishing an incidence of 3.9%. All injuries were associated with surgery longer than six hours and were characterized by sensory deficits including numbness 89% (8/9) and tingling 56% (5/9), which were diagnosed by postoperative day one. Conclusions Our results suggest that gender affirmation surgery is a high-risk procedure for postoperative neuropathy, with an incidence similar to other high-risk procedures, and an incidence that is higher than the general surgical population. However, given this has not been previously reported and our study includes a heterogenous population from a single institution, our results should be considered hypothesis generating. Additional studies that include multiple institutions are needed to confirm our findings and identify modifiable risk factors for postoperative neuropathy.

The Impact of Testosterone Therapy on Cardiovascular Risk Among Postmenopausal Women.

To summarize the current state of knowledge surrounding the impact of testosterone therapy on cardiovascular risk factors in postmenopausal women. In this scoping review, a comprehensive search of peer-reviewed literature was conducted in adherence to a methodological framework comprising 4 distinct stages: conceptualizing a comprehensive search strategy, screening relevant publications, extracting pertinent data, and organizing and synthesizing the resultant findings. The search used electronic databases, including MEDLINE, Embase, and Google Scholar, to ensure an exhaustive survey of the available literature. The database search yielded 150 articles, including systematic reviews, registered trials, and peer-reviewed studies, of which 48 duplicates were removed. Following the title/abstract screening, 36 publications were included in the full-text review. On completion of the full-text review, using the inclusion/exclusion criteria, 29 articles were excluded and 7 remained for data extraction and qualitative synthesis. Existing research provides promising insights into the benefits of low-dose testosterone therapy, typically combined with estrogen therapy. These benefits may include positive impacts on body composition, functional capacity, insulin sensitivity, inflammatory markers, and cholesterol. However, there remains a substantial lack of knowledge surrounding the effects and mechanisms behind testosterone therapy in postmenopausal women in relation to its impacts on cardiovascular risk. High-quality, evidence-based clinical intervention research is needed to investigate testosterone therapy's potential implication on cardiovascular risk factors in post-menopausal women.

Current trends in the prevention and treatment of genitourinary menopausal syndrome

Genitourinary menopausal syndrome is still a widespread problem that significantly affects the quality of life in postmenopause. The cause of this state is hypoestrogenism that is associated with menopause and the following change in the vaginal microflora due to the elimination of lactobacilli. The disturbance of the vulval and vaginal microflora provides risks for the invasion of pathogenic microorganisms, and the deficiency of sex hormones is associated with atrophy of the epithelium of the urogenital tract. An analysis of published clinical studies using a combination of L. acidophilus and 0.03 mg estriol (Gynoflor® E) in postmenopausal women with vulvovaginal atrophy, breast cancer survivors, in postmenopausal women with breast cancer on aromatase inhibitors was performed. Treatment with a combination of L. acidophilus and 0.03 mg of estriol (Gynoflor® E) can be evaluated as safe without risk of endometrial effects or other systemic effects. Local estrogen therapy in postmenopausal women can restore the vaginal epithelium, and a useful lactobacillus flora is needed to prevent urogenital infections. Local application of estriol is preferable, as it causes a local proliferative response and has no stimulating effect on the endometrium. This method of therapy may also be considered for hormone-sensitive women with breast cancer on aromatase inhibitors. However, today, there are not enough clinically validated studies proving the absolute safety of this treatment method among breast cancer women. The effect of this therapy is achieved due to the synergistic action of estriol and lactobacilli.

The role of oestrogen therapy in reducing risk of Alzheimer's disease: systematic review.

Studies have shown a relationship between oestrogen and Alzheimer's disease. However, there is neither clear nor strong evidence on the use of oestrogen-only therapy in reducing the risk of Alzheimer's disease. To assess the effects of oestrogen-only therapy on reducing the risk of Alzheimer's disease. Inclusion criteria was determined with the PICO framework. Outcome was cognitive function measured by neuropsychological tests and strict protocols. Exclusion criteria included non-Alzheimer's dementia, progesterone-only therapy and pre-menopausal women. Searches were conducted in nine electronic healthcare databases, last searched in July 2022. Quality assessments conducted on randomised controlled trials (RCTs) were performed with the GRADE assessment, and cohort studies and case-control studies were assessed with the Newcastle-Ottawa Scale. Extracted data were used to analyse participants, interventions and outcomes. Twenty-four studies satisfied the search criteria (four RCTs, nine cohort studies, 11 case-control studies). Fifteen studies showed positive associations for oestrogen-only therapy reducing the risk of Alzheimer's disease, and the remaining nine found no evidence of association. Fifteen studies showed that oestrogen-only therapy effectively reduced the risk of Alzheimer's disease, whereas nine showed no correlation. Studies also investigated oestrogen-related variables such as length of oestrogen exposure, being an apolipoprotein E ε4 carrier and concomitant use of non-steroidal anti-inflammatory drugs, and their role in neuroprotection. This review was limited by the limited ranges of duration of oestrogen treatment and type of oestrogen-only therapy used. In conclusion, oestrogen-only therapy has potential for use in preventing Alzheimer's disease, although current evidence is inconclusive and requires further study.

Gonadoblastoma in Turner syndrome with puberty delay: A case report and literature review.

Y chromosome material stands as an independent risk determinant for the onset of gonadoblastoma (GB) and subsequent gonadal germ cell tumours in individuals with Turner syndrome (TS). However, the delayed and underestimated identification of Y chromosome material through karyotyping within primary care settings exacerbates the intricacies of managing these patients over the long term. We present a case involving TS accompanied by Y chromosome material, wherein puberty delay and GB were identified during prophylactic gonadectomy. Subsequently, we delve into the literature to explore the GB-related malignancy risk in TS patients with Y chromosome material, the incidence of Y chromosome presence in TS patients using methodologies beyond routine chromosomal testing, and the diagnosis and treatment of puberty delay in TS patients, all based on our case. A spectrum of more sensitive molecular techniques, including polymerase chain reaction (PCR) and fluorescence in situ hybridisation, effectively augments the detection of Y chromosome material alongside karyotyping. In addition to gonadectomy, the implementation of appropriate oestrogen therapy and a holistic, multidisciplinary approach to care can enhance the quality of life, while mitigating the long-term morbidity and mortality risks for TS patients harbouring Y chromosome material. Beyond gonadectomy, adopting a multifaceted approach the Y chromosome material detection, prompt initiation of puberty, tailored oestrogen therapy, and coordinated multidisciplinary management significantly contributes to the comprehensive health oversight of TS patients with Y chromosome material.

Perioperative Factors Affecting the Healing of Rectovaginal Fistula.

Rectovaginal fistula is rare, but a severe complication in gynecology, which despite the effort of clinicians is still not treated successfully in many cases. According to statistics, the healing rates of surgery in patients with RVF range from 20 to 100%. The treatment effectiveness depends on the etiology of fistula, the age of the patients, the presence of comorbidities, the type of surgery and many other factors. Considering the low efficiency of treatment and the high risk of recurrence, the question of possible methods to improve the results occurs. In our review, we analyzed both modifiable and non-modifiable factors which may influence the treatment, healing rate and future fate of the patients. Taking into account all analyzed risk factors, including age, comorbidities, smoking status, microbiology, medications, stoma and stool features, we are aware that rectovaginal fistula's treatment must be individualized and holistic. In cases of poorly healing RVF, the drainage of feces, the use of antibiotic prophylaxis or the implementation of estrogen therapy may be useful. Moreover, microbiome research in women with RVF and towards estrogen therapy should be performed in order to create treatment algorithms in women with fistulae. Those interventions, in our opinion, may significantly improve the outcome of the patients.

Vulvovaginal atrophy in the CRETA study: the healthcare professionals’ perception

Objectives The objective is to assess the perception of gynecologists regarding patients’ adherence to vulvovaginal atrophy (VVA) treatments, to evaluate the gynecologists’ opinions on what their patients think about treatment adherence, and to compare the gynecologists’ opinions with the patients’ own perceptions within the CRETA study. Methods Spanish gynecologists who participated in the CRETA study were asked to fill out an online 41-item questionnaire to evaluate their views on VVA management. Results From 29 centers across Spain, 44 gynecologists completed the survey. Their mean age was 47.2 years old, two-thirds of them were women, and the average professional experience was over 20 years. According to the gynecologists, the therapy most frequently used by VVA-diagnosed women was vaginal moisturizers (45.5%), followed by local estrogen therapy (36.4%) and ospemifene (18.2%). Nevertheless, ospemifene was viewed as the therapeutic option with the most efficacy, easiest route of administration, shorter time to symptom improvement, lower percentage of dropouts, and higher treatment adherence. Conclusions Spanish gynecologists are in general agreement with their patients regarding VVA treatment preferences and the main issues for adherence and effectiveness. However, there is an opportunity for doctor–patient communication improvement. Among the three therapeutic options evaluated, ospemifene is regarded as offering some competitive advantages.

FRI451 Effect Of Estrogen Replacement On Various Metabolic Parameters In Turner’s Syndrome

Abstract Disclosure: I. Mishra: None. S. Jena: None. A.K. Baliarsinha: None. Turner’s Syndrome is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, liver dysfunction and dyslipidemia. Estrogen therapy was initially focused on pubertal induction and preservation of bone health. Recent longitudinal studies have shown the beneficial effect of estrogen therapy on various metabolic parameters, liver dysfunction and insulin resistance in these patients.To study the effect of estrogen therapy on various metabolic parameters, a cohort of 24 adolescent girls with Turner’s Syndrome planned for hormonal replacement therapy were recruited. Baseline data of detailed history, clinical examination, biochemical evaluation including glycemic status, lipid profile, liver function test and fibroscan were collected. At 6 month follow-up of estrogen replacement, repeat biochemical evaluation and fibroscan were done.The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.). The normal distribution of data was confirmed with Shapiro-Wilk's test and appropriate parametric tests were employed. Mean and standard deviation were computed for all continuous variables. At baseline visit and 6 month follow up, statistically significant improvement, was found in fasting plasma glucose, post-prandial plasma glucose, fasting insulin, HOMA-IR, VLDL and total bilirubin with estrogen therapy. Maximum reduction (p <0.001) was seen in LDL, AST, ALT and fibroscan values .No improvement was seen in triglyceride, HDL, direct bilirubin and ALP levels. Estrogen has been shown to improve insulin sensitivity and suppress gluconeogenesis by transcription factor Foxo1(1). Hepatoprotective role of estrogen has been explained by anti-inflammatory effects and protection from oxidative stress, mainly mediated via β estrogen receptor(2). Beneficial effects of estrogen on lipid profile have been verified in several studies. We conclude that the benefits of estrogen therapy in Turner’s Syndrome are much beyond the limit of puberty induction and bone health and pleiotropic actions of estrogen still need to be elucidated with further studies. Reference: (1) Yan et al; Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes 1 February 2019; 68 (2): 291–304. (2) Koulouri O et al. Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen. ClinEndocrinol (Oxf). 2008 Aug;69(2):306-10. Presentation: Friday, June 16, 2023

SAT400 Evaluation Of Lipid Profile Of Transgender Women On Long-Term Estrogen Therapy

Abstract Disclosure: L.A. Alvares: None. L.M. Santos: None. B.B. Mendonça: None. E.M. Costa: None. S. Domenice: None. Introduction: For transgender women (TW), previous exposed to male puberty, on long-term estrogen therapy, the knowledge about the lipid profile is important since it impacts on cardiovascular risk. Methods: A cross-sectional study was carried out with 15 TW (34.2 +/- years old), 14 CW and 13 CM. The TW received hormone therapy for 14.4 +/- 3.5 years. The IPAQ was used to measure the level of physical activity. Body composition was assessed by an InBody 720 device. The subjects (TW, CW and CM) were classified into five categories (sedentary, insufficiently active A and B, active and very active) according to IPAQ recommendations. Results: Age (years) TW: 34.2 SD +/- 5.2; CW: 35.6 SD +/- 4.1 and CM: 36.7 SD +/- 3.8. BMI (kg/m2) TW 25.5 SD +/- 2.8, CW 23.1 SD +/- 3.3 and CM 26.3 SD +/- 3,0. Total testosterone (ng/dL) TW 18.0 (range 12-637), CW 19 (range 12-40.1) and CM 524 (SD+/- 169). Median total cholesterol analysis (mg/dL): TW 154 SD +/- 33.0, CW 177 SD +/- 18.7 and CM 173 SD +/- 23.0 (p>0.05 in all subanalyses), HDL (mg/dL) TW: 46.5 SD +/- 10.9; CW:67.0 SD +/- 15.6 and CM: 46.5 SD +/- 9.8 p value <0.05; significant difference between TW and CW; between CW and CM; LDL (mg/dL) TW: 93 SD +/- 30.4; CW 94.5 SD +/- 14.2 and CM 104 SD +/- 22.0. The % FAt mass of TW was lower than that of CW (29.5±5.7 vs 32.9±5.7; p>0.05) and higher than that of CM (20.2±5.7; p<0.001). There was no significant difference in the level of physical activity between the groups (TW vs CW, p>0.05; TW vs CM, p>0.05; CW vs CM, p>0.05), with most participants being active or very active in all groups. Discussion: studies show that in the first few months of estrogen therapy HDLc increases about 10%. Conclusion: after long term on estrogen therapy, TW present HDLc pattern similar to CM, different of the usually observed in the first months analyses. Presentation: Saturday, June 17, 2023

FRI089 Massive Hypertriglyceridemia? Think Oral Contraceptive Pills!

Abstract Disclosure: I. Ali: None. M. Hamdi: None. Introduction: Oral contraceptive pills (OCPs) are common cause of Hypertriglyceridemia (TG) that should be recognized early by clinicians. Concern is raised regarding pursing further genetic test for Familial hypertriglyceridemia for female who developed massive hyper triglyceridemic after starting hormonal therapy. Case: A 37-year-old female patient with history of prediabetes with A1c of 5.7% and one attack of pancreatitis. Normal BMI, No regular medications, negative family history for lipid disorder. Rare social intake of alcohol. Routine annual lab showed triglycerides level of 164 in 2016, otherwise normal biochemical evaluation. No treatment pursued. Later She was started on OCPs (Kariva 0.15-0.02 mg) for contraception. Late 2019, blood work-up showed cholesterol level of 979, TG of 3170 and HDL level of 22. She was started on a statin therapy and fenofibrates beside stopping OCP, she maintained normal lipid profile while being off OCPs, until 2022 when she restarted an OCPs (Lo Loestrin 1mg-10 mcg) for 2 months that resulted in elevated cholesterol level of 1222, triglycerides of 5177 and HDL of 10.OCP was stopped, lipids level trended down with cholesterol of 961, triglycerides of 2005 and HDL of 22 then normalized after 2 months. Patient did not have any clinical symptom or complain. Discussion: High triglyceride concentration is an independent predictor of coronary heart disease and ischemic stroke. Many patients with triglycerides >1000 mg/dl have familial hypertriglyceridemia with superimposed additional exogenous factors which further raise triglyceride concentrations like exogenous estrogens, SERMs, hyperestrogenemia of pregnancy, poorly controlled diabetes mellitus, hypothyroidism, alcohol excess, exogenous corticosteroids, and drugs including isotretinoin and protease inhibitors. OCP induced hypertriglyceridemia occurs due to estrogen’s action in decreasing hepatic triglyceride lipase and lipoprotein lipase activity. This causes an overall increase in low and intermediate-density triglycerides and cholesterol that can increase free fatty acids to toxic level. The marked increase of TG and cholesterol in this patient while being on OCP is unusual and strongly indicate underlying familial hypertriglyceridemia exacerbated by starting OCP. Further genetic work up is being done. As OCP or other estrogen therapy are frequently given unwittingly to women with preexisting hypertriglyceridemia that lead to severe clinical consequences. Estrogen containing medication should not be considered if fasting triglyceride is above 500 mg/dl. In women on hormonal treatment with treatment-resistant hypertriglyceridemia, the likelihood that the hormonal treatment is nullifying drug efficacy is high so it should be stopped for a short trial while continuing modifying triglyceride-lowering medications. Presentation: Friday, June 16, 2023

THU201 Atypical Presentation Of Kallmann Syndrome With A Rare Genetic Mutation

Abstract Disclosure: E.L. Montgomery: None. B. Thrasher: None. S. Watson: None. Kallmann Syndrome presents as idiopathic hypogonadotropic hypogonadism with additional findings of hyposmia or anosmia and midline facial defects, including cleft lip/palate. We present a case of Kallmann Syndrome due to a rare genetic mutation with absent Mullerian structures. A 15 year, 6 month old female with history of cleft lip and palate and short stature was referred for primary amenorrhea. Clinical history was notable for limited sense of smell and no signs of puberty, including thelarche or adrenarche. Family History unknown (adopted). Significant physical exam findings include tanner 1 breast, no pubic or axillary hair, normal external female genitalia without clitoromegaly, unestrogenized vaginal introitus. Height 147cm (0.88%ile for age). Lab evaluation consisted of: LH 0.66 mIU/ml (2.4-12.6 mIU/ml), FSH 1.63 mIU/ml (3.5-12.5 mIU/ml), prolactin 11.30 ng/ml (4.79-23.30 ng/ml), BhCG negative, testosterone 8 ng/dl (2-17 ng/dl), free testosterone 1.1 pg/ml (<2.2 pg/ml), estradiol 3.0 pg/ml (9.0-249.0 pg/ml), AMH 2.46 ng/ml (1.05-12.86 ng/ml), thyroid function testing and growth factors normal. Imaging included pelvic ultrasound that showed no uterus or gonads. An MRI was obtained that confirmed these findings and also a blind-ending vaginal canal. While the presentation is suggestive of Kallmann Syndrome, the lack of Mullerian structures on imaging has not previously been described. Further evaluation included karyotype (46, XX) and hypogonadotropic hypogonadism genetic panel that identified a mutation in the FGFR1 gene with c.2172C>G (p.Asn724Lys), heterozygous, variant of uncertain significance. Estrogen replacement therapy was initiated with subsequent expected pubertal progression. Repeat imaging after seven months of treatment demonstrated presence of normal developing uterus and bilateral ovaries. Clinical Lesson/Conclusion: 1.Rare mutation with now 3 reports suggesting it is a true pathologic variant2.Unique presentation with hypoplastic Mullerian structures not detected on imaging.This patient’s particular variant has previously been described in in 2 individuals (mother/son) with features of Kallmann Syndrome (PMID: 16606836) with normal and partial puberty respectively, increasing the suspicion that this variant is pathogenic. Newly described FGFR1 variant associated with Kallmann Syndrome / hypogonadotropic hypogonadism. Kallmann Syndrome is not associated with lack of Mullerian structures, however this patient presented with features of Kallmann Syndrome and imaging that did not demonstrate presence of Mullerian structures. Since initiating estrogen therapy, she has had appropriate development of uterus and ovaries. This case demonstrates that prior to estrogen therapy, patients with Kallmann Syndrome may have underdeveloped Mullerian structures that not recognized on imaging prior to estrogen replacement therapy. Presentation: Thursday, June 15, 2023

FRI398 A Case Of Secondary Amenorrhea: Is It Only PCOS To Blame?

Abstract Disclosure: P. Panjawatanan: None. S. Riahi: None. S.S. Chaidarun: None. Background: One of the most common causes of secondary amenorrhea is PCOS (polycystic ovary syndrome) which accounts for 30% of the cases. Though not as common, hyperprolactinemia similarly contributes to the condition. Here we describe a patient who presented with secondary amenorrhea from medication-induced hyperprolactinemia with underlying PCOS. Clinical Case: A 31-year-old female with a past medical history of bipolar disorder, hypothyroidism, and PCOS, presented with secondary amenorrhea. The patient started menarche at 11 years old and was diagnosed with PCOS a year later due to irregular menses and hirsutism. The estrogen-containing pill was prescribed, but she developed a blood clot due to Factor V Leiden thrombophilia. She was taking atomoxetine, lithium, mirtazapine, and olanzapine for her psychiatric issues and recently started on paliperidone last year. She reported no period in the past two years after stopping oral contraception. Pregnancy was ruled out. She tried progesterone challenge test but did not have any flow. Transvaginal ultrasound showed thin endometrium. She had IUD placed for contraception. Laboratory testing four months and one year after starting paliperidone showed prolactin of 79.2 ng/mL and 110 ng/mL consecutively. The patient reported headaches but denied galactorrhea or visual loss. There are no signs or symptoms of Cushing’s disease, acromegaly, or hypothyroidism. Further workup showed TSH 1.52 mcIU/mL, estradiol 16 pg/mL, FSH 5.6 mIU/mL, 17-OH progesterone <40 ng/dL, total testosterone 14 ng/dL, ACTH 11 pg/mL, IGF-1 z-score -0.67 SD. MRI brain was ordered, which ruled out pituitary adenoma. Repeat prolactin level remained elevated at 87.7 ng/mL without treatment. We concluded that the patient has secondary amenorrhea from PCOS and antipsychotic-induced hyperprolactinemia. Patient was referred to a psychiatrist for antipsychotic medication changes. Conclusion: Antipsychotics, typically first-generation, are known to cause hyperprolactinemia due to their dopamine-antagonist effect. Prolactin level ranging from 25-100 ng/mL is seen in medication-induced hyperprolactinemia, while particular medication like risperidone and phenothiazines can raise the level to more than 200 ng/mL. Newer agent paliperidone has been reported to induce hyperprolactinemia similarly to risperidone which explains significant prolactin elevation in this patient. Hyperprolactinemia poses a risk for hypogonadism due to suppressed pituitary-gonadal axis, resulting in anovulation and bone loss. Estrogen therapy is considered an adjunct to help with hypogonadism. However, it is contraindicated in patients with thrombophilia. The guideline recommends switching to a low-risk antipsychotic agent if feasible. Despite having an established diagnosis of PCOS, it is important to consider other secondary causes of amenorrhea which may occur concomitantly. Presentation: Friday, June 16, 2023

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