Transdermal Estradiol Research Articles

Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration

The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.

Menopausal hormone therapy and risk of dementia: health insurance database in South Korea-based retrospective cohort study.

Menopausal hormone therapy (MHT) is used to alleviate the symptoms associated with menopause, despite the lack of recommendations for MHT in preventing dementia. Recent nationwide studies have explored the association between MHT and dementia risk, but the findings remain limited. This study aims to investigate the association between MHT and the incidence of Alzheimer's disease (AD) and non-AD dementia using national population data from Korea. We conducted a retrospective study using data from the National Health Insurance Service in Korea between January 1, 2002, and December 31, 2019. Women over 40 years were eligible for this study and classified into the MHT or non-MHT groups. The MHT group consisted of women who used Tibolone (TIB), combined estrogen plus progestin by the manufacturer (CEPM), estrogen, combined estrogen plus progestin by a physician (CEPP), and transdermal estrogen during menopause. We compared the risk of dementia between the MHT and non-MHT groups. The study included 1,399,256 patients, of whom 387,477 were in the MHT group, and 1,011,779 were in the non-MHT group. The median duration of MHT was 23 months (range: 10-55 months). After adjusting for available confounders, we found that different types of MHT had varying effects on the occurrence of dementia. TIB (HR 1.041, 95% confidence interval (CI) 1.01-1.072) and oral estrogen alone (HR 1.081, 95% CI 1.03-1.134) were associated with a higher risk of AD dementia. In contrast, there was no difference in the risk of AD dementia by CEPM (HR 0.975, 95% CI 0.93-1.019), CEPP (HR 1.131, 95% CI 0.997-1.283), and transdermal estrogen (HR 0.989, 95% CI 0.757-1.292) use. The use of TIB, CEPM, and oral estrogen alone increased the risk of non-AD dementia (HR 1.335, 95% CI 1.303-1.368; HR 1.25, 95% CI 1.21-1.292; and HR 1.128, 95% CI 1.079-1.179; respectively), but there was no risk of non-AD dementia in the other MHT groups (CEPP and topical estrogen). Our findings indicate that MHT has varying effects on the incidence of AD and non-AD dementia. Specifically, TIB, CEPM, and oral estrogen alone increase the risk of non-AD dementia, while transdermal estrogen is not associated with dementia risk. It is essential to consider the type of MHT used when assessing the risk of dementia in women.

Benefits for cardiovascular system, bone density, and quality of life of a long-term hormone therapy in hysterectomized women: a 20-year follow-up study.

The safety, consequences, and dosage of long-term hormone therapy (HT) for postmenopausal women remain unclear. Our aim was to analyze the effects of HT after 20 years of therapy in women after hysterectomy, focusing on the symptoms of menopause, blood pressure, lipid profiles, and bone density. A prospective observational longitudinal study was designed. The initial transdermal estradiol dose was reduced in half (0.025 mg/d) at 60 years of age. Different parameters including demographic, cardiovascular, bone density, and metabolic variables, as well as quality of life characteristics, were analyzed using bivariate analyses. Multivariate generalized estimating equations for longitudinal data were fitted for differences over time and between doses (<60 vs ≥60 y) using the R package geepack. After 20 years of HT, the mean age of 56 studied hysterectomized women was 67.1 years. The mean Kupperman index score decreased from 26.7 to 12.0 ( P < 0.001). A trend with total and low-density lipoprotein cholesterol reduction and high-density lipoprotein cholesterol increase was observed over time. A decrease in very-low-density lipoprotein cholesterol ( P = 0.05) and an increase in T score vertebral densitometry ( P = 0.014) were detected after HT. No changes in health outcome were detected in women older than 60 years with the reduced dose of HT. Breast cancer was the reason for dropouts in 0.02% women. HT for up to 20 years after hysterectomy may be beneficial for bone and cardiovascular health and for the overall quality of life. Our data suggest the importance of evaluating the dose and the timing of HT.

Endocrinology of Underweight and Anorexia Nervosa.

More than any other mental illness, the course, prognosis, and therapy of anorexia nervosa are shaped by the physical changes associated with being underweight. This article provides an overview of the endocrine changes associated with malnutrition and underweight. This overview serves as a basis for understanding the other articles in this special issue, which deal with the health risks associated with being underweight. In this context, the differences between underweight in anorexia nervosa and in constitutional thinness are of particular importance in assessing the impact of intentional weight loss. In this context, the regulation of hunger and satiety deserves special interest, as this is the area in which the intentional influence on body weight comes into play. Clinical consequences on, for example, fertility, bone metabolism, the homeostasis of, for example, serum glucose levels, or body temperature have been observed for a long time; nonetheless, the medical responses, apart from vitamin supplementations and advice to gain weight, are still limited. Therefore, emphasis was placed on the potential improvement of outcomes through the administration of central or peripheral hormones. Studies were identified on PubMed via a selection of relevant keywords; original texts that were cited in reviews were studied where it was advantageous. This review found some promising data on bone health and the administration of transdermal oestrogen, which is not yet widely used, as well as distinct hormonal markers to differentiate between CT and AN. We concluded that the continuous efforts to investigate the role of endocrinology in underweight and/or anorexia nervosa lead to outcome benefits and that more and higher-powered studies are needed.

Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial

Depression is highly prevalent during the menopause transition (perimenopause), and often presents with anxious and anhedonic features. This increased vulnerability for mood symptoms is likely driven in part by the dramatic hormonal changes that are characteristic of the menopause transition, as prior research has linked fluctuations in estradiol (E2) to emergence of depressed mood in at risk perimenopausal women. Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent stressful life events. This research extends prior work by examining the relation between E2 and reward seeking behaviors, a precise behavioral indicator of depression. Specifically, the current study utilizes a randomized, double blind, placebo-controlled design to investigate whether mood sensitivity to E2 flux (“hormone sensitivity”) predicts the beneficial effects of TE2 interventions on reward seeking behaviors in perimenopausal women, and whether recent stressful life events moderate any observed associations. MethodParticipants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Participants were recruited from a community sample; therefore, mood symptoms varied across the continuum and the majority of participants did not meet diagnostic criteria for a depressive or anxiety disorder at the time of enrollment. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations and weekly anxiety (State Trait Anxiety Inventory) and anhedonia ratings (Snaith-Hamilton Pleasure Scale). Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). ResultsParticipants who were randomized to receive transdermal estradiol and who demonstrated greater anxiety sensitivity to E2 fluctuations at baseline, demonstrated more reward seeking behaviors on the EEfRT task. Notably, the strength of the association between E2-anxiety sensitivity and post-randomization EEfRT for TE2 participants increased when women experienced more recent stressful life events and rated those events as more stressful. E2-anhedonia sensitivity was not associated with reward-seeking behaviors. ConclusionPerimenopausal women who are more sensitive to E2 fluctuations and experienced more recent life stress may experience a greater benefit of TE2 as evidenced by an increase in reward seeking behaviors.

(017) Systemic Estradiol Menopause Management: Return to the Old-Fashioned Way

Abstract Introduction The mean systemic estradiol value in menopausal women is &amp;lt; 10 pg/ml, consistent with ovarian failure. Such low values are associated with multiple symptoms including hot flashes, night sweats, insomnia, mood changes and irritability, cognitive changes, weight gain and slowed metabolism. Contemporary management with systemic estradiol, maximizing safety and efficacy, emphasizes non-oral, non-injection estradiol replacement therapies including systemic daily gels, twice weekly or weekly patches or three-month vaginal rings. Most women (&amp;gt;60%) who try these systemic therapies in our sexual medicine clinic have been successful at reducing bothersome symptoms. We have identified a subset of women who cannot achieve sufficient symptom relief despite using contemporary estradiol strategies due to lack of efficacy, negative side effects, (rings cannot stay in the vagina or values are too high initially and then too low, patches cause rashes or fall off, gels are too messy) or financial concerns. For these patients, we have advised a return to the “old-fashioned way” using weekly intramuscular (IM) injection of either estradiol valerate or cypionate. Estradiol cypionate was first described as well as introduced for medical use in 1952. Objectives This study examines the experiences of this subset of women in one practice using weekly injections of estradiol valerate or cypionate for either efficacy or financial reasons. Methods This chart review identified a subset of 16 patients (mean age 59 +/− 8 years) at a single site who had been prescribed estradiol valerate or cypionate when symptoms of genitourinary syndrome of menopause (GSM) persisted despite use of estradiol replacement gels, patches or rings, or cost was prohibitive. We have advised weekly IM injection of either estradiol valerate (20 mg/ml; starting dose 0.05 ml or 1 mg) or estradiol cypionate (5 mg/ml; starting dose 0.2 ml or 1 mg). We compared relief of bothersome symptoms from earlier estradiol treatments to current IM injection and compared monthly costs of each treatment based on GoodRx prices, assuming medications were not covered by insurance. Results All patients using weekly injections of estradiol valerate or cypionate had their estradiol-based GSM symptoms ameliorated without complaint of inconvenience or discomfort using injections. The risks of IM injections of estradiol are similar to those of topical administration, requiring concomitant progesterone use in women with a uterus. Concerning finances, using a GoodRx coupon, a 5 ml bottle of estradiol valerate costs approximately $50 and should last at least one year, reducing monthly cost to approximately $5/month. A 5 ml bottle of estradiol cypionate costs approximately $150 and should last at least 6 months, thus about $25/month. In contrast, generic patches are approximately $40/month, gels $150/month and the ring $170/month. While there remains an abhorrence for injections, the motivation for systemic estradiol replacement superseded any inconvenience of using an injectable medication and the 27-gauge ½ inch needle is associated with minimal pain. No significant side effects were noted with IM injection. Conclusions For certain individuals, sometimes the “old-fashioned way” works better both in terms of efficacy and cost, providing relief of bothersome menopausal symptoms. Disclosure No.

P-475 Effect of transdermal estradiol on endometrial preparation in frozen-thawed embryo transfer: A randomized control study.

Abstract Study question Is patient usage of transdermal estradiol more effective than oral estradiol on endometrial preparation in frozen-thawed embryo transfer cycles? Summary answer This study showed no significant differences in clinical pregnancy rates between the 2 groups. Transdermal gel have advantage of better patient comfort, lesser side effects. What is known already Estrogen and progesterone are crucial factors for endometrial preparation in frozen embryo transfer (FET) cycles. Studies assessing different forms of estradiol in FET have already been published. However, literature and studies in Vietnam are still limited to evaluating, research evaluating transdermal estrogen in ART. This study aimed to evaluate the use of transdermal estradiol gel and compare it with oral estradiol for the endometrium preparation in frozen-thawed embryo transfer (FET) cycles. Study design, size, duration This randomized clinical trial (RCT) included 380 frozen embryo transfer (FET) cycles from February 2020 to August 2021 at the IVF Department, Hung Vuong Hospital. Participants/materials, setting, methods They were randomized into one of the two groups. Group A (n = 190) received oral estradiol and group B (n = 190) received estradiol gel. In both groups, medication was started on day 2 of the menstrual, and endometrial thickness was monitored by ultrasound. Main outcomes were the following: serum estradiol level , endometrial thickness,.... Secondary outcomes were CPR, MR, and side effects in the 2 groups. Statistical testing was performed with Stata 14. Main results and the role of chance There was a significant difference in estradiol level on the day of progesterone administration and embryo transfer between the two groups (270.5 pg/ml versus 186.5 pg/ml, p, p. &amp;lt;0.001). According to the comparison, the two groups were not significantly different in the endometrial thickness on the day of progesterone administration (p = 0.85). as the data suggest, the total dose of estradiol used and the total number of days of dosing were similar in the two groups. The biochemical and clinical pregnancy rates were similar between the two groups and did not a significantly differ (56.2% vs. 52.2%, p = 0.474). The rate of miscarriage was higher than in the study group, but it was not statistically significant. Almost 20.3% of patients (n = 37) in group A had mild adverse effects when compared with only 10.1% (n = 18) in group B, and this was clinically significant (P = 0.007). Limitations, reasons for caution The limitation of our study was not asses ongoing pregnancy rate and live-birth rate. Wider implications of the findings Patients who estradiol valerate is contraindicated such as, high risk for deep vein thrombosis, hyperlipidemia, and clotting disturbance we can use oestrogel to be safe. It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles Trial registration number ISRCTN15301227

P-511 Prolonging the time of vaginal progesterone supplementation does not improve pregnancy outcomes after day 6 blastocyst transfer

Abstract Study question Does the administration of vaginal progesterone for 6 days improve pregnancy outcomes when transferring day 6 blastocysts, as opposed to 5 days of progesterone treatment? Summary answer We observed similar pregnancy outcomes after 5 and 6 days of vaginal progesterone supplementation following day 6 blastocyst transfer in oocyte recipient cycles. What is known already Progesterone administration promotes the final phase of endometrial preparation for embryo transfer. However, the optimal duration of progesterone transformation still remains unknown. The implantation potential of blastocysts formed at different timepoints is also contentious, as blastocysts on day 6 have been linked to poorer clinical outcomes compared to their day 5 counterparts. It is unclear whether this effect stems from an intrinsic impaired implantation capacity of slow-developing blastocysts, or a displaced window of implantation (WOI). It has been hypothesized that 6 days of progesterone administration may improve clinical outcomes after frozen day 6 blastocyst transfer. Study design, size, duration Retrospective cohort study of oocyte recipients undergoing single day 6 blastocyst transfer, between January 2020 and December 2022. This study compared two groups: day 6 blastocysts transferred after 5 days of progesterone administration (n = 284) and day 6 embryo transfers performed after 6 days of progesterone administration (n = 69). Participants/materials, setting, methods Our study included oocyte recipients who underwent a single embryo transfer of a day 6 blastocyst and hormonal replacement treatment for endometrial preparation with vaginal external progesterone administration (800mg/24h) for either 5 or 6 days prior to embryo transfer. Outcomes were analyzed using unpaired t-test or Fisher’s test and logistic regression. Multivariate models were adjusted for oral or transdermal estrogen administration and endometrial thickness on the day of embryo transfer. P-values &amp;lt;0.05 were considered significant. Main results and the role of chance Mean maternal age was 43.5 years, while patients had a mean BMI of 25.1. Mean days of estrogen therapy prior to embryo transfer were 22.4, with 75.3% of patients using transdermal estrogen administration, and achieving a mean endometrial thickness of 9.6 mm on the day of transfer. Mean progesterone levels on the day of transfer were 11.9 ng/ml. Thirty-seven percent of the day 6 blastocysts were of high quality. None of the demographic or cycle characteristics were significantly different between the study groups. When considering outcomes of day 6 blastocyst transfers, we found no significant differences in biochemical (26.33% vs 20.13%, p = 0.343), clinical (22.06% vs 17.46%, p = 0.49) and ongoing (14.64% vs 9.52%, p = 0.41) pregnancy rates between 5 and 6 days of progesterone administration. Our adjusted analysis further corroborated these results. Limitations, reasons for caution The retrospective nature of the study and low number of transfers performed after 6 days of progesterone treatment warrant careful interpretation. This study only evaluated endometrial preparation by vaginal progesterone administration in oocyte recipients and cannot be extrapolated to other routes of progesterone administration or other patient populations. Wider implications of the findings Poorer reproductive outcomes associated with the transfer of day 6 blastocysts appear to be related to a reduced implantation capacity of slow-developing embryos rather than a displaced WOI due to rising progesterone. WOI appears wider than assumed, as prolonged progesterone transformation times had no effect on pregnancy outcomes. Trial registration number Not applicable

Hormone sensitivity and stressful life events predict the effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial

Internalizing mood symptoms are highly prevalent during the menopause transition (perimenopause). Prior research demonstrates that perimenopausal women with greater estradiol (E2) variability are more likely to experience depression symptoms, especially following recent stressful life events (SLEs). Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent SLEs. This research extends prior work by examining the relation between E2 and precise behavioral indicators of depression, including reward-seeking behaviors. The current study utilizes a randomized, double blind, placebo-controlled design to investigate whether sensitivity to E2 flux predicts the effects of a TE2 intervention on reward-seeking behaviors in perimenopausal women, and whether SLE’s moderate any observed associations. Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations, anxiety symptoms, and anhedonia levels. Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). There were no differences in EEfRT performance between randomized groups at baseline. Greater hormone sensitivity predicted more reward-seeking behaviors on the EEfRT task post-randomization, but only for participants randomized to TE2. Notably, the strength of this association increased when women experienced more SLEs. Perimenopausal women who are hormone sensitive with recent life stress may experience a greater benefit of TE2.

Menopausal treatment in women with diabetes and hypertension

Menopausal transition is associated with increased risk of hypertension and metabolic changes predisposing for type 2 diabetes. Moreover, hypertension and type 2 diabetes are independent risk factors for cardiovascular disease, which is the leading cause of morbidity and mortality in women. It is well-known that endogenous estrogen protects against cardiovascular disease by vasodilatation through mechanisms including increased nitric oxid synthesis and reduced angiotensin receptor activity leading to reduced blood pressure. What about menopausal hormone treatment (MHT), could MHT be beneficial and prevent from development of diabetes and cardiovascular disease? Furthermore, is MHT safe in women with pre-existing diabetes and hypertension? Well-controlled diabetes and/or hypertension are not contraindications for MHT. Vasomotor symptoms should be indication for treatment also in these women with special consideration of cardiovascular risk. In fact, MHT can improve diabetic control. However, there is no clear evidence to support that MHT can prevent from developing diabetes. The oral route of MHT can affect blood pressure by liver induction of plasma proteins, which may increase blood pressure and aggravate hypertension. Furthermore, oral estrogen increaes coagulation factors and therby increases the risk of thrombosis. In women with hypertension, transdermal estrogen might be the most appropriate MHT. Transdermal estrogen does not increase blood pressure and is preferable for women with moderate risk for cardiovascular disease. Progestogens with neutral effect on metabolic parameters could also be recommended. The risk benefit balance of using MHT for healthy women is favorable if introduced early in relation to menopause, but the timing hypothesis for primary prevention of cardiovascular disease is still under debate. These questions and the management of menopausal symptoms in women with diabetes and hypertension will be illustrated by a patient case.

Managing the menopause during the pandemic

The structure of the presentation will be 1)Pandemic-Epidemiology 2)General Pandemic-Management 3)HRT and COVID 4)Different spectrum of menopausal symptoms (Europe/Asia) 5)Different risks lead to different HRT. 1)Pandemic-Epidemiology: SARS-COVID-19 has got to be a new disease, China was the first to suffer from the pandemic starting in December 2019 with spread all over the world. Diagnosis, treatment and protective measures have started in Europe in March 2020; up from autumn 2022 in Europe the pandemic changed to endemic, but protective measures still should be continued in risk patients like in hospitals and nursing homes. Rehabilitation will for long-time be an issue like treatment of "Post-" and "Long-COVID". China pursued a zero-COVID-policy until Dec 2022. The sudden stop of almost all measures led to a sharp increase in infections, which shows that the disease will remain a global risk. 2)General Pandemic-Management: Protective measures like vaccination, surgical masks, screening/testing, isolation management, travel/residence history in high-risk regions, education of patients and families had to be the first priority, ahead of other issues such as the management of menopause. 3)HRT and COVID: Already the first prelimary data assessed in Wuhan/China have shown that women with low estradiol-levels had more severe infections with COVID. An analysis of health records of 68,466 COVID-positive patients from 17 countries showed that the fatality risk for women > 50 years receiving HRT was reduced by more than 50% compared to those women not taking HRT (Seeland, 2020). Likewise from a case-control study analyzing the self-reported data of 1.6 million UK menopausal women through the COVID-Symptoms Study Smartphone application (control populations adjusted for age, body mass index, and smoking status) was concluded, that HRT not only can be used, but even can protect from COVID-infections and/or their sequelae (Costeira, 2021). 4)The different spectrum of menopausal symptoms (independent of COVID-infections) comparing data in Europe (showing more vasomotor symptoms) and China (more somatic symptoms) will be presented, including own data. 5)Different risks during HRT consequently lead to different use of HRT, especially more transdermal estrogen combined with progesterone in Europe due to much higher VTE-risk, but more management of the high bleeding-problems in China using individualized (mostly oral) estrogen/progestogen combinations.

Association Between the Route of Administration and Formulation of Estrogen Therapy and Hypertension Risk in Postmenopausal Women: A Prospective Population-Based Study.

Hypertension is the leading global cause of cardiovascular disease and premature mortality in women. The effects of postmenopausal hormone therapy (HT) on blood pressure are uncertain but may be related to route of estrogen administration and formulation of estrogen. We sought to determine the association between route of administration and formulation of estrogen HT and hypertension risk in postmenopausal women. Population-based cohort study with women aged ≥45 years who filled ≥2 consecutive prescriptions for estrogen-only HT, identified from linked provincial health administrative data from Alberta, Canada, between 2008 and 2019. The primary outcome, incident hypertension, was identified using standardized International Classification of Diseases, Ninth and Tenth Revision. Cox proportional hazard models were used to calculate hazard ratios (HRs) for hypertension in women using oral HT compared with nonoral HT (transdermal, vaginal, or intramuscular). In total, 112 240 women used an estrogen-only form of HT. Oral estrogen was associated with a higher risk of hypertension compared with both transdermal (HR, 1.14 [95% CI, 1.08-1.20]) and vaginal (HR, 1.19 [95% CI, 1.13-1.25]) estrogens. Conjugated equine estrogen was associated with an increased risk of hypertension compared with estradiol (HR, 1.08 [95% CI, 1.04-1.14]) but not estrone (HR, 1.00 [95% CI, 0.93-1.10]). Duration of estrogen exposure and cumulative dose of estrogen was positively associated with risk of hypertension. Oral estrogen-only HT use was associated with an increased risk of hypertension in women. In women using estrogen-only HT, nonoral estradiol at the lowest dose and for the shortest time-period is associated with the lowest risk of hypertension.

Advancing menopause care in Australia: barriers and opportunities.

Advancing menopause care in Australia: barriers and opportunities.

Hormone Replacement Therapy after Pubertal Induction in Adolescents and Young Adults with Turner Syndrome: A Survey Study

Introduction: Turner syndrome (TS) is associated with primary ovarian insufficiency (POI) and most adolescents and young adults (AYA) with TS require treatment with hormone replacement therapy (HRT). International consensus guidelines are unclear on the optimal formulation and dosing for HRT after pubertal induction. This study assessed current HRT practice patterns of endocrinologists and gynecologists in North America. Methods: Email listserv members of the North American Society for Pediatric and Adolescent Gynecology (NASPAG) and the Pediatric Endocrine Society (PES) were invited to complete a 19-question survey to assess HRT treatment preferences for the management of POI after completion of pubertal induction in AYA with TS. Descriptive analysis and multinomial logistic regression to predict factors associated with preferred HRT are presented. Results: 155 providers (79% pediatric endocrinology, 17% pediatric gynecology) completed the survey. Although 87% (135) reported confidence in prescribing HRT, only half (51%, 79) were aware of published guidelines. Factors significantly associated with preferred HRT included specialty (p = 0.032) and number of patients with TS seen every 3 months (p = 0.024). Gynecologists were 4 times less likely than endocrinologists to prefer hormonal contraceptives and 4 times more likely to favor transdermal estradiol dose of 100 μg/day as compared to lower doses. Conclusion: Although most endocrinologists and gynecologists report confidence in prescribing HRT to AYA with TS after pubertal induction, there are clear differences in provider preferences based on specialty and higher volume of patients with TS in their practice. Additional studies on comparative effectiveness of the HRT regimens and evidence-based guidelines are necessary for AYA with TS.

403. Independent Effects of Transdermal Estrogen and Oral Micronized Progesterone on Neuroactive Steroids Across the Menstrual Cycle: Descriptive Evidence From a Three-Period, Double-Blind, Crossover Randomized Controlled Trial in Patients With Suicidal Ideation

403. Independent Effects of Transdermal Estrogen and Oral Micronized Progesterone on Neuroactive Steroids Across the Menstrual Cycle: Descriptive Evidence From a Three-Period, Double-Blind, Crossover Randomized Controlled Trial in Patients With Suicidal Ideation

Thrombosis risk with estrogen use for puberty induction in congenital disorders of glycosylation

Congenital disorders of glycosylation are a group of rare related disorders causing multisystem dysfunction, including ovarian failure in females that requires early estrogen replacement. Glycosylation defects also disrupt normal synthesis of several coagulation factors, increasing thrombotic risks and complicating hormone replacement. This series describes four females with different types of CDG who developed venous thromboses while on transdermal estrogen replacement. The authors highlight the knowledge gaps around anticoagulation for this population and propose further investigations.

Pubertal induction in Turner syndrome without gonadal function: A possibility of earlier, lower-dose estrogen therapy.

Delayed and absent puberty and infertility in Turner syndrome (TS) are caused by primary hypogonadism. A majority of patients with TS who are followed at hospitals during childhood will not experience regular menstruation. In fact, almost all patients with TS need estrogen replacement therapy (ERT) before they are young adults. ERT in TS is administered empirically. However, some practical issues concerning puberty induction in TS require clarification, such as how early to start ERT. The present monograph aims to review current pubertal induction therapies for TS without endogenous estrogen production and suggests a new therapeutic approach using a transdermal estradiol patch that mimics incremental increases in circulating, physiological estradiol. Although evidence supporting this approach is still scarce, pubertal induction with earlier, lower-dose estrogen therapy more closely approximates endogenous estradiol secretion.

Endometrial cancer risk with menopausal hormone therapy: Health Insurance Database in South Korea-based cohort study.

To determine the risk of endometrial cancer according to the types of menopausal hormones used. This retrospective cohort study recruited postmenopausal women older than 40 years from 2003 to 2011, utilizing data from the Korean national health insurance system from 2002 to 2019. The menopausal hormone therapy (MHT) group consisted of women who had been prescribed MHT for greater than 6months between 2003 and 2011. The non-MHT group consisted of women who had never used menopausal hormones between 2003 and 2011. A non-MHT group of 1000 550 women and a MHT group of 353 025 women were chosen. In comparison to never-users, the risk of endometrial cancer was not higher in women who reported last using tibolone (adjusted hazard ratio [aHR] 1.08, 95% confidence interval [CI] 0.96-1.2), combined estrogen plus progestin by the manufacturer (aHR 0.83, 0.72-0.96), combined estrogen plus progestin by the physician (aHR 0.88, 0.7-1.12), and transdermal estrogen (aHR 1.13, 0.36-3.52). Tibolone, combined estrogen plus progestin by the physician, and transdermal estrogen do not affect the risk of endometrial cancer. The combination of estrogen plus progestin by the manufacturer decreases the risk of endometrial cancer.

Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Individuals with Turner Syndrome

Study ObjectiveIncidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterized factors associated with AUB among individuals with TS. A secondary objective was to evaluate the management of AUB among this patient population. Design, Setting, Participants, and InterventionWe conducted a retrospective chart review to evaluate individuals with TS undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen. A total of 45 participants were identified between January 2007 and June 2019. ResultsOf the 45 individuals with TS included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs 28%) and a duration of unopposed estrogen greater than 18 months (63% vs 41%), undergo progestin cycling less often than monthly (69% vs 0%), use a micronized progestin dose of less than 200 mg (25% vs 14%), and be noncompliant with HRT (19% vs 0%) compared with those who did not experience AUB. ConclusionThere is a relatively high incidence of AUB among individuals with TS undergoing pubertal induction with transdermal estrogen. Care providers should consider the clinical factors examined to guide monitoring and management of individuals with TS on HRT.

Menopausal hormone therapy and the risk of type 2 diabetes mellitus: Health Insurance Database in South Korea-based retrospective cohort study.

Menopausal hormone therapy (MHT) is known to reduce the incidence of type 2 diabetes mellitus (T2DM); however, since the Women's Health Initiative study, the types and doses of female hormones used for MHT have changed considerably. Therefore, this study was conducted to determine whether MHT, which is currently widely prescribed, increases the risk of T2DM. We performed a retrospective cohort study based on national health insurance data and cancer screening data from 2002 to 2019. We included the MHT group as postmenopausal women older than 40 years who used at least one MHT for at least 6 months between 2003 and 2011. We subclassified the MHT group into five categories; tibolone, combined estrogen plus progestin by the manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by the physician (CEPP), and transdermal estrogen. We selected the non-MHT group as postmenopausal women who had never been prescribed MHT from 2002 to 2019. We compared the incidence of T2DM between the MHT group and the non-MHT group. We enrolled 330,771 women in the MHT group and 798,550 women in the control group. T2DM was diagnosed in 15.2% of the non-MHT group, 16.6% of the tibolone group, 12.1% of the CEPM group, 16.6% of the oral estrogen group, 15.4% of the CEPP group, and 17% of the transdermal estrogen group. In Cox proportional hazard analysis adjusted for variable factors, tibolone, oral estrogen, CEPP, and transdermal estrogen increased the incidence of T2DM. In contrast, there was no change in the risk of T2DM in the CEPM group. MHT, including tibolone, which is currently the most prescribed agent, increased the risk of T2DM; however, CEPM did not increase the risk of T2DM. Only tibolone increased the risk of T2DM in participants older than 70 years.