Estradiol Gel Research Articles

A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.

Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited. We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding. Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up. The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05). Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements. Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health. This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co., Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests. CHiCTR2100053565. 24 November 2021. 9 March 2022.

Evaluating the effectiveness and adverse effects of oral versus transdermal estradiol for endometrial preparation in frozen-thawed embryo transfer: a randomized controlled trial

BackgroundEndometrial preparation significantly influences the success of embryo transfer procedures. Although both oral and transdermal estradiol are common methods for endometrial priming, their efficacy and potential side effects remain uncertain. This randomized controlled trial aims to compare the effectiveness of oral and transdermal estradiol in endometrial preparation, while also evaluating their respective side effects in patients undergoing assisted reproduction treatments.MethodThis randomized clinical trial (ISRCTN15301227) was conducted at Hung Vuong Hospital between July 2020 and March 2022. Among 550 eligible patients undergoing frozen embryo transfer cycles, we included 380 patients for the study. The study protocol and all materials received approval from the Ethics Committee of Hung Vuong Hospital (1315/CN-HĐĐĐ). Participants were randomly assigned to one of two groups: Group A (n =190) received oral estradiol at an initial dose of 4 mg per day for 7 days, with the dose increased according to clinical response. Group B (n =190) received transdermal estradiol at an initial dose of 2 measures of 2.5 g estradiol gel per day for 7 days, with the dose similarly increased according to clinical response. Treatment in both groups began on days 2–3 of the menstrual cycle, with the maximum duration of estradiol administration being 27 days. We compared estradiol levels on the day of progesterone administration, duration of treatment, total estradiol dose, endometrial thickness, pregnancy outcomes, and any observed side effects between the two groups.ResultsGroup A exhibited significantly higher estradiol levels on the day of progesterone administration compared to Group B (270.5 pg/ml versus 186.5 pg/ml, p < 0.001). However, the comparison revealed no significant difference in endometrial thickness between the two groups (10.5 mm versus 10.6 mm, p = 0.85). Furthermore, pregnancy rates including positive human chorionic gonadotropin, clinical pregnancy, ongoing pregnancy, live birth, and pregnancy failure were also found to be similar between the two groups. Notably, a greater proportion of patients in Group A experienced mild side effects compared to those in Group B (20.3% versus 10.1%, respectively; n =37 versus n =18), and this discrepancy was found to be statistically significant (p = 0.007).ConclusionTransdermal estradiol offers comparable endometrial thickness and pregnancy outcomes, along with improved patient compliance and fewer side effects compared to oral estradiol.

P-410 A modified artificial cycle-frozen embryo transfer(mAC-FET) protocol with evidence of corpus luteum(CL) formation as determined by serum relaxin-2 in early pregnancy :a prospective proof-of-concept study

Abstract Study question Can a mAC-FET protocol for endometrial preparation in ovulatory patients lead to formation of a CL as evidenced by serum relaxin-2 in the pregnant patients? Summary answer CL forms in the mAC-FET protocol as serum relaxin-2 in early pregnancy was comparable to that in spontaneous conception.Late luteal rise of relaxin-2 wasn’t demonstrated. What is known already Clinical evidence points to increased incidence of preeclampsia in pregnancies by AC-FET cycles compared to ovulatory FET cycles-natural cycle(NC) and mNC. The absence of CL and it’s secretory products like relaxin-2 is a contributing factor. FET protocols for endometrial preparation in ovulatory patients need to be optimised. NC/mNC-FET protocols need frequent monitoring. Also there is a temporal variability between LH/hCG and progesterone levels. We studied a mAC-FET protocol in ovulatory patients with a delayed start(day3-5 of the cycle),low dose transdermal 17β estradiol gel to see the formation of CL as elucidated by the presence of serum relaxin-2 in early pregnancy. Study design, size, duration A proof-of- concept prospective study was conducted at a tertiary centre (July2023-Dec2023). Serum relaxin-2(R&amp;D/Quantikine/ELISA) was determined in 4 groups of patients- Group-A. mAC-FET(n = 34) 1.On the day of start of progesterone 2.Post-ET day5-9 (along with serum progesterone) 3.In pregnancy(6-9 weeks of gestation) Group-B. AC-FET(n = 8) 1.On the day of start of progesterone 2.In pregnancy(6-9 weeks) Group-C. Spontaneous conception (n = 9) 1.In pregnancy(6-9 weeks) Group-D. Infertility patients ( n = 24) 1.Preovulatory. All patients were ≤40 years with a BMI ≤30kg/m2. Participants/materials, setting, methods In the AC-FET cohort-oral estradiol 6mg/day was started from day1/2 of the cycle. When endometrial thickness was&amp;gt;7mm,progesterone&amp;lt;1ng/ ml then intramuscular progesterone was started- 50mg/day-3 days,100mg on day4-the day of ET(Day-3 embryos) and continued every alternate day.Progesterone gel was added post-ET. In the mAC-FET cohort-17β transdermal estradiol gel(0.06%) 3mg/day was started from day3-5,rest of the protocol was similar. Statistical analysis was performed using appropriate non-parametric tests.Pearson coefficient(r) was used to assess linear-relationship.Two-tailed P&amp;lt;.05 indicated statistical significance. Main results and the role of chance Mean age and BMI of the patients with mAC-FET was 33.3±4.7 years and 24.4±3.7 kg/ m2 which was comparable across all groups (P=.14,P=.52 respectively). Clinical pregnancy rate in the mAC-FET group was 52.94%(18/34). 3 patients had an early abortion. Baseline relaxin-2 levels, median[Interquartile range(IQR)] were comparable- AC-FET cohort-9.1pg/mL(8.6-16.8), mAC-FET cohort-11.5pg/mL(9.6-13.7) and the infertility cohort-10.9pg/mL(8.4-14.5) (P=0.74) The primary outcome was the comparable levels of serum relaxin-2, in early pregnancy in the mAC-FET group and spontaneous conception group - median (IQR) 449.8pg/mL(73.1-492.3) and 487.9pg/mL(419.1-497.8) respectively (P=.12) The relaxin-2 levels, in early pregnancy in the mAC-FET group were significantly higher than the AC-FET group median(IQR) 449.8pg/mL(73.1-492.3) and 7.9pg/mL(7.8-9.5) respectively (P=.0005). As secondary outcomes, we studied the late luteal rise of relaxin-2 in the mAC-FET group and the relationship of late luteal progesterone with relaxin-2 in early pregnancies in the mAC-FET cohort. A late luteal rise of relaxin-2 was not demonstrated in the mAC-FET cohort. The serum relaxin-2, on the day of start of progesterone and on day5-9 post ET- median(IQR) 11.5pg/mL(9.6-13.7) and 11.4pg/mL(9.0-18.5), respectively was comparable (P=.18). The relationship between serum relaxin-2 in early pregnancy and the progesterone levels on day5-9 post ET in the mAC-FET cohort was not significant r = -.059 (P=.07) Limitations, reasons for caution This was a small proof- of-concept single centre study. Due to the limited numbers and short duration of the study, we could not compare efficacy, cancellation rates and pregnancy outcomes of the mAC-FET protocol with other FET protocols. Wider implications of the findings The mAC-FET protocol studied for endometrial preparation was similar to the AC -FET protocol regarding monitoring,flexibility and consistent progesterone exposure with the added advantage of the presence of the CL.This may decrease the risk of maternal/neonatal complications. Larger studies are needed to confirm it’s efficacy and impact on pregnancy outcomes. Trial registration number Not Applicable

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

Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men

Possible interactions of the neuropeptide oxytocin and the sex hormone estradiol may contribute to previously observed sex-specific effects of oxytocin on resting-state functional connectivity (rsFC) of the amygdala and hippocampus. Therefore, we used a placebo-controlled, randomized, parallel-group functional magnetic resonance imaging study design and measured amygdala and hippocampus rsFC in healthy men (n = 116) and free-cycling women (n = 111), who received estradiol gel (2 mg) or placebo before the intranasal administration of oxytocin (24 IU) or placebo. Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis. In men, both oxytocin and estradiol significantly decreased rsFC between the left amygdala and the right and left lingual gyrus, the right calcarine fissure, and the right superior parietal gyrus compared to placebo, while the combined treatment produced a significant increase in rsFC. In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus, whereas the combined treatment had the opposite effect. Collectively, our study indicates that exogenous oxytocin and estradiol have different region-specific effects on rsFC in women and men and that the combined treatment may produce antagonistic effects.

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Abstract The patient is 24-years old male with no previous medical history. He has worked for the last 3 years in the packaging line of Divigel, the estradiol gel of the pharmaceutical company Orion. He sought medical attention 11/2014 due to soreness of both breasts, that had continued for a few weeks. In laboratory tests taken in primary health care, E2 was elevated at 0.49 nmol/l (reference range &amp;lt;0.15 nmol/l), LH immeasurably low (1,7–8,6 U/l), testosterone 33 nmol/l (10–38 nmol/l). Liver and thyroid values were normal. An ultrasound examination of the breasts revealed gynecomastia: mammary gland tissue was seen under the nipple on both sides, 2 cm on the left, 1.5 cm on the right. The ultrasound examination of the testicles did not reveal any abnormality. The patient was referred to the endocrinology outpatient clinic. E2 was then 0,236 nmol/l, testosterone 42, free testosterone 547 pmol/l (190–560 pmol/l), SHGB 51 (18–54 nmol/l), LH &amp;lt;0,10 U/l, FSH 0,12 U/l (1,5–12,4 U/l), PRL 426 (86–324 mU/l), hCG elevated 37 U/l (&amp;lt;2 U/l) and free β-hCG 5,8 pmol/l (&amp;lt;2 pmol/l). In 12/2014, the patient underwent a CT scan of the body and ultrasound examination of the testicles was repeated: no abnormality was found in either examination. 18F-FDG PET/CT of the body was performed in the same month, also with normal findings. At the beginning of 2015, MRI examinations of the mediastinum, lower and upper abdomen, and head were performed; no explanation was found. Cerebrospinal fluid hCG, which was low &amp;lt;1,0 IU/l, and S-AFP, which was 2 kU/l (&amp;lt;10 kU/l), were also checked. At follow-up, hCG continued to rise to 135 U/l and E2 to 0.424 nmol/l. Imaging studies were repeated: CT of the body was performed in 11/2015 and 8/2015, ultrasound examination of the testicles in 4/2015, 8/2015 and 12/2015. In 3/2016, a 11C-metionine PET/MRI of the body was performed. No abnormal findings were found. In the sixth ultrasound examination of the testicles in 6/2016, a 5×6 mm low-echo, solid tumor was finally found on the surface of the left testicle at the very front edge. No abnormalities were found in the right testicle. Testicular operation was performed 6/2016. Findings suitable for seminoma were found in the ice section, after which the left testicle was removed. Histopathological findigs were consistent with seminoma. In immunostaining, the tumor cells were PLAP- and CD117-positive, and a widely positive reaction was seen around the tumor in the seminiferous tubules, consistent with carcinoma in situ findings. CD30-, CKPan-, hCG-, inhibin- and AFP-stainings were negative. The findings were consistent with seminoma, and no other germ cell tumor components were found. After surgery, E2 and hCG values normalized. Abdominal CT examination did not reveal any metastases. Follow-up by an oncologist continued for five years, and no signs of recurrence were found. Sometimes we know what we are looking for, but reaching a diagnosis may require persistence and repeated examinations.

Branch retinal vein occlusion secondary to hormone replacement therapy in a transgender woman

To report a case of branch retinal vein occlusion (BRVO) in a transgender woman having undergone hormone replacement therapy. Observational case report. A 44-year-old transgender woman on hormone replacement therapy with transdermal estradiol gel for the past 6 years was referred for sudden loss of vision and metamorphopsia in her left eye (LE) for the past 3 weeks. Best-corrected visual acuity (BCVA) was 20/20 in her right eye (RE) and 20/40 in her LE. Dilated fundus examination showed deep flame-shaped hemorrhages, cotton wool spots, and arteriovenous crossing changes. Spectral-domain optical coherence tomography (SD-OCT, Spectralis; Heidelberg Engineering, Heidelberg, Germany) showed retinal edema in the superonasal perifoveal area. Optical coherence tomography angiography (OCTA PlexElite, Carl Zeiss Meditec, Inc, Dublin, CA) revealed the presence of areas of non-perfusion, disorganization of the capillary network and capillary ectasia and dilation. The patient was treated with 3 monthly intravitreal injections of aflibercept. Three-month follow up revealed complete resolution of the macular edema, with BCVA having improved to 20/20 in the LE. As estrogen increases cardiovascular risk when used in hormone replacement therapy, RVO is a complication that must be taken into account by clinicians, especially in transgender women (male-to-female) who are more at risk.

Assessment of estrogen exposure from transdermal estradiol gel therapy with a dried urine assay

Transdermal estradiol gel is a commonly used menopausal hormone therapy. In research studies investigating the pharmacokinetics and clinical utility of transdermal estradiol gels, serum is often used to measure estradiol levels. Serum results only represent a moment in time during phlebotomy and thus provide little information and allow for limited inference unless serial measurements are performed. In contrast, dried urine may provide a representation of serum estradiol levels over a longer period of time, while also being non-invasive and easier to collect. The primary aim of this study was to evaluate a dried urine method to determine if it may be a viable option for evaluating estrogen exposure resulting from transdermal estradiol gel use. A secondary aim was to explore differences in the urinary estrogen profiles of premenopausal women on no therapy and postmenopausal women who were either on transdermal estradiol gel therapy or no therapy at all. The results of this study demonstrated that the expected dose-proportional changes in estrogen exposure can be observed in the urinary estrogen profile using a GC–MS/MS dried urine assay. The GC–MS/MS assay also showed the differences in the urinary estrogen profiles of premenopausal women, postmenopausal women on estrogen replacement therapy, and postmenopausal women on no therapy.

Impact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women

Postmenopausal women with genitourinary symptoms of menopause are often prescribed vaginal estradiol or moisturizer for symptom improvement, but the impact of these treatments on the local microenvironment is poorly understood. To compare changes in the vaginal microbiota, metabolome, and pH among women using low-dose vaginal estradiol tablet or low pH moisturizer gel for 12-weeks vs low pH placebo. This is a post hoc prespecified secondary analysis of a 12-week multicenter randomized clinical trial among postmenopausal women with moderate to severe genitourinary symptoms. Women were enrolled between April 2016 and February 2017; final follow-up visits occurred in April 2017. Data were analyzed from November 2018 to July 2021. Ten-μg vaginal estradiol plus placebo gel vs placebo tablet plus vaginal moisturizer vs dual placebo. The main outcome measures were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Of 302 postmenopausal women from the parent trial, 144 women (mean [SD] age, 61 [4] years) were included in this analysis. After 12 weeks, the microbiota was dominated with Lactobacillus and Bifidobacterium communities among 36 women (80%) in the estradiol group, compared with 16 women (36%) using moisturizer and 13 women (26%) using placebo (P < .001). The composition of vaginal fluid metabolites also varied after 12-weeks among women in the estradiol group with significant changes in 90 of 171 metabolites measured (53%) (P < .001), including an increase in lactate. The 12-week pH among women in the estradiol group was lower vs placebo (median [IQR] pH, 5 [4.5-6.0] vs 6 [5.5-7.0]; P = .005) but not the moisturizer group vs placebo (median [IQR] pH, 6 [5.5-6.5]; P = .28). There was a decrease in pH from baseline to 12-weeks within the moisturizer (median [IQR] pH, 7 [6.0-7.5] vs 6 [5.5-6.5]; P < .001) and placebo (median [IQR] pH, 7 [7.0-7.5] vs 6 [5.5-7.0]; P < .001) groups. Women with high-diversity bacterial communities at baseline exhibited greater median change in pH compared with women with low-diversity communities (median [IQR] change, -1 [-2 to -0.5] vs -0.3 [-1.1 to 0], P = .007). This secondary analysis of a randomized clinical trial found that use of vaginal estradiol tablets resulted in substantial changes in the vaginal microbiota and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline. Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH. Estradiol use may offer additional genitourinary health benefits to postmenopausal women. ClinicalTrials.gov Identifier: NCT02516202.

Assessment of Estrogen Exposure from Transdermal Estradiol Gel Therapy with a Dried Urine Assay

Assessment of Estrogen Exposure from Transdermal Estradiol Gel Therapy with a Dried Urine Assay

Effects of menopausal hormone therapy on ambulatory blood pressure and arterial stiffness in postmenopausal Korean women with grade 1 hypertension: a randomized, placebo-controlled trial

BackgroundEstrogen therapy in early menopausal women decreases the risk of coronary heart disease and parenteral, but not oral, estrogen is reported to reduce blood pressure (BP). Progestogens are typically added to estrogens to prevent unopposed endometrial stimulation. The effects of progestogen on BP have been less well studied to date. This study was conducted to explore the impacts of micronized progesterone (MP4) combined with percutaneous estradiol gel (PEG) on hemodynamics in postmenopausal Korean women with grade 1 hypertension.MethodsFifty-two postmenopausal women (aged 49–75 years) with systolic BP (SBP) of 140–160 mmHg or diastolic BP (DBP) of 90–100 mmHg were randomly assigned for 12 weeks to placebo (n = 16), estrogen therapy (ET) (n = 19) with PEG (0.1 %, 1 g./d), or estrogen + progestogen therapy (EPT, n = 17) with PEG and MP4 (100 mg/d). The primary endpoint was ambulatory BP and the secondary endpoints were arterial stiffness as brachial–ankle pulse-wave velocity (baPWV) and aortic parameters on applanation tonometry.ResultsOne woman in the ET group dropped out, so 51 participants were finally analyzed. Outcome measures for ambulatory BP and arterial stiffness were not different between groups. Within-group comparisons showed that EPT significantly decreased daytime heart rate and baPWV: the changes from baseline (mean ± standard deviation) were − 2.5 ± 5.7 bpm (P = 0.03) and − 0.6 ± 1.4 m/s (P = 0.04), respectively. After adjusting for baseline, linear regression analysis revealed a significant difference in the relationship between baseline and 12-week baPWV among groups (P = 0.02). The relationship was significantly different between placebo and ET (P = 0.03) and EPT (P = 0.01), respectively, but not between ET and EPT. Additionally, pooled results of active treatments disclosed that SBP, DBP, PWV, and augmentation index at the aorta were significantly reduced relative to baseline.ConclusionsThere was no difference in ambulatory BP between ET and EPT in postmenopausal Korean women with grade 1 hypertension. Further, ET and EPT similarly decreased baPWV from baseline as compared with placebo. MP4 might not adversely influence estrogen effects on ambulatory BP and arterial stiffness.Trial registrationClinical Research Information Registry, KCT0005405, Registered 22 September 2020 - Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do?all_type=Y&search_page=L&pageSize=10&page=1&seq=17608&search_lang=E.

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial

Objectives An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. Methods Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). Results Kaplan–Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. Conclusions MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

Natural cycle versus hormone replacement cycle for transferring vitrified-warmed embryos in eumenorrhoeic women. A retrospective cohort study

ObjectiveTo compare pregnancy, miscarriage and live birth rates and cycle monitoring parameters between Natural Cycle (NC-FET) and Hormone replacement cycle (HRC-FET) in eumenorrhoeic women undergoing vitrified-warmed autologous embryo transfer. Study designSingle-centre retrospective cohort study analyzed 173 NC-FET and 507 HRC-FET cycles with transfer of day2/3/5/6 embryos. Natural cycle monitoring occurred with serial ultrasound with the first day of the scan determined by the shortest cycle frequency. Serum progesterone was ordered when ultrasound was ambiguous in ascertaining ovulation. For HRC-FET oral estradiol valerate was used in fixed or escalating doses with maximum daily dose of 12 mg. Transdermal estradiol gel was added when desired endometrial thickness was not achieved. Vaginal progesterone was introduced with Endometrial thickness(ET)> = 7 mm. Embryos were transferred after stage-appropriate progesterone exposure. Luteal support was given with vaginal progesterone in NC-FET and vaginal and oral progesterone in HRC-FET. Primary outcome was live-birth-rate. Secondary outcomes were ET, length-of-estrogenic-phase, numbers-of-ultrasounds&hormone-monitoring, pregnancy&miscarriage rate. The odds ratio for live-birth was adjusted for age, embryo number, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Quantitative variables were compared using unpaired-t-test and qualitative variables with chi-square test. Two tailed p-value < 0.05 was considered significant. Binary logistic regression was used to calculate adjusted odds for live-births. ResultsThe two cohorts were comparable in age, infertility-duration, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Length-of-estrogenic-phase was significantly shorter for NC-FET than HRC-FET 14.32 ± 2.83vs.18.18 ± 4.48; p = 0.0001) as was mean ultrasound-monitoring-scans (2.73 ± 0.95vs. 3.3 ± 1.04; p = 0.0001). Mean-endometrial-thickness (8.75 ± 1.83vs. 8.5 ± 1.25; p = 0.25) and mean-hormonal-tests (1.75 ± 1.28 vs. 1.88 ± 0.69; p = 0.09) did not differ significantly between NC-FET vs HRC-FET. Significantly higher live births took place in NC-FET vs. HRC-FET (87/173 = 50.3%vs.204/507 = 40.2%;p = 0.026). No significant difference was found in pregnancy rate (66.5% vs. 58%; p = 0.058) or in the pregnancy loss rate (24.3%vs30.6%; p = 0.23). The odds ratio for live-births adjusted for relevant variables was 1.48 (1.03–2.13) in NC-FET compared to HRC-FET. ConclusionsNC-FET is a superior method of endometrial preparation compared to HRC-FET in eumenorrhoeic women since it has a shorter estrogenic phase, reduces patient visits to the hospital and improves live birth rates. Future adequately powered studies should look at antenatal and perinatal outcomes, patient satisfaction rates and cost-effectiveness in the two endometrial preparation regimes.

Comparison of art outcome in frozen embryo transfer cycle using oral estradiol valerate and estradiol transdermal gel

Aim: Endometrial preparation with exogenous estrogen is a common practice in frozen embryo transfer (FET) cycles. The aim of this study was to compare the clinical outcome of oral estradiol valerate versus transdermal estrogen (17-β estradiol) gel in FET cycles. Materials and Methods: A prospective pilot study was carried out at a tertiary fertility clinic after Ethics Committee approval from January 2018 to December 2018. It included 103 infertile women who underwent FET cycles. Either oral estradiol valerate or transdermal 17-beta estradiol was used for endometrial preparation. Combination was used in case of breakthrough bleeding or if optimal endometrial thickness was not achieved. Baseline demographic parameters and details of the stimulation protocol and embryogenesis in fresh cycle were noted. In the FET cycle, the patient was seen on day 2 of menstrual cycle, where baseline ultrasound (USG), estradiol, and progesterone levels were done. If normal, the patients were given either oral or dermal preparation. The patient was seen again on day 9 for endometrial thickness and if required again after 2 days till endometrial thickness was 9 mm. If optimal endometrial thickness was not achieved or there was breakthrough bleeding, combination of both oral and dermal preparation was used. Once the endometrial thickness was 9 mm or more, progesterone was started, and ET was done on day 5. On the day of progesterone initiation, endometrial thickness, endometrial volume by 3D, and Doppler indices [pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)] were noted. The primary outcome of the study was clinical pregnancy rate (CPR) and live birth rate (LBR). Results: There was no statistical difference in any of the demographic parameters in groups A and B. In group C, the pregnant patients were younger with higher body mass index and follicle-stimulating hormone and lower anti-Mullerian hormone and antral follicle count when compared with those who did not conceive. Demographics of the fresh cycle did not show any significant difference in dose and duration of stimulation, fertilization, cleavage, and blastulation rate in group A. In group B, the fertilization rate was significantly higher in the pregnant group (0.001), whereas the other parameters were similar. In group C, the pregnant group required more dose and days of stimulation and had lower oocytes retrieved but had a higher blastulation rate. In the hormone replacement therapy (HRT) cycle, there was no difference in the mean duration of HRT in groups A and B but was significantly higher in group C when compared with group A. The CPR with oral estradiol valerate, transdermal gel, and combination therapy was 34.85%, 35%, and 52.94%, respectively. The LBR with oral estradiol valerate, transdermal gel, and combination therapy was 25.76%, 30%, and 47.06%, respectively. Though the CPR and LBR were higher in group C, it did not reach statistical significance and this could be due to small sample size. There was no difference in the abortion rate (oral 7.58%, gel 5%, combination 5.88%) between the three groups. The implantation rate (oral 26%, gel 25.8%, combination 29.03%) in the three groups was also similar. There was also no statistical difference in the endometrial thickness, volume, and blood flow between the three groups. The cut-off values for Doppler indices for a positive pregnancy were as follows: Group A—PSV: >8.7, RI: <0.99, PI: >1.54; Group B—PSV: >5, RI: <0.72, PI: >2.1; Group C—PSV: >5.6, RI: <0.64, PI: >1.29. Conclusion: Both the oral estradiol valerate and transdermal 17-beta estradiol were equally effective for optimal outcome in an FET cycle in HRT. Those not responding to single preparation may benefit from combination therapy. Transdermal 17-beta estradiol gel may be of use in those patients who have breakthrough bleeding with oral preparation which may be due to hepatic bypass effect.

A prospective randomized comparative study between transdermal estradiol gel and oral estradiol valerate tablets for successful clinical outcome in frozen-thawed embryo transfer cycles

A prospective randomized comparative study between transdermal estradiol gel and oral estradiol valerate tablets for successful clinical outcome in frozen-thawed embryo transfer cycles

A prospective randomized comparative study between transdermal estradiol gel and oral estradiol valerate tablets for successful clinical outcome in frozen-thawed embryo transfer cycles

Background: The aim of this study was to evaluate the use of transdermal estradiol gel and compare it with oral estradiol valerate tablets for the preparation of endometrium in frozen-thawed embryo transfer (FET) cycles. Methods: This prospective trial included 100 women undergoing FET cycles during study period and they were randomized into one of the two groups. Group 1 (n = 50) received oral estradiol valerate tablet and group 2 (n = 50) received transdermal estradiol gel from day 2 of menstrual cycle and endometrial thickness monitored with transvaginal ultrasonography. Primary outcome of this study was to compare clinical pregnancy rate (CPR) between the two groups. Secondary outcomes were implantation rates (IRs), CPRs, miscarriage rates (MRs), endometrial thickness at the start of progesterone, cycle cancellation rates, undesirable side effects, and patient satisfaction score. Statistical testing was performed with SPSS 17.0. Results: There was no clinically significant difference in biochemical pregnancy rate, CPR, IR, and MR between the two groups. Endometrial thickness on day of progesterone start was higher in group 2 as opposed to group 1 (9.81 ± 0.861 vs. 9.46 ± 0.830; P-value = 0.043) which was clinically significant. Almost 37.5% patients (n = 18) in group 1 had mild adverse effects when compared with only 12.76% (n=6) in gel group (group 2). Conclusion: We conclude that transdermal estradiol gel is equally efficacious as oral estrogen in hormone replacement FET cycles but with added advantage of better patient comfort and lesser side effects with transdermal gel.

Effect of estradiol vaginal gel on vaginal atrophy in postmenopausal women: A randomized double-blind controlled trial.

To evaluate the efficacy and safety of 25 μg of estradiol gel on postmenopausal vaginal tissue. This randomized double-blind controlled trial included postmenopausal women with vaginal atrophy who attended our menopause clinic during July 2017-January 2018. Women were randomly assigned to the estradiol gel group or control group (K-Y® Jelly). Treatment consisted of 2 mL of product applied intravaginally daily for 2 weeks, and two doses per week for the next 6 weeks. The most bothersome symptom (MBS), vaginal health index (VHI), vaginal pH, vaginal maturation index, vaginal maturation value (VMV), female sexual function index (FSFI), serum estradiol level and endometrial thickness were evaluated at baseline, 4 and 8 weeks. Seventy-five of 80 women completed the trial. After 8 weeks of treatment, VMV, VHI, vaginal pH and FSFI improved significantly in the estradiol group, with no observed change in the control group. The MBS was decreased in both groups with no significant difference between groups. Serum estradiol level and endometrial thickness were not significantly different between groups at baseline or at week 8. Estradiol vaginal gel demonstrated an ability to reverse vaginal atrophy with a high safety profile and low systemic absorption of estradiol.

MON-198 Feminizing Regimen Requirements in Transgender Females Following Orchiectomy

Introduction: Transgender females (TF) may undergo orchiectomy as part of their treatment. However, there is no clear recommendation in hormonal transition between pre- and post-orchiectomy (1, 2). Methods: All TF with orchiectomy in the transgender registry at Boston Medical Center (BMC) were reviewed. Feminizing regimens prior to and after orchiectomy were evaluated. The type, form and dose of hormones along with serum estradiol, testosterone, FSH and LH were assessed. Results: 124 TF consented to be included in the transgender registry at BMC. 23 of 124 (18%) TF had orchiectomy. 10/23 TF had the hormonal regimen available pre-orchiectomy and 6 months or more post-orchiectomy. All 10 TF used oral 17-beta estradiol. 6 TF were prescribed less estradiol relative to their pre-orchiectomy regimen, 3 were prescribed the same estradiol dose and 1 was prescribed a higher estradiol dose. An average of adjusted post-orchiectomy estradiol doses was 78% (range 50%-150%) of pre-orchiectomy dose. Among 10 TF with an available hormone regimen pre-and post-orchiectomy, 5 (50%) had serum estradiol at goal (100-200 pg/mL) and FSH in a pre-menopausal cis-female range. Among these 5 TF, the average of the adjusted post-orchiectomy estradiol dose was 96% (range 50%-150%) of the pre-orchiectomy dose. Estradiol doses up to 6 months or more following orchiectomy were available in 17 TF. 15 used oral 17-beta estradiol (average dose of 3.1mg/day with the range of 1-8 mg), 1 used oral conjugated estradiol and 1 used 17-beta estradiol gel. 7/17 had estradiol level at goal (100-200 pg/mL) and FSH in the pre-menopausal female range. All 7 TF used oral 17-beta estradiol. An average of post-orchiectomy estradiol doses was 2.85 mg/day (range 1-5 mg). Conclusion: Most TF who underwent orchiectomy had a lower estradiol dose (approximately 75% of the pre-orchiectomy regimen). However, to achieve the estradiol level at goal and maintain FSH in the the pre-menopausal female range, trans women required estradiol doses closer to the pre-orchiectomy regimen. The dose range of oral 17-beta estradiol in post-orchiectomy TF is 1-5 mg, similar to recommendations for TF who have not undergone orchiectomy (2-6 mg) (1).

The Effects of Menopausal Hormone Therapy on Serum Level of C-reactive Protein in Postmenopausal Korean Women.

ObjectivesInflammation is a major mechanism underlying coronary heart disease (CHD) and C-reactive protein (CRP) is a marker of inflammation. When administered soon after menopause, menopausal hormone therapy (MHT) prevents CHD. This study was conducted to examine the impact of estrogen by administration route on CRP in postmenopausal Korean women using micronized progesterone (MP4) for endometrial protection.MethodsThis retrospective cohort study included 129 healthy women without CHD risk factors. Eighty-nine women took oral estrogen (conjugated equine estrogen, 0.625 mg/day or equivalent), and 40 women applied a 1.5-mg/day 0.1% percutaneous estradiol gel. MP4 was added in 82 women with an intact uterus. The CRP level was measured at baseline and three and six months after initiation of MHT.ResultsThe baseline characteristics were comparable between the MHT groups except current age and age at menopause. After controlling for age, menopausal age, body mass index, and basal CRP, no significant change in CRP was observed in the oral estrogen group (n = 29). Follow-up CRP levels were also similar to the baseline in the percutaneous estrogen group (n = 18). However, three-month CRP was significantly lower than six-month CRP, and there was a significant time trend within the percutaneous estrogen group. However, the group difference did not reach statistical significance. CRP also did not differ by addition of MP4 in either group.ConclusionsIn postmenopausal Korean women, no change in CRP was observed with oral estrogen, while percutaneous estrogen might decrease CRP. The estrogenic impacts were not influenced by adding MP4.

P155 Transdermal oestrogen prevents cyclically-recurrent genital herpes: Abstract P155 Table 1

<h3>Background</h3> Some women suffer cyclical recurrences of genital herpes (c-RGH) immediately prior to menstruation, which are effectively prevented using aciclovir in the luteal phase only. This is more likely to occur in perimenopausal women whose immunity is diminished by premenstrual dysphoric disorder (PMDD), which is treatable with transdermal estradiol. <h3>Aim</h3> To observe the frequency of herpes recurrences in women commencing estradiol treatment for perimenopausal PMDD. <h3>Methods</h3> 12 perimenopausal women median age 41 years (range 36–45) presented between 2006–15, each meeting the criteria for PMDD subsequently defined in DSM-5. Each had at least 4 consecutive monthly episodes of c-RGH (culture-proven HSV2) before some took luteal-phase aciclovir, then all switched to transdermal 17-beta estradiol gel 0.5mg daily for 14 days in the luteal phase or continuously for those using Mirena. Subjects self-reported mood with a modified daily symptom chart and herpetic symptoms over 9 months follow-up during which no aciclovir was taken pre-emptively. Intention-to-treat analysis included 10 cycles where treatment was omitted in error and both conditions recurred. <h3>Results</h3> All women experienced substantial or complete relief of PMDD in all but three treated cycles. Only 13 symptomatic c-RGH episodes occurred on treatment in 108 woman-months’ observation. <h3>Conclusion</h3> Transdermal estradiol treatment is a novel and biologically plausible method of preventing cyclically-recurrent genital herpes as it stabilises the hormonal milieu and diminishes immune suppression caused by PMDD.