Transdermal Estradiol Research Articles

S2989 Excessive Hormonal Therapy in a Male Transitioning to a Female Causing Cirrhosis

Introduction: High doses of progestins/estrogens can cause elevated liver enzymes, serum aminotransferase elevations with no changes in alkaline phosphatase or bilirubin, 1 to 2 weeks after treatment. These side effects are usually transient and resolve with dose modification or discontinuation. We present a unique case where a male in-transition to female was found to be cirrhotic from hormonal dose therapy. Gastroenterologists should be aware of the importance of starting hormonal therapy in the transgender process as exogenous estrogen therapy may lead to underlying liver disease. Case Description/Methods: This is a 63 year male on hormone replacement therapy who presented to the hospital for evaluation of hyperlipidemia, hypertension, diabetes, and gender dysmorphia with concerns of questionable abdominal pain and early findings of cirrhosis. During evaluation, he complained of abdominal pain, jaundice, and dark urine. His LFTs were unremarkable prior to the visit. Upon inquiry of a prior history of fatty liver disease, he admitted not following up with his doctor. The patient then described how he had recently begun hormonal therapy to transition to a female. He reported first starting on an estrogen patch with a transition to estradiol 2mg daily. He denied having a prior history of alcohol abuse or other risk factors of cirrhosis. His liver function tests were noted to be T. Bili of 6.3, D. Bili of 3.2, ALK phos of 263, AST of 51, ALT of 176 and lipase of 100. Given his elevated LFTs an ultrasound and MRCP were performed which showed cirrhosis with portal hypertension and cholelithiasis. He did not have any synthetic liver dysfunction. Upon discontinuation of his estradiol his LFTS resolved back to baseline after five days. Discussion: Gastroenterologists should be aware of gender-affirming hormonal therapies in the transgender population as they can lead to long term sequale such as developing cirrhosis. Evidence in the literature is sparse with no consensus on the long term effects of high dose hormone therapy. Further studies should focus on the risk factors of starting hormonal therapy using demographic characteristics, BMI, and alcohol use as further parameters for gauging cirrhosis. We present the case of a 63-old trans-female patient whose hormone therapy can be associated directly with liver cirrhosis.

Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study.

The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women. Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month. There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment. Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.

Persistent gap in menopause care 20 years after the WHI: a population-based study of menopause-related symptoms and their management

ObjectivesTo assess the current management of menopause in France with regard to menopause-related and genitourinary symptoms, with a focus on use of menopause hormone therapy (MHT). Design, setting, and participantsThe ELISA Study is a population-based survey of 5004 French representative women aged 50 to 65 years. From July to August 2020, the participating women answered an online computer-assisted web interview on menopause-related and genitourinary symptoms and their management, including use of MHT. Main outcomes and measuresPrevalence of menopause-related and genitourinary symptoms in postmenopausal women. Management of these symptoms, including the reasons for not doing so, management by health care providers, and use of MHT. ResultsAmong the 5004 selected women, 4041 whose postmenopausal status was confirmed were included in the final analyses. Of the untreated 3685 women, 87 % reported at least 1 menopausal symptom, with a significantly higher percentage of symptomatic women in the 50–54 age group (92 %, p < 0.05) than in the other two age groups (55–59 years: 89 % and 60–64 years: 82 %). 68 % of the surveyed women experienced on average 2.5 symptoms of the genitourinary syndrome of menopause (GSM). Using a visual analogue scale (VAS) from 0 (no impact) to 10 (high impact) to evaluate the impact of menopausal/GSM symptoms on their quality of life, mean VAS score was 5.9 (SD: 2.2), with 25 % of the women aged 55–59 years rating their quality of life between 8 and 10. 61 % of the surveyed women reported being regularly followed by a health care professional. 44 % of women reported never having discussed their menopausal/GSM symptoms with a health care provider. The main reasons were because menopause is “a normal part of women's lives”, because it was not “necessary to do so”, or their symptoms were “not serious enough”. Only 242 women (6 %) were current MHT users, of whom 49 % were using estrogen-alone therapy and 71 % were using transdermal estrogens. Fear of hormones (35 %) and MHT side-effects (25 %) were the main reasons given for not using MHT. 62 % of the women reported that the decision not to take MHT was supported by their physician. Conclusions and relevanceThis large population-based survey confirmed not only the high prevalence of menopause-related and GSM symptoms in postmenopausal women within the first 10–15 years after menopause, but also the very low percentage of MHT users in France. Twenty years after the publication of the initial Women's Health Initiative (WHI) results, management of postmenopausal women is still characterized by unmet needs in menopausal care. Therefore, there is a strong need to educate the public and health care providers about menopause-related problems and possible solutions, including MHT, through dedicated educational programs.

Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women – A randomized clinical trial

BackgroundThe menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown. This study aimed at determining relationships between E2 fluctuations, mood symptoms, and physiologic stress-reactivity (cortisol and interleukin-6) and whether differences in mood-sensitivity to E2 fluctuations predict mood responses to TE2 treatment. MethodsThis randomized, double-blind, placebo-controlled trial investigated medically healthy women (46–60 years) in the early or late menopause transition. Baseline E2-sensitivity strength was calculated from eight weekly individual correlations between week-to-week E2 change and index week anxiety (State-Trait Anxiety Inventory) and anhedonia (Snaith-Hamilton Pleasure Scale). Women then received eight weeks of TE2 or transdermal placebo. ResultsAnalyses included 73 women (active TE2 n = 35). Greater baseline E2 fluctuations predicted greater anhedonia (p = .002), particularly in women with more SLEs. Greater E2 fluctuations also predicted higher cortisol (p = .012) and blunted interleukin-6 (p = .02) stress-responses. Controlling for baseline symptoms, TE2 was associated with lower post-treatment anxiety (p < .001) and anhedonia (p < .001) versus placebo. However, the efficacy of TE2 for anxiety (p = .007) and also for somatic complaints (p = .05) was strongest in women with greater baseline E2 sensitivity strength. ConclusionsTE2 treatment reduced perimenopausal anxiety and anhedonia. The ability of baseline mood-sensitivity to E2 fluctuations to predict greater TE2 efficacy has implications for individualized treatment of perimenopausal anxiety disorders.

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa.

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14–25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.

Fibromyalgia and menopause: an open study on postmenopausal hormone therapy.

Fibromyalgia women (FM) seems to get worse at menopause suggesting some influence of estrogens on its pathophysiology. We aimed to study the influence of postmenopausal hormone therapy (HT) in FM, the relationship with sleep and FM impact. We analyzed prospectively 69 menopausal women, divided in two groups, FM group (FMG; N.=32) and comparison group (CG; N.=28) submitted to HT for twelve weeks (1.2 mg/g transdermal estradiol, 100 mg micronized natural progesterone oral/daily). Data on Utian Quality of Life Questionnaire (UQOL) and Pittsburgh Sleep Quality Index (PSQI) were obtained in both groups, at entrance and twelve weeks after HT. FM patients also completed the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) and fibromyalgia severity (FS). FM patients improved significantly the FIQ-R (P=0.0001, median FIQ-R score 30% lower), mainly the severity of FM, assessed by FS (P<0.0001). Both groups had improved quality of life and sleep (UQOL: P=0.0001; P=0.001, PSQI: P<0.0001; P=0.007, respectively). Differences between first and second PSQI were greater for CG than for FMG (P=0.008). HT improving sleep and quality of life in both groups; it was a significant clinical improvement seen by FIQ and FS in FM patients. These changes characterize improvement of functional status and symptoms severity.

016 Case report: Turner syndrome

This is the case report of a 16-year-old adolescent with Turner Syndrome and a family and personal background of migraines without auras. The diagnosis was at the neonatal stage with XO karyotype [ [1] Thayalan K, Chung K, Kothari A. Turner syndrome – The clinical spectrum and management dilemmas. AJUM November 2018 21 (4) 219. Google Scholar ]. Growth Hormone and steroid therapy to induce growth and puberty was prescribed [ [2] Irzyniec T. Jeż W. Lepska K. Maciejewska-Paszek I. Frelich J. Childhood growth hormone treatment in women with Turner syndrome - benefits and adverse effects. Sci Rep. 2019 Nov 4; 9: 15951 Crossref PubMed Scopus (11) Google Scholar ]. Sex hormone treatment consisted of transdermal estrogens in increasing doses. Over the last 6 months micronized progesterone was added and the patient had withdrawal bleeding [ [3] Viuff M.H. Berglund A. Juul S. Andersen N.H. Stochholm K. Gravholt C.H. Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality. J Clin Endocrinol Metab. 2020; (Feb 1;105(2):dgz039) Crossref PubMed Scopus (19) Google Scholar ]. Later on, the patient received contraceptives for a year as steroid substitution treatment [ [4] Mathez ALG, Monteagudo PT, do Nascimento Verreschi IT, Dias-da-Silva MR. Levonorgestrel correlates with less weight gain than other progestins during hormonal replacement therapy in Turner Syndrome patients. Sci Rep. 2020 May 19;10(1):8298. Google Scholar ]. The reason for consultation was a refusal to continue receiving contraceptives due to poor tolerance with permanent headaches and poor quality of life. An interdisciplinary approach was made and steroid treatment in Turner Syndrome patients was highlighted. The advised treatment was transdermal estrogens and cyclic micronized progesterone together with Topiramate to prevent migraines, and psychological support was recommended. Fertility counseling was performed [ [5] Oktay K. Bedoschi G. Berkowitz K. Bronson R. Kashani B. McGovern P. et al. Fertility Preservation in Women with Turner Syndrome: A Comprehensive Review and Practical Guidelines. J Pediatr Adolesc Gynecol. 2016 Oct; 29: 409-416 Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar ].

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.

Acute progesterone feedback on gonadotropin secretion is not demonstrably altered in estradiol-pretreated women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) demonstrate gonadotropin‐releasing hormone (GnRH) pulse generator resistance to suppression with 7 days of progesterone and estradiol administration. It remains unknown whether such women demonstrate impairments in acute progesterone negative feedback on LH pulse frequency or progesterone positive feedback on gonadotropin release. This was a randomized, double‐blind, placebo‐controlled crossover study designed to test the hypothesis that acute, progesterone‐related suppression of LH pulse frequency and progesterone‐related augmentation of gonadotropin release are impaired in PCOS. Twelve normally cycling women and 12 women with PCOS completed study. Volunteers were pretreated with transdermal estradiol (0.2 mg/day) for 3 days and then underwent a frequent blood sampling study (20:00–20:00 h), during which they received micronized progesterone (100 mg) or placebo at 06:00 h. In a second study admission, volunteers received the intervention they did not receive during the first admission, but the protocol was otherwise identical. The primary outcome measures were LH secretory characteristics and circulating gonadotropin concentrations. Exogenous progesterone did not reduce LH pulse frequency in either group. Mean LH, pulsatile LH secretion, LH pulse mass, and mean FSH increased more with progesterone compared to placebo in both groups. Although trends toward less pronounced changes in LH pulse mass and pulsatile LH secretion were observed in the PCOS group, these differences were not statistically significant. In summary, exogenous progesterone did not suppress LH pulse frequency within 12 hours in estradiol‐pretreated women, and the positive feedback effect of progesterone on gonadotropin release was not demonstrably impaired in PCOS.New & NoteworthyThis study indicated that exogenous progesterone does not reduce LH pulse frequency within 12 h in women with PCOS, but progesterone acutely increased gonadotropin in these women. This study suggested that progesterone‐related augmentation of gonadotropin release may be impaired in PCOS compared to normally cycling women, but this finding was not statistically significant.

Oral Versus Transdermal Estrogen for Uterine Maturation in Girls with Turner Syndrome

Background: Turner syndrome (TS) is a genetic disorder caused by the absence of a part or whole X-chromosome with an estimated prevalence of 25-50/100,000 females. The predominant gynecologic manifestation of TS is primary ovarian insufficiency (POI) and inadequate development of secondary sexual characteristics and uterine size. Although uterine growth to allow for future spontaneous pregnancy or embryo transfer is an important goal of care for girls with TS, the optimal method of estrogen delivery and dosing for uterine maturation is unknown.

The effect of transdermal gender-affirming hormone therapy on markers of inflammation and hemostasis.

Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone therapy on markers of inflammation and hemostasis. In this exploratory study, 48 trans women using estradiol patches plus cyproterone acetate (CPA) and 47 trans men using testosterone gel were included. They were between 18 and 50 years old and did not have a history of cardiovascular events. Measurements were performed before and after 3 and 12 months of hormone therapy. After 12 months, in trans women, systemic and endothelial inflammatory markers decreased (hs-CRP -66%, (95% CI -76; -53), VCAM-1-12%, (95% CI -16; -8)), while platelet activation markers increased (PF-4 +17%, (95% CI 4; 32), β-thromboglobulin +13%, (95% CI 2; 24)). The coagulation marker fibrinogen increased transiently, after 3 months (+15%, (95% CI 1; 32)). In trans men, hs-CRP increased (+71%, (95% CI 19; 145)); platelet activation and coagulation markers were not altered. In both trans women and trans men, leptin and adiponectin changed towards reference values of the experienced gender. Platelet activation and coagulation marker concentrations increased in trans women using transdermal estradiol plus CPA, but not in trans men using testosterone. Also, concentrations of inflammatory markers decreased in trans women, while hs-CRP increased in trans men. Our results indicate that hormone therapy may affect hemostasis in transgender persons, which could be an underlying mechanism explaining the increased cardiovascular risk in this population.

Addition of dydrogesterone to vaginal progesterone and transfer postponement improve outcomes in patients with low progesterone levels in hormonally substituted cycles for frozen-thawed embryo transfer

Purpose: Adding dydrogesterone (DYD) to vaginal micronized progesterone (VMP) and postponing embryo transfer in order to improve outcomes in patients with low progesterone (P) levels in hormonally substituted cycles prior to frozen/thawed embryo transfer (FET). Methods: Endometrial preparation comprised sequential administration of vaginal estradiol until endometrial thickness reached 7 mm, followed by transdermal estradiol combined with 800 mg/day VMP. Our previous analysis of serum P levels on FET day showed that the optimal P level was &gt; 11 ng/mL for live birth. Serum P was measured on day1 (D1) following exogenous VMP introduction in the evening. When P levels were &gt; 11 ng/mL, FET was performed “in phase” on day-2, day-3, or day-5 depending on embryo stage at cryopreservation (n = 139 cycles). When P levels were &lt; 11 ng/mL, DYD 10 mg three times a day orally, was added to VMP and FET was postponed by one day (n = 237 cycles, 63%). The primary endpoint was the comparison of live birth rates (LBR) between the two groups. Results: Mean serum P level on D1 was 10.2 + 3.7 ng/mL. Characteristics of patients in both groups were similar for age, body mass index, endometrial thickness prior to P introduction, quality of transferred embryos, and embryo transfer stage. Regarding the primary endpoint, LBR was similar between the VMP+DYD group and the VMP group (26.1% vs. 27.3%, NS). Conclusion: These results suggest that adding DYD to VMP and postponing the transfer in patients with low P levels in hormonally substituted FET cycles might optimize outcomes.

Menopause-associated risk of cardiovascular disease.

Cardiovascular disease (CVD) is of major concern in women entering menopause. The changing hormonal milieu predisposes them to increased CVD risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia, dysregulation in glucose homeostasis, non-alcoholic fatty liver disease and arterial hypertension. However, an independent association of menopause per se with increased risk of CVD events has only been proven for early menopause (<45 years). Menopausal hormone therapy (MHT) ameliorates most of the CVD risk factors mentioned above. Transdermal estrogens are the preferable regimen, since they do not increase triglyceride concentrations and they are not associated with increased risk of venous thromboembolic events (VTE). Although administration of MHT should be considered on an individual basis, MHT may reduce CVD morbidity and mortality, if commenced during the early postmenopausal period (<60 years or within ten years since the last menstrual period). In women with premature ovarian insufficiency (POI), MHT should be administered at least until the average age of menopause (50–52 years). MHT is contraindicated in women with a history of VTE and is not currently recommended for the sole purpose of CVD prevention. The risk of breast cancer associated with MHT is generally low and is mainly conferred by the progestogen. Micronized progesterone and dydrogesterone are associated with lower risk compared to other progestogens.

Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome

PurposeTo study differences in metabolic outcomes between testosterone and estradiol replacement in probands with complete androgen insensitivity syndrome (CAIS).MethodsIn this multicentre, double-blind, randomized crossover trial, 26 women with CAIS were included of whom 17 completed the study. After a two-months run in phase with estradiol, probands either received transdermal estradiol followed by crossover to transdermal testosterone or vice versa. After six months, differences in lipids, fasting glucose, insulin, hematocrit, liver parameters and blood pressure between the treatment phases were investigated.ResultsLinear mixed models adjusted for period and sequence did not reveal major group differences according to treatment for the investigated outcomes. In each treatment group, there were however significant uniform changes in BMI and cholesterol. BMI increased significantly, following six months of estradiol ( + 2.7%; p = 0.036) as well as testosterone treatment ( + 2.8%; p = 0.036). There was also a significant increase in total ( + 10.4%; p = 0.001) and LDL-cholesterol ( + 29.2%; p = 0.049) and a decrease in HDL-cholesterol (−15.8%; p < 0.001) following six months of estradiol as well as six months of testosterone treatment (total cholesterol: + 14.6%; p = 0.008; LDL-cholesterol: + 39.1%; p = 0.005, HDL-cholesterol: −15.8%; p = 0.004). Other parameters remained unchanged.ConclusionTransdermal estradiol as well as testosterone treatment in women with CAIS results in worsening in lipid profiles. Given the relatively small sample size, subtle group differences in other metabolic parameters may have remained undetected.

The effect of micronized progesterone and medroxyprogesterone acetate in combination with transdermal estradiol on hemostatic biomarkers in postmenopausal women diagnosed with POI and early menopause: a randomized trial.

To compare the impact of micronized progesterone (MP) or medroxyprogesterone acetate (MPA) in combination with transdermal estradiol (t-E2) on traditional coagulation factors and thrombin generation parameters in postmenopausal women diagnosed with premature ovarian insufficiency or early menopause. Randomized prospective trial conducted in women diagnosed with premature ovarian insufficiency or early menopause and an intact uterus, recruited over 28 months. All participants were prescribed t-E2 and randomized to either cyclical MP or MPA using a web-based computer randomization software, Graph Pad. Thrombin generation parameters were measured at baseline and repeated after 3-months. Traditional hemostatic biomarkers were measured at baseline and repeated after 3, 6, and 12-months. Seventy-one participants were screened for the study, of whom 66 met the inclusion criteria. In total, 57 participants were randomized: 44 completed the thrombin generation assessment arm of the study, whilst 32 completed 12-months of the traditional coagulation factor screening component of the trial. Thrombin generation parameters did not significantly change from baseline after 3-months duration for either progestogen component when combined with t-E2, unlike the traditional coagulation factors. Protein C activity, free Protein S, and Antithrombin III levels decreased with time in both treatment arms. Fluctuations in traditional hemostatic biomarkers were not reproduced by parallel changes in thrombin generation parameters that remained neutral in both groups compared with baseline. The absence of statistically significant changes in thrombin generation for the first 3-months of hormone therapy use is reassuring and would suggest a neutral effect of both progestogens on the global coagulation assay.

368. Maternal mental health (mama) trial evaluating short-term estrogen as a strategy to prevent postpartum depression in high-risk women: Protocol for a double-blind, randomized, placebo-controlled trial

Introduction and aims of the study:Perinatal depression affects 10–15% of women postpartum and has a recurrence rate of 40% in subsequent pregnancies. Women who develop perinatal depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of three weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression.

Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial.

Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. Randomized trial of transdermal estradiol 0.9 mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory, and spatial problem solving over time. Men receiving androgen deprivation therapy (ADT) for prostate cancer. Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, Month 1, Month 3, and Month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Seventy-eight participants were randomized. Baseline mean scores were 21.0 (standard deviation [SD] 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (SD 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% confidence interval [CI] -1.2 to 2.5), p = .36, or the GML, MAD -3.2 (95% CI -12.0 to 5.6), p = 0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by the administration of estradiol.

Local estrogen for nonsurgical recontouring of auricular cartilage

5% of children are born with auricular deformities. Permanent recontouring can be achieved through splinting during early infancy. Beyond this time, splinting is ineffective, and patients require surgical correction. Neonatal cartilage malleability is hypothesized to be secondary to retained maternal estrogens, increasing hyaluronic acid concentration. In this article, we evaluate the efficacy of local estrogen treatments for the nonsurgical recontouring of mature auricular cartilage. Ears of New Zealand rabbits were folded and splinted and then were randomly assigned to an experimental group, n=10 (injected estrogen, topical estrogen, saline, or untreated). Treatment ears received injected estrogen or saline twice weekly or topical estrogen daily for 4 weeks. Two weeks post-treatment, splints were removed, and ear angles were measured. Biopsies were taken for histologic and mechanical analysis, and systemic estrogen levels were assayed. Ear angles stabilized by 9 days post-splinting. Topical estrogen led to a significantly smaller resting angle (121.6° ± 13.5°) compared with saline and control (135.9° ± 11.2° and 145.3° ± 13.0°, respectively). Injected estrogen led to the most pronounced angle decrease (64.5° ± 35.3°). Ears injected with estrogen also showed a significant increase in cartilage thickness. Hyaluronic acid concentration was increased in both estrogen treatment groups compared with saline. At 3 weeks post-treatment, there was no significant differences in the elastic modulus of the cartilage or serum estrogen levels among the groups. Results show the potential result of local estrogen treatment to achieve a stable nonsurgical remodeling of mature auricular cartilage. Further study is needed to evaluate the molecular mechanism and improve the transdermal estrogen delivery to optimize treatment regimen.

Impact of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol on cardiovascular markers in women diagnosed with premature ovarian insufficiency or an early menopause: a randomised pilot trial

To compare the difference between micronised progesterone (MP) and medroxyprogesterone acetate (MPA) in combination with transdermal oestradiol (t-E2) on cardiovascular disease (CVD) risk markers in women diagnosed with an early menopause and premature ovarian insufficiency (EMPOI). The European Society for Cardiology has identified carotid femoral pulse wave velocity (cfPWV) as the gold standard cardiogenic biomarker for risk stratification of arterial disease. Menopause has been shown to augment the age-dependent increase in arterial stiffness, with hormone replacement therapy (HRT) being the mainstay of management of women diagnosed with EMPOI. A pilot randomised prospective open-label trial. Women were randomised to either cyclical MP (Utrogestan® 200mg) or MPA (Provera® 10mg) in conjunction with t-E2 (Evorel® Patches 50mcg/day) for 12 months. Seventy-one subjects were screened, and baseline data are available for 57 subjects. Carotid-femoral pulse wave velocity (cfPWV). PWV did not significantly change from baseline in either treatment arm. MP+t-E2 demonstrated a positive effect on traditional CVD markers, with a significant improvement seen in cardiac output (CO) (0.71±1.01mL/min, 95% CI 0.20 to 1.21) and reduction in diastolic blood pressure (DBP) (-3.43±6.31mmHg, 95% Cl -6.57 to -0.29) and total peripheral resistance (TPR) (-0.15±0.19mmHg⋅min⋅mL-1, 95% CI -0.24 to -0.05) after 12 months. MPA+t-E2, in contrast, did not demonstrate significant changes from baseline in traditional haemodynamic parameters. The positive changes in traditional markers were not reflected in the cardiogenic biomarker, cfPWV, which has demonstrated a higher positive predictive value for cardiovascular events than traditional measurements.

Does Supplemental Estrogen Improve Bone-Related Symptoms of Female Athlete Triad in Female Athletes? A Critically Appraised Topic.

Clinical Scenario: Due to the Female Athlete Triad (Triad) being a 3-pronged syndrome, treatments can vary depending on the symptoms that clinicians focus on. With reproductive and bone health compromised, assessment and recovery methods include monitoring menstrual regularity and dual-energy X-ray absorptiometry scans. Low levels of estrogen have demonstrated negative effects on bone mineral density (BMD). Clinical Question: Does supplemental estrogen improve BMD in athletes with Female Athlete Triad symptoms? Summary of Key Findings: Supplemental estrogen does improve BMD with estrogen patches demonstrating increased improvement compared with oral contraceptive pills. Clinical Bottom Line: Restoration of regular menstruation, improvement of BMD, and ensuring optimal energy levels is the best approach for treating Triad symptoms. Transdermal patches are a new treatment option that address both menstrual function and BMD but still require further research. Strength of Recommendation: Available studies demonstrated a level 2 evidence for supplemental estrogen (oral contraceptive pills and estrogen patches) providing improvements for bone health related to the Triad.