Transdermal Estradiol Research Articles

The safety of oral versus transdermal estrogen.

There exists a growing number of treatment options available to women who choose hormone therapy for management of systemic menopause symptoms. Choosing the product that is the "best fit" for each individual woman can be a challenging task. One of these decisions pertains to the optimal route of estrogen administration. This Practice Pearl will explore some of the differences between oral and transdermal estrogens.

Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women.

Most types of hereditary angioedema (HAE) are worsened by endogenous or exogenous estrogens. Conversely, androgens can improve HAE with abnormal C1-Inhibitor (C1-INH) by increasing C1-INH concentrations. Menopause is associated with an extinction of ovarian estrogenic and androgenic secretion. There is currently insufficient information on postmenopausal women with HAE. The objective of this study was to describe the activity of HAE in postmenopausal women. This was a French retrospective, multicenter study in postmenopausal women with HAE with or without C1-INH deficiency/dysfunction. The patients were classified before and after menopause with a previously validated HAE disease severity score. We included 65 women from 13 centers in France. The mean age was 62.7± 9.2years, and the mean time between menopause and inclusion was 12.5± 9.1years. HAE was associated with C1-INH deficiencyin 88% (n= 57) of the patients, a mutation of factor 12 in 8% (n= 5), a mutation in plasminogen gene in one, and unknown HAE for two. The HAE course was not different after menopause in 46.1% (n= 30), improved in 38.5% (n= 25), and worsened in 15.4% (n= 10). Improvement was correlated with estrogen sensitivity of angioedema before menopause (p= 0.06 for improvement vs no effect or worsening). In addition, we observed that only ten women received treatment (transdermal or oral estradiol+ progestogen) for their menopause symptoms. Among them, only 3 experienced worsening of symptoms (2 on transdermal and 1 on oral estradiol). Following menopause, most women with HAE remain stable but some worsen. Improvement was mainly observed in patients with previous estrogen sensitivity. More research is required in menopausal women with HAE to better understand how to manage climacteric symptoms.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

Effects of estradiol on biological age measured using the glycan age index.

Glycan age is a recently developed biomarker based on glycans attached to immunoglobulin G (IgG). In large population cohorts, glycan age associates well with lifestyle and disease-risk biomarkers, while some studies suggested that glycan changes precede development of several age-associated diseases. In this study we evaluated effects of estrogen on the glycan age. Gonadal hormones were suppressed in 36 healthy young women by gonadotropin releasing hormone agonist therapy for 6 months. In 15 of them estradiol was supplemented, while 21 received placebo resulting in very low estrogen levels during intervention. IgG was isolated from plasma samples before intervention, after 6 months of intervention and after subsequent 4-month recovery. Deprivation of gonadal hormones resulted in median increase of glycan age for 9.1 years (IQR 6.8 – 11.5 years, p = 3.73×10-8), which was completely prevented by transdermal estradiol therapy (change in glycan age = -0.23 years, IQR (-2.20 – 2.98). After the recovery period glycan age returned to baseline values in both groups. These results suggest that IgG glycans and consequently also the glycan age are under strong influence of gonadal hormones and that estradiol therapy can prevent the increase of glycan age that occurs in the perimenopausal period.

A direct comparison of women's perceptions and acceptability of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol in the management of young postmenopausal women, under 45 years of age.

To assess the acceptability and perception of postmenopausal women, to two different hormone replacement therapy regimens, in relation to the control of their symptoms and development of adverse effects. Prospectively recruited postmenopausal women, <45 years, were randomised to one of two treatment arms for 12-months: cyclical micronised progesterone or medroxyprogesterone acetate in combination with transdermal oestradiol. A self-reported questionnaire with matrix rating scales was completed and repeated after 3, 6 and 12-months. Symptom control and development of adverse effects. Seventy-one individuals were screened, with baseline data available for 67 subjects. A total of 190 questionnaires were returned. The most commonly reported symptoms were low energy levels, vasomotor symptoms and sexual dysfunction. The prevalence of adverse effects ranged between 57.89 and 87.50%, with a reduction seen in the transdermal oestradiol + micronised progesterone arm (73.91% at 3-months, decreasing to 57.89% at 12-months; p = 0.33), compared to the transdermal oestradiol + medroxyprogesterone acetate arm (76.92% at 3-months, increasing to 87.50% at 12-months; p = 0.69). The main reported adverse effects were bloating, weight change and psychological symptoms. A significant difference was documented between the groups after set intervals, with a greater proportion reporting breast tenderness after 3-months (p = 0.01), lower numbers reporting mood swings at 6-months (p = 0.01) and irritability at 12-months (p = 0.03) in the transdermal oestradiol + micronised progesterone arm compared to the transdermal oestradiol + medroxyprogesterone acetate arm. The acceptability of both regimens was high despite adverse effects, but tolerability of transdermal oestradiol combined with micronised progesterone appeared to be better with fewer women reporting psychological concerns.

Transdermal estradiol as a novel treatment for Peyronie's disease: A case report

Introduction: This is a single‐patient case report of a (now) 75-year old married male with long-standing Peyronie’s disease (PD). The patient’s main symptoms were painful erections as well as secondary anxiety and depression. Resolution of these symptoms was achieved with transdermal estradiol treatment.&#x0D; Objectives: To describe a patient with PD, whose persistently painful erections and psychologic distress were eliminated by a novel treatment involving transdermal estradiol. This report also aims to present a novel treatment for patients with paraphilias.&#x0D; Methods: An interview with the patient, chart review, and a literature search were conducted. Informed consent was obtained from the patient and this report was approved by the Research Ethics Committee at the Royal Hospital in Ottawa.&#x0D; Results: Treatment with transdermal estradiol decreased the patient’s sex drive and virtually eliminated his erections with no undesirable side effects. The patient and his wife still enjoy sexual relations without the need for penile erection.&#x0D; Conclusions: This case report presents a novel treatment for PD. It also introduces a novel method to treat men who wish to decrease their sex drive (e.g. men with paraphilic disorders). Replication of this treatment intervention in men with PD and new studies of its use in men with paraphilic disorders are warranted.

PROPOSED ESTROGEN THERAPY FOR COVID 19 AND OTHER MICROBIAL INFECTIONS

The novel coronavirus or SARS CoV-2 infection or COVID 19, which originated in Wuhan, China is an infection with a new coronavirus. Since there was no previous human exposure to this virus, there was no herd immunity. Despite this universal absence of herd and adaptive immunity, there are considerable gender differences in mortality among men and women. In addition, mortality in children is considerably low as compared to adults (https://www.worldometers.info/coconavirus/Coronavirus-age-sex-demographics/ Coronavirus Age, Sex, Demographics (COVID 19) – Worldometer). This implies stronger innate and adaptive immunity are at play in children and women as compared to that in adult men. Less severe affliction of women may be due to higher levels of estradiol in pre-menopausal women that in men. Estradiol has a favorable influence on innate and adaptive immunity (Carmen Giefing-Kröll et al. Aging Cell. 2015 Jun; 14(3): 309–321). Arsenicum Album 30, a homeopathic medicine, recommended by the Ministry of AYUSH, Government of India, (https://www.ayush.gov.in/docs/homeopathy-guidelines.pdf) has arsenic, which is a metalloestrogen (P D Darbre J Appl Toxicol. May-Jun 2006; 26(3):191-7); which appears to be the reason for its effectiveness in the treatment of COVID 19 or SARS Cov-2. Estradiol has thromboembolic effects when administered orally. However, transdermal estradiol is safer, without thromboembolic effects and is already in use in some countries (Archer DF et al. Climacteric. 2012 Jun;15(3):235-40.; Marianne Canonico et al Circulation. 2007;115:840–845). Estrogen therapy is given in some forms of prostatic cancer in men. In view of these potential benefits of estrogen, estradiol transdermal therapy should be tried as a repurposed or investigational drug along with routine treatment of COVID 19 in men and post-menopausal women and in similar infections with new microbes in the absence of specific treatment.

REPEATED APPLICATION OF LUTEAL PHASE ESTRADIOL / GnRH ANTAGONIST PRIMING INCREASES IVF SUCCESS FOR POOR OVARION RESERVE PATIENTS

The aim of this study is to compare the results of repeated luteal phase estradiol patch / GnRH antagonist protocol (LPP) in patients with poor ovarian response (POR) with other protocols. 226 patients and 293 cycles were applied to POR patients who underwent luteal estradiol patch / GnRH antagonists priming protocol (LPP), microdose flare up protocol or antagonist protocol in the Gulhane training and research hospital between January 2013 and March 2019. Among these, 38 patients underwent LPP protocol in the first cycle and LPP protocol in the second cycle. In 29 patients, LPP protocol was applied in second cycle after microdose flare up or antagonist protocol. 128 patients who underwent LPP only once and 31 patients who received only microdose flare up were also evaluated. The clinical pregnancy rate was higher in the group that had repeated LPP protocol compared to the group applied with LPP after different protocol (p: 0.035). In this group, b hcg positivity and clinical pregnancy rate per embryo were also significantly higher (p: 0.000, p: 0.001). Recurrent LPP protocol seems to be a suitable option in POR patients

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress.

Endothelial function declines progressively across stages of the menopause transition; however, the mechanisms contributing to this decline are unknown. We hypothesized that differences in endothelial function among pre-, peri, and postmenopausal women are related to differences in estradiol and oxidative stress. Brachial artery flow-mediated dilation (FMD) was measured in 87 healthy women categorized by menopause stage (24 premenopausal, 17 early and 21 late perimenopausal, and 25 postmenopausal) before and after 3 days of ovarian hormone suppression (gonadotropin releasing hormone antagonist [GnRHant]) alone, and an additional 3 days of GnRHant with concurrent transdermal estradiol or placebo add-back treatment. In 82 women, FMD during acute vitamin C (antioxidant) infusion was measured before and after GnRHant + add-back. Before GnRHant, FMD was different among groups (p < 0.005; reduced across stages of menopause). Vitamin C increased FMD in late peri- and post- (p < 0.005) but not pre- or early perimenopausal women (p > 0.54). After GnRHant alone, FMD decreased in pre- and peri- (p < 0.01), but not postmenopausal women, and was restored to premenopausal levels by estradiol add-back in the pre- and perimenopausal groups. Vitamin C improved FMD in pre-, peri-, and postmenopausal women on GnRHant + placebo. There was no effect of vitamin C on FMD in women on GnRHant + estradiol. These observations support the concept that the decline in endothelial function across the menopause transition is related to the loss of ovarian estradiol. The decline in estradiol may alter redox balance, thereby increasing oxidative stress and impairing endothelial function.

A prospective study of oral estrogen versus transdermal estrogen (gel) for hormone replacement frozen embryo transfer cycles

Aim This study was done to compare the efficacy of transdermal estrogen (gel) to oral estradiol in hormone replacement frozen embryo transfer cycles (HR- FET). Materials and methods This was a prospective study conducted between March 2019 and December 2019. We included 294 HR FET cycles: 156 cycles using oral estrogen tablets (oral group) and 138 cycles using transdermal gel (17 beta estradiol 0.06% w/w) (gel group). Primary objective of this study was to compare endometrial thickness (ET) on the day of progesterone start between the two groups. Our secondary objective was to compare implantation rates (IR), clinical pregnancy rates (CPR), miscarriage rates (MR), duration of estrogen administration, estradiol (E2) levels before the start of progesterone, cycle cancellation rates, patient satisfaction score and undesirable side effects between both the groups. Results There was no significant difference in the ET, IR, CPR, MR and duration of E2 administration and cycle cancellation rates between both the groups. Patient satisfaction score was significantly higher (8.02 ± 1.07 vs 6.96 ± 0.99 p < .01) and side effects were significantly lower (18.1% vs 55.1%, p≤.01), in the gel group compared to the oral group. Conclusion This study concluded that transdermal estrogen (gel) is equally efficacious as oral estrogen in HR FET cycles with transdermal gel having an added benefit of better patient comfort with less side effects and better safety profile.

HIP INJURY- CROSS COUNTRY

HISTORY 18-year-old high school female cross-country runner presented with one week of left anterior hip pain. Denied a specific injury. Pain started during a late season meet causing her to finish at a slower pace. Pain progressively worsened requiring crutches to ambulate, despite no further activity. Max mileage was 40 miles/week, had tapered to 20 miles/week prior to injury. History of stress fracture 4 years prior. Initial x-ray of left hip revealed open epiphyseal plates, no other osseous abnormalities. Inquiring about menstrual history, she had yet to reach menarche. Per the patient’s mother, she had been trialed on growth hormone and is currently on estradiol patches. She has a known eating disorder for which she is not actively receiving help, despite multiple hospitalizations. PMHX Primary amenorrhea, followed by endocrinology. Lab work revealed low estradiol, LH, FSH with high alkaline phosphatase. Normal labs were thyroid studies, BMP, LFT, vitamin D and prolactin. Genetics showed 46XX. Multiple XR for bone age showed that of an 11-year-old. Cardiac work up showed sinus bradycardia on EKG and normal echo. Brain/pituitary MRI revealed normal pituitary and mild enlargement of ventricles, sulci, cerebellar folia. PHYSICAL EXAMINATION Patient stands 55 inches tall, weighing 61 pounds with a BMI of 14. She appears much younger than stated age. Hair is full, though fine. Breast tissue is not appreciated. On left hip exam, there is TTP along flexor tendon, lateral hip, and piriformis. She has pain with external rotation, weakness and pain with hip flexion, abduction, and adduction against resistance. She is unable to do a single leg hop due to groin pain. She is neurovascularly intact. DIFFERENTIAL DIAGNOSIS 1. Femoral neck stress fracture 2. Primary amenorrhea 3. Hip flexor strain 4. Relative Energy Deficiency in Sports syndrome 5. ASIS avulsion fracture TESTS/RESULTS MRI left hip 1. Partial thickness tear at attachment of left iliopsoas tendon to lesser trochanter with intramuscular hematoma 2. Minimal partial thickness tear of the left common hamstring origin FINAL DIAGNOSIS 1. Partial tear of left iliopsoas tendon and hamstring 2. RED-S TREATMENT/OUTCOMES 1. Shut down from all activities 2. Weightbearing as tolerated 3. Referral to gynecology for transvaginal ultrasound 4. Referral to Eating Recovery Center

Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy.

The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. Cross-sectional case-control study. General community. Transgender women, cisgender male and cisgender female controls. Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.

SAT-266 Accelerated Osteoporosis - a Rare Presentation of Cushing’s Disease

Background:Osteoporosis in post-menopausal women is usually due to bone loss from estrogen deficiency and/or age. Secondary osteoporosis (SO) is less common. Up to 30% of postmenopausal women and 50% of men with osteoporosis may have an underlying cause. Cushing’s disease (CD) is one cause of SO but rarely the presenting symptoms. The prevalence of osteoporosis (69.6% vs 37.8%) is significantly higher in patients with adrenal rather than pituitary CD. Diagnosing CD remains a challenge to physicians in spite of advances in diagnostic techniques. We report a case of CD in a post-menopausal woman presenting as accelerated osteoporosis.Clinical CaseA 63-year-old Caucasian female with a history of hypertension and hysterectomy in her 50s on transdermal estrogen was referred to our Endocrine clinic for evaluation of osteoporosis and incidental finding of bilateral adrenal hyperplasia on CT spine. The patient rapidly developed kyphoscoliosis within the past 2 years. She was debilitated by pain and decreased mobility from compression fractures and spinal stenosis, and underwent thoracic and lumbar fusion surgery.On physical examination, her heart rate was 64 beats per minute, blood pressure 130/92 mmHg, weight 188 lbs. and Height 5.1 ft; a year ago it was 5.5 ft. Her face appeared round but not red. Buffalo hump and supraclavicular pad were noted. No striae or bruises noted. Healing surgical scars over the thoracic and lumbar spine were violaceous.The patient’s urine free cortisol levels, tested a month apart, were 190 mcg and 132 mcg (n 3.5-45 mcg/24h). Midnight salivary cortisol levels taken consecutive nights were 160 ng/dL and 513 ng/dL (n < 100 ng/dL). Morning Serum Cortisol and ACTH were 20.2 ug/dL and 14 pg/mL (n Cortisol 6.0-27.0 ug/dL and ACTH 7.2-63 pg/mL). Following low dose (1mg) dexamethasone suppression testing, her serum cortisol were 12.6 ug/dL, ACTH levels were 32 pg/mL and dexamethasone were 187 ng/dL (n < 30 ng/dL). 25-Hydroxy D total, TSH, Free T4, PTH intact, calcium, renin, aldosterone and SPEP levels were normal. Renal and liver functions were normal except alkaline phosphatase was 142 U/L (n 34-104 U/L). Pituitary MRI with contrast showed pituitary microadenoma. The patient was referred to a neurosurgeon and is planned for an inferior petrosal sinus sampling prior to transsphenoidal resection.ConclusionCushing’s disease as a cause of osteoporosis is rare. Diagnosis of Cushing’s can be challenging in patients without obvious signs, as in our patient who was referred to an endocrinologist due to incidental finding of bilateral adrenal hyperplasia. A high degree of clinical suspicion is needed when investigating CD, as initial test results can be indecisive. As in our patient, initial ACTH and cortisol levels were normal, the low dose dexamethasone suppression test helped us direct our diagnosis towards CD.

SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals

Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport. Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up. Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels. Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.

Effect of transdermal estradiol therapy on bone mineral density of amenorrheic female athletes.

The effects of transdermal estradiol treatment (HT) in amenorrheic athletes (AA) with low body weight (BW) and low bone mineral density (BMD) are unknown. To investigate whether HT increases BMD in AA with low BW and to compare the results with levels in AA who have recovered spontaneous menstruation (SM). Female athletes (n=151) were recruited at the Japan Institute of Sports Sciences and the University of Tokyo. All participants were divided into four groups: an AA group (untreated group) (n=36), a HT group (n=55), a SM group (n=21), and an eumenorrheic athletes (EA) group (n=39). Height, body weight, blood tests, and dual-energy X-ray absorptiometry were measured at baseline and after 12months. The HT group was treated daily for 12months with transdermal estrogen therapy. In addition, participants received oral progestin for 7days once every 3months. After 12months, BMD in the AA group was significantly lower than at baseline; however, BMD in the other three groups was significantly higher than at baseline. The ratio of the change in BMD values before and after 12months was -1.6±3.2% for the AA group, 5.3±8.7% for the HT group, 11.1±8.9% for the SM group, and 2.3±5.7% for the EA group. The rate of change in BMD values in the SM group was greater than that in the HT group. HT increased BMD in AAwith low BW, and the increase in those with SM was greater than that in those treated with HT.

Efficiency of the combination of transdermal estrogens and a hormone-releasing intrauterine system for the correction of menopausal symptoms

Hypothesis/aims of study. The aim of this study was to assess the efficiency of Mirena (levonorgestrel-releasing intrauterine system) combined with EstroGel (17-estradiol transdermal gel) being applied in the test group of peri- and postmenopausal women as menopausal hormonal therapy.&#x0D; Study design, materials and methods. The study involved 62 patients aged 42 to 55 years. The main group included 33 women who were prescribed Mirena in combination with EstroGel. The control group consisted of 29 women who were prescribed a combined two-phase tablet preparation containing micronized 17-estradiol as an estrogen component and dydrogesterone as a gestagen component. The condition of the patients was evaluated at the beginning of therapy and after 3, 6 and 12 months.&#x0D; Results. During therapy, patients in the main group decreased climacteric symptoms and improved lipid profile and blood biochemical parameters characterizing the hepatobiliary system. Patients in the control group had a comparable decrease in menopausal symptoms; however, there were changes in biochemical parameters, such as hypertriglyceridemia and a significant increase in bilirubin and transaminases, which required discontinuation of therapy. All the patients using Mirena in combination with EstroGel demonstrated good tolerability, efficiency of the therapy and no significant symptoms requiring its withdrawal. During the menopausal hormonal therapy, there were no cases of relapse of endometrial hyperplasia, growth of myomatous nodes and an increase in endometriosis prevalence. Patients in the control group during the first three months of therapy noted acyclic spotting, breast engorgement and tenderness, headaches, and exacerbation of cholelithiasis, which resulted in decreased adherence to therapy.&#x0D; Conclusion. The use of estrogen transdermally in combination with the intrauterine administration of levonorgestrel is an effective and safe method that helps to relieve menopausal symptoms and to improve the health and quality of life of women with extragenital pathology, endometrial and mammary gland hyperplastic processes, endometriosis, and menometrorrhagia.

Taking a fresh look at mood, hormones, and menopause.

Depression, with or without concomitant anxiety, is one of the most burdensome medical conditions worldwide. Depression affects women more often than men and may cause significant impairment. Reproductive phase-related windows of vulnerability for depression (new or recurrent) have been recognized, including the menopause transition. Midlife depression is likely influenced by both menopause- and nonmenopause-related factors. Antidepressants and cognitive behavioral therapy remain first-line treatment options for moderate to severe major depressive disorder at any time, with proven efficacy and tolerability in midlife women. Transdermal estradiol can also be part of the treatment armamentarium, but its use as a prophylaxis against midlife depressive symptoms, although promising, warrants further investigation.

Red and White Blood Cell Counts Are Associated With Bone Marrow Adipose Tissue, Bone Mineral Density, and Bone Microarchitecture in Premenopausal Women.

Bone marrow adipose tissue (BMAT) resides within the bone marrow microenvironment where its function remains poorly understood. BMAT is elevated in anorexia nervosa, a disease model of chronic starvation, despite depletion of other fat depots. In addition to BMAT, the marrow microenvironment also consists of osteoblast and hematopoietic progenitors. BMAT is inversely associated with bone mineral density (BMD) in multiple populations including women with anorexia nervosa, and regulates hematopoiesis in animal models. We hypothesized that BMAT would be associated with circulating populations of hematopoietic cells (red and white blood cells) in humans and performed a post hoc analysis of two studies-a cross-sectional study and a longitudinal study-to investigate this hypothesis. We studied 89 premenopausal women cross-sectionally (median age [interquartile range], 27 [24.5, 31.7] years), including 35 with anorexia nervosa. We investigated associations between red blood cell (RBC) and white blood cell (WBC) counts and BMAT assessed by 1 H-magnetic resonance spectroscopy, BMD assessed by DXA, and bone microarchitecture assessed by HR-pQCT. In addition, we analyzed longitudinal data in six premenopausal women with anorexia nervosa treated with transdermal estrogen for 6 months and measured changes in BMAT and blood cell counts during treatment. Cross-sectionally, BMAT was inversely associated with WBC and RBC counts. In contrast, BMD and parameters of bone microarchitecture were positively associated with WBC and RBC. In women with anorexia nervosa treated with transdermal estrogen for 6 months, decreases in BMAT were significantly associated with increases in both RBC and hematocrit (rho = -0.83, p = 0.04 for both). In conclusion, we show that BMAT is inversely associated with WBC and RBC in premenopausal women, and there is a potential association between longitudinal changes in BMAT and changes in RBC. These associations warrant further study and may provide further insight into the role and function of this understudied adipose depot. © 2020 American Society for Bone and Mineral Research.

Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.