Topical Estrogen Treatment Research Articles

Effect of topical estrogen cream compared with observation in prepubertal girls with labial adhesions

Topical estrogen treatment has been considered the first-line treatment of labial adhesions in prepubertal girls. However, the effect of topical estrogen cream is different according to studies, and no study compared estrogen cream to observation. This study aims to investigate the efficacy of topical estrogen cream treatment compared with observation in prepubertal girls with labial adhesions. The medical records of prepubertal girls diagnosed with labial adhesions from April 2005 to June 2019 were retrospectively analyzed. Baseline characteristics such as age at diagnosis and initial symptoms were collected. The primary outcome was the resolution of labial adhesion. Secondary outcomes were recurrence and side effects. A total of 114 patients were enrolled and divided into two groups, topical estrogen cream (n=94), and observation (n=20). Girls who were treated with estrogen cream had older age (24.6±19.0 vs. 16.7±15.3 months, p=0.037) and higher resolution rate than the observation group (100.0% vs. 85.0%, respectively, p=0.005). Girls younger than 23.3 months showed a significantly higher resolution rate to topical estrogen treatment (100% vs. 86.7%, p=0.043). Side effects and recurrences occurred exclusively in children treated with topical estrogen therapy without significant differences compared to the observation group. Topical estrogen therapy showed a higher resolution rate than observation for the treatment of prepubertal girls with labial adhesions, especially in younger girls.

Genital surgical procedures for feminization in gender dysphoria

The necessity and the benefits of genital approximating surgery in gender dysphoria are established, therefore the indications after careful diagnostics are indisputable. For vaginoplasty, the method of choice is penile inversion, in which the penile skin is inserted as a pedicled flap into the prepared vaginal space. Alternatively, free skin grafts or intestinal segments can be used. Lifelong bougienage of the vagina is obligatory for all methods. The spectrum of complications after vaginoplasty is broad. Of particular note, although rare, is injury to the anterior rectal wall, from which rectovaginal fistulas can result. During the course strictures of the urinary meatus or also the neovagina occur. Corrections must often be surgically undertaken but conservative measures, e.g. intensified bougienage and topical estrogen treatment, can also be successful. Neovaginal infections are treated analogously to infections of a native vagina. A special situation is inflammation of the intestinal neovagina, which must be treated with mesalazine.

Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin

The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic Escherichia coli (UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate, in vitro, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with E.coli flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml E.coli flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including DEFβ4A, DEFB103A, LCN2 as well as those associated with keratinisation eg CNFN and SPRR family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the DEFβ4 gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced DEFβ4, DEF103A and S100A7 expression (P < 0.05). Origins of vaginal IL-17 in vivo remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.

Preoperative Topical Estrogen Treatment vs Placebo in 244 Children With Midshaft and Posterior Hypospadias.

Urethral fistula and dehiscence are common after hypospadias surgery. Preoperative androgens have been considered to reduce these complications although this consideration is not evidence-based. Dermatologists have reported the benefits of topical estrogens on skin healing. We investigated whether the preoperative use of topical promestriene could reduce healing complications in hypospadias surgery. Our primary objective was to demonstrate a reduction of healing complications with promestriene vs placebo. Impact on reoperations and other complications, clinical tolerance, bone growth, and biological systemic effects of the treatment were also considered. We conducted a prospective, randomized, placebo-controlled, double-blind, parallel group trial between 2011 and 2015 in 4 French centers. One-stage transverse preputial island flap urethroplasty (onlay urethroplasty) was selected for severe hypospadias. Promestriene or placebo was applied on the penis for 2 months prior to surgery. The primary outcome was the presence of postoperative urethral fistula or dehiscence in the first year postsurgery. For safety reasons, hormonal and anatomical screenings were performed. Out of 241 patients who received surgery, 122 patients were randomized to receive placebo, and 119 patients received promestriene. The primary outcome was unavailable for 11 patients. Healing complications were assessed at 16.4% (19/116) in the placebo vs 14.9% (17/114) in the promestriene arm, and the odds ratio adjusted on center was 0.93 (95% confidence interval 0.45-1.94), P = 0.86. Although we observed an overall lower risk of complications compared to previous publications, postsurgery complications were not different between promestriene and placebo, because of a lack of power of the study or the inefficacy of promestriene.

Minimally Invasive Burch Colposuspension - The Robotic Approach

Video Objective To demonstrate a minimally invasive technique to the Burch procedure for treatment of stress urinary incontinence as an alternative therapeutic modality for women who do not want or cannot have mesh products. Setting Surgical intervention for a 68 yo G12 P10-0-2-10 with prolapse and stress urinary incontinence (SUI). After undergoing appropriate counseling and discussion regarding risks, benefits and alternatives the patient and family declined use of mesh products for any portion of the repair. The decision was made to proceed with a hysterectomy, uterosacral colpopexy and Burch colposuspension. Preoperative optimization of her health and multiple co-morbidities required a multidisciplinary approach. Blood pressure control, diabetes and thyroid management as well as topical estrogen treatment of vaginal epithelium for 3 months prior to surgery. Interventions Robotic colposuspension for genuine SUI following a robotic hysterectomy and uterosacral colpopexy. The procedure took 62 minutes to complete, the blood loss was minimal and there were no complications. She was observed overnight, had a successful voiding trial in the morning and was discharged shortly after. Follow up at 2 and 6 weeks after surgery she reported no pain and no complications. She reports significant improvement in bladder function and bladder control. Conclusion The Burch procedure is well known as an effective treatment for SUI but generally not frequently performed due to morbidity associated with laparotomy requiring procedures and the availability of less invasive approachesmsuch as a transvaginal suburethral sling. With the minimally invasive surgery evolution being inclusive of nearly all gynecologic procedures, a robotic or laparoscopic Burch colposuspension as an alternative to transvaginal suburethral sling with mesh should be considered. This videos demonstrates a reproducible, safe and efficient approach to this procedure.

Plasticity of Auricular Cartilage in Response to Hormone Therapy.

Correction of auricular deformities can be accomplished through splinting within the first few weeks of life. This is hypothesized to be due to retained circulating maternal estrogens decreasing the structural density of collagen; however, this has not been fully tested. Cartilage elasticity is dependent on the concentration of the proteoglycan aggregate, and hyaluronic acid, a constituent of proteoglycan aggregate, is increased by estrogens. Nonsurgical correction of these deformities in more developed patients has the potential to change clinical practice and eliminate surgical risks. Previous studies have demonstrated preliminary promise with the use of injectable estrogen to treat auricular deformities. For this study, we have validated an animal model and demonstrated the feasibility of a more therapeutically appropriate topical estrogen treatment in restoring neonatal plasticity of auricular cartilage. Ears of 12 New Zealand rabbits were folded and splinted, and assigned an experimental group (estrogen, placebo, and untreated control) (n = 8 ears). Treatment ears received topical estrogen or placebo cream daily for 4 weeks, whereas controls received no treatment. The splints were removed following 2 additional weeks, and photographs were taken to calculate the retained fold angle. Biopsies were also taken for histologic analysis. The 8 control ears showed a statistically increased angle from a folded orientation of 46.6 degrees to return of ear position to a normal upright position of 151.2 degrees by the fourth day after splint removal. Both the estrogen-treated and placebo-treated ears responded to splinting with maintained folding (36.6 degrees and 32.5 degrees, respectively). Auricular cartilage thickness trended toward thicker in ears treated with estrogen, consistent with increased matrix components. Estrogen and placebo treatment with splinting of ears lead to a significant change to the cartilage configuration, validating the model. The results of this study are very encouraging and provide the foundation for a noninvasive therapeutic approach for correcting auricular deformities. Future work will include a more detailed mechanistic study evaluating the dosing of estrogen and the efficiency of dermal penetration as well as evaluating the long-term outcomes and molecular mechanism-associated cartilaginous responses to estrogen.

Focal depth measurements of the vaginal wall: a new method to noninvasively quantify vaginal wall thickness in the diagnosis and treatment of vaginal atrophy

The aim of the study was to evaluate if vaginal focal depth measurement could be a noninvasive method to quantify vaginal wall thickness. Postmenopausal women undergoing topical estrogen therapy because of vaginal atrophy (VA) were recruited. VA was diagnosed based on the presence of symptoms and vaginal pH at least 5.5. The control group consisted of women above 40 years without VA. Focal depth measurements were performed before and after treatment using the Cytocam-Incident Dark Field device assessing the distance between the subepithelial microcirculation and the epithelial surface. Measurements were performed before and after treatment in the intervention group and at two different time points in the control group. Vaginal pH was measured. Symptoms were evaluated using the most bothersome symptom approach. Eight women with VA and nine controls were included. Pretreatment median focal depth was not significantly different between both groups. Pretreatment focal depth more than doubled after a median of 7 weeks of topical estrogen treatment (80 μm [interquartile range 80-120 μm] vs 220 μm [148-248 μm], P = 0.02), whereas the measurements in the control group did not change. Pretreatment vaginal pH differed between both groups (5.5 vs 5.1, respectively, P < 0.01). Vaginal pH did not change after treatment. Using in vivo microscopy we introduced a new noninvasive measure of vaginal wall thickness. A significant increase in vaginal focal depth was observed in participants with VA treated with topical estrogens. This innovative measurement of vaginal wall thickness could become the preferred objective measure to evaluate treatment effect. Moreover, it has great potential for other applications in the field of urogynecology.

Detection of RXFP1 receptors in skin biopsies from children with congenital adrenal hyperplasia: A preliminary report

Relaxin may potentiate the effect of topical estrogen treatment to eradicate post-incisional scarring in congenital adrenal hyperplasia (CAH) patients undergoing genitoplasty. The aim of this study was to determine whether CAH skin is capable of responding to relaxin. Skin biopsies were obtained from four female CAH patients (aged 2-9 years; Prader 4-5, salt-wasting, 21-hydroxylase deficiency, Caucasian) during routine genitoplasty surgery and screened for relaxin receptors. All received corticosteroid and mineralocorticoid replacement therapy. Specimens were sectioned, mounted and screened for the presence of the putative H2 relaxin receptor using conventional two-antibody immunohistochemistry. Tissue controls were processed concurrently. Tissue controls evidenced appropriate staining. Biopsies from CAH patients stained positively for RXFP1 expression while some variation between specimens was evident. Staining occurred adjacent to the basement membrane of the epithelium, localized to germinative basal keratinocytes. Based on a limited patient sample, germinative keratinocytes in CAH patients appear competent to respond to relaxin perhaps topically applied. Given that relaxin downregulates collagen accretion and upregulates collagenases, its use may potentiate the effects of estradiol and abrogate post-incisional wound scarring. More research is needed to confirm or refute this thesis.

Significance of Topical Estrogens to Labial Fusion and Vaginal Introital Integrity

Purpose One theory for labial fusion is low prepubertal estrogen levels. Topical estrogens remains the mainstay of therapy. Some patients require surgical lysis of the adhesion. Estrogen's action in regard to collagen may influence recurrent adhesions and adhesions that form after manual disruption or surgical separation. This study assesses the efficacy of topical estrogen to separate the labia, recurrence, and estrogen related side effects. Estrogens may have a role in vaginal healing in genital surgery. Materials and Methods Retrospective chart review of 109 girls from 3 months to 10 years old (mean 44 months) who had labial fusion. Data was collected on the length of topical estrogen treatment, rate of successful separation, rate of recurrence, percentage requiring surgery, and post-operative outcomes. Results Mean length of topical estrogen treatment was 3.7 months (range 0 to 36 months), with separation in 79% (85/107) of patients. Forty-one percent (44/107) had recurrence of labial fusion one to five times (range 2 to72 months). Surgery was required in 21% (22/107). Ten percent of patients (2/21) had recurrence of labial fusion post-operatively (age 6,10 years, at 1, 18 month post-operatively). Neither of these two patients was responsive to topical estrogen cream post-operatively and required a second surgical separation. Side effects of estrogen were minimal breast development in 6 children and vaginal bleeding in one child. Discontinuance resulted in resolution of side effects. Conclusion Topical estrogens were effective treatment for labial fusion. After surgical separation of adhesions there was a 10% recurrence rate. Estrogen therapy initiated after surgical failure was unsuccessful.

Hormonal and reproductive factors in melanoma risk

It is difficult to trace when and why the question arose of a possible relationship between female hormones and the risk of malignant melanoma of the skin. Beral et al, in the late seventies, reported for the first time a positive association between oral contraceptive (OC) use and malignant melanoma of the skin and thus suggested a causal relationship. 1 Another reason could be observations of higher incidence rates in premenopausal women compared with men of the same age. 2 Moreover, the hormone hypothesis may have been nourished by such early observations as benign hyperpigmentation during pregnancy as well as during OC use, or following menopausal estrogen replacement and topical estrogen treatment. 3 Early laboratory data on steroid receptors suggested the existence of estrogen receptors on melanocytes and melanoma cells, 4 but more recent investigations have been unable to identify all requirements defining a specific receptor. It has been proposed that the apparent receptor may to some extent bind to the enzyme tyrosinase. 5 Clinical trials on the antiestrogen tamoxifen have been negative. 6,7 Very few patients responded, and there was no relationship between receptor levels and probability of response. Finally, epidemiologic data clearly prove a higher melanoma mortality in men compared with women and multivariate analyses of clinical series have shown that male gender is a separate, negative prognostic factor. 8 There is no good theoretical explanation of why estrogens should increase the risk of melanoma but retard growth and dissemination of the tumor. Therefore, it is very important to obtain epidemiologic evidence for possible relationships between female hormones and risk of melanoma, especially because OCs have been suspected of increasing melanoma risk. A number of case-control studies and a couple of cohort studies from the 1980s focused on possible relationships between characteristics of female endocrine status and the risk of melanoma. The studies included questions about use of OCs and postmenopausal estrogen therapy, and parity and age at menarche, menopause, and first childbirth, which reflect influences of exogenous and endogenous hormones, respectively.