-
Physiological Reports Aug 2023Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically,...
Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically, a chronic hypoestrogenic state fosters debilitating vaginal symptoms like atrophy, dryness, and dyspareunia. Current treatment options, including vaginal estrogen and hyaluronan (HA), anecdotally improve symptoms, but rectifying mechanisms are largely understudied. In order to study the hypoestrogenic vaginal environment, in particular the extracellular matrix (ECM), as well as understand the mechanisms behind current treatments and develop new therapies, we characterized a reliable and reproducible animal model. Bilateral ovariectomies (OVX) were performed on 9-week-old CD1 mice. After 1 month of estrogen loss due to ovarian removal, a phenotype that is similar to human vaginal tissue in an estrogen reduced state was noted in mice compared to sham-operated controls. The uterine to body weight ratio decreased by 80% and vaginal epithelium was significantly thinner in OVX compared to sham mice. Estrogen signaling was altered in OVX, but submucosal ERα localization did not reach statistical differences. HA localization in the submucosal area was altered and CD44 expression decreased in OVX mice. Collagen turn-over was altered following OVX. The inflammation profile was also disrupted, and submucosal vaginal CD45 and F4/80 cell populations were significantly reduced in the OVX mice. These results show altered cellular and molecular changes due to reduced estrogen levels. Developing new treatments for hypoestrogenic vaginal symptoms rely on better understanding of not only the cellular changes, but also the altered vaginal ECM environment. Further studies using this mouse model has the potential to advance women's vaginal health treatments and aid in understanding the interplay between organ systems in both healthy, aged, and diseased states.
Topics: Humans; Mice; Female; Animals; Aged; Vagina; Estrogens; Receptors, Estrogen; Uterus; Ovariectomy
PubMed: 37549960
DOI: 10.14814/phy2.15762 -
Journal of Clinical Medicine Jul 2023Hormonal vaginal therapy is an effective treatment option for women who experience vaginal symptoms related to hormonal changes. Estrogen and prasterone are widely used... (Review)
Review
Hormonal vaginal therapy is an effective treatment option for women who experience vaginal symptoms related to hormonal changes. Estrogen and prasterone are widely used as vaginal treatments, particularly for urogenital atrophy. These symptoms may include vaginal dryness, itching, burning, and pain during sexual intercourse, all of which can significantly affect a woman's quality of life. Previous studies have indicated that such treatment improves tissue elasticity, moisturizes the vagina, and can have a substantial impact on urine incontinence and vaginal microflora and decreases dyspareunia. Hormonal therapy is also useful and commonly used before vaginal surgical treatment. Prasterone is quite a new option for vaginal therapy in Poland and is mainly recommended for dyspareunia in menopausal women. The study related to prasterone therapy emphasizes its effectiveness and safety, making it advantageous to explore its beneficial impact. This paperwork aims to summarize the mechanism of action as well as the effects of both drugs and their beneficial action during vaginal treatment.
PubMed: 37510854
DOI: 10.3390/jcm12144740 -
Radiology and Oncology Sep 2023The term genitourinary syndrome of menopause was first used in 2014 by the North American Menopause Society and the International Society for the Study of Women's Sexual... (Review)
Review
BACKGROUND
The term genitourinary syndrome of menopause was first used in 2014 by the North American Menopause Society and the International Society for the Study of Women's Sexual Health to describe conditions previously known as atrophic vaginitis, urogenital atrophy, or vulvovaginal atrophy. It is a complex, chronic, progressive condition characterized by a wide range of signs and symptoms affecting sexual function and the tissues of the urinary and genital tracts. The main cause of genitourinary syndrome of menopause is estrogen deficiency caused by ovarian removal or dysfunction. The most bothersome symptoms are vaginal dryness, decreased vaginal lubrication, and pain during penetration and intercourse. They all have a negative impact on the quality of life.
CONCLUSIONS
The main goal of treatment is to relieve the symptoms. Treatment modalities are pharmacological or non-pharmacological. The first-line treatment for mild to moderate symptoms is the use of personal lubricants and moisturizers, but the gold standard is estrogen replacement therapy. Hormone therapy may not be an option for women with hormone-dependent cancer.
Topics: Female; Humans; Quality of Life; Vagina; Genital Neoplasms, Female; Vulva; Syndrome; Hormones; Atrophy
PubMed: 37494601
DOI: 10.2478/raon-2023-0038 -
Breast Cancer Research and Treatment Oct 2023To analyze serum estradiol (E2) and estrone (E1) during letrozole treatment and their association to Quality of Life (QoL) and side-effects. (Clinical Trial)
Clinical Trial
Effects of letrozole on serum estradiol and estrone in postmenopausal breast cancer patients and tolerability of treatment: a prospective trial using a highly sensitive LC-MS/MS (liquid chromatography-tandem mass spectrometry) method for estrogen measurement.
PURPOSE
To analyze serum estradiol (E2) and estrone (E1) during letrozole treatment and their association to Quality of Life (QoL) and side-effects.
METHODS
Postmenopausal breast cancer patients starting adjuvant letrozole were eligible. Serum samples were taken at baseline, three, and 12 months. E2 and FSH were measured with routine chemiluminescent immunoassays. E2 and E1 were analyzed after trial completion with a highly sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) with lower limits of quantification (LLOQ) of 5 pmol/L. QoL was measured at baseline and at 12 months with the EORTC QLQ-C30 and QLQ-BR23 and the Women's Health questionnaires, and menopause-related symptoms with the modified Kupperman Index.
RESULTS
Of 100 screened patients 90 completed the trial. Baseline mean LC-MS/MS E2 and E1 were 12 pmol/L (range < 5-57) and 66 pmol/L (< 5-226), respectively. E2 levels measured by immunoassay and LC-MS/MS showed no correlation. E2 and E1 were completely suppressed by letrozole except for one occasion (E1 11 pmol/L at 3 months). Pain, side effects of systemic therapy, vasomotor symptoms, joint and muscle aches, and vaginal dryness increased during letrozole treatment. A high baseline E2 was significantly associated with increased aching joints and muscles, but not with the other side effects.
CONCLUSIONS
Letrozole supresses E2 and E1 completely below the LLOQ of the LC-MS/MS in postmenopausal women. High pre-treatment E2 levels were associated with more joint and muscle pain during letrozole. Automated immunoassays are unsuitable for E2 monitoring during letrozole therapy due to poor sensitivity.
Topics: Female; Humans; Breast Neoplasms; Chromatography, Liquid; Estradiol; Estrogens; Estrone; Letrozole; Postmenopause; Prospective Studies; Quality of Life; Tandem Mass Spectrometry
PubMed: 37491651
DOI: 10.1007/s10549-023-07054-3 -
Cureus Jun 2023Introduction The use of virgin coconut oil (VCO) as an over-the-counter (OTC) treatment for vaginal dryness and dyspareunia (VDD) in the general population has increased...
Virgin Coconut Oil in Paste Form as Treatment for Dyspareunia and Vaginal Dryness in Patients With and Without Rheumatic Autoimmune Diseases: An Efficacy and Safety Assessment Pilot Study.
Introduction The use of virgin coconut oil (VCO) as an over-the-counter (OTC) treatment for vaginal dryness and dyspareunia (VDD) in the general population has increased worldwide despite the absence of evidence-based studies supporting its efficacy. The principal objective of our pilot study was to scientifically validate the significant benefits and safety of using intra- and peri-vaginal application of VCO in paste form (VCOPF) for the treatment of VDD in patients with and without rheumatic autoimmune diseases (RAD). Additionally, multiple psychosocial, sexuality, and disease activity variables were also assessed. Methods A survey study of patients with chronic VDD, with and without RAD, treated with a single proprietary brand of VCOPF via the 'CocoRelief' protocol continuously for at least six months in an outpatient rheumatology practice setting. We evaluated the comparison of group characteristics, treatment outcomes, and satisfaction questions by Fisher's exact test or chi-square test for independence for categorical variables and two-sample t-tests for continuous variables. Results Of the 53 respondents, 31 (58%) had an RAD and 22 (42%) did not. Rheumatoid arthritis and primary Sjogren's syndrome comprised 75% of the RAD group. The non-RAD cohort had both a higher baseline mean of intercourse pain (on a scale of 0-5) before VCOPF use (4.4 (SD 1.1) vs 3.9 (SD 1.0) (p = 0.094)) and a higher mean intercourse pain after VCOPF (2.0 (SD 1.3) vs 1.3 (SD 1.1) (p = 0.039)). VDD decreased by 55% in the non-RAD and 66% in the RAD population. Although not statistically significant (p = 0.195), VCOPF was at worst comparable to estrogen-containing therapies (ECT). No adverse events (AE) were documented. Conclusion A high percentage of women with VDD, with and without RAD, needlessly continue to experience quality-of-life-altering physical and psychosocial morbidity due to the underutilization and lack of awareness of VCO-containing therapy. The small sample size, non-blinded, non-randomized, pilot platform, and the use of a non-validated assessment tool represent the principal limiting factors. This study revealed that VCOPF, when used in paste form via the CocoRelief protocol, provided statistically significant long-term VDD-related efficacy not inferior to ECT without AE in patients with and without RAD. VCOPF is, therefore, likely to be a useful, cost-effective alternative in a substantial percentage of patients with and without RAD, particularly in women hesitant to utilize ECT due to cost and/or fear of adverse effects.
PubMed: 37461787
DOI: 10.7759/cureus.40501 -
Cureus Jul 2023Introduction Sexual dysfunction is rarely studied in Indonesian patients with breast cancer. We aimed to assess the prevalence of sexual dysfunction symptoms following...
Introduction Sexual dysfunction is rarely studied in Indonesian patients with breast cancer. We aimed to assess the prevalence of sexual dysfunction symptoms following chemotherapy, as well as the pattern and the associated factors. Methods This cross-sectional study included 135 female breast cancer patients receiving primary chemotherapy. The present study measured the prevalence of sexual dysfunction symptoms using an e-questionnaire containing Common Toxicity Criteria for Adverse Events (CTCAE) version 4 at different time points. Other data included sociodemography, clinicopathology, treatment, and other concurrent symptom characteristics. Bivariate and multivariate logistic regression tests were used to analyze any association among variables. Results In the whole panel, 86 (63.7%) of 135 cases experienced sexual dysfunction. The most common symptom was vaginal dryness (45.9%), followed by decreased libido (45.2%), dyspareunia (13.3%), delayed orgasm (11.1%), and anorgasmia (8.9%). When observed at five different time points, the frequency of symptoms increased during chemotherapy and persisted until six months after completing treatment. Chemotherapy duration of >120 days was associated with a higher probability of vaginal dryness (p=0.012) and decreased libido (p=0.033). Spouse age ≥55 years old and body mass index (BMI) ≥23 kg/m were associated with a reduced probability of decreased libido (p=0.033 and 0.025, respectively). The presence of comorbidity was associated with a reduced probability of delayed orgasm (p=0.034). Conclusions A significant proportion of patients with breast cancer had sexual dysfunction following chemotherapy. Vaginal dryness, decreased libido, and dyspareunia were the commonest symptoms observed. Duration of chemotherapy, spouse age, BMI, and comorbidity were associated with the risk of sexual dysfunction occurrence.
PubMed: 37449290
DOI: 10.7759/cureus.41744 -
Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211 -
Nutrients May 2023Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as...
Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of () and () on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERβ (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERβ expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis.
Topics: Female; Humans; Rats; Animals; Estrogen Receptor beta; Estrogen Receptor alpha; Plant Extracts; Polygonatum; Endometriosis; Receptors, Estrogen; Menopause; Cholesterol; Osteoporosis; Hormones; Ovariectomy
PubMed: 37299404
DOI: 10.3390/nu15112443 -
Journal of Clinical Medicine May 2023This study evaluates the efficacy and safety of fractional CO lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three...
This study evaluates the efficacy and safety of fractional CO lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three laser applications at an interval of 4 weeks each. The severity of GSM symptoms was assessed using a visual analog scale (VAS) at baseline and at every visit. The objective scale was measured using the vaginal health index score (VHIS) and Vaginal Maturation Index (VMI) after completion of the laser procedure. During each procedure, the patients' pain in the VAS score was recorded. In the last visit, patients evaluated their satisfaction with the laser therapy using a 5-point Likert scale. Thirty women completed all the study protocols. After two sessions of laser therapy, some GSM symptoms (vaginal dryness and urgency) and VHIS improved significantly. After completion of the treatment, all GSM symptoms improved ( < 0.05), and the VHIS further increased significantly (VHIS at baseline, 8.86 ± 3.2 vs. V3, 16.83 ± 3.15, < 0.001). The average satisfaction was 4.3. This study shows that fractional CO laser treatment is effective and safe for Korean women with GSM. Further studies are needed to confirm these results and assess the long-term effects of laser therapy.
PubMed: 37297874
DOI: 10.3390/jcm12113679