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Medicina (Kaunas, Lithuania) Jun 2022Vulvovaginal atrophy (VVA) is a chronic progressive disease involving the female genital apparatus and lower urinary tract. This condition is related to hypoestrogenism... (Review)
Review
Vulvovaginal atrophy (VVA) is a chronic progressive disease involving the female genital apparatus and lower urinary tract. This condition is related to hypoestrogenism consequent to menopause onset but is also due to the hormonal decrease after adjuvant therapy for patients affected by breast cancer. Considering the high prevalence of VVA and the expected growth of this condition due to the increase in the average age of the female population, it is easy to understand its significant social impact. VVA causes uncomfortable disorders, such as vaginal dryness, itching, burning, and dyspareunia, and requires constant treatment, on cessation of which symptoms tend to reappear. The currently available therapies include vaginal lubricants and moisturizers, vaginal estrogens and dehydroepiandrosterone (DHEA), systemic hormone therapy, and Ospemifene. Considering, however, that such therapies have some problems that include contraindications, ineffectiveness, and low compliance, finding an innovative, effective, and safe treatment is crucial. The present data suggest great efficacy and safety of a vaginal laser in the treatment of genital symptoms and improvement in sexual function in patients affected by VVA. The beneficial effect tends to be sustained over the long-term, and no serious adverse events have been identified. The aim of this review is to report up-to-date efficacy and safety data of laser energy devices, in particular the microablative fractional carbon dioxide laser and the non-ablative photothermal Erbium-YAG laser.
Topics: Atrophy; Female; Humans; Lasers, Gas; Menopause; Treatment Outcome; Vagina; Vaginal Diseases
PubMed: 35744033
DOI: 10.3390/medicina58060770 -
World Journal of Clinical Oncology Feb 2022There is increasing attention about managing the adverse effects of adjuvant therapy (Chemotherapy and anti-estrogen treatment) for breast cancer survivors (BCSs).... (Review)
Review
There is increasing attention about managing the adverse effects of adjuvant therapy (Chemotherapy and anti-estrogen treatment) for breast cancer survivors (BCSs). Vulvovaginal atrophy (VVA), caused by decreased levels of circulating estrogen to urogenital receptors, is commonly experienced by this patients. Women receiving antiestrogen therapy, specifically aromatase inhibitors, often suffer from vaginal dryness, itching, irritation, dyspareunia, and dysuria, collectively known as genitourinary syndrome of menopause (GSM), that it can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of quality of life (QoL). The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Systemic estrogen treatment is contraindicated in BCSs. In these patients, GSM may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment, but it is normally undertreated by oncologists because of fear of cancer recurrence, specifically when considering treatment with vaginal estrogen therapy (VET) because of unknown levels of systemic absorption of estradiol. Lifestyle modifications and nonhormonal treatments (vaginal moisturizers, lubricants, and gels) are the first-line treatment for GSM both in healthy women as BCSs, but when these are not effective for symptom relief, other options can be considered, such as VET, ospemifene, local androgens, intravaginal dehydroepiandrosterone (prasterone), or laser therapy (erbium or CO2 Laser). The present data suggest that these therapies are effective for VVA in BCSs; however, safety remains controversial and a there is a major concern with all of these treatments. We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. We include recommendations for an approach to the management of GSM in women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.
PubMed: 35316932
DOI: 10.5306/wjco.v13.i2.71 -
Medicina (Kaunas, Lithuania) Oct 2019During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a... (Review)
Review
During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a physiologic deterioration of hypothalamic-pituitary-ovarian axis function associated with fluctuating hormone levels. During this transition, women can suffer symptoms related to menopause (such as hot flushes, sleep disturbance, mood changes, memory complaints and vaginal dryness). Neurological symptoms such as sleep disturbance, "brain fog" and mood changes are a major complaint of women transitioning menopause, with a significant impact on their quality of life, productivity and physical health. In this paper, we consider the associations between menopausal stage and/or hormone levels and sleep problems, mood and reduced cognitive performance. The role of estrogen and menopause hormone therapy (MHT) in cognitive function, sleep and mood are also discussed.
Topics: Affect; Cognition; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Menopause; Middle Aged; Quality of Life; Sleep
PubMed: 31581598
DOI: 10.3390/medicina55100668 -
Journal of Comparative Effectiveness... Aug 2022Despite significant controversy, vaginal laser therapy continues to be used for treatment of many gynecologic and pelvic conditions including vaginal atrophy, vaginal... (Review)
Review
Despite significant controversy, vaginal laser therapy continues to be used for treatment of many gynecologic and pelvic conditions including vaginal atrophy, vaginal dryness, dyspareunia, urinary incontinence and pelvic pain. This commentary reviews the controversy surrounding vaginal laser therapy and summarizes the important distinction between ablative and non-ablative vaginal lasers. While much research is still needed, the article describes what is important for healthcare professionals to know before making the decision to integrate this technology into their clinical practice.
Topics: Female; Humans; Laser Therapy; Lasers, Solid-State; Menopause; Vagina; Vaginal Diseases
PubMed: 35726603
DOI: 10.2217/cer-2021-0281 -
Cureus Apr 2020The genitourinary syndrome of menopause (GSM) is a relatively new term for the condition previously known as vulvovaginal atrophy, atrophic vaginitis, or urogenital... (Review)
Review
The genitourinary syndrome of menopause (GSM) is a relatively new term for the condition previously known as vulvovaginal atrophy, atrophic vaginitis, or urogenital atrophy. The term was first introduced in 2014. GSM is a chronic, progressive, vulvovaginal, sexual, and lower urinary tract condition characterized by a broad spectrum of signs and symptoms. Most of these symptoms can be attributed to the lack of estrogen that characterizes menopause. Even though the condition mainly affects postmenopausal women, it is seen in many premenopausal women as well. The hypoestrogenic state results in hormonal and anatomical changes in the genitourinary tract, with vaginal dryness, dyspareunia, and reduced lubrication being the most prevalent and bothersome symptoms. These can have a great impact on the quality of life (QOL) of the affected women, especially those who are sexually active. The primary goal of the treatment of GSM is to achieve the relief of symptoms. First-line treatment consists of non-hormonal therapies such as lubricants and moisturizers, while hormonal therapy with local estrogen products is generally considered the "gold standard''. Newer therapeutic approaches with selective estrogen receptor modulators (SERMs) or laser technologies can be employed as alternative options, but further research is required to investigate the viability and scope of their implementation in day-to-day clinical practice.
PubMed: 32399320
DOI: 10.7759/cureus.7586 -
Pharmaceuticals (Basel, Switzerland) Apr 2023(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can... (Review)
Review
(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.
PubMed: 37111307
DOI: 10.3390/ph16040550 -
Frontiers in Reproductive Health 2021The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium,... (Review)
Review
The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type "," with a predominance of , type II, with a predominance of , type III, where predominates, and type V with a predominance of . Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.
PubMed: 36304005
DOI: 10.3389/frph.2021.780931 -
Frontiers in Oncology 2023Endocrine therapy-related symptoms are associated with early discontinuation and quality of life among breast cancer survivors. Although previous studies have examined...
BACKGROUND
Endocrine therapy-related symptoms are associated with early discontinuation and quality of life among breast cancer survivors. Although previous studies have examined these symptoms and clinical covariates, little is known about the interactions among different symptoms and correlates. This study aimed to explore the complex relationship of endocrine therapy-related symptoms and to identify the core symptoms among breast cancer patients.
METHODS
This is a secondary data analysis conducted based on a multicenter cross-sectional study of 613 breast cancer patients in China. All participants completed the 19-item Chinese version of the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES). Multivariate linear regression analysis was performed to identify significant factors. A contemporaneous network with 15 frequently occurring symptoms was constructed after controlling for age, payment, use of aromatase inhibitors, and history of surgery. Network comparison tests were used to assess differences in network structure across demographic and treatment characteristics.
RESULTS
All 613 participants were female, with an average age of 49 years (SD = 9.4). The average duration of endocrine therapy was 3.6 years (SD = 2.3) and the average symptom score was 18.99 (SD = 11.43). Irritability (n = 512, 83.52%) and mood swings (n = 498, 81.24%) were the most prevalent symptoms. Lost interest in sex (mean = 1.95, SD = 1.39) and joint pain (mean = 1.57, SD = 1.18) were the most severe symptoms. The edges in the clusters of emotional symptoms ("irritability-mood swings"), vasomotor symptoms ("hot flashes-cold sweats-night sweats"), vaginal symptoms ("vaginal discharge-vaginal itching"), sexual symptoms ("pain or discomfort with intercourse-lost interest in sex-vaginal dryness"), and neurological symptoms ("headaches-dizziness") were the thickest in the network. There were no significant differences in network structure (P = 0.088), and global strength (P = 0.330) across treatment types (selective estrogen receptor modulators vs. aromatase inhibitors). Based on an evaluation of the centrality indices, irritability and mood swings appeared to be structurally important nodes after adjusting for the clinical covariates and after performing subgroup comparisons.
CONCLUSION
Endocrine therapy-related symptoms are frequently reported issues among breast cancer patients. Our findings demonstrated that developing targeted interventions focused on emotional symptoms may relieve the overall symptom burden for breast cancer patients during endocrine therapy.
PubMed: 37064124
DOI: 10.3389/fonc.2023.1081786 -
The Cochrane Database of Systematic... Mar 2020Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression (OFS) as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy). This review examined the role of adding OFS to another treatment (i.e. chemotherapy, endocrine therapy, or both) or comparing OFS to no further adjuvant treatment.
OBJECTIVES
To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer.
SEARCH METHODS
For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 26 September 2019. We screened the reference lists of related articles, contacted trial authors, and applied no language restrictions.
SELECTION CRITERIA
We included all randomised trials assessing any method of OFS, that is, oophorectomy, radiation-induced ovarian ablation, or LHRH agonists, as adjuvant treatment for premenopausal women with early-stage breast cancer. We included studies that compared (1) OFS versus observation, (2) OFS + chemotherapy versus chemotherapy, (3) OFS + tamoxifen versus tamoxifen, and (4) OFS + chemotherapy + tamoxifen versus chemotherapy + tamoxifen.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Toxicity, contralateral breast cancer, and second malignancy were represented as risk ratios (RRs), and quality of life data were extracted when provided.
MAIN RESULTS
This review update included 15 studies involving 11,538 premenopausal women with hormone receptor-positive early breast cancer; these studies were conducted from 1978 to 2014. Some of these treatments are not current standard of care, and early studies did not assess HER2 receptor status. Studies tested OFS versus observation (one study), OFS plus chemotherapy versus chemotherapy (six studies), OFS plus tamoxifen versus tamoxifen (six studies), and OFS plus chemotherapy and tamoxifen versus chemotherapy and tamoxifen (two studies). Of those studies that reported the chemotherapy regimen, an estimated 72% of women received an anthracycline. The results described below relate to the overall comparison of OFS versus no OFS. High-certainty evidence shows that adding OFS to treatment resulted in a reduction in mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.78 to 0.94; 11 studies; 10,374 women; 1933 reported events). This treatment effect was seen when OFS was added to observation, to tamoxifen, or to chemotherapy and tamoxifen. The effect on mortality was not observed when OFS was added to chemotherapy without tamoxifen therapy (HR 0.95, 95% CI 0.82 to 1.09; 5 studies; 3087 women; median follow-up: range 7.7 to 12.1 years). The addition of OFS resulted in improved DFS (HR 0.83, 95% CI 0.77 to 0.90; 10 studies; 8899 women; 2757 reported events; high-certainty evidence). The DFS treatment effect persisted when OFS was added to observation, to tamoxifen, and to chemotherapy and tamoxifen. The effect on DFS was reduced when OFS was added to chemotherapy without tamoxifen therapy (HR 0.90, 95% CI 0.79 to 1.01; 5 studies; 2450 women). Heterogeneity was low to moderate across studies for DFS and OS (respectively). Evidence suggests that adding OFS slightly increases the incidence of hot flushes (grade 3/4 or any grade; risk ratio (RR) 1.60, 95% CI 1.41 to 1.82; 6 studies; 5581 women; low-certainty evidence, as this may have been under-reported in these studies). Two other studies that could not be included in the meta-analysis reported a higher number of hot flushes in the OFS group than in the no-OFS group. Seven studies involving 5354 women collected information related to mood; however this information was reported as grade 3 or 4 depression, anxiety, or neuropsychiatric symptoms, or symptoms were reported without the grade. Two studies reported an increase in depression, anxiety, and neuropsychiatric symptoms in the OFS group compared to the no-OFS group, and five studies indicated an increase in anxiety in both treatment groups (but no difference between groups) or no difference overall in symptoms over time or between treatment groups. A single study reported bone health as osteoporosis (defined as T score < -2.5); this limited evidence suggests that OFS increases the risk of osteoporosis compared to no-OFS at median follow-up of 5.6 years (RR 1.16, 95% CI 1.10 to 28.82; 2011 women; low-certainty evidence). Adding OFS to treatment likely reduces the risk of contralateral breast cancer (HR 0.75, 95% CI 0.57 to 0.97; 9 studies; 9138 women; moderate-certainty evidence). Quality of life was assessed in five studies; four studies used validated tools, and the fifth study provided no information on how data were collected. Two studies reported worse quality of life indicators (i.e. vaginal dryness, day and night sweats) for women receiving OFS compared to those in the no-OFS group. The other two studies indicated worsening of symptoms (e.g. vasomotor, gynaecological, vaginal dryness, decline in sexual interest, bone and joint pain, weight gain); however these side effects were reported in both OFS and no-OFS groups. The study that did not use a validated quality of life tool described no considerable differences between groups.
AUTHORS' CONCLUSIONS
This review found evidence that supports adding OFS for premenopausal women with early, hormone receptor-positive breast cancers. The benefit of OFS persisted when compared to observation, and when added to endocrine therapy (tamoxifen) or chemotherapy and endocrine therapy (tamoxifen). The decision to use OFS may depend on the overall risk assessment based on tumour and patient characteristics, and may follow consideration of all side effects that occur with the addition of OFS.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Humans; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 32141074
DOI: 10.1002/14651858.CD013538