Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

Hirschberg, Angelica Lindén; Sánchez‐Rovira, Pedro; Presa-Lorite, Jesús; Campos-Delgado, Miriam; Gil-Gil, Miguel; Lidbrink, Elisabet; Suárez-Almarza, Javier; Nieto-Magro, Concepción

doi:10.1097/gme.0000000000001497

Cited by 28 publications

(37 citation statements)

References 27 publications

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“…With the gradual increase of age, the activity D gradually decreases, the parathyroid gland gradually increases, and the sex hormones gradually decrease. These changes cause increased osteoclast activity and decreased osteoblast activity ( Delgado et al, 2016 ; Hirschberg et al, 2020 ). In postmenopausal women, in addition to the above factors, there are also the decline in estrone, estradiol, and estriol, which accelerate the decline in osteoblast activity, reduce bone matrix formation, and increase bone resorption ( Fallah et al, 2013 ; Knuplez et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

Zhou

Shen

et al. 2020

Front. Pharmacol.

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Postmenopausal osteoporosis (PMOP) is the most common metabolic bone illness among the elderly especially in postmenopausal women resulting from a reduction in bone mineral density, but there is no effective drug at present. The study was aimed at evaluating efficacy of osthole against osteoporosis using high-throughput metabolomics method. The blood samples for illustrating the pathological mechanism of PMOP and exploring the efficacy of osthole treatment (ST) were collected to perform metabolites and metabolic profiles and pathways analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and pattern recognition methods. In addition, backbone weight, the bone density, and some vital biochemical indexes were also detected. A total of 28 metabolites were identified as biomarkers for ovariectomized-osteoporosis model, and ST could significantly regulate 19 of them including lysine, linoleic acid, 3-hydroxybutyric acid, prostaglandin F2a, taurocholic acid, LysoPC(15:0), l -carnitine, glucose, arginine, citric acid, corticosterone, ornithine, tryptophan, arachidonic acid, Cer(d18:0/18:0), glutamine, uric acid, 8-HETE, estriol, which mainly related with 13 metabolic pathways, such as linoleic acid metabolism, starch, and sucrose metabolism, arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, citrate cycle (TCA cycle), and arginine biosynthesis. The ovariectomized model (OVX) rats display a significant decrease bone density, TGF-β1, NO, and NOS level, and a significant increase bone weight, IL-6, TNF-α, and Ca 2+ level. These parameters in the ST rats were evidently improved as compared to the OVX group. ST effectively mitigated ovariectomy-induced osteoporosis in rats by affecting endogenous metabolite-related metabolic mechanism and showed the natural alternative with potential for the treatment of PMOP.

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Section: Discussionmentioning

confidence: 99%

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

Zhou

Shen

et al. 2020

Front. Pharmacol.

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“…Summary of study characteristics is presented in Tables 1 and 2. Of the 36 studies, 11 described topical interventions; 11 described laser interventions; 8 described psychoeducational interventions; 3 described multimodal approaches; and 3 described pharmacological studies 40-75 . All 22 nonrandomized studies were before-after studies (without a control group), consisting of 17 interventional trials and 5 cohort studies.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of interventions to manage sexual dysfunction in women with cancer: a systematic review

et al. 2022

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Importance: Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous studies have addressed treatment options for sexual dysfunction in women with cancer, but it still remains a challenge to select the most efficacious option for patients.Objective: To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors.Evidence Review: A literature search of the electronic databases MEDLINE, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) was conducted using general search terms of ''women'', ''cancer'', ''intervention'', ''sexual dysfunction''. We included randomized controlled trials (RCTs) and uncontrolled before-after studies that evaluated the efficacy of intervention for female sexual dysfunction in women with history of cancer. Methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies.Findings: Thirty-six studies were included for qualitative synthesis (14 RCTs (n ¼ 1284), 17 uncontrolled trials (n ¼ 589), and 5 cohort studies (n ¼ 497). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intravaginal dehydroepiandrosterone (DHEA) (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements of sexual function. Both laser therapy (fractional CO 2 and erbium) and multimodal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function.Conclusions and Relevance: The most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multimodal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10-70 participants), with moderate to high risk of bias. Therefore, large-scale, double-blind, RCTs with long-period follow-up, and at low risk of bias are needed to show efficacy for these interventions.

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“…Conversely, Hirschberg et al [ 192 ], in sixty-one BCS patients receiving AIs (50 received estriol vaginal gel and 11 received placebo), found that ultra-low-dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy and that estriol levels increased initially and normalized by week 12, while estradiol and estrone remained mostly undetectable throughout the study. They concluded that the negligible impact of the product on the levels of estrogens, FSH, and LH supported the safe use of this ultra-low-dose estriol vaginal gel as a treatment option for vulvovaginal atrophy in BCSs receiving AIs [Qa = Good].…”

Section: Current Treatment Options For Genitourinary Syndrome Of Meno...mentioning

confidence: 99%

Management of genitourinary syndrome of menopause in breast cancer survivors: An update

López¹

2022

WJCO

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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.

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Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

Cited by 28 publications

References 27 publications

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

Efficacy of interventions to manage sexual dysfunction in women with cancer: a systematic review

Management of genitourinary syndrome of menopause in breast cancer survivors: An update

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