Comparison of the effect of noninvasive radiofrequency with vaginal estrogen and vaginal moisturizer in the treatment of vulvovaginal atrophy in postmenopausal women: a randomized clinical trial.

OBJECTIVE: To compare the effect of noninvasive radiofrequency (RF) with vaginal estrogen (E), and vaginal moisturizer (M) on improving vulvovaginal atrophy (VVA) in women with genitourinary syndrome of menopause. METHODS: A total of 32 postmenopausal women who met the inclusion criteria were randomized into three intervention arms to receive one of the following treatments: three sessions of noninvasive RF therapy (RF arm); intravaginal estriol cream 1 mg applied daily for 2 weeks, followed by 1 mg applied two times weekly or 1 mg of estradiol vaginal fast-dissolving film applied daily for 2 weeks, followed by 1 mg applied two times weekly (E arm); and intravaginal moisturizer two times a week (M arm). Assessments at baseline and after 4 months were conducted using Vaginal Health Index score, Vaginal Maturation, visual analog scale for VVA symptoms (dyspareunia, dryness, and burning), and Menopause Rating Scale (MRS) for urogenital symptoms. Vaginal wall biopsies were administered to participants who consented, pretreatment and posttreatment (at baseline and after 4 months of follow-up). RESULTS: After 4 months, the Vaginal Health Index showed an increase of 6.6 points in mean total score in the RF arm, also in the E arm (+7.3 points), with no significant improvement in the M arm (+1.5 points) (interaction effect: RF, E ≠ M, P < 0.001). Regarding vaginal maturation, there was a significant increase in superficial cells in the E arm (+31.3), with no significant changes in the RF (+9.3) and M (-0.5) arms (interaction effect: E ≠ M, P < 0.001). Vaginal pH decreased significantly in the E arm (-1.25), with a similar response in the RF arm (-1.7), with no significant improvement in the M arm (-0.25) (interaction effect: RF, E ≠ M, P < 0.001).There was a significant improvement in the MRS score for VVA symptoms in the three intervention arms, with no predominance of any arm, whereas the improvement in the total MRS score for urogenital symptoms showed a predominance of the RF arm (ΔRF: -7.8; ΔE: -3.5; ΔM: -2.3; RF ≠ E, M). According to histopathologic analysis, there was no statistically significant increase in glycogenation ( P = 0.691) or epithelial cone height ( P = 0.935), despite an increase in the median delta (difference between pretreatment and posttreatment) in the three intervention arms (glycogenation: RF arm Δ = +118.4%; E arm Δ = +130.9%; M arm Δ = +24.9%; epithelial cone height: RF arm Δ = +33.5%; E arm Δ = +18.6%; M arm Δ = +22.3%). CONCLUSION: The effect of noninvasive RF on the treatment of vulvovaginal symptoms of genitourinary syndrome of menopause was similar to vaginal estrogen, except for hormonal cytology, and superior to vaginal moisturizer, with improvement in some histomorphometric parameters. These findings are promising, especially for the population that cannot or prefers not to use vaginal estrogen therapy.

Treatments of Epistaxis in Hereditary Hemorrhagic Telangiectasia: Systematic Review and Network Meta-Analysis.

PURPOSE OF REVIEW: To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. RECENT FINDINGS: Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.

Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol.

In multiple sclerosis (MS), demyelination occurs in the cerebral cortex, and cerebral cortex atrophy correlates with clinical disabilities. Treatments are needed in MS to induce remyelination. Pregnancy is protective in MS. Estriol is made by the fetoplacental unit, and maternal serum estriol levels temporally align with fetal myelination. Here, we determined the effect of estriol treatment on the cerebral cortex in the preclinical model of MS, experimental autoimmune encephalomyelitis (EAE). Estriol treatment initiated after disease onset decreased cerebral cortex atrophy. Neuropathology of the cerebral cortex showed increased cholesterol synthesis proteins in oligodendrocytes, more newly formed remyelinating oligodendrocytes, and increased myelin in estriol-treated EAE mice. Estriol treatment also decreased the loss of cortical layer V pyramidal neurons and their apical dendrites and preserved synapses. Together, estriol treatment after EAE onset reduced atrophy and was neuroprotective in the cerebral cortex.

New developments in the management of vulvovaginal atrophy: a comprehensive overview.

INTRODUCTION: Proper recognition and individualized therapy of vulvovaginal atrophy (VVA) is paramount. AREAS COVERED: Assessment of VVA should be performed using several questionnaires in combination with wet mount microscopy to determine Vaginal Cell Maturation Index (VCMI) and infections. PubMed searches were carried out between 1 march 2022 and 15 October 2022.Low dose vaginal estriol seems safe, efficient, and could be used in patients with contraindications for steroid hormones such as women with a history of breast cancer, and should therefore be considered as first choice hormonal treatment, when non-hormonal treatments fail. New estrogens, androgens, and several Selective Estrogen Receptor Modulators (SERMs) are being developed and tested. Intravaginal Hyaluronic Acid (HA) or Vit D can help women who can't or don't want to use hormones. EXPERT OPINION: Proper treatment is not possible without a correct and full diagnosis, including microscopy of the vaginal fluid. Low dose vaginal estrogen treatment, especially with estriol, is very efficient and is preferred in most women with VVA. Oral ospemifene and vaginal dihydroepiandrosterone (DHEA) are now considered efficient and safe alternative therapies for VVA. More safety data are waited for several SERMs and for a newly introduced estrogen: estetrol (E4), although so far no major side effects were seen from these drugs. Indications for laser treatments are questionable.

Decreased neurofilament light chain levels in estriol-treated multiple sclerosis.

Estrogens have neuroprotective actions depending on estrogen type, dose, and timing in both preclinical models and in women during health and disease. Serum neurofilament light chain is a putative biomarker of neurodegeneration in multiple sclerosis, aging, and other neurodegenerative diseases. Here, oral treatment with an estrogen unique to pregnancy (estriol) using an 8 mg dose to induce a mid-pregnancy blood estriol level reduced serum neurofilament light chain in nonpregnant MS women at mean age of 37 years. This is consistent with estriol-mediated protection from neuro-axonal injury and supports the use of serum neurofilament light chain as a biomarker in MS.

Vaginal hormone-free moisturising cream is not inferior to an estriol cream for treating symptoms of vulvovaginal atrophy: Prospective, randomised study.

This prospective, open-label, multicentre, multinational, randomised trial investigated the non-inferiority of treatment with a vaginal hormone-free moisturising cream compared to a vaginal estriol (0.1%) cream in a panel of post-menopausal women suffering from symptoms of vulvovaginal dryness in a parallel group design. In total, 172 post-menopausal women were randomly allocated to either one of the two treatments, each administered for 43 days. The primary endpoint was the total severity score of subjective symptoms (dryness, itching, burning and pain unrelated to sexual intercourse) of the respective treatment period. Secondary endpoints were severity of single subjective symptoms (including dyspareunia if sexually active), impairment of daily life, Vaginal Health Index, as well as assessment of safety. In both groups, women treated with hormone-free moisturising cream and those treated with estriol cream, total severity score improved significantly compared to baseline by 5.0 (from 6.1 to 1.1) and by 5.4 (from 6.0 to 0.6), respectively, after 43 days of treatment (p < 0.0001). One-sided test of baseline differences (for a clinically relevant difference Δ = 1.5) confirmed the hormone-free moisturising cream to be non-inferior to the estriol cream. Severity of dyspareunia as well as impairment of daily life due to subjective symptoms, significantly improved for both treatment groups (p<0.0001). Subgroup analysis of women with mild or moderate impairment of daily life at baseline caused by "vaginal dryness" symptoms benefited from both creams, while women with severe impairment showed a significantly greater benefit from the estriol cream (p = 0.0032). Both treatments were well tolerated with no serious adverse events occurring. This study provides clinical evidence that a hormone-free vaginal moisturising cream cannot only improve vaginal dryness compared to an 0.1% estriol cream but also can relieve dyspareunia as well as improve woman's impairment of daily life, justifying its use as a first choice for mild or moderate vulvovaginal dryness symptoms.

Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy.

BACKGROUND: Among treatments for vulvo-vaginal atrophy (VVA), there is a new kind of energy-based device, the non-ablative CO2 laser. AIM: This study aimed to assess the efficacy and safety of the non-ablative CO2 laser in menopausal women with VVA as a monotherapy or in association with vaginal estriol or moisturizer. METHODS: Seventy-five women with VVA received laser treatment (Laser group), laser plus estriol gel (Laser+E) or laser plus moisturizers (Laser+M). The study protocol consisted of 3 monthly laser sessions (t0, t1, t2) and a gynecological examination at baseline and 1 month after last laser treatment (t3). Objective measures included VHI (Vaginal Health Index) and VuHI (Vulvar Health Index); subjective symptoms of VVA (Dryness, Burning, Itching, Dysuria) evaluated via visual analog scales, sexual function evaluated by FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) and MENQOL (Mopause-specific Quality Of Life). Adverse events and discomfort encountered during the procedure were also assessed. OUTCOMES: Primary outcomes were the evaluation of VHI and VuHI and secondary outcomes were changes in VVA symptoms (VAS), sexual function (MENQOL, FSFI, FSDS) and discomfort during the procedure. RESULTS: Seventy-five women (25 in Laser, 25 in Laser+E and 25 in Laser+M group) completed the study. At t3, mean VHI, VuHI, dryness, burning and itching VAS scores improved significantly with no differences between the groups. The lubrication domain of FSFI improved significantly only in the Laser+M group, while the pain domain improved significantly in all women with no differences between the groups. FSFI and FSDS overall scores and MENQOL sexual domain improved in all women with no significant difference between the groups. The mean score of the pain during the procedure was low at t0 and did not change throughout the study. CLINICAL IMPLICATIONS: This study extends knowledge concerning the effectiveness of a new non-ablative CO2 laser in post-menopausal women with VVA. STRENGTHS & LIMITATIONS: This is one of the first studies on this kind of laser and is the first to compare the effectiveness of laser treatment alone or in combination with vaginal estriol or moisturizers. Parameters of VVA and sexual function were evaluated using validated tools. Study limitations include short follow-up time, the limited number of participants and the absence of a sham-controlled group. CONCLUSION: Non-ablative CO2 laser seems to be an effective treatment for VVA in menopausal women. Our preliminary data shows that it can be effective as monotherapy or with adjuvant treatments. Alvisi S, Lami A, Baldassarre M, et al. Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med 2022;19:761-770.

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.

OBJECTIVE: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs. METHODS: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study. CONCLUSIONS: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens. : Video Summary:http://links.lww.com/MENO/A531.

Video Summary:http://links.lww.com/MENO/A531.

Pharmacotherapy for the treatment of vaginal atrophy.

INTRODUCTION: Despite its frequency, recognition and therapy of vulvovaginal atrophy (VVA) remain suboptimal. Wet mount microscopy, or vaginal pH as a proxy, allows VVA diagnosis in menopause, but also in young contraception users, after breast cancer, or postpartum. Intravaginal low dose estrogen product is the main therapy. Ultra-low-dose vaginal estriol is safe and sufficient in most cases, even in breast cancer patients, while hyaluronic acid can help women who cannot or do not want to use hormones. AREAS COVERED: The authors provide an overview of the current pharmaceutical treatment for vulvovaginal atrophy and provide their expert opinions on its future treatment. EXPERT OPINION: The basis of good treatment is a correct and complete diagnosis, using a microscope to study the maturity index of the vaginal fluid. Minimal dose of estriol intravaginally with or without lactobacilli is elegant, cheap and can safely be used after breast cancer and history of thromboembolic disease. Laser therapy requires validation and safety data, as is can potentially cause vaginal fibrosis and stenosis, and safer and cheaper alternatives are available.

Management of ASC-US/HPV positive post-menopausal woman.

BACKGROUND: The aim of our study was to determine which diagnostic course is best to identify women at risk of CIN2+ among post-menopausal women with cytological diagnosis of ASCUS METHODS: We selected women who had been post-menopausal for at least one year , and who had completed the entire diagnostic-therapeutic course that they had undertaken. The sample was divided into two arms: in the first arm, we considered 146 ASCUS positive women who had undergone the HPV test, colposcopy and then underwent more detailed diagnostics by means of LEEP or a scraping of the cervical canal. The second arm was made up of 124 ASCUS positive women who had undergone a vaginal administration of estriolo, the HPV test and colposcopy. Estriol was administered for 5 weeks: the first week one vaginal suppository every evening, the other four weeks the administration was twice a week. Then, the patients underwent colposcopy. In cases of positivity a biopsy was carried out, the patients positive for CIN2+ at the biopsy underwent excisional therapy using LEEP and were followed up. The patients, who were negative at colposcopy or with histological diagnosis of CIN1, were examined again at 1 year. RESULTS: In the first arm the HPV test had an SE of 94%, an SP of 68%, NPV of 99%, and PPV of 28%. The PPV is very low because of the elevated percentage of false positives that the HPV test gave (71%). In the second arm the HPV test maintained its high SE (100%), an SP of 74%, a NPV of 100%, and a PPV of 43%. The use of estrogen increased the specificity of the test. CONCLUSION: It is important to say that the second arm indicates the use of local estrogen therapy only for ASCUS/HPV positive postmenopausal women. Therefore, the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women.

Resolution of Hematocolpos in Adolescents Affected with Graft vs Host Disease.

BACKGROUND: Bone marrow transplantation is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients, however, will develop graft vs host disease (GVHD), acute or chronic, with serious long-term sequalae. CASES: We present 2 cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In 1 girl blunt lysis of the adhesions was performed with the patient under general anesthesia, followed thereafter by local hydrocortisone and estriol treatment. SUMMARY AND CONCLUSION: Genital symptoms might not be readily reported by adolescents after bone marrow transplantation. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms, and be acquainted with addressing complications, such as vaginal obstruction.

Does vaginal estriol make urodynamic changes in women with overactive bladder syndrome and genitourinary syndrome of menopause?

OBJECTIVES: OAB is a common finding in postmenopausal women. Hypoestrogenism is the root cause of many signs and symptoms of Genitourinary Syndrome of Menopause (vaginal dryness, atrophy, dyspareunia, urinary disorders, etc.). As such the aim of this study was to evaluate the urodynamic effects of ultralowdose estriol vaginal gel formulation to treat women with Genitourinary Syndrome of Menopause and Overactive Bladder Syndrome. STUDY DESIGN: This open-labeled, single center, prospective study involved 37 women with OAB recruited in our Urogynecological Unit between January and July 2016. They received estriol 50 mcg/g vaginal gel, one applicator-dose per day for 3 weeks followed by one dose twice a week for 12 weeks. Objective and subjective parameters were evaluated before and after treatment through the urodynamic examination, Overactive Bladder symptom score and Short Form Health Survey-36 questionnaires. RESULTS: Vaginal atrophy symptoms and signs as well as the overactive bladder subjective symptom parameter improved significantly. Urodynamic evaluation showed significant improvement in first desire to void and maximum cystometric capacity after estriol usage. Patients who had detrusor overactivity did not show any improvement for this parameter after treatment. The voiding function parameters did not significantly change. Short form-36 showed a better quality of life after treatment especially for the emotional role, as well as mental and general health. CONCLUSIONS: A local ultra-low dose concentration of estriol could be effective in women with vaginal atrophy and Overactive Bladder Syndrome for improving both subjective symptoms and urodynamic parameters of storage function not affecting voiding function.

Plantar keratoderma climatericum: Successful improvement with a topical estriol cream.

Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma. Although its pathophysiology is still unknown, there has been speculation about its relation to hormonal dysregulation (possibly a local estrogen deficiency) since the 1930s. A female patient with long-lasting keratoderma climatericum was initially prescribed a topical 50% urea ointment and clobetasol propionate 0.05% ointment, with just a slight improvement after 2 months of daily use. The patient was started on topical estriol 0.125 mg/g vaginal cream applied on the plantar surface after her daily shower and application of the same topical 50% urea ointment and clobetasol propionate 0.05% ointment on alternate nights. There was a marked improvement under this regimen with total and fast control of the pruritus. At 6-month follow-up the patient retained total symptomatic control and was just applying the estriol cream and the 50% urea containing ointment. We report a case of a difficult to treat plantar keratoderma that markedly improved after adding a daily topical application of a vaginal cream containing estriol 0.125 mg/g. Trials that determine the efficacy and safety of topical estrogens for keratoderma climatericum are warranted.

Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women.

OBJECTIVE: The aim of the study was to evaluate efficacy of fractional CO2 vaginal laser treatment (Laser, L) and compare it to local estrogen therapy (Estriol, E) and the combination of both treatments (Laser + Estriol, LE) in the treatment of vulvovaginal atrophy (VVA). METHODS: A total of 45 postmenopausal women meeting inclusion criteria were randomized in L, E, or LE groups. Assessments at baseline, 8 and 20 weeks, were conducted using Vaginal Health Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and burning), Female Sexual Function Index, and maturation value (MV) of Meisels. RESULTS: Forty-five women were included and 3 women were lost to follow-up. VHI average score was significantly higher at weeks 8 and 20 in all study arms. At week 20, the LE arm also showed incremental improvement of VHI score (P = 0.01). L and LE groups showed a significant improvement of dyspareunia, burning, and dryness, and the E arm only of dryness (P < 0.001). LE group presented significant improvement of total Female Sex Function Index (FSFI) score (P = 0.02) and individual domains of pain, desire, and lubrication. In contrast, the L group showed significant worsening of pain domain in FSFI (P = 0.04), but FSFI total scores were comparable in all treatment arms at week 20. CONCLUSIONS: CO2 vaginal laser alone or in combination with topical estriol is a good treatment option for VVA symptoms. Sexual-related pain with vaginal laser treatment might be of concern.

Estriol: emerging clinical benefits.

OBJECTIVE: Estriol is the main estrogen in pregnancy, but has received less attention outside gestation. It is well known that pregnancy has an immunosuppressive effect on many autoimmune diseases such as multiple sclerosis, psoriasis, thyroiditis, uveitis, and rheumatoid arthritis. Emerging evidence indicates that estriol has potential immunomodulatory benefits for many disease states including autoimmune, inflammatory, and neurodegenerative conditions. In this review, we discuss emerging roles for estriol in the treatment of menopausal symptoms, osteoporosis, cancer, hyperlipidemia, vascular disease, and multiple sclerosis. Estriol appears to offer a potentially cost-effective approach to a variety of conditions and may offer a wide range of health benefits. METHODS: We reviewed the English language MEDLINE literature with estriol in the title with emphasis on publications including nonpregnant females between January 1974 and August 2016. Approximately 393 such articles were considered and 72 articles have been referenced in this review. RESULTS: Estriol offers considerable benefits for postmenopausal women with reduced risks that are normally associated with traditional hormone therapies. These benefits include improved control of menopausal symptoms and better urogenital health. Moreover, the immunomodulatory role of estriol in reducing proinflammatory cytokines may be an important new therapeutic option for chronic autoimmune and neurodegenerative illnesses. Since it is a relatively weak estrogen, there is potential for use in men for conditions such as multiple sclerosis. CONCLUSIONS: We conclude transvaginal estriol potentially offers a suitable physiologic delivery and cost-effective alternative to currently available estrogen regimens in selected patients. Additional studies on mode of delivery, safety, and efficacy merit further investigation.

Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule?

OBJECTIVE: The aim of this study was to evaluate the effectiveness of the application of 0.005% estriol gel to the vulvar vestibule in the management of postmenopausal dyspareunia. STUDY DESIGN: Postmenopausal women with dyspareunia were enrolled in this study. Patients were instructed to use a fingertip to apply 0.25g of vaginal gel containing 25µg of estriol to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. RESULTS: Assessment of symptoms (dyspareunia and cotton swab test) and signs of vestibular atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 63 women were included. Of the 63, 59 (93.6%) completed the 12-week treatment period, and four dropped out for vestibular burning. Dyspareunia improved or was cured (score ≤1) by week 12 in 81.4% of patients. The patients also showed a statistically significant reduction in vestibular atrophy and cotton swab test at the end of treatment. CONCLUSIONS: Application of 0.005% estriol gel to the vulvar vestibule is effective in correcting menopausal coital pain. This suggests that reduction in sensory vestibular innervation sensitivity is likely to play a pivotal role in the relief of dyspareunia. One limitation of this study is the limited follow-up, but the therapy may be continued for as long as the patients are distressed by their symptoms without estrogen intervention.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application.

Translational research generally refers to a "bench to bedside" approach where basic science discoveries in models move to clinical trials in humans. However, a "bedside to bench to bedside" approach may be more promising with respect to clinical relevance, since it starts with a clinical observation that can serve as a research paradigm to elucidate mechanisms and translate them back into novel therapeutic approaches. The effect of pregnancy on human autoimmune disorders in general, and multiple sclerosis (MS) in particular, serves as an intriguing example of how this can be used to understand disease pathobiology and discover new therapeutic targets. Disease activity in MS undergoes pronounced shifts in the time before, during, and after pregnancy. The most well-known and established example is a reduction in relapse rates in the last trimester by 70-80 %. However, disease activity reappears in the first few months after delivery, temporarily overshooting pre-pregnancy levels. This phenomenon has since its first description served as a model for investigating novel treatment options in animal models and has cumulated in successful phase 2a and 2b trials in female MS patients. However, recently, a number of other clinical observations have been made that might be similarly suitable to offer additional insights into pathobiological mechanisms of MS activity, progression, and possibly even incidence. Here, we outline the various changes in the clinical course of MS that have been described in relation to pregnancy, both short term and long term, and discuss how these may inform the development of novel treatments for autoimmune diseases.