Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial.

BACKGROUND: We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer. METHODS: open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18-75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression. RESULTS: the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37). CONCLUSIONS: there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-23w5fv . Registered 10 January 2017 - Retrospectively registered.

Interventions Preventing Vaginitis, Vaginal Atrophy after Brachytherapy or Radiotherapy Due to Malignant Tumors of the Female Reproductive Organs-A Systematic Review.

BACKGROUND: Radiotherapy, as a method of treatment of cervical and uterine cancers, may induce severe late-onset vaginal side effects. Unfortunately, little evidence on the management of adverse effects has been presented. This study aimed to evaluate the available interventions which reduce symptoms of vaginitis and vaginal atrophy by improving dyspareunia, mucosal inflammation, vaginal pH and vaginal dryness in women who have undergone brachytherapy or radiotherapy due to uterine or cervical malignancies. MATERIALS AND METHODS: A comprehensive literature search was performed following PRISMA guidelines. The systematic search was conducted using electronic databases, namely Scopus, Web of Science and PubMed, between October and November 2020 to identify randomized controlled trials (RCT) and, prospective randomized studies (PRS). RESULTS: The analyzed population consists of 376 patients with uterine or cervical cancer, treated with hyaluronic acid, vitamin A, vitamin E, alpha-tocopherol acetate and dienestrol. Intervention with HA along with vitamin A and vitamin E revealed advantage in endpoints such as reduced dyspareunia, vaginal mucosal inflammation, vaginal dryness, bleeding, fibrosis and cellular atypia. Administration of alpha-tocopherol acetate reduced vaginal mucosal inflammation and improved vaginal acanthosis, whereas dienestrol resulted in reduced dyspareunia, vaginal caliber and bleeding. CONCLUSIONS: Vaginal suppositories were found to be clinically effective at the management of late-onset vulvovaginal side effects after radiotherapy.

Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease.

Endogenous retroviruses (ERVs) are genomic sequences that originated from retroviruses and are present in most eukaryotic genomes. Both beneficial and detrimental functions are attributed to ERVs, but whether ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) infection as a model and found that Toll-like receptor 7 (Tlr7-/-) deficient mice that have high systemic levels of infectious ERVs are protected from intravaginal HSV-2 infection and disease, compared to wildtype C57BL/6 mice. We deleted the endogenous ecotropic murine leukemia virus (Emv2) locus on the Tlr7-/- background (Emv2-/-Tlr7-/-) and found that Emv2-/-Tlr7-/- mice lose protection against HSV-2 infection. Intravaginal application of purified ERVs from Tlr7-/- mice prior to HSV-2 infection delays disease in both wildtype and highly susceptible interferon-alpha receptor-deficient (Ifnar1-/-) mice. However, intravaginal ERV treatment did not protect Emv2-/-Tlr7-/- mice from HSV-2 disease, suggesting that the protective mechanism mediated by exogenous ERV treatment may differ from that of constitutively and systemically expressed ERVs in Tlr7-/- mice. We did not observe enhanced type I interferon (IFN-I) signaling in the vaginal tissues from Tlr7-/- mice, and instead found enrichment in genes associated with extracellular matrix organization. Together, our results revealed that constitutive and/or systemic expression of ERVs protect mice against vaginal HSV-2 infection and delay disease.

Vulvovaginal manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevention and treatment.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

Incidence and Prevention of Vaginal Cuff Dehiscence after Laparoscopic and Robotic Hysterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Vaginal cuff dehiscence, a severe and potentially detrimental complication, has significantly increased after the introduction of endoscopic hysterectomy. The aim of this systematic review and meta-analysis of the available literature was to identify the incidence of, and possible strategies to prevent, this complication after total laparoscopic hysterectomy and total robotic hysterectomy. DATA SOURCES: PubMed, ClinicalTrials.gov, Scopus, and Web of Science databases were systematically queried to identify all articles reporting either laparoscopic or robot-assisted hysterectomies for benign indications in which vaginal dehiscence was reported as an outcome. Reference lists of the identified studies were manually searched. Only papers written in English were considered. METHODS OF STUDY SELECTION: The Population, Intervention, Comparison, and Outcome framework for the review included (1) population of interest: women who underwent conventional and robot-assisted laparoscopic hysterectomy; (2) interventions: possible methods to prevent vaginal dehiscence; (3) comparison: experimental strategies vs standard treatment or alternative strategy for each item of intervention; and (4) outcome: rate of vaginal dehiscence. Series of subtotal hysterectomies and radical hysterectomies in addition to reports that combined both benign and malignant cases were excluded. The meta-analysis was performed using RevMan version 5.4.1 (Cochrane Training, London, United Kingdom). Two independent reviewers identified all reports comparing 2 or more possible strategies to prevent vaginal dehiscence. TABULATION, INTEGRATION, AND RESULTS: A total of 460 articles were identified. Of these, 20 (6 randomized, 2 prospective, and 12 retrospective) studies were included in this review for a total of 19 392 patients. The incidence of vaginal dehiscence after total laparoscopic hysterectomy ranged between 0.64% and 1.35%. Robotic hysterectomy was associated with a risk of vaginal dehiscence of approximately 1.64%. No study compared early vs delayed resumption of coital activity nor analyzed the role of training in laparoscopic suturing. No study specifically assessed the impact of electrosurgery on the risk of vaginal dehiscence in endoscopic hysterectomies for benign indications. Double-layer and reinforced sutures did not decrease the risk of dehiscence. Barbed sutures reduced the risk of separation compared with nonbarbed closure (0.4% [4/1108] vs 2% [22/1097]; odds ratio [OR] 0.25; 95% confidence interval [CI], 0.11-0.57). However, these data came mainly from retrospective series. Excluding studies on the use of self-anchoring sutures during robotic hysterectomy, there was no significant difference in the risk of dehiscence between barbed and nonbarbed sutures (0.5% [4/890] vs 1.4% [181/776]; OR 0.38; 95% CI, 0.13-1.10). Transvaginal suture of the vault at the end of an endoscopic hysterectomy seemed to increase the risk of dehiscence when compared with laparoscopic closure (2.3% [23/1002] vs 1.16% [11/944]; OR 1.97; 95% CI, 1.00-3.88). CONCLUSION: There is a paucity of high-quality papers evaluating vaginal dehiscence and possible prevention strategies in the current literature. Only 2 effective strategies have been identified in reducing the risk for this complication: the use of barbed sutures and the adoption of a laparoscopic approach to close the vaginal cuff. When restricting the analysis only to laparoscopic cases, the use of barbed sutures does not protect against vaginal cuff separation.

Time-trend of hospitalizations for anogenital warts in Veneto region in the HPV vaccination era: a cross sectional study (2007-2018).

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted pathogen and the cause of several cancers and of anogenital warts. With this study, we estimated the trend of hospitalizations for anogenital warts (AGWs) in the Veneto region (Italy) from 2007 to 2018. METHODS: The analysis included all the hospital discharge records of public and accredited private hospitals occurred in Veneto residents in the timespan 2007-2018. The ICD9-CM code 078.11 considered were those associated with condyloma acuminatum and those associated with surgical interventions for vulval/vaginal warts, penile warts anal warts. Annual total and sex- and age-specific hospitalization rates and trends were calculated and correlated with the different HPV vaccine coverage over the study period. RESULTS: We observed an overall reduction of hospitalization rates for AGWs: from 15.0 hospitalizations every 100,000 Veneto residents in years 2007-08 to 10.9 hospitalizations every 100,000 Veneto residents in year 2017-18 (- 37.4%; p < 0.05). Reduction has been caused by a drop in hospitalizations in females - from a rate of 20.4/100,000 in 2007-2008 to a rate of 10.8/100,000 in 2017-18 (AAPC: -7.1; 95%CI: - 10.6;-3.4); while in males, we observed a slight - but not statistically significant - increase in hospitalization rates. CONCLUSION: The marked decline in hospitalization rates for AGWs in Veneto Region is probably attributable to the high coverage rates of HPV vaccination programs implemented since 2008.

Society for Maternal-Fetal Medicine Special Statement: Reducing the risk of transmitting infection by transvaginal ultrasound examination.

Recent surveys have shown widespread lapses in the procedures used to reduce the risk of transmitting infection via medical devices. Transvaginal ultrasound examination has the potential to transmit vaginal infections, including human papillomavirus. Areas of particular concern are the use of probe covers with high rates of leakage, disinfectants that are not effective against human papillomavirus, and coupling gel from multiple-use containers. We reviewed these issues, and we recommend 4 steps to reduce the risk of transmitting infection. First, during every transvaginal ultrasound exam, the probe should be covered with a sterile, single-use "viral barrier" cover or a condom. Second, sterile, single-use ultrasound gel packets should be used. Third, after every examination, the probe should be cleaned to remove any visible gel or debris. Finally, after cleaning, the probe should undergo high-level disinfection using an agent with proven efficacy against the human papillomavirus, including hydrogen peroxide, hypochlorite, or peracetic acid. Glutaraldehyde, orthophthalaldehyde, phenols, and isopropyl alcohol have virtually no efficacy against the human papillomavirus.

Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population.

OBJECTIVE: Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured for the five HPV types covered only by 9vHPV vaccine (HPV31/33/45/52/58), but not the four types covered by both vaccines (HPV6/11/16/18). METHODS: Three international, randomized, double-blind studies were conducted using the same methodology. In the 9vHPV vaccine study (NCT00543543), 7106 and 7109 women received 9vHPV or qHPV vaccine, respectively. In the historic qHPV vaccine studies (FUTURE I [NCT00092521] and II [NCT00092534]), 8810 and 8812 women received qHPV vaccine or placebo, respectively, based on the same eligibility criteria. Cervical cytological testing was performed regularly. Biopsy or definitive therapy specimens were assessed for HPV DNA. RESULTS: Among women negative for 14 HPV types prior to vaccination, incidence of high-grade cervical disease (9vHPV, n = 2 cases; placebo, n = 141 cases) and cervical surgery (9vHPV, n = 3 cases; placebo, n = 170 cases) related to the nine HPV types was reduced by 98.2% (95% confidence interval [CI], 93.6-99.7) and 97.8% (95% CI, 93.4-99.4), respectively. The 9vHPV vaccine did not prevent disease related to vaccine HPV types detected at baseline, but significantly reduced cervical, vulvar, and vaginal diseases related to other vaccine HPV types. CONCLUSIONS: Effective implementation of the 9vHPV vaccine may substantially reduce the burden of HPV-related diseases and related medical procedures. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00543543, NCT00092521, NCT00092534.

Clinical Evaluation of Low-Molecular-Weight Hyaluronic Acid-Based Treatment on Onset of Acute Side Effects in Women Receiving Adjuvant Radiotherapy after Cervical Surgery: A Randomized Clinical Trial.

BACKGROUND: Radiotherapy treatment for cervical cancer (CC) often induces side effects, including inflammation, dryness, dyspareunia. Considering its key role in the healing process, hyaluronic acid (HA) could be useful for the completion of radiotherapy. OBJECTIVES: The aim of this work was to evaluate the ability of HA to reduce the onset of side effects due to radiotherapy. MATERIALS AND METHODS: In total, 180 women undergoing radiotherapy were randomized into two arms: controls and those treated with vaginal suppositories containing low-molecular-weight HA from day 1 of radiotherapy. The study lasted 5 weeks and was characterized by three visits: at baseline (T0), 15 days later (T1), and at the end of the radiotherapy cycle (T2). The onset of side effects, pain, safety, efficacy, acceptability of treatment, and compliance to the therapy were evaluated. RESULTS: Patients in the control arm reported the onset and worsening of all symptoms with a moderate or severe grade at T2, whereas in the treatment arm almost 90% of patients reported the absence of symptoms or a mild grade. All patients in the treatment arm referred a lower intensity of pain on a visual analog scale compared with the control arm at T2 (6.85 ± 0.94 vs. 1.88 ± 1.02). CONCLUSIONS: HA was able to help vaginal mucosa healing during radiotherapy in patients with CC.

Extended duration of dilator use beyond 1 year may reduce vaginal stenosis after intravaginal high-dose-rate brachytherapy.

BACKGROUND: Vaginal dilators (VD) are recommended following vaginal or pelvic radiotherapy for patients with endometrial carcinoma (EC) to prevent vaginal stenosis (VS). The time course of VS is not fully understood and the optimal duration of VD use is unknown. METHODS: We reviewed 243 stage IA-II EC patients who received adjuvant brachytherapy (BT) at an academic tertiary referral center. Patients were instructed to use their VD three times per week for at least 1-year duration. The primary outcome was development of grade ≥ 1 VS using CTCAEv4 criteria during the follow-up period. The log-rank test and multivariable Cox proportional hazards modeling were used to evaluate the effect of VD use (noncompliance vs. standard compliance [up to 1 year] vs. extended compliance [over 1 year]) on VS. RESULTS: The median follow-up was 15.2 months over the 5-year study period. At 15 months, the incidence of VS was 38.8% for noncompliant patients, 33.5% for those with standard compliance, and 21.4% for those with extended compliance (median time to grade ≥ 1 VS was 17.5 months, 26.7 months, and not yet reached for these groups, respectively). On multivariable Cox regression analysis, extended compliance remained a significant predictor of reduced VS risk when compared to both noncompliance (HR 0.38, 95% CI 0.18-0.80, p = 0.012) and standard compliance (HR 0.43, 95% CI 0.20-0.89, p = 0.023). CONCLUSIONS: The risk of VS persists beyond 1 year after BT. Extended VD compliance beyond 1 year may mitigate this risk.

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity against Chlamydia muridarum Intravaginal Infection.

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine.

V-Loc™ 180 suture in total laparoscopic hysterectomy: a retrospective study comparing Polysorb to barbed suture used for vaginal cuff closure.

OBJECTIVE: Sutures in laparoscopy have been extensively developed in recent years. In this study, we assessed differences between Polysorb™ braided absorbable suture (CL-914) and V-Loc™ barbed suture (V-Loc 180) used in vaginal cuff closure during laparoscopic hysterectomy from various aspects. STUDY DESIGN: This paper presented a prospective cohort study of 490 consecutive women underwent total laparoscopic hysterectomy (TLH) performed between January 2013 and September 2015 applying identical procedure technique, with cuff closure approaches selected by surgeons. Data collected included operative time, estimated blood loss, postoperative changes in body temperature, perioperative routine blood parameters changes, total average hospital stay, and postoperative hospital stay. In addition, short-term (at least 6 months) outcomes of vaginal cuff granulomatous (VCG) between the two suture approaches were compared. RESULTS: Between groups, statistical differences were detected in operative duration, estimated blood loss, total and postoperative hospital stay, WBC, neutrophil counts and Hb in postoperative routine blood parameters; while there were no significant differences in other data (all P>0.05). Postoperative routine blood parameters in each group: compared to preoperative baseline, in Group 1, WBC, N increased (P<0.05), while RBC, Hb decreased (P<0.05). In Group 2, same tendency in WBC, N and Hb was indicated, but RBC increased with no significant difference. In both groups, vaginal cuff healing was well, with no dehiscence. VCG occurred more often in women used CL-914 than women applied V-Loc 180. CONCLUSIONS: V-Loc barbed suture can be used for vaginal cuff closure during TLH due to advantages such as less operative duration and blood loss, shorter postoperative and total hospital stay, and reduced VCG formation six months after TLH.

Evidence Basis for Hysterectomy.

Although vaginal hysterectomy has long been championed by the American College of Obstetricians and Gynecologists as the preferred mode of uterine removal, nationwide vaginal hysterectomy utilization has steadily declined. This article reviews the evidence comparing vaginal with other modes of hysterectomy and highlights areas of ongoing controversy regarding contraindications to vaginal surgery, risk of subsequent prolapse development, and impacts of changing hysterectomy trends on resident education.

Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

PURPOSE: Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). MATERIALS AND METHODS: Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. RESULTS: The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4±4Gy EQD2 (p<0.001), while doses to bladder and rectum (D2cm3) were reduced by 2±2Gy and 3±2Gy, respectively (p<0.001). CONCLUSIONS: VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis.

The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research.

Many natural substances were screened to develop nutraceuticals that reduce menopausal symptoms. A complex of Cirsium japonicum var. maackii and Thymus vulgaris extracts, named MS-10, had significant positive effects. Under a low concentration of estrogen, which represents postmenopausal physiological conditions, MS-10 had beneficial effects on estrogen receptor-expressing MCF-7 cells by reversibly enhancing estrogen activity. In addition, in the ovariectomized rat model, changes in bone-specific alkaline phosphatase activity and osteocalcin, as well as low-density lipoprotein cholesterol and triglyceride levels were significantly decreased by MS-10. These results show that MS-10 protected bone health and reduced metabolic disturbances. Furthermore, in a clinical study, all menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, vertigo, fatigue, rheumatic pain, palpitations, formication, and headache, as well as colpoxerosis, were significantly improved by taking MS-10 for 90 days. Therefore, the evidence supports that MS-10 is an effective natural substance that can safely improve menopausal symptoms, including colpoxerosis.

Does vaginal estrogen treatment with support pessaries in vaginal prolapse reduce complications?

OBJECTIVE: Pelvic organ prolapse is often co-existant with atrophy of the genital tract in older women who tend to prefer vaginal pessaries for prolapse. Vaginal estrogen therapy is used by some along with a support pessary for prolapse with no robust evidence to back this practice. We aimed to evaluate differences in complications of support pessaries for vaginal prolapse in postmenopausal women, with and without vaginal estrogen use. STUDY DESIGN: We prospectively assessed postmenopausal women attending the urogynaecology clinic for a pessary change. We asked them about the level of discomfort during pessary change (visual analogue scale for pain), discharge, bleeding and infection. Ethics approval was not required as this was a service evaluation project. Statistical analysis for relative risk was performed, including sub-group analysis for 'ring pessary' and 'non-ring group' (Shelf, Gellhorn, Shaatz). RESULTS: Between July 2013 and December 2014, we assessed 120 postmenopausal women using support pessaries for prolapse. The mean age was 70 years; 45% of the patients used vaginal estrogen. There were no statistically significant differences in complications with or without vaginal estrogen use, although the trend was higher amongst non-users. The 'non-ring' sub-group not using vaginal estrogen had a higher risk of vaginal ulceration, bleeding and discharge. CONCLUSION: Postmenopausal women may have lesser complications when using vaginal estrogen with a support pessary for prolapse, particularly with pessaries other than the ring. An adequately powered randomised controlled trial is needed to assess conclusively whether vaginal estrogen enhances comfort and reduces complications of support pessaries for prolapse.

An update on drugs for the treatment of menopausal symptoms.

INTRODUCTION: Vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) are recognized as the most frequent and bothersome symptoms associated with menopause. There are different treatments for both groups of symptoms, being necessary to individualize them. AREAS COVERED: There are different therapies for VMS including hormonal treatments with estrogen, with and without progestins; the new alternative, tissue-selective estrogen complex (TSEC), tibolone, phytoestrogens and only progestins. Evidence also shows efficacy with selective serotonin reuptake inhibitors. Other nonhormonal alternatives exist as second-line treatments, all with not conclusive results. The GSM can be treated with nonhormonal treatments such as vaginal lubricants and moisturizers, other alternatives as vaginal laser needs to have more evidence. On the other hand, there is the possibility to use the hormonal treatments with systemic or local estrogen, which are the most effective treatment, the TSEC and the newest selective estrogen receptor modulator (SERM), ospemifene. Therapies with testosterone and dehydroepiandrosterone (DHEA) are still under study. The GSM can be treated with nonhormonal treatments such as vaginal lubricants and moisturizers, and other alternatives as vaginal laser need to have more evidence. On the other hand, there is the possibility to use the hormonal treatments with systemic or local estrogen, which are the most effective treatment, the TSEC and the newest SERM, ospemifene. Therapies with testosterone and DHEA are still under study. EXPERT OPINION: The increasing numbers of therapies for menopausal symptoms open up new options, but we must individualize treatments. New possibilities arise in patients who did not have them and which can improve compliance and is also important to design strategies using combined or sequential treatments.

Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy.

AIM: During the last decades, therapies targeting cervical cancer have been considerably improved. Surgery and radiotherapy (RT) represent the main common therapeutic approach in cervical cancer. In order to minimize the side effects of radiotherapy approach, several protocols have been developed such as brachytherapy (BRT). Among the side effects associated with RT, the vaginal atrophy is the most important and common one. Vaginal atrophy, in turn, leads to additional alterations like inflammation, associated to relevant symptoms such as itching, burning and dyspareunia. All these alterations heavily affect the quality of women's life. The aim of our study was to evaluate the toxicity induced by RT on vaginal mucosa, and the adjuvant action of a product containing LMWHA, vitamin A, and Vitamin E (Santes®, Lo.Li. Pharma, Rome, Italy). The introduction of adjuvant therapies may have likely had a relevant place in providing that result. METHODS: A prospective randomized study was designed. From October 2006 to October 2008, 45 women with a mean age 38 ± 6 years were enrolled. After surgery, all patients were treated with 4 weeks of RT and 4 weeks of BRT, concomitantly with chemiotherapy. They were randomly assigned in two groups: 23 women were treated with two suppositories (Santes®) per day for 4 months. For the first two months the preventive treatment was simultaneous to RT and BRT. Instead the control groups for composed by 22 patients and they did not undergo any treatment during RT. To evaluate the efficacy of Santes® treatment three biopsies were performed. RESULTS: At the second biopsy, after the BRT therapy, the treated group showed a statistically significant improvement (P<0.05 vs. control) on inflammation, cell atypia, fibrosis, mucositis and bleeding. At the third biopsy, two months after BRT, further statistically improvement were observed for all RT/BRT associated side effects. The treatment showed an efficacy also in terms of pain severity. CONCLUSION: Our data suggest that low molecular weight HA shows good performances in treating RT-damaged tissue and plays a key role in all steps of the healing process. Indeed the results shows that women exposed to RT treatments and simultaneously treated with Santes®, had an optimal resolution of vaginal atrophy and related symptoms.

Incidence of genital warts in adolescents and young adults in an integrated health care delivery system in the United States before human papillomavirus vaccine recommendations.

BACKGROUND: Information on genital wart incidence in adolescents and young adults before human papillomavirus (HPV) vaccination is important for understanding the impact of the vaccine on the epidemiology of this early outcome of HPV infection. METHODS: The study population included 11- to 29-year-old enrollees of Northern California Kaiser Permanente between July 1, 2000, and July 1, 2005, before the availability of the HPV vaccine. We identified genital warts with an algorithm combining genital wart-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes (078.10, 078.11, and 078.19) with physician-recorded anatomic locations. We calculated sex- and age-specific incidence rates of genital warts and described the specific anatomic location of presentation, as well as recurrences of genital warts. RESULTS: We identified 1,682 cases of genital warts among 181,264 individuals. The incidence rate was highest among women (6.3/1000 person-years) and men (2.9/1000 person-years) aged 20 to 24 years old. Among women (n = 96,792), 63.4% of the 1240 incident genital wart cases occurred on the vulva and 21.1% on the cervix. Among men (n = 84,472), 91.6% of the 442 incident genital wart cases did not have a specific anatomic location recorded. Most people with an incident genital wart diagnosis (87.2%) did not have a recurrence during the observation period. CONCLUSIONS: Our study found that the incidence of genital warts was highest among persons aged 20 to 24 years using a unique method to identify the location of the wart. Information on incidence of genital warts before vaccine use provides baseline data that can be used to measure HPV vaccine impact.

Pelvic radiotherapy and sexual function in men and women.

INTRODUCTION: Despite the decrease in overall cancer incidence and mortality rates in developed countries since the early 1990 s, cancer remains a major public health problem. Sexual dysfunction is one of the more common consequences of cancer treatment. AIM: To shortly review the literature and level of evidence on sexual dysfunction in men and women following pelvic radiotherapy. MAIN OUTCOME MEASURES: Male and female sexual dysfunction. METHODS: Literature review. RESULTS: Sexual dysfunction in cancer patients is multidimensional and may result from biological, psychological, and social factors. Anatomic changes caused by surgery and/or radiotherapy, physiological changes following hormonal manipulation, and the secondary effect of medical intervention may impede or preclude sexual functioning, even when sexual desire is intact. Pelvic irradiation constitutes the primary or adjuvant treatment for a large number of both female and male cancers. No randomized controlled trials could be identified regarding the effect of radiotherapy on sexual dysfunction. However, prospective and clinical controlled trials all demonstrated a severe negative effect on sexual functioning in men and women following radiotherapy for a pelvic cancer. Following pelvic radiotherapy for prostate cancer, a positive effect of phosphodiesterase type 5 inhibitors on erectile dysfunction has been demonstrated, whereas no significant effect on female sexuality was found. Few studies evaluated treatment of female sexual dysfunction following radiotherapy; hormone replacement therapy and the use of vaginal dilator in combination with psycho-educational support is recommended. CONCLUSION: Pelvic radiotherapy plays a significant negative role in the complex scenario of male and female sexual dysfunction. The literature has focused on sexual dysfunction and intervention in prostate and cervical cancer patients. Sexual dysfunction following pelvic radiotherapy for cancer in other pelvic organs, e.g., bladder, rectum, and anus, requires more attention in future studies. Health care providers should pay attention to and provide psychological and medical support regarding sexual dysfunction to all patients who have received pelvic radiotherapy.