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- Role of vascular endothelial growth factor polymorphisms (-2578C > A, -460 T > C, -1154G > A, +405G > C and +936C > T) in endometriosis: a case-control study with Brazilians. [JOURNAL ARTICLE]
- BMC Womens Health 2014 Sep 26; 14(1):117.
Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms.This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model.Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 +/- 3.9 versus 27.3 +/- 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 - 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 - 0.95).The present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.
- Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial. [JOURNAL ARTICLE]
- Climacteric 2014 Sep 25.:1-7.
Background Ospemifene is a non-estrogen, tissue selective estrogen receptor agonist/antagonist, or selective estrogen receptor modulator, recently approved for the treatment of dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Postmenopausal dyspareunia is often associated with female sexual dysfunction (FSD). In this report, we present data that demonstrate the effect of ospemifene 60 mg/day on FSD assessed by the Female Sexual Function Index (FSFI), a widely used tool with six domains (Arousal, Desire, Orgasm, Lubrication, Satisfaction, and Pain). Methods A phase-3, randomized, double-blind, 12-week trial (n = 919) compared the efficacy and safety of oral ospemifene 60 mg/day vs. placebo in postmenopausal women with VVA in two strata based on self-reported, most bothersome symptom of either dyspareunia or dryness. Primary data were published previously. We report herein pre-specified secondary efficacy endpoints analyses, including changes from baseline to Weeks 4 and 12 for FSFI total and domain scores as well as serum hormone levels. Results Ospemifene 60 mg/day demonstrated a significantly greater FSFI total score improvement vs. placebo at Week 4 (p < 0.001). Improvement in FSFI scores continued to Week 12 (p < 0.001). At Week 4, the FSFI domains of Sexual Pain, Arousal, and Desire were significantly improved with ospemifene vs. placebo; at Week 12, improvements in all domains were significant (p < 0.05). Changes in serum hormones were minor and uncorrelated with changes in sexual functioning. Conclusion In a large, randomized, double-blind, placebo-controlled trial, ospemifene 60 mg/day significantly improved FSD in women with VVA. Consistent effects across FSFI domains were observed.
- Mesh-related and intraoperative complications of pelvic organ prolapse repair. [Journal Article]
- Cent European J Urol 2014; 67(3):296-301.
To evaluate the rates of complications of pelvic organ prolapse repair and to determine their risk factors.The study included 677 patients operated for pelvic organ prolapse with trocar guided Prolift mesh. Patients were followed up within 1 and 3 months. A phone interview was conducted and patients with complaints were invited and evaluated in office settings.Mean age was 60 years. For the phone interview, 86.5% of patients were available. Overall complication rates were 22.5% (152/677). Fifteen patients (2.2%) developed bleeding over 500 cc; pelvic hematomas - 5.5%; perineal hematomas - 2.5%; urethral injuries - 0.3%; bladder injury in 1.6%; rectal damage in 0.7% and ureteral trauma in 0.2%. MESH RELATED COMPLICATIONS INCLUDED: erosions in 4.8%; vaginal synechiae - 0.3%; protrusion of mesh into the bladder - 0.15%; vesicovaginal fistula with mesh protrusion - 0.3%; mesh shrinkage - 1%; dyspareunia and pain in 2.4% cases. Pelvic abscess was found in 0.6% including one case of lethal necrotizing fasciitis. The risk factors of complications were assessed via logistic regression analysis.Younger age, less prominent prolapse, hematomas and concomitant hysterectomies are associated with higher risk of complications.
- [Recurrent cystitis and vaginitis: role of biofilms and persister cells. From pathophysiology to new therapeutic strategies.] [JOURNAL ARTICLE]
- Minerva Ginecol 2014 Oct; 66(5):497-512.
Recurrent vaginitis and cystitis are a daily challenge for the woman and the physician. The recurrence worsens the symptoms' severity, increases comorbidities, both pelvic (provoked vestibulodynia, bladder pain syndrome, levator ani hyperactivity, introital dyspareunia, obstructive constipation, chronic pelvic pain) and cerebral (neuroinflammation and depression), increases health costs, worsens the quality of life. Antibiotics increase the risk of bacterial resistences and devastate the ecosystems: intestinal, vaginal and mucocutaneous. Pathogenic biofilms are the (still) neglected etiology of recurrences. Biofilms are structured communities of bacteria and yeasts, protected by a self-produced polymeric matrix adherent to a living or inert structures, such as medical devices. Biofims can be intra or extracellular. Pathogens live in a resting state in the deep biofilm layers as "persister cells", resistant to antibiotics and host defences and ready to re-attack the host. The paper updates the evidence on biofilms and introduces new non-antibiotic strategies of preventing and modulating recurrent vaginitis and cystitis.
- Bladder Base Tenderness in the Etiology of Deep Dyspareunia. [JOURNAL ARTICLE]
- J Sex Med 2014 Sep 21.
Bladder base tenderness can be present on pelvic exam in women with pelvic pain. However, its exact prevalence and clinical implications are not well understood.The aim of this study was to determine whether bladder base tenderness is associated with specific symptoms or signs in women, particularly dyspareunia.Retrospective review of 189 consecutive women seen by a gynecologist in 2012 at a tertiary referral center for pelvic pain was conducted. Associations were tested between bladder base tenderness and variables on history/examination using bivariate analyses and multiple logistic regression.Deep dyspareunia and superficial dyspareunia (present/absent) were the main outcome measures.Bladder base tenderness was present in 34% of pelvic pain patients (65/189), which was significantly greater than the prevalence of bladder base tenderness of 3% (1/32) in a control sample of women without pelvic pain (odds ratio [OR] = 16.3, 95% confidence interval [CI] 2.17-121.7, Fisher exact test, P < 0.001). For the pelvic pain patients, on bivariate analyses, bladder base tenderness was significantly associated with deep dyspareunia (P < 0.001), superficial dyspareunia (P < 0.001), bladder symptoms (P = 0.026), abdominal wall trigger point (P < 0.001), and pelvic floor tenderness (P < 0.001). In contrast, bladder base tenderness was similarly present in women with or without endometriosis. On logistic regression, bladder base tenderness was independently associated with only deep dyspareunia (OR = 6.40, 95% CI: 1.25-32.7, P = 0.011), abdominal wall trigger point (OR = 3.44, 95% CI: 1.01-11.7, P = 0.037), and pelvic floor tenderness (OR = 8.22, 95% CI: 3.27-20.7, P < 0.001).Bladder base tenderness is present in one-third of women with pelvic pain, and contributes specifically to the symptom of deep dyspareunia. Bladder base tenderness was also associated with the presence of an abdominal wall trigger point and with pelvic floor tenderness, suggesting a myofascial etiology and/or nervous system sensitization. Nourmoussavi M, Bodmer-Roy S, Mui J, Mawji N, Williams C, Allaire C, and Yong PJ. Bladder base tenderness in the etiology of deep dyspareunia. J Sex Med **;**:**-**.
- Predictors of Task-Persistent and Fear-Avoiding Behaviors in Women with Sexual Pain Disorders. [JOURNAL ARTICLE]
- J Sex Med 2014 Sep 18.
Dyspareunia and vaginismus are the most common sexual pain disorders (SPDs). Literature suggests that many women with dyspareunia continue with intercourse despite pain (task persistence), whereas many women with vaginismus avoid penetrative activities that may cause pain (fear avoidance). Both forms of sexual pain behavior may maintain or aggravate complaints.This study examined (i) whether women with SPD differ from pain-free controls in motives for sexual intercourse, sexual autonomy, maladaptive beliefs regarding vaginal penetration, and partner responses to pain; and (ii) which of these factors best predict whether women with SPD stop or continue painful intercourse (attempts).Women with superficial dyspareunia (n = 50), women with lifelong vaginismus (n = 20), and pain-free controls (n = 45) completed questionnaires.For Aim 1, the main outcome measures were (i) motives for intercourse; (ii) sexual autonomy; (iii) maladaptive beliefs regarding vaginal penetration; and (iv) partner responses to pain. For Aim 2, sexual pain behavior (to continue or discontinue with painful intercourse) was the outcome measure.(i) Women with dyspareunia exhibited more mate guarding and duty/pressure motives for intercourse and were less sexually autonomous than controls. (ii) Symptomatic women had more maladaptive penetration-related beliefs than controls, with women with vaginismus reporting the strongest maladaptive beliefs. (iii) Partners of women with dyspareunia self-reported more negative responses to pain than those of women with vaginismus. (iv) The factors that best predicted sexual pain behavior were the partner responses to pain and the woman's maladaptive beliefs regarding vaginal penetration.Our findings reveal support for task persistence in women with dyspareunia and fear avoidance in women with lifelong vaginismus. As such, it is important to consider these distinct types of responding to sexual pain when treating SPD. Brauer M, Lakeman M, van Lunsen R, and Laan E. Predictors of task-persistent and fear-avoiding behaviors in women with sexual pain disorders. J Sex Med **;**:**-**.
- Acne Tarda and Male-Pattern Baldness Unmasking Primary Ovarian Insufficiency: A Case and Review. [JOURNAL ARTICLE]
- Dermatology 2014 Sep 9.
A 30-year-old woman presented with recurrent acne lesions and progressing male-pattern baldness. Furthermore, she reported amenorrhea, weight loss, mucosal xerosis and dyspareunia since discontinuation of hormonal contraception 6 months earlier in order to conceive. Acne tarda and androgenetic alopecia of female pattern were diagnosed. Hormonal and immunologic serological and ultrasound examinations revealed an autoimmune hypergonadotropic primary ovarian insufficiency (POI) with no ovarian cysts but ovarian fibrosis with marked reduced follicle pool. Immediate ovarian stimulation and in vitro fertilization led to pregnancy and the patient gave birth to a healthy child. Though presenting with clinical findings similar to menopause, 50% of patients with POI exhibit varying and unpredictable ovarian function, and only 5-10% are able to accomplish pregnancy. Genetic disorders affect the X chromosome. In 14-30% of cases POI has been associated with autoimmunity. POI may occur after discontinuation of hormonal contraception, like in our case. © 2014 S. Karger AG, Basel.
- Managing menopause. [Journal Article]
- J Obstet Gynaecol Can 2014 Sep; 36(9):830-3.
To provide updated guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor or urogenital symptoms and on considerations related to cardiovascular disease, breast cancer, urogynaecology, and sexuality.Lifestyle interventions, prescription medications, and complementary and alternative therapies are presented according to their efficacy in the treatment of menopausal symptoms. Counselling and therapeutic strategies for sexuality concerns in the peri- and postmenopausal years are reviewed. Approaches to the identification and evaluation of women at high risk of osteoporosis, along with options for prevention and treatment, are presented in the companion osteoporosis guideline.Published literature was retrieved through searches of PubMed and The Cochrane Library in August and September 2012 with the use of appropriate controlled vocabulary (e.g., hormone therapy, menopause, cardiovascular diseases, and sexual function) and key words (e.g., hormone therapy, perimenopause, heart disease, and sexuality). Results were restricted to clinical practice guidelines, systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Results were limited to publication dates of 2009 onwards and to material in English or French. Searches were updated on a regular basis and incorporated in the guideline until January 5, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, national and international medical specialty societies, and clinical practice guideline collections.The quality of the evidence in this document was rated using the criteria described by the Report of the Canadian Task Force on Preventive Health Care (Table). Summary Statements and Recommendations Chapter 1: Assessment and Risk Management of Menopausal Women Recommendations for Patients 1. Women aged 51 to 70 should consume 7 servings of vegetables and fruits, 6 of grain products, 3 of milk and alternatives, and 2 of meat and alterna-tives daily. (III-A) 2. A diet low in sodium and simple sugars, with substitution of unsaturated fats for saturated and trans fats, as well as increased consumption of fruits, vegetables, and fibre, is recommended. (I-A) 3. Routine vitamin D supplementation and calcium intake for all Canadian adults year round is recommended. (I-A) 4. Achieving and maintaining a healthy weight throughout life is recommended. (I-A) 5. Women aged 18 to 64 should accumulate at least 150 minutes of moderate to vigorous aerobic physical activity per week in bouts of 10 minutes or more. (I-A) Recommendations for Health Care Providers 1. A waist circumference ≥ 88 cm (35 in) for women is associated with an increased risk of health problems such as diabetes, heart disease, and hypertension and should be part of the initial assessment to identify risk. (II-2A) 2. Tobacco-use status should be updated for all patients on a regular basis, (I-A) health care providers should clearly advise patients to quit, (I-C) the willingness of patients to begin treatment to achieve abstinence (quitting) should be assessed, (I-C) and every tobacco user who expresses the willingness to begin treatment to quit should be offered assistance. (I-A) 3. Blood pressure should be assessed and controlled as women go through menopause. (II-2B) If the systolic blood pressure is ≥ 140 mmHg and/or the diastolic blood pressure is ≥ 90 mmHg, a specific visit should be scheduled for the assessment of hypertension. (III-A) 4. Women ≥ 50 years of age or postmenopausal and those with additional risk factors, such as current cigarette smoking, diabetes, and arterial hypertension, should have lipid-profile screening done. (II-2A) 5. A cardiovascular risk assessment using the Framingham Risk Score should be completed every 3 to 5 years for women aged 50 to 75. (II-2A) 6. A history of past pregnancy complications (preeclampsia, gestational hypertension, gestational diabetes, placental abruption, idiopathic preterm delivery, and/or fetal growth restriction) should be elicited since it can often predict an increased risk for premature cardiovascular disease and cardiovascular death and may inform decisions about the need for screening. (II-2B) Chapter 2: Cardiovascular Disease Recommendations 1. Health care providers should not initiate hormone therapy for the sole purpose of preventing cardiovascular disease (coronary artery disease and stroke) in older postmenopausal women since there are no data to support this indication for hormone therapy. (I-A) 2. The risk of venous thromboembolism increases with age and obesity, in carriers of a factor V Leiden mutation, and in women with a history of deep vein thrombosis. Transdermal therapy is associated with a lower risk of deep vein thrombosis than oral therapy and should be considered only if the benefits outweigh the risks. (III-C) Health care providers should abstain from prescribing oral hormone therapy for women at high risk of venous thromboembolism. (I-A) 3. Health care providers should initiate other evidence-based therapies and interventions to effectively reduce the risk of cardiovascular disease events in women with or without vascular disease. (I-A) 4. Risk factors for stroke (obesity, hypertension, elevated cholesterol levels, diabetes, and cigarette smoking) should be addressed in all postmenopausal women. (I-A) 5. If prescribing hormone therapy to older postmenopausal women, health care providers should address cardiovascular risk factors; low- or ultralow-dose estrogen therapy is preferred. (I-B) 6. Health care providers may prescribe hormone therapy to diabetic women for the relief of menopausal symptoms. (I-A) Chapter 3: Menopausal Hormone Therapy and Breast Cancer Recommendations 1. Health care providers should periodically review the risks and benefits of prescribing hormone therapy to a menopausal woman in light of the association between duration of use and breast cancer risk. (I-A) 2. Health care providers may prescribe hormone therapy for menopausal symptoms in women at increased risk of breast cancer with appropriate counselling and surveillance. (I-A) 3. Health care providers should clearly discuss the uncer-tainty of risks associated with systemic hormone therapy after a diagnosis of breast cancer in women seeking treatment for distressing symptoms (vasomotor symptoms or vulvovaginal atrophy). (I-B) Chapter 4: Vasomotor Symptoms Recommendations 1. Lifestyle modifications, including reducing core body temperature, regular exercise, weight management, smoking cessation, and avoidance of known triggers such as hot drinks and alcohol, may be recommended to reduce mild vasomotor symptoms. (I-C) 2. Health care providers should offer hormone therapy, estrogen alone or combined with a progestin, as the most effective therapy for the medical management of menopausal symptoms. (I-A) 3. Progestins alone or low-dose oral contraceptives can be offered as alternatives for the relief of menopausal symptoms during the menopausal transition. (I-A) 4. Non-hormonal prescription therapies, including certain antidepressant agents, gabapentin, and clonidine, may afford some relief from hot flashes but have their own side effects. These alternatives can be considered when hormone therapy is contraindicated or not desired. (I-B) 5. There is limited evidence of benefit for most complementary and alternative approaches to the management of hot flashes. Without good evidence for effectiveness, and in the face of minimal data on safety, these approaches should not be recommended. Women should be advised that, until January 2004, most natural health products were introduced into Canada as "food products" and did not fall under the regulatory requirements for pharmaceutical products. As such, most have not been rigorously tested for the treatment of moderate to severe hot flashes, and many lack evidence of efficacy and safety. (I-B) 6. Estrogen therapy can be offered to women who have undergone surgical menopause for the treatment of endometriosis. (I-A) Chapter 5: Urogenital Health Recommendations 1. Conjugated estrogen cream, an intravaginal sustained-release estradiol ring, and low-dose estradiol vaginal tablets are recommended as effective treatment for vaginal atrophy. (I-A) 2. Routine progestin co-therapy is not required for endometrial protection in women receiving vaginal estrogen therapy in an appropriate dose. (III-C) 3. Vaginal lubricants may be recommended for subjective symptom improvement of dyspareunia. (II-2B) 4. Because systemic absorption of vaginal estrogen is minimal, its use is not contraindicated in women with contraindications to systemic estrogen therapy, including recent stroke and thromboembolic disease. (III-C) However, there are currently insufficient data to recommend its use in women with breast cancer who are receiving aromatase inhibitors (where the goal of adjuvant therapy is a complete absence of estrogen at the tissue level). Its use in this circumstance needs to be dictated by quality-of-life concerns after discussion of possible risks. (III-C) 5. Systemic estrogen therapy should not be recommended for the treatment of postmenopausal urge or stress urinary incontinence given the lack of evidence of therapeutic benefit. (I-A) Vaginal estrogen may, however, be recommended, particularly for the management of urinary urge incontinence. (II-1A) 6. As part of the management of stress incontinence, women should be encouraged to try non-surgical options, including weight loss (in obese women). (I-A) Pelvic floor physiotherapy, with or without biofeedback, (II-1B) weighted vaginal cones, (II-2B) functional electrical stimulation, (I-B) and/or intravaginal pessaries (II-2B) can also be recommended. 7. (ABSTRACT TRUNCATED)
- Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work. [JOURNAL ARTICLE]
- Geburtshilfe Frauenheilkd 2014 Aug; 74(8):733-742.
Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options.
- Female sexual pain disorders: dyspareunia and vaginismus. [JOURNAL ARTICLE]
- Curr Opin Psychiatry 2014 Sep 10.
To analyze literature on sexual pain disorders and to review and summarize the articles published throughout 2013 which contribute to the current knowledge on this subject.By age 40, 7.8% of women reported vulvar pain. Diagnostic and Statistical Manual of Mental Disorders, fifth edition, has combined vaginismus and dyspareunia into the same diagnostic label. The research reviewed in this article seems to differently point toward two conditions, focusing on different aspects both on the etiological and on the treatment area. Higher levels of partner-perceived self-efficacy and lower levels of partner catastrophizing were associated with less pain intensity in women with entry dyspareunia, independent of women's pain perception and self-efficacy. Alexithymia and fear were found to be important etiological factors in vaginismus.The present findings did not provide clear evidence in support of the superiority of any treatment and highlight the need for randomized, placebo-controlled trials that compare treatments in the future. A lot of work remained to be done to understand such a complex and multifaceted disturbance as genital sexual pain, but the articles examined showed that we are slowly adding more knowledge on the etiological cause and treatment models for such conditions.