Pixel CO2 Laser for the Treatment of Stress Urinary Incontinence: A Prospective Observational Multicenter Study.

BACKGROUND AND OBJECTIVES: Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. STUDY DESIGN/MATERIALS AND METHODS: Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. RESULTS: The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. CONCLUSION: Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the procedure. Its safety and efficacy are clearly demonstrated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Baseline ICIQ-UI score, body mass index, age, average birth weight, and perineometry duration as promising predictors of the short-term efficacy of Er:YAG laser treatment in stress urinary incontinent women: A prospective cohort study.

BACKGROUND AND OBJECTIVE: A growing body of evidence indicates that a non-invasive erbium yttrium-aluminum-garnet (Er:YAG) laser may be an effective and highly tolerable treatment for stress urinary incontinence (SUI) in women. The primary objective was to identify pre-intervention predictors of short-term Er:YAG outcomes. The secondary objective was to identify patient segments with the best Er:YAG laser treatment short-term outcomes. METHODS: A prospective cohort study performed in 2016 at Ob/Gyn Clinic, Zagreb, Croatia, recruited 85 female patients who suffered from SUI. The intervention was performed with a 2940 nm wave length Er:YAG laser (XS Dynamis, Fotona, Slovenia). Outcomes were absolute change in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF) and a relative decrease in ICIQ-UI score of ≥30% 2-6 months after the intervention. RESULTS: Age and pre-intervention ICIQ-UI values were independent significant predictors of laser treatment efficacy for SUI. A decrease in ICIQ-UI score (minimum important difference, MID) of ≥30% was independently significantly associated with body mass index and ICIQ-UI values before the intervention. All patients with four or five positive predictors saw a clinically relevant decrease in ICIQ-UI of ≥30%. The total accuracy of the predictive model defined by the area under the curve was 0.83 (95%CI 0.74-0.91). At the cut-off ≥3 positive predictors, C-index was 0.80 (95%CI 0.71-0.90), positive predictive value was 0.97 (95%CI 0.87-0.99), and negative predictive value was 0.53 (95%CI 0.45-0.55). CONCLUSIONS: A relevant decrease in ICIQ-UI (MID) of ≥30% can be predicted based on age, body mass index, average birth weight, perineometer squeeze duration, and ICIQ-UI scores before the intervention. The association between Q-tip test and treatment outcome was moderated by age. Q-tip was a significant predictor for patients between 44 and 53 years of age. The best results should be expected in younger women with a body mass index of ≤23.3, average birth weight of >3.6 kg, ICIQ-UI at a baseline of ≤10, and perineometer squeeze duration at a baseline of ≥3.51 seconds. The critical age for Er:YAG laser effect is 47.5 years. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Short time efficacy and safety of focused monopolar radiofrequency device for labial laxity improvement-noninvasive labia tissue tightening. A prospective cohort study.

BACKGROUND AND OBJECTIVE: To evaluate safety and efficacy of focused monopolar radio frequency (RF) device for non-invasive labia tissue tightening and improvement of labial laxity. METHODS: This prospective cohort study participants were 17 female subjects aged between 27 and 56 years with lax skin at the labia area. All subjects received four consecutive treatments at 7-day intervals with RF device (Exilis Protege IntimaR, BTL Industries Inc., Boston, MA). The primary efficacy outcome measure was defined as one or more point improvement on 1-4 scale for vulva appearance determined by three blinded evaluators. Digital photographs were taken at the baseline and 1 month after the last treatment. Sexual gratification was assessed with Female Sexual Functioning Index (FSFI) and patient discomfort by Visual Analogue Scale (VAS). RESULTS: An average 2.9 (of maximum 4) points improvement rate in vulvar appearance was observed (P < 0.01). Mean of the total FSFI score enhanced from initial 75-87% (P < 0.001). Resultant 4.7 (18%) points increase was achieved. Ninety four percent of subjects reported mild to none discomfort during the treatment. No adverse events during the study course were reported. CONCLUSION: The present study demonstrates the positive effect of focused monopolar RF device for non-invasive labia tissue tightening. The treatment is effective and safe with high patient satisfaction.

Minimally invasive, non-ablative Er:YAG laser treatment of stress urinary incontinence in women--a pilot study.

The study presents an assessment of mechanism of action and a pilot clinical study of efficacy and safety of the Er:YAG laser for the treatment of stress urinary incontinence (SUI). The subject of this study is a treatment of SUI with a 2940 nm Er:YAG laser, operating in a special SMOOTH mode designed to increase temperature of the vaginal mucosa up to maximally 60-65 °C without ablating the epidermis. Numerical modelling of the temperature distribution within mucosa tissue following an irradiation with the SMOOTH mode Er:YAG laser was performed in order to determine the appropriate range of laser parameters. The laser treatment parameters were further confirmed by measuring in vivo temperatures of the vaginal mucosa using a thermal camera. To investigate the clinical efficacy and safety of the SMOOTH mode Er:YAG laser SUI treatment, a pilot clinical study was performed. The study recruited 31 female patients suffering from SUI. Follow-ups were scheduled at 1, 2, and 6 months post treatment. ICIQ-UI questionnaires were collected as a primary trial endpoint. Secondary endpoints included perineometry and residual urine volume measurements at baseline and all follow-ups. Thermal camera measurements have shown the optimal increase in temperature of the vaginal mucosa following treatment of SUI with a SMOOTH mode Er:YAG laser. Primary endpoint, the change in ICIQ-UI score, showed clinically relevant and statistically significant improvement after all follow-ups compared to baseline scores. There was also improvement in the secondary endpoints. Only mild and transient adverse events and no serious adverse events were reported. The results indicate that non-ablative Er:YAG laser therapy is a promising minimally invasive non-surgical option for treating women with SUI symptoms.

Ureaplasma urealyticum and Ureaplasma parvum in women of reproductive age.

OBJECTIVES: To determine the incidence of Ureaplasma urealyticum and Ureaplasma parvum (UP) in symptomatic and asymptomatic women of reproductive age and to estimate antibiotic susceptibility of ureaplasma isolates. MATERIALS AND METHODS: This study included 424 ureaplasma positive women of 1,370 tested women who visited gynecological practices during 2010. Cervicovaginal or urethral swab specimens from each patient were obtained for cultivation and molecular typing by RT-PCR. RESULTS: Ureaplasma spp. was identified by cultivation in 424 (34.4 %) cases, of which 79.0 % were from women with symptoms and 21.0 % from women without symptoms. Among ureaplasma positive women, 121 (28.5 %) were pregnant. Genotyping was successful in 244 strains, and the majority of samples were identified as UP (92.6 %). Among genotyped isolates, there were 79.5 % from symptomatic and 20.5 % from asymptomatic women; 29.9 % from pregnant and 70.1 % from non-pregnant women. There was no difference in the incidence of ureaplasma type regarding symptoms. Antibiotic susceptibility of 424 ureaplasma isolates identified by cultivation showed that all strains were susceptible to doxycycline, josamycin, erythromycin, tetracycline, clarithromycin and pristinamycin, but there was lower susceptibility to quinolone antibiotics, i.e., 42.9 and 24.5 % isolates were susceptible to ofloxacin and ciprofloxacin, respectively. CONCLUSION: This study shows that UP was the most frequent isolated ureaplasma species (92.6 %). Regarding antibiotic susceptibility, quinolones are not the best choice for the treatment of ureaplasma infections, while macrolides and tetracyclines are still effective.

Sexual health and wellbeing and the menopause: An EMAS clinical guide.

INTRODUCTION: Sexual health and wellbeing are significant aspects of quality of life. However, taking a sexual history is often avoided in medical practice, leaving a void in management and awareness. As the menopause can have a major impact on sexual health, it is imperative that healthcare providers are appropriately trained in sexual health and wellbeing and the aligned disciplines in order to achieve optimal care. AIM: To provide an evidence-based clinical guide for the assessment and management of sexual problems at the menopause and beyond. MATERIALS AND METHODS: Review of the literature and consensus of expert opinion. RESULTS AND CONCLUSION: The assessment of sexual problems includes history taking, examination and laboratory investigation (if indicated), and occasionally the use of specific validated questionnaires. Management of sexual problems requires a multidimensional approach using biopsychosocial measures. Medical management and psychosexual counselling include pharmacological and non-pharmacological interventions, and sex therapy and psychoeducation. Furthermore, perimenopausal women should be advised about the need for contraception if they wish to avoid pregnancy. Also, sexually transmitted diseases can be acquired at any age. To conclude, taking a sexual history should be incorporated into medical practice and healthcare providers should be appropriately trained to assess and manage sexual problems at the menopause and beyond.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

EMAS position statement: Testosterone replacement therapy in older men.

INTRODUCTION: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. AIM: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

EMAS position statement: Vitamin D and menopausal health.

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

Lower urinary tract infections and the effects of hormone therapy in postmenopausal women in the Zagreb region.

Urinary tract infections (UTI) remain one of the most common bacterial infections seen in adult women of all ages. In postmenopausal women, the aging process contributes to local complaints in the lower urogenital tissue, including UTI. Our study was conducted at gynecological practices of the health centers in the Zagreb region, Croatia, during 2009. The study included postmenopausal women with urinary symptoms divided into two groups: hormone therapy (HT) users and controls. The objectives were to estimate microbiologically proven lower UTIs (LUTIs) in postmenopausal women with urinary symptoms and the effect of regular HT use on microbiologically confirmed LUTIs. Out of 2338 postmenopausal patients, there was a significantly higher rate of women with urinary symptoms in HT users, namely 64.4% (143/221), compared to the control group at 4.8% (102/2116). Of the 245 patients with urinary symptoms, in 58.8% (144/245) the infection was microbiologically confirmed. Hormone therapy users showed a statistically significant lower rate of microbiologically proven LUTIs (46.9%, 67/143) compared to controls (75.5%, 77/102, p < 0.001). Data analysis also showed the efficacy of local as well as systemic HT treatment compared with the control group (p < 0.00, p = 0.049). But there was a significant difference in the frequency of LUTIs between patients who used local (30.3%, 20/66) and systemic (61.1%, 47/77) HT (p < 0.001). The patients who, regulary used therapy, in the local HT group as well as in the group on systemic HT showed a lower incidence of LUTIs compared to controls (p < 0.00, p = 0.006). In patients who did not regulary use therapy, there were no significant differences between either local (63.6%, 7/11)) or systemic (76.9%, 20/26) HT non- regular users and the control group (75. 5%, 77/102) (p = 0.917, p = 0.625). The high percentage of patients with non-microbiologically confirmed LUTIs (41.2%, 101/245) suggested the significant role microbiological testing has in LUTI diagnosis. Both local and systemic HT use was related to LUTI reduction.

Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society.

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing.

The essential menopause curriculum for healthcare professionals: A European Menopause and Andropause Society (EMAS) position statement.

INTRODUCTION: The menopause, or the cessation of menstruation, is a stage of the life cycle which will occur in all women. Managing perimenopausal and postmenopausal health is a key issue for all areas of healthcare, not just gynecology. AIM: To provide recommendations for the curriculum of education programs for healthcare professionals worldwide, so that all can receive high quality training on menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Training programs for healthcare professionals worldwide should include menopause and postmenopausal health in their curriculum. It should include assessment, diagnosis and evidence-based management strategies.

The possibilities and limitations of direct digital radiography, ultrasound and computed tomography in diagnosing pleural mesotelioma.

The goal of this study was to compare the possibilities and limitations of direct digital radiography of the chest (DDR), the use of ultrasound of the chest (US) and single slice computed tomography of the chest (CT) in diagnosing pleural mesothelioma. The study was conducted during the course of one year, on 80 patients who were successively referred to a specialized institution, under clinical suspicion of mesothelioma. The method of investigation was the comparison of findings, obtained by the reviewed methods of examination, with the pathohistologic results of a biopsy performed on each patient. The findings that were obtained by the enumerated methods were classified according to the radiologic signs that were found in each individual patient. We evaluated following radiological findings (signs), on each of the investigated methods: plaques, localized and generalized pleural thickenings, calcifications of the pleura, pleural effusions, parapneumonic effusions, pleural empyema, (round) atelectasis, pneumothorax, tumor mass or node, inflammatory infiltrate, elevation of the hemidiaphragm and osteolysis. The results of these were compared with pathohistologic findings and analyzed by means of standard statistical methods. The highest sensitivity was found for CT (94.4%), followed by US (92.6%), and by DDR (90.7%). The highest specificity was obtained with DDR (46.2%), followed by CT (35.5%) and US (23.8%). The comparison of these methods showed 90% diagnostic accuracy for DDR in relation to CT CT as an individual method best satisfied most of the criteria for diagnosing mesothelioma. No pathognomonic radiologic sign for mesothelioma was found.

Laser Therapy in the Treatment of Female Urinary Incontinence and Genitourinary Syndrome of Menopause: An Update.

Vaginal birth trauma is the leading cause of stress urinary incontinence (SUI) in women. Also, the process of ageing and hormonal deprivation in postmenopause alters the metabolism of connective tissues and decreases collagen production leading to pelvic floor dysfunction. Noninvasive treatment is recommended as first-line management of urinary incontinence (UI) in women. Surgical procedures are more likely to be implemented to cure UI but are associated with more adverse events. Sex hormone deficiency affects changes also in the lower urinary tract where estrogens are the main regulators of physiological functions of the vagina. In the last decade, laser treatment of SUI and of the genitourinary syndrome of menopause (GSM) has been shown a promising treatment method in peer-reviewed literature. This review's aim is to present the evidence-based medical data and laser treatment of SUI and GSM in an outpatient setting to be a good treatment option, regarding short-term as well as long-term follow-ups. Long-term follow-up studies are needed to confirm that laser treatment is a good, painless outpatient procedure with no side effects in postmenopausal women.

Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia.

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18-24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

[Alternative hormone therapy in postmenopause]. / Alternative hormonskomu lijecenju u postmenopauzi.

Despite the fact that hormonal combination used in huge Wpmen's Health Initiative (WHI) is not common all over the world, and treated population is, because of age, in risk per se, study results have consternated not only lay users, but prescribers too. Namely, increased cancer, stroke and coronary heart disease risk associated with long term use of postmenopausal hormone therapy (HT) have rapidly declined the number of women treated with HT (either estrogen alone or estrogen plus progestogen). Considering recent position statements from leading organizations dealing with menopause, individualization of therapy and lower dosage HT becomes the state of the art. Not only WHI, but also results of other studies published during past few years, have induced curiosity for non-estrogen containing treatments in climacteric medicine. This review shows not only mandatory list of possibilities, but also emphasises which of the alternative and complementary treatments are evidence based regarding published randomized controlled trials.

Methylated Host Cell Gene Promoters and Human Papillomavirus Type 16 and 18 Predicting Cervical Lesions and Cancer.

Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARß2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5'LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters' methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.

Menopause in Croatia. Socio-demographic characteristics, women's attitudes and source of information, compliance with HRT.

OBJECTIVES: Hormone replacement therapy (HRT) in Croatian postmenopausal women, attitudes towards it and factors influencing this decision. METHODS: A total of 1100 women were interviewed in Ob/Gyn offices using self-response questionnaire of 56 items, dealing with demographic data, personal and family medical history, surgeries, menstrual and menopausal status, body mass index (BMI), sexuality, knowledge and attitudes towards the menopause and HRT. RESULTS: The adherence to HRT in Croatia was found to be very short, averaging only 3 months. Despite the differences between the users, non-users and past users, all groups give more reasons to take HRT, then reasons against it. Among the many demographic and patient history characteristics considered, the differences were only found regarding breastfeeding duration, menopausal age, use of oral contraceptives and IUDs. No differences were found in age, menarche, number of family members, number of deliveries, number of abortions, BMI, marital and employment status or level of education. Regarding personal and family medical history, an increased frequency was found in gallbladder and hepatic disorders for HRT users. The differences in current/past users ratio for different prescribers show that compliance with HRT is highest for university polyclinics and private gynaecological practices, and lowest for GPs and endocrinologists. CONCLUSION: The compliance with HRT in Croatia is very low, recommendations are mostly restricted to gynaecological practices and decision to take HRT is influenced mostly by psychological factors.

[Bone histology in postmenopausal osteoporosis--variations in cellular activity]. / Histologija kosti u postmenopauzalnoj osteoporozi--razlicitosti stanicnih zbivanja.

AIM: Modern understanding of the etiology of postmenopausal osteoporosis is based on the imbalance between bone resorption and formation due to estrogen deficiency, which may take several forms and combinations of decreased and/or increased activity of both or one cell type. Studies of postmenopausal osteoporosis have pointed to the existence of heterogeneity in the remodeling imbalance. Bone histology analyzed in a group of women with established postmenopausal osteoporosis undergoing bone biopsy is part of the diagnostic procedure. Data were compared and grouped according to the published histomorphometric classification of postmenopausal osteoporosis. METHODS: The study included 43 postmenopausal women aged 44-71 years with osteoporosis established by densitometry of the lumbar spine and hip. Secondary causes of osteoporosis were ruled out. Full thickness transiliacai bone biopsy specimens were obtained after double labeling regime with oxytetracycline (Geomycin, Pliva). Biopsy specimens were processed for undecalcified embedding in resin and sections stained by Goldner trichrome and toluidine blue, or used for fluorescence microscopy. A grid attached to the microscope eyepiece was used for histomorphometry. The following parameters were assessed according to the recommendations of the American Society for Bone and Mineral Research: bone volume (BV/TV, %), osteoid surface (OS/BS, %), osteoblast surface (Ob. S/BS, %), osteoid volume (OV/BV, %), osteoid thickness (O. Th, m), osteoclast surface (Oc. S/BS, %), mineral apposition rate (MAR, m/day). Thus obtained data were compared to published reference data for normal healthy population and also expressed as z-scores (the number of standard deviations by which the value differs from the mean of the normal age and sex matched controls). The study was approved by the hospital ethics committee. All patients signed an informed consent to take part in the clinical study. DISCUSSION: Histomorphometric analysis of bone biopsy demonstrated that on an average bone resorption, i.e. osteoclast surface, was considerably increased and osteoid volume moderately increased. The remaining histomorphometric parameters studied were generally normal for age and sex as compared to the published reference data. Increased osteoclast surface in 65% of patients indicated that bone loss was an active and prevailing process in these postmenopausal women, which was considerably more pronounced than in the normal age-matched population. Results of the histomorphometric analysis were categorized according to the published classification of postmenopausal osteoporosis. The percentage of patients in each group differed from literature data, most probably due to the sample size and choice. None of the patients had histomorphometric features of reduced osteoblastic and osteoclastic activity, but in 37% of postmenopausal women osteoclastic activity was increased while osteoblastic activity was normal, a feature not described in the original histomorphometric classification of postmenopausal osteoporosis. CONCLUSIONS: Histomorphometric analysis of bone biopsy in women with postmenopausal osteoporosis revealed bone resorption as a predominant finding. Different groups were recognized based on the diversity of bone cell activity. The difference in the frequencies in study groups, and observation of a distinct group not included in the histomorphometric classification of postmenopausal osteoporosis probably resulted from sample size and nonspecific population traits. Histomorphometric analysis of bone in postmenopausal osteoporosis is an important contribution to better understanding of this most common bone disorder.

Olive oil biophenols and women's health.

Olea europea, the olive tree, is an ancient tree that originates from the Mediterranean environment of Asia Minor. The edible olive fruit is also used for its oil, gained by the process of pressing, a nutrient with proven beneficial effects. Virgin olive oil is the natural juice of the olive fruit, which plays a major role in the healthy Mediterranean diet. The source of its health effects are the biophenols and squalenes (oleocanthal, tyrosol, hydroxytyrosol, oleuropein) it contains. They provide an exceptional antioxidative activity, removing harmful compounds from the body. Oxidants are essential in the genesis of many diseases and conditions, such as cardiovascular disorders, cancer, osteoporosis, Alzheimer disease, and premenstrual syndrome. Oleic acid, an unsaturated fatty acid, has demonstrated a significant effect in the prevention of malignant diseases such as colon cancer and breast cancer. Biophenols from olive oil successfully suppress the synthesis of LDL, a protein that is crucial in the development of cardiovascular disease, by reducing blood pressure and the development of atherosclerotic plaques. In addition, there is strong evidence of the antimicrobic effect of the biphenols from olive oil that successfully destroy colonies of microorganisms which may cause respiratory tract, intestinal, and genital tract infections.