Diagnostic Performance of a Panel of miRNAs (OsteomiR) for Osteoporosis in a Cohort of Postmenopausal Women.

A specific signature of 19 circulating miRNAs (osteomiRs) has been reported to be associated with fragility fractures due to postmenopausal osteoporosis. However, it is unknown whether osteoporotic fractures or low BMD phenotypes are independently contributing to changes in osteomiR serum levels. The first aim was to characterize the abundance, sensitivity to hemolysis, and correlation of osteomiR serum levels, the second objective to evaluate the diagnostic accuracy of osteomiRs for osteoporosis according to the WHO criteria and on basis of major osteoporotic fracture history. Fifty postmenopausal women with osteoporosis (with or without fragility fracture) and 50 non-osteoporotic women were included in this cross-sectional study. The diagnostic performance of osteomiRs for osteoporosis based on the WHO definition or fracture history was evaluated using multiple logistic regression and receiver-operator curve (AUC) analysis. The osteomiR® signature is composed of four clusters of miRNAs providing good performance for the diagnosis of osteoporosis in postmenopausal women defined by WHO criteria (AUC = 0.830) and based on history of major osteoporotic fractures (AUC = 0.834). The classification performance for the WHO criteria and for fracture risk is driven by miR-375 and miR-203a, respectively. OsteomiRs, a signature of 19 emerging miRNA bone biomarkers, are measurable in human serum samples. They constitute a panel of independent bone and muscle biomarkers, which in combination could serve as diagnostic biomarkers for osteoporosis in postmenopausal women.

Age-related prevalence of osteoporosis and fragility fractures: real-world data from an Austrian Menopause and Osteoporosis Clinic.

OBJECTIVES: Age and bone mineral density (BMD) are the most relevant determinants for public health authorities to govern the management of osteoporosis. The objectives of this study were to determine the age-related prevalence of osteopenia and osteoporosis according to WHO criteria and fragility fractures in middle-aged and older women. METHODS: Women ≥40 years, who were referred to a menopause and osteoporosis outpatient clinic for BMD measurements, were assessed for patient characteristics, BMD and previous fragility fractures of the hip, the distal forearm and the vertebrae. Only records of their initial consultations were used for data analysis. RESULTS: Between 1990 and 2012, 99,399 women, mean age 56.1 years, were referred to the clinic for BMD testing. Of the total population, 52.5% showed normal, 34.0% osteopenic and 13.5% osteoporotic BMD. Fragility fractures were reported by 6540 patients, with 3070 (47%) non-vertebral fractures, namely 2518 (38.5%) distal forearm and 552 (8.4%) hip fractures; 66.8% of patients with the non-vertebral fractures were <65 years. CONCLUSION: The prevalence of osteoporosis and fragility fractures in middle-aged women, < 65 years, is hitherto under-recognized. Measuring BMD alone is not sufficient to identify patients at risk for fractures. Supplemental screening for clinical risk factors already during perimenopause may be advantageous.

For how long should osteoporosis treatment continue?

Studies on the most effective of the commonly used bone-specific drugs, the antiresorptives zoledronic acid and denosumab, as well as up-to-date menopausal hormone therapy for early prevention refer to sound long-term safety data. However, depending on both the patient's characteristics and the properties of the respective regimens, the rates of side-effects, tolerability and persistence differ substantially. They are crucial limiting factors for actual efficacy in the clinical setting and thus determine the length and continuation of treatment.

Hypertension in women: the role of progesterone and aldosterone.

The age-related course of blood pressure and its gender-related difference, as well as the incidence of hypertension, have been the subject of multiple experimental, clinical and epidemiological studies over the past decades. The role of the sex hormones estradiol and testosterone within this gender dimorphism has been investigated without conclusive results. In this review, we provide background information on the gender difference in blood pressure, describe the impact of progesterone and aldosterone, and discuss the pathophysiology of aldosteronism as well as the potential role of drospirenone as a gender-specific agent for the prevention and treatment of hypertension and for cardiovascular protection.

Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium.

Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture. PURPOSE: Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence. METHODS: Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression. RESULTS: The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients. CONCLUSIONS: Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females.

OBJECTIVE: To evaluate the relation of bone mineral density (BMD) to inherited polymorphisms within the gene coding for the vitamin D receptor (VDR) in postmenopausal women. METHODS: DNA samples from 163 post-menopausal women and from 112 controls were genotyped for common allelic determinants within the VDR gene as defined by the restriction enzyme sites for BsmI, ApaI, and TaqI. BMD was evaluated at the lumbar spine (L2-L4) by dual energy X-ray absorptiometry. Single restriction enzyme site polymorphisms as well as their joint genotypes were evaluated for their association with BMD in postmenopausal women. RESULTS: The three restriction site polymorphisms showed a close association indicating linkage disequilibrium (P < 0.0001). There was no relationship between any of the single restriction site polymorphisms and BMD. The distribution of the five most common joint genotypes among postmenopausal women and controls was similar. There was no relation of BMD and any of the five most common VDR genotype groups. Females more than 5 years after menopause had a significantly lower BMD than those less than 5 years after menopause (P < 0.001). This age-related decrease of BMD was also decernible within genotype groups. CONCLUSION: In our population, the postmenopausal period has a major influence on BMD, but BMD is not controlled significantly by any of the common allelic variations within the VDR gene.

[Therapy of the surgical menopause syndrome with depot medroxyprogesterone acetate and its objective evaluation testing the reaction of the anterior pituitary gland to stimulation with gonadotropin-releasing hormone]. / Die Therapie des operativen klimakterischen Syndroms mit Depotmedroxyprogesteronazetat und ihre objektive Uberprüfung durch die Reaktion des Hypophysenvorderlappens auf Stimulation mit Gonadotropin-Releasing-Hormon.

A randomized placebo-controlled double-blind study was conducted to evaluate the effect of 150 mg depot medroxyprogesterone acetate (DMPA) intramuscularly on the surgical menopause syndrome. The clinical material consisted of 30 hysterectomized and bilaterally salpingo-oophorectomized women between 38 and 54 years of age. Inclusion criteria were regular menstrual cycles until operation, the appearance of frequent vasomotor flushes (VMF) after operation, and serum FSH levels exceeding 20 mIU per ml. Since it has been shown that an increase in "LH pulses" and basal serum LH levels constitute objective parameters of VMF, determination of LH was chosen as biochemical criterion of therapeutic efficacy. DMPA was proven to reduce basal serum LH levels owing to its suppressive effect on the adenohypophysis. In order to clarify and quantify the suppressive potency of DMPA and obtain precise information on its mechanism of action, pituitary stimulation tests with gonadotropin releasing hormone (GnRH tests) were performed before and then at 2 and 6 weeks after initiation of therapy. Pituitary response to GnRH remained unaltered, however, at a level corresponding to the decreased basal concentrations, i.e. "LH peaks" dropped by more than 50% (p less than 0.005, Student t-test). The incidence of VMF decreased significantly and remained at a low level until 6 weeks after the administration of DMPA. Treatment with placebo resulted in a slight, but not significant decrease in VMF and did not affect the functional capacity of the adenohypophysis. A remarkable correlation was observed between the reduced size of "LH peaks" and the diminished incidence of VMF. Therefore, evaluation of pituitary response to stimulation with GnRH represents a helpful objective parameter in the assessment of the efficacy of DMPA.

[Severe changes in the fundus oculi in pregnancy toxemia. 3 cases]. / Schwere Fundusveränderungen bei EPH-Gestose. 3 Fallberichte.

Three cases of severe retinal changes in conjunction with EPH gestosis are presented. 2 patients showed 4th degree hypertensive fundus changes (Keith-Wagener classification) and one suffered from bilateral exudative retinal detachment after an eclamptic fit in the 32nd week of pregnancy. The possible causes of retinal changes and visual disturbances in EPH gestosis are reviewed.

Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study.

OBJECTIVES: To establish whether transdermal continuous hormone replacement therapy (HRT) with estrogen/progestogen provides adequate long-term endometrial protection in postmenopausal women over a period of 96 weeks. METHODS: This multicenter, randomized, open-label, parallel-group study evaluated the endometrial effects and overall safety and tolerability of a transdermal matrix patch delivering estradiol (E2) 50 microg/day and norethisterone acetate (NETA) 140 microg/day (Estalis; patches applied twice weekly without intermediate breaks) and a once-daily oral comparator (Kliogest; one tablet containing E2 2 mg/NETA 1 mg) in postmenopausal women. A total of 406 women with an intact uterus, aged 44-69 years, were randomized in the 48-week core phase of the study, and 239 continued into the 48-week extension phase. Subjects were randomized in the ratio 3 : 1 to transdermal or oral E2/NETA treatment. RESULTS: No cases of endometrial hyperplasia or endometrial cancer were reported with either treatment during the core or extension phase. Both treatments were generally well tolerated, with most adverse events (>90%) being mild to moderate, although minor differences in the tolerability profile were observed between treatments. CONCLUSIONS: Continuous combined transdermal HRT with E2/NETA shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period.

[Report of 22 cases of congenital adrenal genital syndrome (AGS) observed in the reproductive age group (author's transl)]. / Das kongenitale adreno-genitale Syndrom (AGS) im geschlechtsreifen Alter. Bericht über 22 Fälle.

22 adolescent and adult female patients - 15 to 37 years old - with the Congenital Adrenogenital Syndrome (AGS) were examined. In only 7 cases the disease was diagnosed immediately after birth. Among 16 patients, which had already undergone a reconstructive operation of the external genitalia, only 5 were satisfied with its cosmetic and functional results. 11 women could not do a sexual intercourse due to the malformed external genitalia. Menarche occurred spontaneously in only 10 cases under cortisone-therapy. At the time of investigation only 4 patients had regular menstrual-cycles. Adolescents suffering from AGS should be referred to a pediatric-gynecologist not later than puberty to assure an individual guidance relating to menstruation, surgical intervention, sexual-life and fertility.

[Effect of ear-acupuncture on the LH-concentration in serum in patients with secondary amenorrhea (author's transl)]. / Das Verhalten des LH-Serumspiegels nach Ohrakupunktur bei sekundãarer Amenorrhoe.

In 13 patients at an age of 17 to 26 years with intermittent or secondary amenorrhea an attempt was made to stimulate the pituitary gland by ear-acupuncture. The objective parameter for the comparison was the concentration of the luteinizing hormone (LH) in the serum during acupuncture and the LH-RH-releasing test. 6 of these patients were subjected to a so-called "placebo-acupuncture" to perform a blind-test. The results showed, that ear-acupuncture caused a significant decrease of the LH-concentration in the serum. The clinical results showing a positive effect of ear-acupuncture in the mentioned types of amenorrhea could therefore be explained as a rebound phenomenon.

[Improvement of utero-placental perfusion by transcutaneous nerve stimulation (author's transl)]. / Verbesserung der plazentaren Durchströmung durch transkutane Nervenstimulation.

A report is given on 37 patients with a diminished utero-placental perfusion. 12 patients underwent only once, 25 patients daily over 2 to 3 weeks a transcutaneous lumbo-sacral electric nerve stimulation. Both, the 12 patients stimulated only once and the 25 patients with daily stimulation, showed a significant increase of utero-placental perfusion measured by the method of radioisotope placental perfusion. Transcutaneous nerve stimulation (TNS) therefore could be used for therapeutic purpose in cases of placental dysfunction.

[Vulvovaginitis in childhood. Experiences in a pediatric-gynecologic clinic]. / Die Voulvovaginitis im Kindersalter. Erfahrungen einer kindergynäkologischen Ambulanz.

Vulvovaginitis was diagnosed in 43% of more than 1000 gynecologic-pediatric patients. The etiology, the diagnosis and the treatment of nonspecific as well as of specific infections are discussed according to the frequency of occurrence during the different hormonal (endocrinological) periods. An easy and practicable application of diagnostic and therapeutic measurements is of importance for the treatment of this most common disease in gynecologic pediatric patients.

The acceptability of a novel oral contraceptive containing drospirenone and its effect on well-being.

Low-dose combined oral contraceptives are generally well tolerated and represent an excellent reversible form of contraception that is suitable for most women. Certain aspects of the clinical profile of combined oral contraceptives, such as intermenstrual bleeding and a tendency to weight gain, are, however, known to have an adverse effect on compliance, which may in a few women lead to contraceptive failure or pill discontinuation. Conversely, factors that have a positive effect, such as relief from the symptoms of premenstrual syndrome, can enhance compliance. An oral contraceptive that minimizes the adverse and enhances the positive effects would, therefore, be likely to improve compliance. Recently, a new combined oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin, EE/DRSP) has been developed. The pharmacological profile of drospirenone is very similar to that of natural progesterone; in particular, it has antimineralocorticoid activity. This counteracts estrogen-mediated fluid retention, resulting in stable or slightly lowered body weight. In addition, drospirenone has antiandrogenic activity and therefore a positive effect on skin conditions. Present data also indicate that EE/DRSP has a favorable effect on the symptoms of premenstrual syndrome. In order to evaluate whether the positive effects of drospirenone on body weight, skin and the symptoms of premenstrual syndrome are also observed on well-being, a survey was carried out. This asked women who had been involved in two major clinical trials how they felt after these trials had ended, in comparison with the study periods when they were taking EE/DRSP or a combined oral contraceptive containing 30 microg ethinylestradiol/150 microg desogestrel (Marvelon, EE/DSG). The returned questionnaires demonstrated that, with respect to their disposition before and during menses, women who had taken EE/DRSP felt worse after the trial had ended and they had returned to taking a conventional preparation. This was also evident on the basis of their body weights and the condition of their skin and hair. These results from clinical trials with EE/DRSP indicate that it is a well-tolerated combined oral contraceptive that has a positive effect on body weight, skin and the symptoms of premenstrual syndrome. Overall, the combination of 30 microg ethinylestradiol/3 mg drospirenone appears to improve specific aspects associated with feelings of well-being, which may result in better compliance.

Vaginal organisms in prepubertal children with and without vulvovaginitis. A vaginoscopic study.

In a prospective clinical and microbiological study covering 67 prepubertal children the vaginal flora of 31 asymptomatic children was compared to 36 children suffering from abnormal vaginal discharge and/or vulvovaginitis. Vaginoscopy was employed to obtain bacteriological specimens without contamination. Swabs were inoculated into prereduced transportmedia (PORT A CUL, BBL) and cultured aerobically and anaerobically. The most prevalent aerobic organisms were Staphylococcus epidermidis. Enterococci and Escherichia coli; the predominant anaerobic bacteria were Peptococcus and Peptostreptococcus, Veillonella parvula, Eubacteria, Propionibacterium and Bacteroides species. A similar microbiological pattern was found in both groups, although anaerobes, like Peptococci and Peptostreptococci and Bacteroides species, as well as yeasts, like Candida albicans were significantly more frequent in the group with signs and symptoms. Lactobacilli were less common in this group.

[Anaerobic microflora of praepubertal children (author's transl)]. / Aerobe und anaerobe Vaginalflora von Kindern--eine vaginoskopische Studie.

Bacteriologic cultures of the vagina and the cervix of 38 praepubertal children, aged 3 months to 16 years (average age 9 years) from the outpatient department for infants and juveniles of the 1st Department of Obstetrics and Gynecology of the University of Vienna were obtained vaginascopically using anaerobic transportmedia (Port a Cul) and were examined for aerobic and anaerobic bacteria. An average of 5.3 species was also isolated per child (2.9 aerobic and 2.5 anaerobic species). The commonest anaerobes were Peptococcus, Peptostreptococcus, Bact. melaninogenicus, Proprionibacterium and Veillonella parvula, the prevalent aerobes, were Enterococci, E coli and Staphylococcus epidermidis. Our results suggest that anaerobic bacteria amount a significant component of the flora of the lower genital-tract of healthy children, as well as of infants with vaginal discharge.

The effects of estradiol valerate plus medroxyprogesterone acetate and conjugated estrogens plus medrogestone on climacteric symptoms and metabolic variables in perimenopausal women.

BACKGROUND: Two sequential hormone replacement regimens, containing either estradiol valerate plus medroxyprogesterone acetate (E2V/MPA) or conjugated estrogens plus medrogestone (CE/MED), were compared with respect to effects on climacteric symptoms, lipid metabolism, and hemostasis. METHODS: In an open, multicenter study, 51 perimenopausal women were randomized to E2V/MPA and 50 to CE/MED. Assessment of climacteric complaints was performed at baseline and at months 1, 3, and 6. The effects on lipid and hemostatic variables were measured at baseline and at month 6. Quantitative data were analyzed using analysis of variance, the paired t-test or the chi2 Mantel-Hanszel test, where appropriate. RESILTS: Efficacy regarding treatment of climacteric symptoms was with E2V/MPA as good as with CE/MED, with a statistically significant reduction of most symptoms in both groups. After 6 months, total cholesterol and triglycerides had remained unchanged in both groups. High-density lipoprotein cholesterol showed no significant change with E2V/MPA, whereas an increase was noted in the CE/MED group (p<0.05). Low-density lipoprotein cholesterol was decreased with E2V/MPA (p<0.01) and was unchanged in the CE/MED group. Hemostatic parameters showed no significant changes after 6 months, with the exception of a decreased prothrombin time with E2V/MPA (p<0.05). Acceptability was excellent, expressed by the low incidence of treatment-related drop-outs in both groups. CONCLUSIONS: E2V/MPA is a one tablet per day sequential HRT regimen, which is as effective and acceptable as hormone replacement therapy with CE/MED regarding treatment of climacteric symptoms. Neither preparation had negative effects on lipid metabolism and hemostatic variables.

Markers of bone turnover in postmenopausal women receiving hormone replacement therapy.

We investigated the effects of hormone replacement therapy (n = 27) on biochemical markers of bone turnover in a cross-sectional study of 127 postmenopausal women (according to WHO guidelines 18 patients had normal bone mineral density and 109 suffered from bone loss). Urinary excretion of free deoxypyridinoline and C- or N-telopeptide fragments of type I collagen served as bone resorption markers, serum osteocalcin as a bone formation marker. In women with no hormone replacement therapy, only C- and N-telopeptides correlated significantly with the lumbal T-score as an index for bone mineral density. Patients with bone loss receiving hormone replacement therapy exhibited significantly lower C-telopeptide, N-telopeptide and osteocalcin levels than those with no therapy (mean -45%, -43% and -26%, respectively), while deoxypyridinoline showed no significant differences. Among the markers investigated, C- and N-telopeptides seemed to be more reliable to detect therapeutic effects on bone metabolism. We present a preliminary model to evaluate bone turnover and resorption/formation rate.

[Treatment of breast cancer at the 1st Gynecology Clinic at the University of Vienna]. / Die Behandlung des Mammakarzinoms an der I. Universitäts-Frauenklinik Wien.

Since 1979 diagnosis, operative therapy and postoperative treatment and follow-up is performed at the Ist University-Clinic of Obstetrics and Gynecology in Vienna. This management brought a close cooperation with radiologists and other oncotherapists. A standard operation method, in our case a modified radical mastectomy with a complete dissection of the axilla after radioisotope marking of the axillary lymph nodes enables us to perform a randomised prospective study of adjuvant therapy. Though the observation time is relatively short, first results show, that metastases or local recurrences were observed only in the non-treated control group. That leads in our opinion to the cautious conclusion, that any form of adjuvant therapy is of therapeutic value. Which form of adjuvant therapy should be qualified best cannot be decided yet because of the too short follow-up period.