[HPV infection in women : Diagnostics, treatment and the relevance of vaccination]. / Humane Papillomavirusinfektion bei Frauen : Diagnostik, Therapie und Bedeutung der Impfung.

BACKGROUND: Benign, premalignant and malignant changes in the anogenital region, as in the oropharynx are often affected by a persistent HPV infection. Since a causal therapy isn't possible, the focus is on early diagnosis of dysplasia. Better knowledge of the human papilloma virus led to the development of the HPV vaccine and now primary prevention of cancer is possible. These findings will also influence the German cervical cancer screening. OBJECTIVES: This article illustrates prevalence, significance, diagnostics, treatment and prevention of HPV infection and HPV-associated diseases in women. MATERIAL AND METHODS: A literature research under pubmed.de has been carried out. In addition up-to-date guidelines and internet-based sources were considered. RESULTS: Persistent infection can lead to dysplasia and carcinoma of the cervix, vagina and vulva, the anus and the oropharynx. In future an additional HPV testing is planned to be integrated in the German screening for cervical cancer for women above 35 years. Management of dysplasia is operative or topical. Accordingly, a primary prevention through vaccination is even more important. The German Standing Vaccination Committee recommends the vaccination for girls and boys between 9 to 14 years. CONCLUSION: HPV vaccination is a secure and efficient procedure to prevent cancer. In the following years it is of great importance to improve acceptance and vaccination rates.

Integrated morphologic and molecular analysis of Trichomonas vaginalis, Mycoplasma hominis, and human papillomavirus using cytologic smear preparations.

Pathogenic microbes may colonize the female genital tract via sexual transmission and cause health issues like inflammation or malignancy, summarized as sexually transmitted disease (STD). A major representative of such pathogens is Trichomonas vaginalis (T.v.), whose role in the etiology of cervical cancer remains elusive. Traditional morphologic screening of cervical smears is able to detect T.v., although its identification may be complicated by look-alikes such as degenerated granulocytes and basal cells. In addition, the parasite's endosymbiont Mycoplasma hominis (M.h.) cannot be detected in the Pap test. This investigation was aimed at designing a PCR-based method to detect specific pathogenic germs by using cervical cytology slides to overcome morphologic uncertainty and increase diagnostic accuracy. To test our molecular screening method on T.v., M.h., and HPV in archival smears, we elaborated a multiplex PCR approach based on microdissection. This assay was applied to a minute quantity of starting material which harbored or was suspected to harbor T.v.; the resulting isolated DNA was used for subsequent molecular analyses of T.v., M.h., and HPV. We clarified the diagnosis of genital T.v. infection in 88 and 1.8% of morphologically suspicious and T.v.-negative cases, respectively. We also revealed a tendency of M.h. co-infection in high-risk HPV cases. In conclusion, a microdissection-based approach to detect pathogenic microbes such as T.v., HPV, and M.h. is a molecular tool easy to implement and may help to better understand the interactivity of these germs with respect to pathogenesis.

Hormonal Smartphone Diagnostics.

Mobile point-of-care diagnostics are paramount for the provision of healthcare. Hormonal diagnostics are powerful tools to monitor timely changes in human physiology. Hormone concentrations in serum directly correlate with urine excretions with minor time delays. Therefore, rapid tests for hormones in urine have been widely used for decades as means of early diagnostics, particularly in lateral flow immunoassay formats. However, the challenge of reading and interpreting these binary tests remains. Here we present a method for utilizing mobile technologies to quantitatively read and interpret hormonal test strips. The method demonstrates the detection of a urinary by-product of progesterone, pregnanediol glucuronide (PdG), and its relation to ovulation and the fertility cycle.

Vitamin D and Mammographic Findings.

Introduction: Pleiotropic immune-modulatory and anti-proliferative effects of vitamin D and hopes to stop cancerogenesis have led to an increased interest in possible reduction of breast cancer with higher vitamin D levels. Mammographic density is an established risk factor for breast cancer risk, and its association with serum vitamin D is complex, as recent studies have shown. Patients and Methods: In this cross-sectional study, 1103 participants were recruited in the breast diagnostic unit of the Klinikum rechts der Isar, TU Munich. A standardised questionnaire and blood samples for 25-OH-vitamin D were taken on the day of mammography. Histologic results of biopsies in suspicious mammographies were documented. Results: In the 1090 data-sets analysed, vitamin D-deficiency was common among women under 40. Highest vitamin D values were observed in participants aged 60-69 years, but average values for all age cohorts were below 20 ng/ml of vitamin D. 15.6 % of all participants had very low vitamin D values (< 10 ng/ml), 51.3 % were vitamin D-deficient (10-19 ng/ml) and only 5.7 % were above 30 ng/ml, i.e. showed sufficient vitamin D. Patients with malignant results had vitamin D < 10 ng/ml more often (16.9 %; p = 0.61), and only 3.4 % in this group had sufficient vitamin D supply (> 30 ng/ml). There were no significant differences in vitamin D-levels between density groups according to the American College of Radiology (ACR) criteria. Conclusion: Vitamin D values were lower than in comparable US women. Up to now, there is no direct clinical evidence for a relationship between the risk for breast cancer and a specific vitamin D value.

Non-reproductive Effects of Anovulation: Bone Metabolism in the Luteal Phase of Premenopausal Women Differs between Ovulatory and Anovulatory Cycles.

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17ß-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal phase and that of the following cycle. The interaction between ovulation and bone metabolism is complex. Since anovulation may occur in low estrogen states such as pre-anorexic dietary restraint, as well as with high estrogenic circumstances e.g. from functional perimenopausal ovarian cysts, the association with bone changes has been variable in the literature. Accumulating physiological and clinical evidence however point towards a role for ovulation in enhancing bone formation and limiting bone resorption.

Do Pregnancy and Parenthood Affect the Course of PCO Syndrome? Initial Results from the LIPCOS Study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS]).

Introduction: The impact of pregnancy and parenthood on the long-term course of PCOS (polycystic ovary syndrome is still not known. The LIPCOS study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS] - using the example of pregnancy and parenthood) systematically investigates long-term changes in PCOS symptoms. Method and Patients: The LIPCOS pilot study sent out a questionnaire to 403 patients who had presented with oligomenorrhea between 1991 and 2002. The prospective LIPCOS main study systematically investigated 64 women using structured interviews about lifestyle changes in the last 10 years, created a detailed hormone profile of these women and carried out vaginal ultrasound to calculate ovarian score. Results: Ovarian volume and ovarian score were not significantly lower for women with children (n = 25) compared to women with PCOS who had not had children (n = 39; p = 0.226). More women with children than women who did not have children currently reported a regular daily lifestyle, and the difference was statistically significant (92 % [n = 23/25] vs. 61.5 % [n = 24/39]; p = 0.009). Ten years ago or before the birth of their first child, respectively, no such difference was found between both groups (52 vs. 51.3 %). Over the last 10 years, women with children were more likely to have shorter cycles compared to women without children (p = 0.441). 88 % of women with children compared to 69.2 % of women without children reported that currently they had a "healthy diet" (p = 0.130). Serum testosterone levels were slightly lower for women with children (67.6 % of the upper limits of normal ranges) compared to women without children (80 % of the upper limits of normal ranges), but because of the small subgroup sizes the difference was not statistically significant (p = 0.106). Conclusion: The LIPCOS study shows for the first time that pregnancy and parenthood may have an impact on the long-term course of PCOS. Women with children reported shorter cycles and had lower testosterone levels compared to women without children.

Progesterone and bone: a closer link than previously realized.

Decreasing rates of ovulation, hormonal changes, and increasing bone loss pre-date menopause by several years. Data suggest that, in addition to estradiol, progesterone may play a significant role in the interrelationship between the ovaries and the skeleton in women. Indeed, the differentiation of human osteoblasts from perimenopausal women has been shown to be dose-dependent on progesterone at physiological concentrations. Data from a pilot study in perimenopasual women also suggested that higher progesterone levels, as seen in the luteal phase of ovulatory cycles, may be associated with more bone formation and with slightly less bone resorption than anovulatory cycles in which progesterone levels are low (< 5.8 ng/ml). These data led to the initiation of a large, prospective, 2-year observational study in perimenopausal women (the PEKNO study). Interim data from the PEKNO study indicate that a decrease in ovulation correlated with an increase in the loss of bone mineral density (BMD). A meta-analysis estimated a BMD increase of 0.5% per year in women with normal ovulation, and a BMD decrease of 0.7% per year in young women with ovulatory disturbances (anovulation or short luteal phase). A meta-analysis in postmenopausal women demonstrated a 1.3% increase per year in BMD when receiving hormone replacement therapy with unopposed estrogens, and a further 0.4% increase in BMD in women receiving estrogens plus progestogens. The role of progesterone in bone metabolism in perimenopausal women who are estrogen-replete requires further study.