[Contraception in Women at Risk]. / Kontrazeption bei Risikopatientinnen.

Contraception in Women at Risk Abstract. Healthy non-obese non-smokers without personal contraindications may use all hormonal and non-hormonal contraceptive methods up to the normal menopausal age. However, underlying diseases or an unfavourable lifestyle may change this liberty of choice. Vascular risks are potentiated by age, obesity, smoking, arterial hypertension, and diabetes. The presence of any arterial disease is an absolute contraindication against combined oral contraceptive (CHC). In regard of internal diseases, CHC possess the highest risk for serious complications among the methods known to be safe, whereas the lowest risk is seen in users of Cu-IUDs. The hormonal alternatives to CHC are gestagen-only preparations including levonorgestrel-releasing IUS. If no further pregnancies are intended, sterilisation of one of the partners is also a valid alternative. Because of their lack of reliability, barrier methods and natural family planning should be strongly discouraged in women with an underlying disease. Any unplanned pregnancy may present a high risk for mother and child. In presence of an underlying disease, it is strongly recommended to consult the treating specialist before a hormonal method is chosen. Independently of the method used, all women at risk for sexually transmitted diseases should also use a barrier method.

[Menopausal Hormone Therapy in women with other underlying diseases: how to proceed?] / Kurzreview: Internistische Erkrankungen und Menopausale Hormontherapie.

Menopausal Hormone Therapy in women with other underlying diseases: how to proceed? Abstract. Postmenopausal women frequently suffer, in addition to classical climacteric symptoms, from other diseases. Therefore, it is important to know when, in which form, and with which dosage menopausal hormone therapy (MHT) may be prescribed with regard to the underlying chronic disease. All women's health specialists have to know when MHT is contraindicated. To minimize the risks of MHT in the presence of a chronic disease, the following basic rules should be kept in mind: If there is no absolute contraindication, MHT should be started within the "window of opportunity" (age < 60 years or within 10 years of menopause). Continuous transdermal administration has to be preferred; in the presence of most chronic diseases, a hepatic first pass effect should be avoided. The lowest efficient dosage should be selected because most side effects are dose dependent. Cyclical fluctuations of hormone blood levels should be avoided. Metabolically neutral progestagens, such as micronized progesterone, dydrogesterone and dienogest or transdermal administration of norethisterone acetate (NETA) should be chosen. Medroxyprogesterone acetate has to be avoided. If there are doubts, the treating physician should be contacted. Angiopathies (e. g., in arterial hypertension, diabetes mellitus, lupus erythomatodes) are an absolute contraindication for MHT. In the absence of angiopathies, transdermal MHT might be prescribed in women suffering from these diseases after an extensive risk-benefit evaluation and in agreement with the treating physician.

[Climacteric depression and anxiety]. / Depressionen und Angstzustände im Klimakterium.

Climacteric depression and anxiety Abstract. Women of all ages have a higher incidence of depression than men. The lifetime prevalence of depressive disorders in women is twice the prevalence in males and amounts to 18 - 21 %. The menopausal transition is a "window of increased vulnerability" and might trigger a depressive disorder. In this period, the risk to get depressive is 1.5 - 4 times higher than in the premenopause, particularly in women suffering from vasomotor symptoms and presenting additional risk factors for mood disorders and depression. Depression in climacteric women is still underestimated and has to be actively looked for by family doctors and gynaecologists. Oestrogens modulate the metabolism of serotonin and noradrenalin, as do SSRI / SNRI and antidepressants, and influence therefore mood, mental function and cognition. In the menopausal transition, there is suggestive evidence that Oestrogen therapy can improve mood, anxiety and depression. In peri- and early postmenopausal women with climacteric vasomotor symptoms, Oestrogens might be considered as a first-line treatment for depressive symptoms. However, Oestrogens do not improve depression in the late postmenopause. In depressed elderly postmenopausal women without hot flushes, SSRI / SNRI and antidepressants remain the first-line treatment. Each pharmacological treatment should always be embedded in a global therapeutic concept including among others frequently psychotherapy and social measures.

Urinary steroid profiling in women hints at a diagnostic signature of the polycystic ovary syndrome: A pilot study considering neglected steroid metabolites.

BACKGROUND: Although the polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women with vast metabolic consequences, its etiology remains unknown and its diagnosis is still made by exclusion. This study aimed at characterizing a large number of urinary steroid hormone metabolites and enzyme activities in women with and without PCOS in order to test their value for diagnosing PCOS. METHODS: Comparative steroid profiling of 24h urine collections using an established in-house gas-chromatography mass spectrometry method. Data were collected mostly prospectively. Patients were recruited in university hospitals in Switzerland. Participants were 41 women diagnosed with PCOS according to the current criteria of the Androgen Excess and PCOS Society Task Force and 66 healthy controls. Steroid profiles of women with PCOS were compared to healthy controls for absolute metabolite excretion and for substrate to product conversion ratios. The AUC for over 1.5 million combinations of metabolites was calculated in order to maximize the diagnostic accuracy in patients with PCOS. Sensitivity, specificity, PPV, and NPV were indicated for the best combinations containing 2, 3 or 4 steroid metabolites. RESULTS: The best single discriminating steroid was androstanediol. The best combination to diagnose PCOS contained four of the forty measured metabolites, namely androstanediol, estriol, cortisol and 20ßDHcortisone with AUC 0.961 (95% CI 0.926 to 0.995), sensitivity 90.2% (95% CI 76.9 to 97.3), specificity 90.8% (95% CI 81.0 to 96.5), PPV 86.0% (95% CI 72.1 to 94.7), and NPV 93.7% (95% CI 84.5 to 98.2). CONCLUSION: PCOS shows a specific 24h urinary steroid profile, if neglected metabolites are included in the analysis and non-conventional data analysis applied. PCOS does not share a profile with hyperandrogenic forms of congenital adrenal hyperplasias due to single steroid enzyme deficiencies. Thus PCOS diagnosis by exclusion may no longer be warranted. Whether these findings also apply to spot urine and serum, remains to be tested as a next step towards routine clinical applicability.

Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO.

Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

Consensus: soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints.

The association between an increased uptake of isoflavones and a reduced frequency of menopausal hot flushes was first described in 1992, based on a lower incidence of hot flushes in countries with a high consumption of soy. Since then, numerous clinical trials with various sources of isoflavones including soy and red clover have been presented, with practically all of the studies with adequate design delivering an outcome in favour of isoflavone supplementation. An in-depth risk assessment (EFSA 2015) concludes that the amply available human data does not indicate any suspected harmful effects from a potential interaction of isoflavones with hormone-sensitive tissues in the mammary gland, the uterus and the thyroid gland. Safety was ascertained with long-term intake of up to 150 mg isoflavones per day ingested for the duration of at least 3 years. Moreover, high isoflavone intake was found to have preventive effects with respect to breast cancer. Clinical findings indicate potential benefits of isoflavone exposure even during breast cancer treatment with tamoxifen or anastrozole.

EMAS position statement: The ten point guide to the integral management of menopausal health.

With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

Menopause - wann und wie therapieren?

The publication of the first report of the Women's Health Inititiave in 2002, which evaluated the efficacy and the risks of substitution of postmenopausal women with estrogens and gestagens, has exerted a profound negative impact on the utilization of hormonal treatment. On the one hand, the WHI-studies have left both the medical community and the patients community in a state of anxiety and uncertainty, on the other has an entire set of differentiated and clarifying post hoc analyses contributed to re-define the role and the safety of hormonal treatment of menopausal women and the preventive effect on osteoporotic fractures has remained uncontested. As a result, new protocols based on lower dosages with new combinations of endocrine products allow for an early start of hormonal substitution in menopause within the so-called "window of opportunity" thereby not only ameliorating the climacteric symptoms but also preventing the early onset of cardiovascular disease. In addition, the risk of invasive breast cancer can now be better quantified, whereas participation in a mammographic screening programme helps to improve the safety of the treatment.

Gynaecologists' awareness of bone healthcare in Switzerland.

PRINCIPLES: To assess gynaecologists' awareness of bone healthcare in women and the prevalence of application of national recommendations on bone healthcare in Switzerland. METHODS: During the annual meeting of the Swiss Society of Gynaecology and Obstetrics 2012, the Swiss Association against Osteoporosis (SVGO) performed standardised interviews with conference participants (n = 210). Questions addressed responsibility for bone healthcare, and whether diagnostic procedures, initiation of bone-specific treatment and follow-up were performed in accordance with SVGO recommendations. RESULTS: The majority of respondents were aged 30-50 years (60%), female (70%) and working as board-certified gynaecologists (69%). Ninety-three percent of respondents considered care for bone health as part of the gynaecologist's expertise. As diagnostic procedures, 44% recommended performing bone densitometry (DXA) only, 34% ordered additional laboratory testing. Seventy-two percent of respondents initiated a bone-specific treatment. Predictors for not performing diagnostic procedures and not initiating a bone-specific treatment were physician's age below 30, being a trainee gynaecologist, and working at a university clinic. Particularly, young trainee gynaecologists working at a university clinic were especially unlikely to initiate a bone-specific treatment (regression coefficient = -2.68; odds ratio [OR] 0.069, 95% confidence interval [CI] 0.01-0.61; p = 0.16). Follow-ups were performed by 77% of respondents, but were less likely to be by female physicians (OR 0.27, 95% CI 0.09-0.84; p = 0.024). CONCLUSIONS: Although the majority of board-certified gynaecologists follow national recommendations on bone healthcare, current medical training in obstetrics and gynaecology does not sufficiently cover the subject of women's health. However, since this is a small study our findings may not reflect the findings in the total population.

Effects of acupuncture and Chinese herbal medicine (Zhi Mu 14) on hot flushes and quality of life in postmenopausal women: results of a four-arm randomized controlled pilot trial.

OBJECTIVE: The aim of this study was to evaluate the feasibility of a clinical trial investigating the effects of acupuncture (AP) and Chinese herbal medicine (CHM) on hot flushes and quality of life in postmenopausal women. METHODS: Forty postmenopausal women reporting at least 20 hot flushes per week were enrolled in a randomized controlled trial. They were randomly allocated to receive traditional Chinese medicine (TCM) AP, sham AP, verum CHM, or placebo CHM for 12 weeks. Follow-up assessment was conducted 12 weeks after intervention. Primary outcome measures included hot flush frequency and severity. As a secondary outcome measure, the severity of menopausal symptoms was assessed using the Menopause Rating Scale (MRS) II. RESULTS: TCM AP induced a significant decline in all outcome measures from pretreatment to posttreatment compared with sham AP (hot flush frequency, P = 0.016; hot flush severity, P = 0.013; MRS, P < 0.001). In the TCM AP group, a larger decrease in MRS scores persisted from pretreatment to follow-up (P = 0.048). No significant differences were noted between the verum CHM group and the placebo CHM group. Compared with the verum CHM group, there was a significant decrease in MRS scores (P = 0.002) and a trend toward a stronger decrease in hot flush severity (P = 0.06) in the TCM AP group from pretreatment to posttreatment. CONCLUSIONS: TCM AP is superior to sham AP and verum CHM in reducing menopausal symptoms, whereas verum CHM shows no significant improvements when compared with placebo CHM.

Ethical issues in human reproduction: Protestant perspectives in the light of European Protestant and Reformed Churches.

Protestantism is not a centralized religion. It is composed by many independent Churches having different moral and ethical standards. This review concentrates on the ethical principles prevalent in most modern European Reformed Churches. It does not intend to discuss the ethical principles of many other Protestant Churches present mainly in the USA. The common foundations of Protestant theology are the "five sola ("Sola scriptura", Sola fide", "Sola gratia", Solus Christus or Solo Christo", "Soli deo gloria"). In opposition to the Catholic Church, no intermediary is needed between the Bible and the believer. As a consequence, Protestant Churches have no Magisterium, such as the Catholic Church. Therefore Protestant Churches cannot declare a certain position to be the "official position". Each Christian is personally responsible for all his acts, including his ethical behaviour. There is no complete unanimity among all Protestants on ethics or on any other issue. Human dignity, personal rights and self-determination have to be respected in each ethical consideration. The supersession of the Old Mosaic Covenant (including traditional Jewish law or Halakhah, maintained in Catholicism) by the New Covenant and by Christian Theology has an important impact on Protestant ethics in reproductive medicine. In the New Covenant, the Protestants Churches did not maintain the mandatory obligation from the old Mosaic Covenant to be fruitful and to multiply: there is no divine obligation by God to procreate. As a consequence, contraception is not a sin and not unethical. The status of the embryo is the key for the ethical consideration of all methods used in reproductive medicine. Most representatives of modern Protestant theology and bioethics defend the opinion that the embryo is not an independent human being as is the newborn child. For most Protestant bio-ethicists, as long as an embryo has no nervous system, no organs and no pain receptors, it cannot be seen as a human being sensu strictiori: the zygote is not yet a "human being". The ethical right to be protected prenatally increases gradually with the age and the development of the embryo. Following this so-called gradualist interpretation, the early stages of an embryo merit ethically a special status: although they have already "human life", they are not yet a "human being". All ethical considerations in modern reproductive medicine discussed in this review are based on this concept of the status of the embryo. It depends largely on the acceptance or rejection of this special status of the embryo, if a Protestant considers a certain method in reproductive medicine to be ethical or unethical.

Origin and outcome of multiple pregnancies in Bern, Switzerland, 1995-2006 and the current proposal of the Swiss parliament to revise the Swiss law of reproductive medicine: Switzerland quo vadis?

INTRODUCTION: Infertility treatments are a major source of the increase in multiple pregnancies (MPs). AIMS: The aims of the present study were (1.) to investigate the origin and maternal/neonatal outcomes of MP and (2.) to review the different measures that can be adopted to reduce these serious complications. METHODS: The study included all women with multiple births between 1 January 1995 and 31 December 2006 at the University Hospital of Bern, Switzerland. The outcomes associated with the various origins of MP (natural conception, ovarian stimulation [OS]--in-vitro fertilisation [IVF-ICSI]) were analysed using a multinomial logistic regression model. An analysis of the Swiss law on reproductive medicine and its current proposed revision, as well as a literature review using Pubmed, was carried out. RESULTS: A total of 592 MP were registered, 91% (n = 537) resulted in live births. There was significantly more neonatal/maternal morbidity in MP after OS compared with natural conception and even with the IVF-ICSI group. With a policy of elective single embryo transfer (eSET), twin rates after IVF-ICSI can be reduced to <5% and triplets to <1%. CONCLUSIONS: After OS, more triplets are found and the outcome of MP is worse. MP is known to be associated with morbidity, mortality, and economic and social risks. To counteract these complications (1.) better training for physicians performing OS should be encouraged and (2.) the Swiss law on reproductive medicine needs to be changed, with the introduction of eSET policies. This would lead to a dramatic decrease in neonatal and maternal morbidity/mortality as well as significant cost reductions for the Swiss healthcare system.

Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. RESULTS: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

[Selective Estrogen Receptor Modulators (SERMs) for prevention and treatment of postmenopausal osteoporosis]. / Selektive Östrogen-Rezeptormodulatoren (SERMs) zur Prävention und Therapie der Postmenopausalen Osteoporose.

The three modern Selective Estrogen Receptor Modulators (SERMs) Raloxifene, Lasoxifene and Bazedoxifene registered in Europe reduce in postmenopausal women with a high risk for osteoporosis the incidence of vertebral fractures by 30 - 50 %, depending on the subgroup they belong to. Solid prospective fracture data for risk reduction in non-vertebral fractures, including the hip, are missing for Raloxifene and Bazedoxifene. However, a post hoc analysis suggests that the risk for non-vertebral fractures is significantly reduced by Raloxfene in women with severe osteoporosis. The simultaneous decrease of the incidence of ER-positive invasive breast cancer in Raloxifene users is highly relevant for clinicians. Unfortunately, Raloxifene and Bazedoxifene are, in the EU and in Switzerland, only labelled for the use in the prevention and treatment of postmenopausal osteoporosis. SERMs may induce or augment vasomotor symptoms. Therefore, SERMs are not a first line therapy in early postmenopause. Looking at other hormonal options, Hormone Replacement Therapy (HRT) remains the first line therapy for fracture reduction in the peri- and early postmenopause. SERMs are an appropriate choice for the continuation of fracture prevention after an initial HRT, particularly for the prevention of vertebral fractures. SERMs are safe if (as in oral HRT) the slightly increased risk for venous thrombo-embolism is respected. In conclusion, SERMs have today their well established place in the prevention and treatment of postmenopausal osteoporosis, particularly in women with a simultaneously increased breast cancer risk.

Vaginal prolapse, pelvic floor function, and related symptoms 16 years after sex reassignment surgery in transsexuals.

OBJECTIVE: To evaluate the prevalence of prolapse and related bladder, bowel, and sexual problems in transsexual patients (TS) after sex reassignment surgery. DESIGN: A cross-sectional study. SETTING: A tertiary referral center. PATIENT(S): 55 transsexuals, comprising 52 male-to-female and 3 female-to-male patients. INTERVENTION(S): Gynecologic examination with pelvic floor testing, measurements for pelvic organ prolapse applying International Continence Society pelvic organ prolapse (ICS-POP) staging, and the Sheffield prolapse questionnaire to assess prolapse symptoms, and bladder, bowel, and sexual function. MAIN OUTCOME MEASURE(S): ICS-POP score and Sheffield prolapse questionnaire. RESULT(S): Of the 55 transsexuals who participated in this study (52 male-to-female and 3 female to male), 7.5% showed a prolapse greater than or similar to ICS-POP stage 2, and 3.8% required surgical intervention. For bladder symptoms, 47% reported voiding difficulties, 24.6% urgency, 17% urge incontinence, and 23% stress incontinence. Fecal urgency and incomplete emptying of the bowel occurred in 9.4% and 7.6% of patients, respectively. In addition, 23% reported that they were never satisfied with their sexual function. CONCLUSION(S): Pelvic floor symptoms may occur in transsexuals involving the bladder, bowel, and sexual function. Surgical corrective options should be determined on an individual basis as with other patients who have prolapse symptoms.