Virtual academy of women's health / 《全球健康杂志（英文）》

In this paper,we explored to develop a new concept of computer-and internet-based learning and training method in medicine,especially in obstetrics and gynecology,which is named as Virtual Academy of Women'Health(VA).Especially in the times of infectious disease pandemics worldwide,learning at home rather than in big lectures hall,might be necessary and practical as never before.The VA is based on worldwide knowledge in medicine—free accessible on the internet—in terms of homepages,video and audio platforms,scientific papers,medical books,and different guidelines.A collection of different video-clips in various fields of women's health can assist the student or doctor in understanding the symptoms,diagnostics,and treatment of various diseases.There are two major targets of it—one is online education,and one is testing the knowledge by simulation of clinical cases.

Intrauterine contraception and menstrual bleeding / 《全球健康杂志（英文）》

After more than half a century of development,the intrauterine contraception (IUD) has become a relatively mature method of contraception and treatment of gynecological diseases.This paper reviewed the development of IUDs,different types of IUDs,and some problems due to them,such as bleeding,infection,malposition,dis-location,expulsion,etc.And the causes of clinical side effects,complications,and corresponding treatments of IUDs were overviewed as well.

Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate.

Uterine fibroids are the most frequent benign tumours in women of child-bearing age. Their symptoms are diverse and the quality of life of the women affected can be significantly impaired. While treatment to date has been primarily by means of surgical intervention, selective progesterone receptor modulators (SPRMs) open up new medication-based treatment options. EMA's Pharmacovigilance Risk Assessment Committee (PRAC) has recently completed its review of ESMYA® (ulipristal acetate, 5 mg), following reports of serious liver injury, including liver failure leading to transplantation in postmarketing settings. We will provide some information on the PRAC's recommendations to minimize this risk. Nevertheless, the effectiveness and safety of the SPRM ulipristal acetate (UPA), both with regard to preoperative administration and with regard to an intermittent administration as long-term treatment for patients with symptomatic uterine fibroids, have been shown in several clinical studies (PEARL I-IV).

Corrigendum to "Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate".

[This corrects the article DOI: 10.1155/2018/1374821.].

Symptoms of uterine myomas: data of an epidemiological study in Germany.

PURPOSE: Currently, no reliable data are available concerning the type and frequency of symptoms in premenopausal women with uterine myomas. METHODS: 2296 women were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. From this population, 1314 premenopausal women between the ages of 30 and 55 years were evaluated to determine the type and frequency of myoma-related symptoms and their relationship to anamnestic factors, and the number, size, and location of the myomas. Standardised questionnaires were used to record the symptoms. RESULTS: Prevalence: In almost every second premenopausal woman (n = 639; 48.6%), uterine myomas were diagnosed. The frequency of myomas increased continuously with age and was highest in women between 46 and 50 years (65.2%). Age itself was found to be the main risk factor for the presence of myomas (p < 0.001). SYMPTOMS: 54.3% (n = 347) of the women suffered from myoma-related symptoms. The four main symptoms were identified as: Heavy menstrual bleeding (40.7%), dysmenorrhoea (28.2%), lower abdominal pain (14.9%), and intermenstrual bleeding (14.1%). In the majority of cases, the symptoms occurred simultaneously. Determinants for symptoms: Symptoms did not follow a clear age-related trend, whilst the number and size of the myomas did determine the presence of symptoms. The main influencing factor for the presence of intermenstrual bleeding was the location of the myomas. CONCLUSIONS: The high prevalence of uterine myomas highlights the importance of the diagnosis uterine myomas in standard gynaecological practice: The presence of only one myoma caused symptoms in 46.5% and small myomas of up to 2 cm in diameter resulted in symptoms in 39.5%.

Prevalence of uterine myomas in women in Germany: data of an epidemiological study.

PURPOSE: Currently, no reliable data are available concerning the prevalence of uterine myomas in Germany. In this prospective study, we examined the prevalence of myomas in women older than 30 years by means of vaginal ultrasound. METHODS: 2296 women, who consented to the procedure, were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. PREVALENCE: myomas were detected in 41.6 % of all women. Age dependence: With increasing age, the prevalence of uterine myomas rose from 21.3 % (30-35 years) to 62.8 % (46-50 years). Later, the number of myomas decreased again from 56.1 % (51-55 years) to 29.4 % in women older than 55 years. Menarche/BMI: no correlation could be found between the age at first menstrual period or the body mass index and the occurrence of myomas. Parity: since the group of nulliparous women and the group of women with more than four deliveries stand out by increased occurrence of myomas, a non-linear correlation seems to exist, necessitating more in-depth discussion with regard to age dependency. CONCLUSIONS: The results of this study suggest that more than 40 % of women over 30 years of age suffered from myomas and more than 50 % of all women in Germany may develop uterine myomas at some time in their life.

Hyperandrogenemia in polycystic ovary syndrome: exploration of the role of free testosterone and androstenedione in metabolic phenotype.

OBJECTIVE: To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. METHODS: We analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT). RESULTS: Polycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p<0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34-5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p<0.05 for all). CONCLUSIONS: Polycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile.

Vitamin D and female fertility.

PURPOSE OF REVIEW: Apart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D and female fertility published over the past year. RECENT FINDINGS: In the past year, several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma, and ovarian reserve in late reproductive aged women. SUMMARY: In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥30 ng/ml) should be obtained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis.

Use of and attitudes towards emergency contraception: a survey of women in five European countries.

OBJECTIVE: To identify knowledge of and attitudes towards emergency contraception (EC) in women from five European countries. METHODS: In an internet-based survey, sexually active women aged 16 to 46 years from France, Germany, Italy, Spain, and the UK were asked about their use of and opinions on EC. RESULTS: Overall, 7170 women completed the survey. Thirty percent reported having had unprotected sexual intercourse during the previous 12 months (population at risk). Twenty-four percent of the population at-risk reported using EC. The most common reasons given for not using EC were: not perceiving themselves to be at risk of pregnancy; and not thinking about EC as an option. A third of respondents indicated they did not know how EC works, with several misconceptions about EC noted e.g., leading to infertility, similar to abortion. Seventy-nine percent of women agreed that EC is a responsible choice to prevent unwanted pregnancy, but nearly a third of women who used EC felt uncomfortable or judged when obtaining it. CONCLUSIONS: EC is underutilised by three-quarters of the women surveyed. Women do not recognise they may be at risk of pregnancy when contraception fails. There are still several misbeliefs about EC indicating a need for better education of the public.

Emergency contraception.

There have been numerous attempts to control fertility after unprotected sexual intercourse (UPSI). From very bizarre methods like the vaginal application of Coca Cola to the more serious attempts using calcium antagonists influencing fertility parameters in sperm to hormonal methods or intrauterine devices. So far, hormonal methods preventing or delaying ovulation have proved to be the most popular starting with the combination of ethinyl estradiol and levonorgestrel (LNG), known as the Yuzpe regimen. The first dose had to be taken within 72 hours of UPSI, a second one 12 hours later. Later on, LNG alone, at first in a regimen similar to the Yuzpe method (2 × 0.75 mg 12 hours apart) showed to be more successful, eventually resulting in the development of a 1.5 mg LNG pill that combined good efficacy with a high ease of use. Several efficacious and easy to use methods for emergency contraception (EC) are available on the market today with the most widely spread being LNG in a single dose of 1.5 mg (given as one tablet of 1.5 mg or 2 tablets of 0.75 mg each) for administration up to 3 days (according to WHO up to 5 days) after UPSI. Its limitations are the non-optimal efficacy which is decreasing the later the drug is taken and the fact that it is only approved for up to 72 hours after UPSI. This regimen has no effect on the endometrium, corpus luteum function and implantation, is not abortive and don't harm the fetus if accidentally taken in early pregnancy. It has no impact on the rate of ectopic pregnancies. It has become the standard method used up to this day in most countries. Since the mid 1970s copper IUDs have been used for EC, which show a high efficacy. Their disadvantages lie in the fact that EC is considered an off label use for most IUDs (not for the GynFix copper IUD in the European Union) and that they might not be acceptable for every patient. Furthermore IUD-insertion is an invasive procedure and it is required trained providers and sterilized facilities. Mifepristone in the dosages of 10 or 25 mg is used with good results as an emergency contraceptive in China for up to 120 hours after UPSI, but has never received any significant consideration in Western countries. While high doses of mifepristone has an effect on endometrial receptivity and will inhibit ovulation if given in the follicular phase and prevent implantation if given in the early luteal phase, low doses such as 10 mg has no impact on the endometrium. Mifepristone does not increase the rate of ectopic pregnancies. The most recent development is the approval of the selective progesterone receptor modulator ulipristal acetate (UPA) in the dosage of 30 mg for EC up to 5 days after UPSI, combining the safe and easy application of the single dose LNG pill with an even higher efficacy. It has shown to be more efficacious than LNG and can be used for up to 120 hours after UPSI; the difference in efficacy is highest for 0-24 hours, followed by 0-72 hours following UPSI. No VTE has been reported following UPA-administration or any progesterone receptor modulator. No effect on endometrium, corpus luteum function and implantation has been observed with doses used for EC. Independent of the substance it should be noted that, if there is a choice, the intake of an oral emergency contraceptive pill should happen as soon as possible after the risk situation. A pre-existing pregnancy must be excluded. Possible contraindications and drug interactions must be considered according to the individual special product informations.

Hormonal contraception and risk of endometrial cancer: a systematic review.

More than 15 case-control studies and at least four large cohort studies demonstrated a decrease in the risk of endometrial cancer of about 50% for ever use of combined oral contraceptives (COCs). In most of these studies, this protective effect persisted for more than 10-15-20 years after cessation of the COC. An increasing protective effect with longer duration of COC use has been found in most studies. The beneficial effect was independent of the composition of COC, i.e. dosage and type of progestogen, combined with ethinyl estradiol 30-50  µg/day. COCs with higher progestogen potency seem to be somewhat more effective. Nonhormonal uterine devices have also been found to be strongly protective; however, data on oral or injectable progestogen-only preparations (POPs) including the levonorgestrel-releasing intrauterine system (LNG-IUS) are still rare, but also suggest similar protective action. COCs, POPs, as well as LNG-IUS can effectively reduce endometrial hyperplasia but should only be used in exceptional cases in patients with or after endometrial cancer. In contrast to nonhormonal IUS, systemic side effects cannot be excluded with LNG-IUS, but they are certainly rare, as the main effect has decreased the endometrial estrogen response because of the high endometrial tissue levels of LNG.

Endometrial safety of a novel monophasic combined oral contraceptive containing 0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 24/4-day regimen over six cycles.

BACKGROUND: This study was conducted to examine whether small doses of ethinylestradiol (EE, 0.02 mg) and chlormadinone acetate (CMA, 2 mg) administered in a novel 24/4-day regimen during six cycles would suffice to suppress proliferation and to cause secretory changes in the endometrium. STUDY DESIGN: This Phase II, randomized (two assessment groups), single-center, open, uncontrolled, multiple-dosing study treated 59 female subjects. The subjects underwent three endometrial biopsies: one pretreatment, one during medication (either at Cycle 3 or Cycle 6) and one during the first post-treatment cycle. RESULTS: The study revealed that 0.02 mg EE/2 mg CMA effectively transformed the endometrium from a proliferative state into a secretory or inactive state after three (90% of subjects) and six (76% of subjects) medication cycles. The mean endometrial thickness decreased markedly from 10.2 (SD±3.0) mm (pretreatment) to an unfavorable level for the nidation of a blastocyst [5.3 (SD±2.1) and 4.1 (SD±2.2) mm in Medication Cycles 3 and 6, respectively]. Correspondingly, estradiol and progesterone levels decreased during treatment. In the post-treatment cycle, endometrial biopsy and ultrasound evaluation as well as sex hormone levels suggested a quick return to fertility. There were no signs of hyperplasia, endometrial polyps, neoplasia or other detrimental histopathological changes at any time during the trial. Treatment-related adverse events (AEs) were reported by 22 (37%) of 59 subjects and were reported most commonly in Cycle 1, decreasing continuously thereafter. No AEs led to discontinuation of the trial medication and there were no serious AEs. CONCLUSIONS: The 24/4-day regimen of 0.02 mg EE/2 mg CMA provided effective and reversible endometrial effects with secretory transformation or suppression without inducing pathological changes.

[S2k-guideline for therapy of acne]. / S2k-leitlinie zur therapie der akne.

To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post-acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text.

[Hormonal antiandrogens in acne treatment]. / Hormonelle Antiandrogene in der Aknetherapie.

BACKGROUND: An enhanced sebaceous gland activity with production of proinflammtory sebaceous lipids belongs to the major pathogenetic factors of acne. Hormonal antiandrogen treatment targets the androgen-metabolizing cells of the pilosebaceous unit, i. e. follicular kertinocytes and sebocytes, and leads to sebostasis, with a reduction of the sebum secretion rate of 12.5 to 65 %. Concerning their mechanism of action, hormonal antiandrogens are classified in androgen receptor blockers, inhibitors of circulating androgens by affecting the ovarial function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotrophin-releasing hormone agonists and dopamin agonists in hyperprolactinemia), inhibitors of the adrenal function, and inhibitors of peripheral androgen metabolism (5-reductase inhibitors, inhibitors of other enzymes). METHODS: In this study, all original and review publications on hormonal antiandrogen treatment of acne as monotherapy or in combination included in MEDLINE, EMBASE and COCHRANE libraries were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog*" and "treatment" and classified according to their level of evidence. RESULTS: Antiandrogen treatment is overall active on acne lesions. The combinations of ethinyl estradiol with cyproterone acetate chlormadinone acetate, dienogest desogestrel and drospirenone have shown the strongest antiacne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotrophin-releasing hormone agonists and inhibitors of peripheral androgen metabolism are not recommended according to the current stand of knowledge. Low dose prednisolone is to only be administered at late onset congenital adrenal hyperplasia and dopamine agonists at hyperprolactinemia. Treatment with hormonal antiandrogens requires missing of any contraindications. CONCLUSIONS: Hormonal antiandrogen treatment is limited to female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, females with acne tarda, persistent acne recalcitrant to treatment, with parallel wish of contraception, and as a requirement for a systemic isotretinoin treatment can be treated with hormonal antiandrogens. Hormonal antiandrogen treatment is not a primary monotherapy for uncomplicated acne.

The ESHRE/ASRM consensus on polycystic ovary syndrome (PCOS)--an extended critical analysis.

The 'ESHRE/ASRM consensus on diagnosis, nomenclature and long-term health risks of polycystic ovarian syndrome (PCOS)' (conference in Rotterdam, Netherlands, March, 2003), which was criticized shortly after its oral presentation in 2003, is still being debated following its publication in 2004. Therefore, an extended, intensive analysis of all parameters and their combinations has been performed, differentiating between inclusion and exclusion criteria. By doing this, the profound significance of the endocrinological part of the syndrome is highlighted. The nomenclature, semantic meaning of terms, definitions, structural balancing, specificity, practicability, flexibility, limitations and reproducibility for both individualization, as well as grouping from the clinical and scientific perspective, have been examined in detail. This analysis supports previous critical comments, and reaches the conclusion that the recommendations of the consensus lack accuracy and specificity, a weakness that results in the risk of overdiagnosis and in a lack of reproducibility. Altogether, they fail to fulfil the criteria of universal guidelines on several levels. Instead, a profound paradigm shift is demanded, from an inconsistent perception to a more systematic, balanced and comprehensive view. A short indication on an alternative sweeping concept of a strictly defined, therapy-targeted classification and diagnostic procedure of female functional androgenization is presented.

Luteal-phase inhibin A and follicular-phase inhibin B levels are not characteristic of patients with an elevated LH-to-FSH ratio.

PURPOSE: To test whether serum inhibin levels are related to differences in gonadotropin concentrations between patients with an elevated LH-to-FSH ratio (ELF patients) and controls. METHODS: 32 ELF patients were matched with controls by age, body mass index (BMI), and cycle length. RESULTS: No statistically significant difference was found in follicular-phase inhibin B levels or midluteal inhibin A levels between cases and controls. Significant negative correlation was observed between follicular-phase inhibin B concentrations and BMI in ELF patients but not among controls. LH and FSH were positively related to inhibin B levels in ELF patients. Midluteal inhibin A correlated with sex hormone-binding globulin in controls but not in ELF patients. CONCLUSIONS: Neither follicular-phase inhibin B levels nor midluteal inhibin A levels are characteristic of patients with an elevated LH-to-FSH ratio. Opposite correlations with LH and BMI suggest dysregulation of inhibin secretion rather than dimeric inhibins having a central role to the endocrinological imbalance observed in polycystic ovary syndrome.

Intraoperative venous blood sampling to localize a small androgen-producing ovarian tumor.

BACKGROUND: Among other causes of virilization, ovarian tumors can be the cause of excessive androgen production. We report the case of a Leydig cell tumor of the ovary where diagnostic attempts to localize the source of hyperandrogenism preoperatively failed owing to relatively small tumor size. CASE: A 36-year-old woman presented with clinical signs of severe virilization including progressive balding, increased hirsutism, secondary amenorrhea and enlargement of the clitoris. Extensive work-up included endocrinological tests, pelvic ultrasound, magnetic resonance imaging, chromosomal analysis, norcholesterol scintigraphy and selective venous sampling, without direct localization of the source of hyperandrogenism. Persistently high plasma testosterone prompted an explorative laparotomy. Intraoperative selective blood sampling of the ovarian veins and palpation gave evidence of a right ovarian tumor, which was then removed. Histological examination revealed the presence of a pure Leydig cell tumor. CONCLUSION: Exploratory laparotomy with intraoperative selective blood sampling of the ovarian veins might be a useful approach in patients without accurate preoperative localization of androgen-producing tumors of the ovaries.