Time-efficient consultation hours in the department of gynecological endocrinology.

BACKGROUND: The aim was to conduct a benchmark pilot study to find the best practice for consultation hours in the field of gynecological endocrinology. Suitable benchmarking participants were found in China, Germany, Greece, and Switzerland. Specifically, the study aimed to find the most time-efficient and beneficial consultation type in gynecological endocrinology focused on menopause and whether a shorter face-to-face consultation correlates with lower patient satisfaction. METHODS: This was an observational study. To analyze the processes of all benchmarking participants three tools were used: a measurement of time needed for the different consultation types, a questionnaire for patients and one for physicians. The primary endpoint was the time measurement of first consultations. Secondary endpoints were the time measurements of follow-up consultations and phone consultations and patient satisfaction. RESULTS: The mean overall duration of a first consultation differed from 20.4 min to 39.7 min (p = 0.003), mainly based on differences of the mean time to acquire the patient history, 5.6 to 21.6 min (p < 0.001). The percentage of patients who felt they had enough time to discuss questions ranged from 70% to 100% (p < 0.001). The percentage of patients who felt fully understood by their physician ranged from 62.5% to 92% (p = 0.006). The duration of a first consultation did not correlate with patients feeling well consulted (r=-0.048, p = 0.557). CONCLUSIONS: A concise patient history that concentrates on the most relevant points can reduce the total consultation time. Reducing consultation time can be made without compromising how well patients feel consulted.

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.

The influence of Black Cohosh on hippocampal and hypothalamic gene expression profiles in ovariectomized rats and its potential to treat menopausal decrease in smell discrimination.

PURPOSE: Menopause is associated with a decrease in smell discrimination ability. This study assessed the impact of black cohosh on hippocampal (HC) and hypothalamic (HT) gene expression profiles in rats, to understand, if herbal treatment has an impact on neurologic changes due to menopause and whether this could address a decrease in smell discrimination. METHODS: HC and HT tissues from female Sprague Dawley rats (total n = 19) were analyzed at three different life stages: intact tissues of the HC (n = 4) and the HT (n = 4), oophorectomized tissues 3 months after oophorectomy (OVX) of the HC (n = 4) and the HT (n = 3), and tissues after treatment with an isopropanolic extract (iCR) from the rhizomes of black cohosh (60 mg/kg) for 3 months after OVX of the HC (n = 2) and the HT (n = 2). MAIN OUTCOME MEASURES: To reveal underlying biological processes a gene set enrichment analysis (GSEA) was performed. RESULTS: The GSEA revealed gene ontology terms that were significantly enriched, including several genes associated with the olfactory system, indicating biological processes regulated by treatment with iCR. Six olfactory receptor genes were further analyzed by another GSEA, demonstrating the possibility of iCR treatment to compensate for oophorectomy-induced changes. CONCLUSION: Findings suggest that herbal treatment, such as iCR, has an esteeming impact on HC and HT genes that are changed through menopause. Further studies are needed to suggest black cohosh as a treatment option for decreased smell discrimination.

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation.

RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

Transfer of preclinical study data on the influence of cimicifuga racemosaon functional changes in the hippocampus during menopause.

Menopausal transition in women involves complex neurobiochemical changes linked to ovarian dysfunction, resulting in symptoms like vasomotor symptoms (VMS), sleep disturbances, anxiety, and cognitive impairments. Hormone replacement therapy is the first-line treatment. However, many women are reluctant to use HRT or have contraindications toward HRT and seek for alternatives. Non-hormonal therapies with extracts of Cimicifuga racemosa rhizomes like the isopropanolic extract (iCR, black cohosh) offer a promising alternative. A preclinical pilot study exploring iCR's effects on gene expression in the hippocampus and hypothalamus of ovarectomized (OVX) rats mimicking menopausal conditions identified important signaling pathways and CNS-based contributions to the multitargeted modes of action of iCR. Especially in the hippocampus, iCR compensated effects of OVX on gene expression profiles. These changes are reflected by the genes AVPR1A, GAL, CALCA, HCRT, PNOC, ESR1, ESR2 and TAC3 contributing to the formation of hot flushes or thermoregulation as well as to secondary effects such as blood pressure, metabolism, hormonal regulation, homeostasis, mood regulation, neuroendocrine modulation, regulation of sleep and arousal, and in learning, memory and cognition. To understand the mechanisms in the brain of estrogen-depressed animals (OVX) and subsequent iCR treatment we combined the results of the pilot study with those of up-to-date literature and tried to transfer the current knowledge to humans during menopausal transition and adaptation. Focus was laid on changes in the hippocampal function, that is disturbed by hormonal fluctuations, but can also be brought back into balance by iCR.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

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.

Self-management eHealth solutions for menopause - a systematic scoping review.

OBJECTIVE: The purpose of this scoping review was to highlight the current scientific evidence on eHealth-based information tools for menopause in terms of quality, requirements and previous intervention outcomes. METHODS: We systematically searched electronic databases (Embase, CINAHL, Cochrane Library, Global Health Database [Ovid], Web of Science, ClinicalTrials.gov [NLM], LIVIVO Search Portal [ZB MED] and Google Scholar) from 1974 to March 2022 for relevant records. RESULTS: Our search yielded 1773 records, of which 28 met our inclusion criteria. Thirteen of 28 selected studies were cross-sectional with qualitative content analysis of websites about menopause; 9 studies were cohort studies examining the impact of an eHealth intervention; two studies were randomized controlled trials comparing eHealth tools with conventional ones; and four studies were non-systematic literature reviews. CONCLUSION: This scoping review highlights the potential of eHealth-based information tools for the management of menopause and shows that most eHealth-based information tools are inadequate in terms of readability and the balanced view on information. Providers of eHealth-based information tools should pay attention to a participatory design, readability, balance of content and the use of multimedia tools for information delivery to improve understanding.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Unmet clinical needs in women with polycystic ovary syndrome in regard to mental health: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. Despite the existence of a detailed, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE), it remains unclear to what extent healthcare providers adhere to this guideline. Our aim is to evaluate the gynaecological medical care provided in women with PCOS, particularly in terms of mental health, from the patients' perspective. METHODS: For this cross-sectional online cohort study in women with PCOS, we designed a standardized, non-validated questionnaire covering aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic non-communicable diseases. RESULTS: Among 1879 participants, various mental health aspects were reported: body image (n = 1879), eating patterns/habits (n = 1878), and emotional well-being (n = 1874). Although nearly all women (99.7%) reported complaints on at least one session of mental health, consultation rates were low (body image 9.7%, eating patterns/habits 16.6%, emotional well-being 4.4%). Mean satisfaction with counselling on the different domains varied from moderate to fairly satisfying, with scores of 56.0 points (SD 31.7), 53.5 points (SD 32.0), and 63.7 points (SD 30.2), respectively. More complaints were associated with lower satisfaction. The overall satisfaction with the management provided by the healthcare practitioner (HCP) was low, averaging 36.5 points (SD 29.7). Consequently, most women wished for more counselling (58.9%). CONCLUSION: Women affected by PCOS are not properly managed according to ESHRE guideline in regard to mental health issues. Overall consultation rates and corresponding satisfaction with management were poor, highlighting the need for significant improvements in healthcare provision.

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Use of Vitex agnus-castus in patients with menstrual cycle disorders: a single-center retrospective longitudinal cohort study.

PURPOSE: To evaluate clinical characteristics, quality of life (QoL) and effectiveness in patients with menstrual cycle disorders (MCDs) including abnormal uterine bleeding, dysmenorrhea and mastodynia/mastalgia related to premenstrual syndrome taking the Vitex agnus-castus (VAC) products Cyclodynon® or Mastodynon® in a real-world setting. METHODS: A single-center retrospective longitudinal cohort study (3 ± 1 months), using data obtained from healthcare data archive and telephone interviews. The main study variables were changes in bleeding, menstrual pain, breast tenderness and patients' QoL. RESULTS: Data from 1700 women with a mean age of 30.2 years (± 6.3) were analyzed. The most common MCDs were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%). Three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). Improvement in bleeding intensity, frequency and menstrual pain was experienced by 83.4%, 79.2%, and 85.2% of the patients, respectively. When analyzed by disease category, these parameters improved in almost all dysmenorrhea patients, while they improved to a lesser extent in mastodynia/mastalgia patients. QoL improved in all aspects, but was reported by a higher proportion of dysmenorrhea patients compared to mastodynia/mastalgia patients. Treatment was overall well tolerated with a favorable safety profile. CONCLUSION: These real-world data demonstrate the effectiveness of the VAC-containing products Cyclodynon® and Mastodynon® in the three-month treatment of MCDs, with a pronounced improvement in key disease symptoms and QoL. Intriguingly, while QoL was generally greatly improved, the response to VAC therapy varied depending on the type of underlying MCD.

Measuring Quality of Life: Incorporating Objectively Measurable Parameters within the Cross-Sectional Bern Cohort Study 2014 (BeCS-14).

Up until now, the measurement of Quality of Life (QoL) was based on validated subjective rating tools rather than objective measurement. To become more independent of the self-assessment of probands, a way to objectively measure QoL should be found. A monocenter, cross-sectional, observational, non-interventional trial was performed from 2012 to 2014 at Inselspital Bern to evaluate the bio-functional status (BFS), a complex, generic, non-invasive, sex- and age-validated assessment tool, in a wide range of areas. A standardized battery of assessments was performed on 464 females and 166 males, ages 18 to 65 (n = 630). In addition to the survey of the BFS, participants replied-among others-to the validated questionnaire SF-36 for health-related QoL (n = 447, subgroup 1). Since the accepted cut-off value for BFA calculation is age ≥ 35 years, subgroup 2 included 227 subjects (all participants aged ≥ 35 years out of subgroup 1). In order to be able to compare the eight SF-36 subscales to BFS parameters, a comparable score set of single BFS items had to be constructed. Subsequently, we aimed to statistically identify BFS item combinations that best represented each SF-36 subscale. All eight SF-36 subscales were significantly represented by various different combinations of BFS items. A total of 24 single BFS items significantly correlated with SF-36 subscales, of which 15 were objective and nine were subjective. All eight SF-36 subscales were significantly represented by various different combinations of BFS items leading to stronger correlations (range five to nine BFS items), and overall, sex and age did not affect these associations, but in the SF-36 subscales 'bodily pain' (sex) and 'role limitations due to physical health problems' (age in men). To our knowledge, we are the first to correlate a validated set of 34 objective and 9 subjective parameters with subjectively evaluated SF-36 subscales. This first study on the objectifiability of the SF-36 questionnaire demonstrated that questions on quality of life can be answered independently of a subjective assessment by subjects in future scientific studies.

Progestogens for endometrial protection in combined menopausal hormone therapy: A systematic review.

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen.

Depot medroxyprogesterone acetate and breast cancer: a systematic review.

PURPOSE: Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer. METHODS: Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review. RESULTS: All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk. CONCLUSION: There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.

Impact of progesterone on the immune system in women: a systematic literature review.

PURPOSE: The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle. METHODS: The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters. RESULTS: We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone. CONCLUSION: The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.

Motives for desiring children among individuals of different sexual-romantic orientations: a cross-sectional study.

PURPOSE: Little is known about the reasoning behind the desire to have children in non-heterosexual individuals. This study compares the motives of different sexual-romantic orientations and their preferred ways of fulfilling this desire. METHODS: This was a monocentric cross-sectional study. Subjects were recruited via social media, personal contacts and queer organisations in Switzerland. An anonymous questionnaire comprised general questions about the participant's background, a validated survey about the desire to have children and additional non-validated questions addressing the impact of sexual-romantic orientation on the desire to have children. The inclusion criteria were adults without children and a completed questionnaire. RESULTS: Of 837 participants, 642 were included in the study. Four groups of sexual-romantic orientations consisted of more than 35 participants: bisexual-biromantic (n = 38), heterosexual-heteroromantic (n = 230), homosexual-homoromantic (n = 159) and pansexual-panromantic (n = 55). Subgroups with a positive wish for a child rated all motives in the same order and with minimal numeric difference. The most important aspect seemed to be emotional involvement. Non-heterosexual-heteroromantic showed concerns about adverse reactions regarding their wish for a child. All orientations hoped for a biological child. CONCLUSION: Our findings about bi-, hetero-, homo- and pansexual people and their motives for a desire to have children agree with the existing literature about hetero, homo and bisexual. The impact of the fear of adverse reaction and discrimination has been discussed before and is supported by our data. We suggest better support before and during the realization of the wish for a child as well as support for non-traditional aspiring parents.

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.