Oral contraception (OC) is used by approximately fifty-five million women in the USA alone and is listed as an essential medicine by the World Health Organisation. Altered mood is a common reason for OC cessation. Here we investigate the effects of OC on hormones that are linked to mood. We obtained blood samples from 185 young women (average age 21.2) in two cohorts and tested the effects of OC on plasma levels of oxytocin, adrenocorticotropic hormone (ACTH), estradiol, progesterone and testosterone. We related plasma hormone levels with self-reported measures of mood, well-being and depression. OC-users in both cohorts showed elevated basal oxytocin, lower ACTH, estradiol, progesterone and testosterone compared with non-OC users. Satisfaction With Life Score (SWLS) was higher in OC -users compared to non-OC users, with no differences in the Beck Depression Score (BDI) and Positive And Negative Affect Schedule (PANES). In conclusion, our data show alterations in hormone levels and SWLS in response to OC.
This article reviews the competition of two natural family planning methods in the mid-1970s when the Catholic Natural Family Planning program was underway in Korea. The Catholic Church, emphasizing the natural law, has recommended Natural Family Planning (NFP), a method of regulating childbirth by abstinence during the fertile period, since the mid-twentieth century. However, a group of gynecologists working at St. Mary's Hospital, a Catholic general hospital in Korea, questioned the utility of NFP. As an alternative, they proposed the method of Ovulation Regulation (OR), which regulates the menstrual cycle by inducing ovulation with steroids agents. This seemed to be no different than contraception with oral contraceptives disapproved of by the Catholic Church, but many doctors who advocated OR thought that this could be a new 'natural' family planning method to replace NFP. What is noteworthy here is the fact that not only NFP advocates, but also OR advocates attempted to justify their methods based on the authority of the 'nature.' In the debate over natural family planning methods, nature's legitimacy was given premise, not the object of doubt. Rather, the issue was the definition of nature. First, 'nature' in NFP signifies 'innate nature,' which excludes human intervention. According to this point of view, OR with steroids agents could not be natural. On the contrary, a group of doctors who advocated OR considered nature 'primal completeness.' If the natural order of the menstrual cycle could be restored, the artificial intervention of the administration of steroids was not a problem. Thus, both groups defended their arguments by redefining nature, rather than raising an issue of nature itself. The competition between 'innate nature' and 'complete nature,' a proxy war between NFP and OR, resulted in the victory of the former as the meaning of nature became fixed. Advocates of NFP pointed out that OR inhibits other physiological functions in the process of inducing ovulation, suggesting that the idea of 'complete nature' could never be achieved. The meaning of nature could no longer be controversial. Since the intervention was unnatural, nature meant innateness, the absence of intervention. Accordingly, the Catholic Bishops of Korea approved the Billings Method, a kind of the NFP, as the official family planning method, and gynecologists at St. Mary's Hospital of Korea also focused on the development and supplementation of the Billings Method. In short, the debate over the methods of natural family planning in mid1970s Korea was a clash of 'innate nature' and 'complete nature.' As a result, this confirmed the limitations of medical practice and reconfirmed the power of magisterium, the church's authority over medical practice.
General OB/GYNEndocrine DisruptorsEnvironmental Risk FactorsCross-Sectional Design
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
Housemaids are part of women with low socioeconomic status and most of them are migrant from rural to central part of Ethiopia, less educated, either with poor, separated, single or divorced family and/or dead parents. Housemaid may experience problems like depression and anxiety more than other groups of women. Therefore, the aim of this study was to assess the magnitude and determinants of those problems among housemaids. To assess the magnitude and determinants of depression & anxiety among housemaids in Addis Ababa; Ethiopia; 2018. Community based cross-sectional study was conducted from May 1 to August 30, 2018 among housemaids working in Addis Ababa, Ethiopia. Multistage sampling technique was applied with a total of 826 samples. Quantitative data was employed by using structured questionnaires. The collected data was coded, entered in to Epi-Info version 7 and analyzed by using SPSS version 20. Descriptive, analytical statistical procedures; bivariate and multivariate binary logistic regressions with odds ratios and 95% confidence interval was employed. The statistical significance was declared at p value < 0.05. This study enrolled 862 participants with response rate 99.5%, 99.5% refers to the number of people who actually completed the interview. The result showed prevalence of depression and anxiety among housemaids 27.5% and 32.3% respectively. Among all participants 44.6% (95% CI= 41.0 - 47.9) have mild, 18.5% (95% CI= 15.7 - 21.2) have moderate and 6.1% (95% CI= 4.5 - 7.8) have severe form of comorbid anxiety with depression. Depression (44.9%) and anxiety (41.9%) found more prevalent among the age group 16 to 20. In this study history of parental divorce, participant's divorce, physical violence and sexual violence are positively associated. Other factors; being less educated and living with relatives; were associated negatively. The prevalence of Depression and Anxiety is found high among housemaid; its prevalence is more among age group 16 to 20 than other age groups. Violence, participant's divorce, history of parental divorce and contraceptive use has positively associated with depression and anxiety.
PCOSCyclic Progesterone TherapyLuteal Phase ReplacementOligomenorrhea Management
Open Access
Women living with androgenic PCOS (WLWP) experience unpredictable oligomenorrhea1 and are at increased risk for endometrial cancer2. Oral micronized progesterone (OMP) given cyclically (14 days/cycle or 4 weeks, Cyclic OMP), in luteal phase doses3 (300 mg at bedtime) as a “luteal phase replacement” therapy would be likely to effectively treat both. In addition, evidence suggests PCOS is causally related to rapid pulsing of GnRH and LH 4; OMP normalizes LH pulsatility if androgen levels are not elevated 4. Previous searches did not find progesterone therapy for PCOS 5. Does the peer-reviewed literature provide evidence for prescribing cyclic progesterone therapy in PCOS? Literature search methods used Medline (Ovid) and PubMed for published articles. “polycystic ovary syndrome”, “androgenic PCOS”, and, “micronized progesterone.” We sought publications with eligible women participants having androgenic PCOS, drug exposures (cyclic
OMP, vaginal progesterone, and in varying doses and durations) and specific outcomes (biochemical or patient-reported data or both) in all languages. We excluded reviews and practice guidelines but searched bibliographies for missed citations. Results discovered 18 articles in combined Medline (n=6) and PubMed (12) searches. After excluding duplicates, articles on estradiol (E2) alone E2 with OMP therapy, five eligible articles remained. We read all in full detail.
Progesterone therapy was beneficial for WLWP as, even in sub-therapeutic doses (<300 mg at bedtime) and in cycles of too short durations (<14 days), it decreased luteinizing hormone (LH) 6,7 and total testosterone 7 levels. Vaginal progesterone (200 mg, b.i.d for 2 to 12 weeks) added to letrozole ovulation induction increased the pregnancy rate from 0 to 21% 8. Although present data suggest Cyclic OMP withdrawal predictively causes flow, we found no evidence it improved women’s cycle-related experiences nor decreased acne and hirsutism. Women-reported data on Cyclic OMP for improving androgenic PCOS cycle regularity, daily experiences and risks for endometrial cancer are needed.
1Azziz R Nat Rev Dis Primers 2016;2:16057. 2Barry J Hum Reprod Update 2014; 20:748. 3Simon J Fertil Steril 1993;60:26. 4Blank S Hum Reprod Update 2006;12:351. 5Teede H Clin Endocrinol (Oxf) 2018;89:251. 6Livadas S Fertil Steril 2010;94:242. 7Bagis T J Clin Endocr Met 2002;87:4536. 8Montville C Fertil Steril. 2010;94:678.
To assess whether paternal health is associated with maternal peripartum and neonatal outcomes. Retrospective cohort study. University research departments. PATIENT(S): Analytic sample of children born to paired fathers and mothers covering live births within the United States between 2009-2016. INTERVENTION(S): Paternal health status (e.g., metabolic syndrome diagnoses, individual chronic disease diagnoses). MAIN OUTCOME MEASURE(S): Primary outcome of preterm birth (i.e., live birth before 37 weeks), and secondary outcomes of low birth weight, neonatal intensive care unit (NICU) stay, gestational diabetes, preeclampsia, eclampsia, and length of maternal stay. RESULT(S): The IBM Marketscan Research database covers reimbursed health care claims data on inpatient and outpatient encounters who are privately insured through employment-sponsored health insurance. We assessed 785,809 singleton live births, with 6.6% born preterm. The presence of paternal comorbidities was associated with higher odds of preterm birth, low birth weight (LBW), and NICU stay. After adjusting for maternal factors, fathers with most or all components of the metabolic syndrome had 19% higher odds of having a child born preterm (95% CI 1.11-1.28), 23% higher odds of LBW (95% CI 1.01-1.51), and 28% higher odds of NICU stay (95% CI 1.08-1.52). Maternal morbidity (e.g., gestational diabetes or preeclampsia) was also positively associated with preconception paternal health. CONCLUSION(S): Increased preconception paternal comorbidity may be associated with negative infant and maternal outcomes. Although the paternal effect remains modest, these findings highlight the importance of the health of both parents, particularly the mother, on healthy pregnancy.
Nose-Ogura S et al., 2020·Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine
To determine whether secondary amenorrhea during teenage years influences bone mineral density (BMD) in female athletes in their 20s. Original research. Japan Institute of Sports Sciences. Two hundred ten elite female athletes older than 20 years were included in the study. Information on the participants' past (ie, during their teenage years) and current menstrual cycle, training time, history of stress fractures, and blood tests for hormones received was obtained. Bone mineral density of the lumbar spine was evaluated by dual-energy x-ray absorptiometry; low BMD was defined as a Z-score ≤-1. We investigated the correlation factors for low BMD in athletes in their 20s by univariable and multivariable logistic regression analysis. A total of 39 (18.6%) female athletes had low BMD. Secondary amenorrhea in their teens [odds ratio (OR), 7.11, 95% confidence interval (CI), 2.38-21.24; P < 0.001] and present body mass index (BMI) (OR, 0.56, 95% CI, 0.42-0.73; P < 0.001) were independent correlation factors for low BMD in the multivariable logistic regression analysis. The average Z-score for those with secondary amenorrhea in their teens and 20s, secondary amenorrhea in their 20s only, and regular menstruation was -1.56 ± 1.00, -0.45 ± 1.21, and 0.82 ± 1.11 g/cm, respectively. Secondary amenorrhea for at least 1 year during teenage years in female athletes and BMI at present was strongly associated with low BMD in their 20s.
For several years, research from around the world has suggested that the neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (allopregnanolone) may have therapeutic potential for treatment of various stress-related diseases including post-traumatic stress disorder (PTSD), depression, alcohol use disorders (AUDs), as well as neurological and psychiatric conditions that are worsened in the presence of stress, such as multiple sclerosis, schizophrenia, and seizure disorders. In this review, we make the argument that the pleiotropic actions of allopregnanolone account for its ability to promote recovery in such a wide variety of illnesses. Likewise, the allopregnanolone precursors, pregnenolone and progesterone, share many actions of allopregnanolone. Of course, pregnenolone and progesterone lack direct effects on GABAA receptors, but these compounds are converted to allopregnanolone in vivo. This review presents a theoretical framework for understanding how endogenous neurosteroids that regulate 1) γ-aminobutyric acid (GABA)A receptors, 2) corticotropin releasing factor (CRF) and 3) pro-inflammatory signaling in the innate immune system and brain could play a key role in both the prevention and treatment of stress-related disease. We further discuss cautions and limitations of allopregnanolone or precursor therapy as well as the need for more clinical studies.
Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor (GABAA-R), in PMDD's pathophysiology. We review evidence of impaired interaction between ALLO and GABAA-Rs in terms of affective symptom expression, with evidence from rodent and human studies. We discuss evidence of increased luteal phase stress sensitivity as a result of poor ALLO-GABA control of the HPA axis. Finally, we describe how treatments such as selective serotonin reuptake inhibitors (SSRIs) and new drugs targeting GABAA-Rs provide evidence for impaired ALLO-GABA function in PMDD. In sum, the literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABAA-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.
Hapgood JP, 2020·AIDS research and human retroviruses
Intramuscular depo-medroxyprogesterone acetate (DMPA-IM) is the most widely used hormonal contraceptive in sub-Saharan Africa. Previous meta-analyses of observational studies found a significant 40%-50% increased risk associated with DMPA-IM use, relative to no contraception or infrequent condom use. This raised substantial concerns, although these studies had important limitations. Consequently, the open-label randomized Evidence for Contraceptive Options and HIV Outcomes trial was conducted, designed primarily to detect a 50% or greater difference in HIV risk between DMPA-IM, the levonorgestrel (LNG) implant, and the copper-intrauterine device. The ECHO study, published in July 2019, concluded that there is no substantial difference in HIV risk among the methods evaluated, and that all three methods are safe and highly effective. In response, the WHO relaxed the Medical Eligibility Criteria for DMPA-IM use among women at high HIV risk in August 2019. However, two of the three comparisons in the ECHO trial could rule out neither a 50% increase nor no change in HIV risk for one contraceptive compared with another. The study had limitations and the results contained considerable uncertainty. They also did not inform on associated HIV risk for any one of the individual methods due to the absence of a control group such as no contraception or only infrequent condom use. The HIV risks associated with LNG implant and copper-IUD relative to no contraception or infrequent condom use are unknown and these cannot be seen as controls, nor did the authors claim them to be. The results will be discussed in the context of their limitations, what they add to the body of work to date on contraception and HIV acquisition, and the implications of the findings and reports thereof for future research and contraceptive choice.
This study investigated the influence of hysterectomy on depression using a national sample cohort from South Korea. We extracted data entered into the Korean Health Insurance data based form 2002 through 2013 and classified patients into a group of women who had undergone a hysterectomy (n = 9,971) and a 1:4 matched control group (n = 39,884). A Cox proportional hazards model was used to analyze the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the risk of depression in the hysterectomy group and the control group. The HR was calculated as the risk of depression in the hysterectomy group compared to that in the control group. The incidence of depression in the hysterectomy group was 6.59 per 1,000 person-years and that in the control group was 5.70 per 1,000 person-years. The adjusted HR for depression was 1.15 in the hysterectomy group (95% CI = 1.03-1.29, P < 0.05). In a subgroup analysis, the adjusted HR for depression was 1.16 (95% CI; 1.03-1.31, P = 0.014) for patients who underwent hysterectomy without bilateral salpingo-oophorectomy. In an additional subgroup analysis, the adjusted HR for depression after hysterectomy was 1.18 (95% CI; 1.04-1.35, P = 0.012) in the younger than 50-year-old group. The incidence of depression was higher in women who underwent hysterectomy than in the matched control group.
Wilcox AJ et al., 2020·Human reproduction (Oxford, England)
What proportion of fertilized human ova are lost before implantation? An estimated 40 to 50% of fertilized ova fail to implant. Preimplantation loss is not detectable with current technology. Published estimates of preimplantation loss range from 10 to 70%. STUDY DESIGN, SIZE, We combine data from epidemiologic, demographic, laboratory and in vitro fertilization studies to construct an empirical framework for the estimation of preimplantation loss. This framework is summarized in a user-friendly Excel file included in supplement. PARTICIPANTS/MATERIALS, SETTING, We draw from multiple sources to generate plausible estimates of fecundability, sterility, transient anovulation, intercourse patterns and the proportion of ova fertilized in the presence of sperm. We combine these estimates to generate a summary estimate of preimplantation loss. This estimate can be considered an average for couples in their prime reproductive years. MAIN Under a plausible range of assumptions, we estimate that 40 to 50% of fertilized ova fail to implant. LIMITATIONS, A crucial factor in estimating preimplantation loss is the probability that an ovum will be fertilized when exposed to sperm. Human data are available only from in vitro fertilization (IVF), which may not accurately represent events in vivo. We therefore assume a range of in vivo fertilization rates, from 64% (human IVF data) to 90% (mouse data). Our estimate of preimplantation loss takes into account the biological processes relevant to fertilization and loss. Using this empirical basis for estimation, we find support for the usual assumption that risk of loss is highest in the earliest days following fertilization. Furthermore, this framework can provide improved estimates as better reproductive data become available. To the extent that our estimates are accurate, more fertilized ova are apparently lost in vitro than in vivo, suggesting that further improvements in IVF success rates may be possible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Professor Adashi serves as Co-Chair of the Safety Advisory Board of Ohana Biosciences, Inc. The other authors have no competing interests. N/A.
Waterfield G et al., 2020·Environmental health : a global access science source
Per- and polyfluoroalkyl substances (PFASs) have been detected in drinking water supplies around the world and are the subject of intense regulatory debate. While they have been associated with several illnesses, their effects on reproductive outcomes remains uncertain. We analyzed birth outcomes in the east Minneapolis-St. Paul metropolitan area from 2002 to 2011, where a portion of the population faced elevated exposure to PFASs due to long-term contamination of drinking water supplies from industrial waste disposal. Installation of a water filtration facility in the highly contaminated city of Oakdale, MN at the end of 2006 resulted in a sharp decrease in exposure to PFASs, creating a "natural experiment". Using a difference-in-differences approach, we compare the changes in birth outcomes before and after water filtration in Oakdale to the changes over the same period in neighboring communities where the treatment of municipal water remained constant. Average birth weight and average gestational age were statistically significantly lower in the highly exposed population than in the control area prior to filtration of municipal water supply. The highly exposed population faced increased odds of low birth weight (adjusted odds ratio 1.36, 95% CI 1.25-1.48) and pre-term birth (adjusted odds ratio 1.14, 95% CI 1.09-1.19) relative to the control before filtration, and these differences moderated after filtration. The general fertility rate was also significantly lower in the exposed population (incidence rate ratio 0.73, 95% CI 0.69-0.77) prior to filtration and appeared to be rebounding post-2006. Our findings provide evidence of a causal relationship between filtration of drinking water containing high levels of exposure to PFASs and improved reproductive outcomes.
Menstrual CycleHIV-AssociatedAmenorrhea EffectsReproductive Health
Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as ageand ethnicity-matched Z-scores) AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.
We examined the association between incorrect knowledge of ovulation and unintentional pregnancy and child among young women in sub-Saharan Africa countries. Using Pearson's Chi-square, t test, multiple logistic regression, and likelihood ratio test, we analyzed Demographic and Health Survey data (2008-2017) of 169,939 young women (15-24 year). The range of prevalence of incorrect knowledge of ovulation was 51% in Comoros and 89.6% in Sao Tome and Principe, while unintentional pregnancy ranged between 9.4% in the Republic of Benin and 59.6% in Namibia. The multivariate result indicates a strong association between incorrect knowledge of ovulation and unintentional pregnancy (OR = 1.17; p < 0.05) and unintentional child (OR = 1.15; p < 0.05). Adolescent women (15-19) generally have poor knowledge of ovulation and are more likely to report an unintentional pregnancy/child than women between ages 20-24. To reduce the burden of unintentional child/pregnancy in Africa, fertility knowledge should not only be improved on but must consider the sociocultural context of women in different countries that might affect the adoption of such intervention programs. Pragmatic efforts, such as building community support for young women to discuss and share their experiences with professionals and educate them on fertility and sexuality, are essential.
Body LiteracyFertility App EvaluationMobile Health ApplicationsmHealth Evidence
There has been a phenomenal worldwide increase in the development and use of mobile health applications (mHealth apps) that monitor menstruation and fertility. Critics argue that many of the apps are inaccurate and lack evidence from either clinical trials or user experience. The aim of this scoping review is to provide an overview of the research literature on mHealth apps that track menstruation and fertility. This project followed the PRISMA Extension for Scoping Reviews. The ACM, CINAHL, Google Scholar, PubMed and Scopus databases were searched for material published between 1 January 2010 and 30 April 2019. Data summary and synthesis were used to chart and analyse the data. In total 654 records were reviewed. Subsequently, 135 duplicate records and 501 records that did not meet the inclusion criteria were removed. Eighteen records from 13 countries form the basis of this review. The papers reviewed cover a variety of disciplinary and methodological frameworks. Three fertility and reproductive health tracking, pregnancy planning, and pregnancy prevention. Motivations for fertility app use are varied, overlap and change over time, although women want apps that are accurate and evidence-based regardless of whether they are tracking their fertility, planning a pregnancy or using the app as a form of contraception. There is a lack of critical debate and engagement in the development, evaluation, usage and regulation of fertility and menstruation apps. The paucity of evidence-based research and absence of fertility, health professionals and users in studies is raised.
Başar Gökcen B et al., 2020·Gynecological Endocrinology
Data on eating disorders in women with PCOS is insufficient. The objective of this case study was to examine the hypothesis that women with PCOS exhibit more impaired eating than healthy women. Women diagnosed with PCOS under the 2003 Rotterdam Diagnostic Criteria (n = 40) were compared with a healthy control group (n = 40). The groups also were divided into two as normal body weight and overweight/obese. The Eating Disorders Assessment Questionnaire (EDE-Q) and the Three Factor Eating Questionnaire (TFEQ-R21), were completed by all participants in order to evaluate eating behaviors in addition to eating disorders. Among the overweight/obese group, the average total and subscale scores of the EDE-Q as well as the total and sub-factor scores of the TFEQ-R21 were higher in women with PCOS compared to controls (p < .05). However, this statistically significant result was not shown among the women with normal weight (p > .05). In comparison to the controls, the PCOS women displayed higher values of the tool scores indicating abnormal restraint eating, body shape concern and weight concern subscale scores (p < .05). This result suggests that the evaluation of eating disorders should be added to routine screening and the monitoring of women with PCOS.
Cito G et al., 2020·The world journal of men's health
To date, the key role of vitamin D in male reproductive system has been suggested, since the expression of vitamin D receptors and metabolizing enzymes was demonstrated in the testis and spermatozoa. Nevertheless, a general consensus about the role of vitamin D in male fertility is still debated. The aim of this review is to provide an updated systematic revision of the current available literature, discussing the experimental and clinical evidence on the role of vitamin D in the regulation of testis hormone production, seminal parameters and male fertility. The consequences of vitamin D deficiency on serum levels of testicular hormones have been analysed by several observational and interventional studies, with controversial results. Equally, the experimental researches not were able to state a certain relationship between vitamin D status and testis hormone production. Possible bias, including age, body mass index, and baseline vitamin D status justified the differences among studies. As well as concerning the effect of vitamin D on semen parameters, most of the studies agreed in the possibility that vitamin D might have a positive effect on human male fertility potential, particularly through better sperm motility. Regarding pregnancy outcomes, normal level of vitamin D seems to be related to better pregnancies. However, all the previous studies displayed a wide heterogeneity in study design, population, methodology, and cut off values used for the evaluation of vitamin D status. Future studies are needed to better clarify the exact role of vitamin D on hormonal and seminal panel in both fertile and infertile men.
To understand how Title X providers currently engage with fertility awareness-based methods (FABMs) for pregnancy prevention in Title X clinics across the United States. We developed a survey to assess knowledge of fertility for purposes of pregnancy prevention, attitudes toward FABMs use for pregnancy prevention, and practices when patients request FABMs for pregnancy prevention. In total, 329 participants who met all inclusion criteria completed the survey. Respondents were generally highly knowledgeable on fertility, felt neutrally toward FABMs or thought they were a nonviable option for most women, and were likely to respond to patient requests for FABMs for pregnancy prevention by providing information. Qualitative responses included several barriers to provision of FABMs for pregnancy prevention and few successes to provision. Fertility knowledge and discussion of specific methods increased with the number of methods included in the clinic's written materials or with the number of different FABMs someone at that clinic had been trained on. Significant clinician or administrative barriers may exist to offering FABMs to patients. Incorporating up-to-date information on a range of FABMs-rather than treating them as one method-into contraceptive counseling represents an opportunity to increase the contraceptive offering for clients who want them, leading to increased patient satisfaction and successful family planning outcomes.
Gnoth C et al., 2020·Archives of gynecology and obstetrics
Many physicians and other healthcare professionals are often asked questions on interfering factors for conception by couples with a desire for children. Such possible disturbances include, for example, the very common minor diseases, stress and also sexual intercourse during the suspected implantation period. Non-scientifically based statements about disturbances in conception cycles, as found in many layman publications and on the internet, can strongly unsettle couples with a desire for children and force them into corset of rules of conduct. Therefore, a systematic scientific evaluation of the impact of disturbances on conception is urgently needed. A search for possible disturbances in natural conception cycles together with up to three of the respective pre-cycles in a large cycle database from users of the symptothermal method of natural family planning in Germany was performed. Disturbances were qualified by scientific panel decision and analysed statistically with their effects on the chances of spontaneous conception. Mixed logistical regression models and survival time analyses were used. A total of 237 women with a total of 747 cycles could be included in the analysis. In 61% of all 237 conception cycles, disturbances occurred. The statistical analysis shows that disturbances in natural conception cycles unexpectedly increase the likelihood of pregnancy by an overall factor of 1.32 (95% CI 1.04-1.70). Sexual intercourse in the window of implantation does not decrease the chances of conception. Relaxation states at the time of ovulation and/or during the implantation period have no representable effect and do not increase the chance of pregnancy. Couples trying to conceive should at least be informed that disturbances in conception cycles, such as minor diseases, stress or sexual intercourse during the implantation period do not interfere with conception. Relaxation has no effect in favour of success. This takes away the guilty feeling of couples, fearing that they possibly did something wrong in cycles without the desired pregnancy.
Tang Z et al., 2020·Journal of Hazardous Materials
Phthalates could be introduced into clothing as chemical additives or impurities, becoming a potential source of human exposure. We measured the concentrations of 15 phthalates in new preschool children's clothing manufactured in seven Asian countries. Phthalates were prevalent in all samples, and total concentrations were 2.92-223 μg/g, indicating a moderate contamination level. Bis(2-ethylhexyl) phthalate, di(isobutyl) phthalate and di-n-butyl phthalate were the most abundant phthalates measured, representing a median of 48.5 %, 13.6 % and 13.4 % of the total concentrations, respectively. Total concentrations did not differ significantly by country of manufacture, while the concentrations of individual phthalates and their composition profiles varied widely. We also found differing phthalate levels by item type, fabric composition, and color. Under the assumed two exposure scenarios, the median of summed dermal exposure doses of six phthalate were 539 and 950 ng/kg of body weight per day, respectively. When children wore trousers, long-sleeved shirts, briefs and socks at the same time, the reproductive risks exceeded acceptable level, although the carcinogenic risk of DEHP was low. Our results suggested that new clothing is an important route of phthalate exposure to preschool children. More research is required to investigate the contaminations and associated with risks in child clothing.
Liew Z et al., 2020·Environmental health perspectives
Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. //doi.org/10.1289/EHP6202.
Premenstrual syndrome (PMS) affects millions of women. While over-the-counter products have helped with the physical symptoms of PMS, emotional symptoms have been less well supported. The objective of this trial was to measure the effect of an oxaloacetate/vitamin C combination on the major emotional symptoms of PMS, including depression, anxiety, perceived stress, aggression, and suicidal ideation. Forty-eight women experiencing PMS completed a baseline survey comprising the Beck's Depression Inventory, Cohen Perceived Stress Scale, Generalized Anxiety Disorder Test, and Buss-Perry Aggression Questionnaire. After baseline measurements, participants were randomly assigned to take either 2 capsules of 100 mg oxaloacetate/150 mg ascorbic acid, or 2 capsules of rice flour (placebo) for their entire menstrual cycle. At menstruation, the women completed the 4 surveys again. The women then switched capsules in a cross-over design and continued the study for an additional menstrual cycle. The final assessment was repeated at menstruation. Statistical analysis of the 4 surveys was performed to examine efficacy. Oxaloacetate/vitamin C supplementation during PMS significantly improved depression, perceived stress, anxiety, aggression, and suicidal ideation. The mean improvement in depression was 54.1%, 35.8% for perceived stress, 51.43% for generalized anxiety, and 17.8% for aggression. Suicidal ideation was reduced by 47.9%. All results were highly significant. A combination of oxaloacetate and vitamin C supplementation helped to alleviate depression, anxiety, perceived stress, aggression, and suicidal ideation symptoms associated with PMS. ClinicalTrials.gov NCT03509714.
No Authors Listed, 2020·LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]
Naltrexone is a synthetic opioid antagonist used in prevention of relapse of opiate addiction and alcoholism. Naltrexone has been associated with low rates of serum enzyme elevations during therapy and with rare instances of clinically apparent liver injury.
Fertility AwarenessSigns and SymptomsPregnancy PreventionFertility Signs
Simmons RG et al., 2020·Best Pract Res Clin Obstet Gynaecol
Fertility awareness-based methods (FABMs) of family planning involve monitoring various signs and symptoms of fertility during the menstrual cycle to identify the "fertile window," or the days of the cycle when unprotected intercourse is most likely to result in pregnancy. Signs and symptoms include menstrual cycle length, basal body temperature, urinary hormone measurements, and/or cervical fluid and may be used alone or in combination. Fertility signs reflect both physiological changes during the menstrual cycle and the life cycle of the ovum and sperm. Women learn to observe or measure and interpret these signs according to the instructions of their chosen FABM and avoid unprotected intercourse on fertile days. FABMs are appropriate for those who choose to use them, are able and willing to observe one or more fertility signs, and are in relationships that support the use of a coitus-related method such as a condom or abstaining from intercourse on fertile days.
While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.
To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss.
Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses.
Four U.S. clinical centers, 2007-2011. PATIENT(S): Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens. MAIN OUTCOME MEASURE(S): Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss. RESULT(S): Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio = 2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss. CONCLUSION(S): Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms. Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight. : Estimar la asociación entre la actividad física y el riesgo de pèrdida gestacional subclínica y clínica entre mujeres con historia de pèrdida gestacional. DISEÑO:: Estudio prospectivo de cohortes como análisis secundario de un estudio aleatorizado de los efectos de aspirina en la gestación y la reproducción, utilizando bajas dosis de aspirina desde la preconcepción entre mujeres con una o dos pèrdidas gestacionales previas. : Cuatro clínicas en Estados Unidos, entre 2007–2011. : Mujeres con embarazo confirmado (n= 785) determinado por pruebas de hCG en muestras biológicas recogidas longitudinalmente. PRINCIPALES MEDIDAS DE RESULTADO(S):: Pérdida gestacional subclínica detectada sólo por la prueba de hCG y la reconocida clínicamente. : Entre 785 mujeres (media de edad [Deviación standard], 28,7 [4,6] años) con una gestación confirmada con hCG, 188 (23.9%) que tuvieron pérdida gestacional. En un modelo multivariante ajustado para factores de confusión comparado con el primer tercil de actividad física (media= 7,7 equivalentes metabólicos de trabajo horas/semana) hubo un riesgo bruto dos veces mayor de pérdida subclínica en el segundo (relación de riesgo= 2,06; Intervalo de confianza 95%, 1,03–4,14) y el tercer tercil (Relación de riesgo = 1,92 Intervalo de confianza 95%, 0,94–3,9) con una media metabólica equivalente de trabajo horas/semana de 27,8 y 95,7 respectivamente. No hubo relación entre actividad física y pérdidas gestacionales clínicas. : El riesgo asociado a actividad física es diferente para fallo gestacional próximo al momento de la implantación comparado con el más tardío de pérdida gestacional clínica. Niveles mayores de actividad física estuvieron asociados con un riesgo elevado de pérdida subclínica (por ejemplo, embarazos detectados solo por hCG, n=55); sin embargo, no se observó relación con pérdida clínicamente reconocida. Se necesitan más trabajos para confirmar estos hallazgos, evaluando de forma general mujeres sin pérdidas gestacionales previas, y evaluar sus mecanismos. APROBACIÓN ÉTICA:: El comité de revisión institucional de cada centro participante aprobó el estudio y los participantes dieron por escrito su consentimiento informado. El ensayo fue registrado en ClinicalTrial.gov (NCT00467363), y el comité de seguridad y monitorización de los datos dio su aprobación
Najmabadi S et al., 2020·Paediatr Perinat Epidemiol
There is variability between women for days of menstrual bleeding, cycle lengths, follicular phase lengths, and luteal phase lengths, related to age and parity. To describe total cycle length; anovulatory cycles; follicular and luteal phase lengths; and days and intensity of menstrual and non-menstrual bleeding in women without known subfertility over the course of 1 year. 581 women (3,324 cycles) with no known subfertility (18-40 years of age) were followed for up to 1 year. Women recorded vaginal bleeding and mucus discharge daily. We used the peak day of cervical mucus as the estimated day of ovulation and the last day of the follicular phase. We used generalised linear mixed models stratified by age and parity to describe menstrual cycle parameters. The majority of women were <30 years of age (74.5%), non-Hispanic White (88.6%), and nulliparous (70.4%). The mean menses length was 6.2 (1.5) days, median 6; cycle length 30.3 (6.7) days, median 29; follicular phase length 18.5 (6.5) days, median 17; and luteal phase length 11.7 (2.8) days, median 12. Nulliparous women aged ≥30 years vs nulliparous women aged <30 had shorter cycles (29.2 days, 95% confidence interval (CI) 27.8, 30.7 vs 31.5 days, 95% CI 30.8, 32.2) and shorter follicular phases (17.6 days, 95% CI 16.2, 18.9 vs 19.6 days, 95% CI 18.9, 20.2). Among all women, within-woman differences between the longest and shortest menses length >3 days, total cycle length >7 days, follicular phase >7 days, and luteal phase >3 days were found in 11.6%, 43.0%, 41.7%, and 58.8% of women, respectively. Our findings confirm variability between women of menstrual cycle parameters related to age and parity, and also highlight within-woman variability in the follicular and luteal phases.
Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded. To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge). This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCare(TM) System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated. Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively. Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation.
Endometriosis is a chronic disease with no known cure. Persons affected by this disease often use complementary therapies such as dietary changes to reduce their symptoms, and so it is important to investigate whether and how these therapies affect endometriosis symptoms. The aim of this study was to explore how persons with endometriosis experienced their health after dietary changes. Semi-structured qualitative interviews were conducted with 12 persons with endometriosis who had made individual dietary changes aimed at decreasing their endometriosis symptoms. The interviews were recorded and transcribed verbatim, and analysed using thematic analysis. Region Västra Götaland and the estern part of Central Sweden, Sweden. Twelve persons with endometriosis aged 28 to 44 were recruited from two Swedish endometriosis support forums on the Internet. Participants experienced an increase in well-being and a decrease in symptoms following their dietary and lifestyle changes. They also felt that the dietary changes led to increased energy levels and a deeper understanding of how they could affect their health by listening to their body's reactions. The participants understood that they could influence their symptoms through lifestyle changes. Support from family and friends was important in implementing and sustaining the dietary changes. However, the participants stressed the lack of support from healthcare professionals. This study contributes to filling the knowledge gap about dietary strategies in endometriosis and lifestyle change as a method of alleviating suffering and increasing well-being. An important finding is that the participants experienced decreased symptoms and increased well-being after adopting an individually-adapted diet. Healthcare professionals should take their patients' knowledge and experience into consideration, and allow patients to participate in their own care. Further research is necessary to give evidenced-based dietary advices in endometriosis.
To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons.
Nationwide prospective study.
Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.
Asthana S et al., 2020·Eur J Obstet Gynecol Reprod Biol
Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear. To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review. Literature search conducted in databases from January 1990 till August 2019 using various search terms. Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language. PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer. Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively. OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.
Bone HealthPredictive ModelsFracture Risk FactorsStructural Equation Modeling
It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk.
Barcikowska Z et al., 2020·International journal of environmental research and public health
Dysmenorrhea often significantly reduces the quality of women's life and is still an important public health problem. Despite numerous studies, the pathomechanism of dysmenorrhea is not fully understood. Previous research indicates the complexity of biochemical reactions between the endocrine, vascular, and immune systems. Prostaglandins play a major role in the pathomechanism of dysmenorrhea. In contrast, cytokines and other proinflammatory factors in primary dysmenorrhea are less studied. In addition to the applied pharmacotherapy, more and more studies proving the effectiveness of non-pharmacological methods appear. Therefore, the present work contains a review of the latest research concerning factors involved in dysmenorrhea, as well as therapeutic options. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual gynecology, physiotherapy journals and books.
Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.
Bordewijk EM et al., 2020·The Cochrane database of systematic reviews
Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive-aged women. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is off-label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC-resistant can be treated with gonadotrophins or other medical ovulation-induction agents. These medications are not always successful, can be time-consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC-resistance. We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies. We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second-look laparoscopy versus expectant management, or different techniques of LOD. Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes. This updated review includes 38 trials (3326 women). The evidence was very low- to moderate-quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding. Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I2 = 0%; low-quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I2 = 0%, low-quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I2 = 2%; moderate-quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%. Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis. There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I2 = 19%; low-quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I2 = 0%; low-quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I2 = 0%; low-quality evidence). Unilateral LOD versus bilateral LOD Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low-quality evidence). There were no data available on multiple pregnancy. The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I2 = 60%, very low-quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I2 = 0%; very low-quality evidence). Other comparisons Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose. AUTHORS' Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.
Bone HealthImminent Risk PredictionRisk Factor ModelingStructural Equation Modeling
We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health.
This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.
The National Institute on Aging-Alzheimer's Association (NIA-AA) has proposed a biological definition of Alzheimer's disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages. We selected individuals with AD pathology (A+T+) and healthy controls (HC, A-T-) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups. The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the d-AD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected. We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.
Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.
Nowadays, most of the swimsuits are mainly made of artificial fibres, which have interesting properties such as water repellence and fast drying. Swimsuits contain a wide range of additives, which can mean a hazard for the environment and/or human health. In this study, the concentrations of formaldehyde (free and water soluble), 24 aromatic amines, and 28 trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were analysed in 39 swimsuits covering a wide range of materials, colours and brands. Dermal exposure and health risks were assessed for adults (men and women) aged > 18 years old, babies between 2 and < 3 years old, children (boys and girls) between 3 and < 6 years old and 6 and < 11 years old, and teenagers (boys and girls) between 11 and < 16 years old, wearing swimsuits for 4 h or 8 h. Formaldehyde and aromatic amines were below their respective detection limits in all samples (<16 and < 1.5 mg/kg, respectively). Regarding trace elements, Ti showed the highest mean levels (1844 mg/kg), being significantly higher in polyamide (3759 mg/kg) than in polyester (24.1 mg/kg) swimsuits. These high Ti levels were confirmed by environmental scanning electron microscope in a single sample made of polyamide. Increased concentrations of Cr were also observed, but only in polyamide black fabrics, with values ranging from 624 to 932 mg/kg. Non-cancer risks (hazard quotients) derived from the exposure to trace elements were in a safe zone for all analysed trace elements. Furthermore, the carcinogenic risks were evaluated for As, Cr and Pb, exhibiting values below the 10-5 threshold, with the exception of Cr in babies and children-girls. For Ti, health risks could not be calculated due to the lack of information on toxicological data. However, because Ti was the element with the highest concentrations in swimsuits, and taking into account the potential toxicity of TiO2 nanoparticles, further research is needed to assess the migration of this element from fibres to skin.
Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report. To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. DESIGN, SETTING, This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018. Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.
Contraception/ComparisonGeneral OB/GYN
Open Access
To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users. We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching. Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5-4.0] cases/1,000 person-years and 5.2 [95% CI 3.7-7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16-0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time. Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.
Cyclophosphamide (CYP) is one of the alkylating chemotherapeutic agents and its adverse effects on folliculogenesis in the ovary are well-known due to the previous scientific research on this topic. Magnesium has various effects in organisms, including catalytic functions on the activation and inhibition of many enzymes, and regulatory functions on cell proliferation, cell cycle, and differentiation. In this study, the effects of magnesium sulfate (MgSO4) on CYP induced ovarian damage were investigated. Immature Wistar-Albino female rats of 28-days were treated with pregnant mare serum gonadotrophin (PMSG) to develop the first generation of preovulatory follicles. Rats of the experimental groups were then treated with either CYP (100 mg/kg, i.p) and MgSO4 (270 mg/kg loading dose; 27 mg/kg maintenance doseX12, i.p) solely or in combination. Following in-vivo 5-bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. In the ovaries, added to the evaluation of general morphology and follicle count; BrdU and TUNEL-labeling, cleaved caspase-3 and p27 (cyclin-dependent kinase inhibitor) staining was also performed immunohistochemically and an ultrastructural evaluation was performed by transmission electron microscopy (TEM). The number of primordial follicles were decreased and multilaminar primary and atretic follicles were increased in CYP group. After MgSO4 treatment, while primordial follicle pool were elevated, the number of atretic follicles were decreased. Additionally, decreased BrdU-labeling, increased cleaved caspase 3 immunoreactivity and increased TUNEL labeling were observed in CYP group. In CYP treated animals, observations showed that while MgSO4 administration caused no alterations in BrdU proliferation index and caspase-3 immunoreactivity, it significantly reduced the TUNEL labeling. It was also observed that, while p27 immunoreactivity significantly increased in the nuclei of granulosa and theca cells in the CYP group; MgSO4 treatment significantly reduced these immunoreactivities. The ultrastructural observations showed frequent apoptotic profiles in granulosa and theca cells in both early and advanced stages of follicles in the CYP group and the MgSO4 treatment before the CYP application led to ultrastructural alleviation of the apoptotic process. In conclusion, our data suggest that MgSO4 may provide an option of pharmacologic treatment for fertility preservation owing to the beneficial effects of on chemotherapy-induced accelerated follicular apoptotic process, and the protection of the primordial follicle pool.
Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.
Contraception/ComparisonBreast Cancer RiskLong-Term Side EffectsMeta-Analysis
Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I(2) = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I(2) = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I(2) = 0%, P = .84). Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.
Delayed childbearing is currently a major challenge in reproductive medicine as increased age has an important impact on successful conception, both in natural and in assisted reproduction. There is a lack of knowledge about the impact of age on fertility, even in highly educated populations. A number of initiatives have been taken to increase fertility awareness. Health care providers have been encouraged to talk with patients about their reproductive life plan (RLP) for almost a decade based on recommendations from the Centres for Disease Control and Prevention. This concept has been explored successfully in Swedish contraception counselling. A growing number of online interventions aim to raise fertility awareness. These websites or interactive tools provide relevant information for individuals and couples as they consider whether they want children, when they should have them, and how many they may wish to have. These interventions are important, because research depicts that knowledge helps people in their decision-making process. With new fertility preservations such as egg freezing now available, additional education is needed to be sure that women and couples are well informed about the cost and low success rates of this intervention.
Contraception/ComparisonSide EffectsMental Health EffectsContraception Impact
Open Access
SoleimanvandiAzar N et al., 2019·Nursing Practice Today
Health service utilization (HSU) is a significant health and political issue. Awareness of factors that affect HSU and the status of health service utilization can help health professionals improve their services. The aim of this study was to investigate the status of HSU and identify the factors affecting health service utilization among households residing in Tehran. The present cross-sectional study included 1200 residing households from different regions of Tehran, the capital of Iran. They were selected by a multi-stage cluster sampling method in accordance with the zoning of Tehran concerning socio-economic development. Interviews were conducted by trained individuals using a health service utilization questionnaire introduced by the World Health Organization, Zimet's social support questionnaire, and demographic checklist during winter 2018 and spring 2019. Simple and multiple logistic regression models were applied to analyze the data. In order to include the factors related to the status of outpatient health service utilization, a set of bivariate analyses was conducted, and then the factors with a p-value of ≤0.20 were included in the multiple models. Data were analyzed using Stata 12 software. The results of the study indicated that the rate of outpatient HSU among households residing in Tehran was 63.61% (CI:60, 66.80). In addition, regarding the results of the study, asset index of family (OR=0.51, 95% CI: 0.28, 0.91), the level of awareness and knowledge of family members regarding health issues (OR=0.55, 95% CI: 0.34, 0.88) as well as the mother knowledge on health issues (OR=0.64, 95% CI: 0.45, 0.93), the level of social support (OR = 0.50, 95% CI: 0.37,0.68), family health expenditure (OR=1.20, 95% CI: 1.18, 4.06), having a member with a sort of disability in family (OR=1.66, 95% CI: 1.01, 2.77), and having an alcoholic member in family (OR=2.44, 95% CI: 1.27, 4.68) were factors associated with outpatient HSU among households. Considering the adjusted values of odds ratios, the prevalence of the HSU varied according to the area of residence. It should be noted that the variables included in the model explained 15% of the changes in the prevalence of HSU. According to the results of the study and in order to increase HSU in different classes, the level of social support, especially among women in the family due to their role in the general health of family members, should be enhanced. Also, policies should be adopted to increase the awareness, knowledge, and information of family members about health issues, lifestyle changes, nutrition, and health behaviors through social media.
Fertility AwarenessReproductive MicrobiomeSexual SelectionEvolutionary Biology
Open Access
All multicellular organisms host microbial communities in and on their bodies, and these microbiomes can have major influences on host biology. Most research has focussed on the oral, skin, and gut microbiomes, whereas relatively little is known about the reproductive microbiome. Here, we review empirical evidence to show that reproductive microbiomes can have significant effects on the reproductive function and performance of males and females. We then discuss the likely repercussions of these effects for evolutionary processes related to sexual selection and sexual conflict, as well as mating systems and reproductive isolation. We argue that knowledge of the reproductive microbiome is fundamental to our understanding of the evolutionary ecology of reproductive strategies and sexual dynamics of host organisms.