Assisted Reproductive Technology in the Presence of Polycystic Ovary Syndrome: Current Evidence and Knowledge Gaps.

OBJECTIVE: In this narrative review, we discuss the current evidence as well as the knowledge gaps concerning assisted reproductive technology (ART) indications, protocols, and results in the presence of polycystic ovary syndrome (PCOS). METHODS: An electronic literature search was performed for English-language publications in the last decade in databases such as PubMed, Medline, the Web of Sciences, Embase, and Scopus. RESULTS: We found evidence that ovarian steroidogenesis and folliculogenesis are deeply altered by PCOS; however, the oocyte quality and pregnancy rates after ART are not affected. Patients with PCOS are more sensitive to the action of exogenous gonadotropins and more likely to develop ovarian hyperstimulation syndrome. This risk can be mitigated by the adoption of the gonadotropin-releasing hormone antagonist protocols for pituitary blockade and ovarian stimulation, along with frozen embryo transfer, without compromising the odds of achieving a live birth. Pregnancy complications, such as miscarriage, gestational diabetes, preeclampsia, and very preterm birth, are more frequent in the presence of PCOS, requiring more intense prenatal care. It remains uncertain whether weight reduction or insulin sensitizers used before ART are beneficial for the treatment outcomes. CONCLUSION: Although PCOS is not a drawback for ART treatments, the patients need special care to avoid complications. More in-depth studies are needed to uncover the mechanisms of follicular growth, gamete maturation, and endometrial differentiation during ART procedures in the presence of PCOS.

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review.

OBJECTIVE: The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included. RESULTS: From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration. CONCLUSIONS: The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42022323757.

Associations of perceived stress and salivary cortisol with the snack and fast-food dietary pattern in women shift workers.

This study aimed to investigate the association of perceived stress and salivary cortisol levels with the snack and fast-food dietary pattern in a sample of women shift workers. We conducted a cross-sectional study of 539 women aged 18-53 years working in the production line of a poultry processing plant. Stress was assessed with the 10-item Perceived Stress Scale (PSS-10) and by salivary cortisol levels (immediately after waking and upon returning home from work). Dietary patterns were identified by principal component analysis. We used linear and Poisson regression models to assess multivariable-adjusted associations of perceived stress and salivary cortisol levels with the snack and fast-food dietary pattern. After adjustments, women with higher PSS-10 scores had a 28% higher probability (95% confidence interval, 1.04-1.56) of consuming snacks/fast food. Mean (SD) waking cortisol levels were inversely associated with quartiles of the dietary pattern: Q1, 6.63 (0.43) nmol/L; Q2, 6.00 (0.38) nmol/L; Q3, 5.62 (0.40) nmol/L; and Q4, 5.29 (0.35) nmol/L (p = 0.019). Perceived stress was not associated with salivary cortisol levels. The work shift was not associated with perceived stress or cortisol levels. This study demonstrated an association of psychological and physiological measures of stress with a dietary pattern characterized by high intakes of hyper-palatable, energy-dense, ready-to-eat foods among women shift workers.

Risk factors associated with coronary artery calcification in midlife women: a population-based study.

The aim of this study was to investigate the association between individual risk factors and coronary artery calcification (CAC), as a marker of subclinical cardiovascular disease, in a population-based nested cross-sectional study of midlife women. Anthropometric and metabolic data from 295 women from the South of Brazil were analyzed. Habitual physical activity was assessed by pedometer. CAC was assessed by a multi-detector computed tomography system. Average Agatston score was used to stratify participants as CAC > 0 and CAC = 0. Women with CAC > 0 (34.7%) were older (58.7 ± 5.4 vs. 56.3 ± 5.2 years, p < .001) and had higher prevalence of central adiposity (71 vs. 59%, p = .04) and hypertension (71 vs. 52%, p = .002) than women in the CAC = 0 group. Hormone therapy (HT) was more prevalent in the group with CAC = 0 (19.7 vs. 9.8%, p = .029). The prevalence ratios for CAC > 0 were 0.545 (95%CI:0.309-0.962, p = .036) for HT and 1.752 (95%CI:1.207-2.541, p = .003) for hypertension, after adjustment for age, educational level, smoking, alcohol intake, and physical activity. The present data in a population-based sample of midlife women indicate that hypertension and age were positively associated with higher risk for CAC > 0 and HT was related with CAC = 0.

Impact of cross-sex hormone therapy on bone mineral density and body composition in transwomen.

OBJECTIVE: Cross-sex hormone therapy (CSHT) has been associated with changes in bone and lean/fat mass. This study assessed bone mineral density (BMD), appendicular lean mass (ALM), and total fat mass in transwomen undergoing CSHT. PATIENTS AND DESIGN: We evaluated 142 transwomen (mean age: 33.7 ± 10.3 years; BMI: 25.4 ± 4.6; 86.6% with previous CSHT) during the first 3 months of regular oestrogen treatment (with or without anti-androgens). A reference group including 22 men and 17 cis women was also studied. MEASUREMENTS: Clinical and hormonal evaluation and dual-energy X-ray absorptiometry (DXA). RESULTS: Bone mineral density was similar in trans and reference women, and lower at all sites in transwomen vs men. Low bone mass for age was observed in 18% of transwomen at baseline vs none of the reference women or men. Appendicular lean mass and total fat mass were positively correlated with L1-L4 BMD, explaining 14.9% of the observed variation in lumbar spine BMD and 20.6% of the variation in total femur BMD. Appendicular lean mass was similar in trans and reference women, and lower in transwomen vs men. Total fat mass was lower in trans vs reference women. Densitometry was repeated after a mean of 31.3 ± 6.5 months in 46 transwomen. There was a significant increase in total fat mass and a significant decrease in ALM. Bone mineral density remained stable over time. CONCLUSIONS: The fairly high prevalence of low bone mass in this sample of transwomen from southern Brazil seems to be related to lower ALM. Non-pharmacological lifestyle-related strategies for preventing bone loss could be beneficial for transgender women receiving long-term CSHT.

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder determined by polygenic traits as well as environmental factors. Lower vitamin D levels have been detected in PCOS women and related to hormone and metabolic disturbances. Vitamin D acts in tissues through the vitamin D receptor (VDR). VDR gene variants have been associated with worse metabolic profile in the general population. We investigated the genotype and haplotype distribution of the Bsm-I (rs1544410), Apa-I (rs7975232), and Taq-I (rs731236) VDR gene polymorphisms in PCOS and non-hirsute women from southern Brazil. We further investigated the associations of these gene variants and their haplotypes with PCOS, vitamin D levels, and metabolic abnormalities, including the metabolic syndrome (MetS). METHODS: A group of 191 women with PCOS (Rotterdam criteria) and 100 non-hirsute controls with regular ovulatory cycles were genotyped for all polymorphisms by real-time PCR, with allelic discrimination assays. MetS and the cutoffs for its isolated components were defined in accordance with the Joint Scientific Statement. RESULTS: Women with PCOS were younger and had significantly higher BMI and total testosterone levels than controls (p < 0.05). The frequency of MetS in PCOS and controls was 26.5% and 4.8% respectively. The CC genotype of Apa-I entailed higher risk of MetS in PCOS (OR: 2.133; 95% CI 1.020-4.464, p = 0.042), and was associated with higher systolic blood pressure (p = 0.009), total cholesterol (p = 0.040), and LDL-cholesterol (p = 0.038) in both PCOS and control groups (two-way ANOVA). The frequencies of VDR haplotypes were similar in PCOS and control women. CONCLUSIONS: The present results suggest that the Apa-I variant in VDR gene may be associated with MetS in southern Brazilian women with PCOS, and with blood pressure, total cholesterol, and LDL-c in women with and without PCOS.

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats.

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28-35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.

Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic review.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is still poorly known, and information from experimental animal models may help improve current understanding of the mechanisms of PCOS initiation and development. Therefore, we conducted a systematic review of currently available methods for simulation of PCOS in experimental models, focusing on two main endocrine traits: ovarian morphology changes and circulating levels of sex hormones and gonadotropins.We searched the MEDLINE database for articles in English or Spanish published until October 2016. Of 933 studies identified, 39 were included in the systematic review. One study compared interventions with androgens versus estrogens, 18 used androgen-induced stimulation, 9 used estrogens or drugs with estrogen action, including endocrine disruptors, to induce PCOS-like models, and 12 used miscellaneous interventions. Broad differences were found among the studies concerning hormonal interventions, animal species, and developmental stage at the time of the experiments, and most models resulted in ovarian morphology changes, mainly increases in the number of cystic and antral follicles and decreases in the corpus luteum. Hyperandrogenism was produced by using androgens and other drugs as the stimulatory agent. However, studies using drugs with estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype, in rhesus macaque and rat models respectively. In rats, postnatal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis. Thus, comparisons between different intervention models may be useful to define the timing of reproductive PCOS phenotypes in experimental animal models.

Salivary Cortisol, Perceived Stress, and Metabolic Syndrome: A Matched Case-Control Study in Female Shift Workers.

Although the pathogenesis of metabolic syndrome (MetS) is complex and multifactorial, there is limited information if psychological factors, such as stress exposure, are involved in the etiology of MetS. Therefore, this study investigated the associations between MetS and cortisol levels and perceived stress levels among women shift workers in Southern Brazil. A matched case-control study was conducted, including 50 cases of MetS and 200 age-matched controls (±3 years, 4 for each case). Salivary cortisol levels were evaluated immediately after waking and one upon returning home from work. Perceived stress levels were measured by the Perceived Stress Scale with 10 items (PSS-10). Multivariate-adjusted associations between MetS and salivary cortisol levels and perceived stress levels were assessed by conditional logistic regression. Means±standard deviations of salivary cortisol levels were not significantly different between cases and controls either immediately after waking (5.37±4.10 vs. 6.03±5.39 nmol/l; p = 0.53) or after work (2.74±2.87 vs. 2.78±2.85 nmol/l; p = 0.93). There was no significant difference in perceived stress level between cases and controls (14.2±5.9 vs. 15.5±5.6; p = 0.15). No independent association was observed in the multivariate model between MetS and salivary cortisol level or perceived stress level after these exposures were stratified into tertiles. Overall, there was no difference between women with or without MetS in regard to the free salivary cortisol and perceived stress. Our results do not support an association between stress exposure and MetS among women shift workers.

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome.

BACKGROUND/AIMS: There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). METHODS: Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). RESULTS: Body mass index (p = 0.041), blood pressure (p < 0.01), and HOMA-IR (p = 0.003) were higher in PCOS vs. CONTROLS: PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake <8.5%. PCOS women with SFA <8.5% consumed more beans, fruits, and vegetables and had better frequency and time domain HRV indices. No differences in HRV were detected between SFA categories in controls. In PCOS, age and SFA intake were independent predictors of HRV. CONCLUSIONS: Lower SFA intake is related to improved cardiovascular autonomic function in PCOS.