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International Journal of Gynaecology... Jul 2024Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved.
OBJECTIVE
To investigate the association between exposure to BPA and PCOS.
SEARCH STRATEGY
Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases.
SELECTION CRITERIA
Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS.
DATA COLLECTION AND ANALYSIS
Following PRISMA guidelines, study characteristics and relevant data were extracted.
MAIN RESULTS
Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present.
CONCLUSIONS
Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.
Topics: Humans; Polycystic Ovary Syndrome; Female; Phenols; Benzhydryl Compounds; Endocrine Disruptors; Environmental Exposure
PubMed: 38197560
DOI: 10.1002/ijgo.15349 -
Applied Physiology, Nutrition, and... May 2024Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a... (Review)
Review
Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a threshold of energy availability (EA) of 30 kcal/kg lean body mass (LBM)/day. This paper is a critical review of the evidence regarding the theory that disruptions to the reproductive axis and menstrual disturbances occur below the proposed threshold. Short-term laboratory studies demonstrated that 4-5 days of an EA below 30 kcal/kg LBM/day, induced with or without exercise, decreased serum triiodothyronine and LH pulse frequency, and increased LH pulse amplitude in sedentary, regularly menstruating women. Fewer studies have investigated downstream ovarian effects after long-term exposure to low EA. The Sargent Camp Study was the first randomized trial that induced luteal phase defects, delayed menses, and anovulation by causing weight loss (-4 ± 0.3 kg) with an abrupt increase in exercise volume for two menstrual cycles. The BioEnergetics Study was a randomized controlled trial that induced varying levels of energy deficits by manipulating energy intake and expenditure for three menstrual cycles. LH pulse frequency and triiodothyronine decreased, and 57% of women developed luteal phase defects, anovulation, and/or oligomenorrhea. An EA below 30 kcal/kg fat free mass/day increased the chance of experiencing a menstrual disturbance by 50%. However, menstrual disturbances were observed above and below that EA threshold, and changes in LH pulse frequency predicted only luteal phase defects, not oligomenorrhea or anovulation. The proposed EA threshold is not a cut-off below which menstrual disturbances occur, but represents an increased risk of experiencing menstrual disturbances.
Topics: Humans; Female; Menstruation Disturbances; Energy Metabolism; Luteinizing Hormone; Exercise; Energy Intake; Menstrual Cycle
PubMed: 38194640
DOI: 10.1139/apnm-2023-0418 -
PloS One 2023Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about...
Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19-35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21-35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater "outside stress" in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with age- and BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.
Topics: Female; Humans; Child; Polycystic Ovary Syndrome; SARS-CoV-2; Case-Control Studies; Molybdenum; Pandemics; COVID-19; Menstrual Cycle
PubMed: 38157371
DOI: 10.1371/journal.pone.0296377 -
Drug Discoveries & Therapeutics Jan 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting fertility and mental health among women of reproductive age. In addition to anovulation and...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting fertility and mental health among women of reproductive age. In addition to anovulation and hyperandrogenism, patients also experience metabolic issues, such as insulin resistance, obesity, and dyslipidemia, as well as chronic low-grade inflammation throughout the body. Recent studies have shown that even with assisted reproductive technology to treat anovulatory issues, patients with PCOS still have higher rates of adverse pregnancy outcomes and abortion compared to normal pregnancies. These findings suggest that PCOS may impair the endometrium and disrupt the onset and maintenance of healthy pregnancies. Decidualization is a crucial step in the process of healthy pregnancy, during which endometrial stromal cells (ESCs) differentiate into secretory decidual stromal cells (DSCs) regulated by hormones and local metabolism. This article comprehensively reviews the pathological processes of PCOS and the mechanisms involved in its impaired decidualization. In addition, we explore how PCOS increases the incidence of adverse pregnancy outcomes (APO). By gaining a better understanding of the adverse effects of PCOS on pregnancy and its specific mechanisms, we hope to provide a theoretical basis for reducing APO and improving the live birth rate among women with PCOS.
Topics: Pregnancy; Humans; Female; Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Insulin Resistance
PubMed: 38148009
DOI: 10.5582/ddt.2023.01096 -
Seminars in Reproductive Medicine Jul 2023Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index... (Review)
Review
Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index (BMI) have higher rates of anovulation and irregular menses, lower success with fertility treatment, and significantly higher rates of pregnancy complications, such as hypertension/preeclampsia, gestational diabetes, and preterm delivery. Many studies have also shown an association between obesity and early pregnancy loss. However, the causal association between BMI and miscarriage has not been elucidated, likely due to the multifactorial effects that BMI may have on early pregnancy development. In addition, BMI as an isolated variable fails to capture other relevant confounding health risk factors, such as nutrition, physical activity, and insulin resistance. In this review, we will summarize the current literature demonstrating the association between BMI and miscarriage, highlight the research that attempts to explain the association, and finally provide data on therapeutic interventions to improve reproductive outcomes in women suffering from obesity and early pregnancy loss.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Adult; Abortion, Spontaneous; Obesity; Risk Factors; Fertility; Infertility, Female; Body Mass Index
PubMed: 38101448
DOI: 10.1055/s-0043-1777759 -
Cell Biochemistry and Function Jan 2024Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen...
Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen and estrogen hormones, thus leading to the formation of multiple cysts, imposing life-threatening conditions. This manuscript aimed to introduce a natural estrogen receptor (ESR) inhibitors that can provide protection against PCOS. The computational analysis of Linum usitatissimum seeds compounds against ESR alpha receptor was performed, and the binding affinities of the ligand compounds and receptor proteins were scrutinized. Nine lignin compounds were docked, and the results were compared with that of reference estrogen receptor inhibitors, clomiphene, and tamoxifen. The binding affinity scores for pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol were -10.67, -10.66, -10.91, and -10.60 kcal mol , respectively. These were comparable to the binding affinity score of reference compounds -11.406 kcal mol for clomiphene and -10.666 kcal mol for tamoxifen. Prime MM-GBSA studies showcased that Linum usitatissimum seeds compounds exhibit significant efficacy and efficiency towards receptor protein. Moreover, MD-simulation studies were performed and the results depict that the lignin compounds form stable complexes at 300 K throughout the simulation time. For further clarity, in-vitro experiments were carried out. The results exhibit the decline in cell proliferation in a concentration-dependent manner by extract 1 (ethyl acetate) EX1 and extract 2 (petroleum ether) EX2. Hence, providing evidence regarding the anti-estrogenic activity of the sample extracts. Collectively, these results showed that flax seed can reduce the levels of estrogen, which can induce ovulation and prevent cyst formation, and ultimately can provide protection against PCOS.
Topics: Humans; Female; Flax; Receptors, Estrogen; Polycystic Ovary Syndrome; Lignin; Seeds; Clomiphene; Estrogens; Tamoxifen; Plant Extracts
PubMed: 38063410
DOI: 10.1002/cbf.3897 -
Endocrine Jun 2024Functional hypothalamic amenorrhea (FHA) is one of the most common causes of both primary and secondary amenorrhea in women of reproductive age. It is characterized by... (Review)
Review
Functional hypothalamic amenorrhea (FHA) is one of the most common causes of both primary and secondary amenorrhea in women of reproductive age. It is characterized by chronic anovulation and the absence of menses that appear as a result of stressors such as eating disorders, excessive exercise, or psychological distress. FHA is presumed to be a functional disruption in the pulsatile secretion of hypothalamic gonadotropin-releasing hormone, which in turn impairs the release of gonadotropin. Hypoestrogenism is observed due to the absence of ovarian follicle recruitment. Numerous neurotransmitters have been identified which play an important role in the regulation of the hypothalamic-pituitary-ovarian axis and of which the impairment would contribute to developing FHA. In this review we summarize the most recent advances in the identification of contributing neuroendocrine disturbances and relevant contributors to the development of FHA.
Topics: Humans; Female; Amenorrhea; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Neurosecretory Systems; Gonadotropin-Releasing Hormone
PubMed: 38062345
DOI: 10.1007/s12020-023-03619-w -
Obstetrics & Gynecology Science Jan 2024Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and...
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and multiple ovarian cysts. PCOS is strongly associated with obesity and insulin resistance. MicroRNAs (miRNAs) are a group of short non-coding RNAs that play a role in the post-transcriptional regulation of gene expression and translational inhibition. They play a vital role in the regulation of multiple metabolic and hormonal processes as well as in oocyte maturation and folliculogenesis in the female reproductive system. miRNAs can be used as diagnostic biomarkers or therapeutic targets because of their stability. The encapsulation of miRNAs in extracellular vesicles or exosomes contributes to their stability. Exosomes are constantly secreted by many cells and size of about 30 to 150 nm. Enveloping miRNAs exosomes can release them for cellular communication. The induced transfer of miRNAs by exosomes is a novel process of genetic exchange between cells. Many studies have shown that along with non-exosomal miRNAs, different types of exosomal miRNAs derived from the serum and follicular fluid can play an essential role in PCOS pathogenesis. These miRNAs are involved in follicular development and various functions in granulosa cells, apoptosis, cell proliferation, and follicular atresia. The present study aimed to comprehensively review the evidence on miRNAs and their affected pathways under both non-exosomal and exosomal circumstances, primarily focusing on the pathogenesis of PCOS.
PubMed: 38050353
DOI: 10.5468/ogs.23193 -
Frontiers in Sports and Active Living 2023The release of luteinising hormone (LH) before ovulation is disrupted during a state of low energy availability (EA). However, it remains unknown whether a threshold EA...
Free-living competitive racewalkers and runners with energy availability estimates of <35 kcal·kg fat-free mass·day exhibit peak serum progesterone concentrations indicative of ovulatory disturbances: a pilot study.
INTRODUCTION
The release of luteinising hormone (LH) before ovulation is disrupted during a state of low energy availability (EA). However, it remains unknown whether a threshold EA exists in athletic populations to trigger ovulatory disturbances (anovulation and luteal phase deficiency) as indicated by peak/mid-luteal serum progesterone concentration (Pk-PRG) during the menstrual cycle.
METHODS
We assessed EA and Pk-PRG in 15 menstrual cycles to investigate the relationship between EA and Pk-PRG in free-living, competitive (trained-elite) Guatemalan racewalkers (= 8) and runners (= 7) [aged: 20 (14-41) years; post-menarche: 5 (2-26) years; height: 1.53 ± 0.09 m; mass: 49 ± 6 kg (41 ± 5 kg fat-free mass "FFM")]. EA was estimated over 7 consecutive days within the follicular phase using food, training, and physical activity diaries. A fasted blood sample was collected during the Pk-PRG period, 6-8 days after the LH peak, but before the final 2 days of each cycle. Serum progesterone concentration was quantified using electrochemiluminescence immunoassay.
RESULTS
Participants that reported an EA of <35 kcal·kg FFM·day (= 7) exhibited ovulatory disturbances (Pk-PRG ≤9.40 ng·mL). Athletes with EA ≥36 kcal·kg FFM·day (= 8) recorded "normal"/"potentially fertile" cycles (Pk-PRG >9.40 ng·mL), except for a single racewalker with the lowest reported protein intake (1.1 g·kg body mass·day). EA was positively associated with Pk-PRG [(9) = 0.79, 95% confidence interval (CI): 0.37-0.94; = 0.003; 1 - = 0.99] after excluding participants (= 4) that likely under-reported/reduced their dietary intake.
CONCLUSIONS
The result from the linear regression analysis suggests that an EA ≥ 36 kcal·kg FFM·day is required to achieve "normal ovulation." The threshold EA associated with ovulatory disturbances in athletes and non-invasive means of monitoring the ovulatory status warrant further research.
PubMed: 38046932
DOI: 10.3389/fspor.2023.1279534 -
Fertility and Sterility Mar 2024To evaluate assisted reproductive technology-associated risk factors for retained products of conception among live births.
OBJECTIVE
To evaluate assisted reproductive technology-associated risk factors for retained products of conception among live births.
DESIGN
Registry-based retrospective cohort study.
SETTING
Not applicable.
PATIENT(S)
Cycle-specific data for a total of 369,608 singleton live births after fresh and frozen-thawed embryo transfers (FETs) between 2007 and 2017 were obtained from the Japanese assisted reproductive technology registry.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Retained products of conception after delivery. Odds ratios and 95% confidence intervals for risk factors associated with retained products of conception during fresh and frozen cycles.
RESULT(S)
In total, 132 deliveries (0.04% of eligible assisted reproductive technology registry deliveries) had retained products of conception; 122 (92.4%) of these deliveries occurred after FET transfer cycles. Cases with retained products of conception were significantly more likely to have undergone vaginal delivery than cases without retained products of conception (78.0% vs. 61.1%); they were also more likely to have been complicated with the placenta accreta spectrum (24.2% vs. 0.45%). Among patients undergoing FETs, factors associated with a significantly increased risk of retained products of conception were embryo stage at transfer, use of hormone replacement cycles, and assisted hatching. Use of hormone replacement cycles represented the largest risk factor (adjusted odds ratio, 4.9; 95% confidence interval, 2.0-12.4), such that retained products of conception occurred in 0.05% (51 of 97,958) of deliveries after hormone replacement cycles but only 0.01% (5 of 47,079) of deliveries after natural cycles. Subgroup analysis showed that hormone replacement cycles and assisted hatching remained significant risk factors for retained products of conception in cases without polycystic ovary syndrome and anovulation and cases with vaginal delivery, but not cases with cesarean section. Among fresh embryo transfers, an increased number of retrieved oocytes was the only significant risk factor for retained products of conception.
CONCLUSION(S)
Our analyses demonstrated that most of the cases involving retained products of conception were derived from FETs, and we identified the use of hormone replacement cycles as the largest risk factor for retained products of conception within this group.
Topics: Pregnancy; Humans; Female; Retrospective Studies; Cesarean Section; Reproductive Techniques, Assisted; Risk Factors; Hormones
PubMed: 38036239
DOI: 10.1016/j.fertnstert.2023.11.028