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Clinical Endocrinology Aug 2021Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing... (Review)
Review
A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors.
INTRODUCTION
Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors.
PATHOPHYSIOLOGY OF FHA
Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release.
IMPLICATIONS FOR FUTURE TREATMENT
Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.
Topics: Amenorrhea; Feeding and Eating Disorders; Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Luteinizing Hormone; Stress, Psychological
PubMed: 33345352
DOI: 10.1111/cen.14399 -
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 -
Handbook of Clinical Neurology 2020The neuroendocrinology of reproduction focuses on the neuromodulation of gonadotropin-releasing hormone (GnRH), the ontogeny of the hypothalamic-pituitary-gonadal axis,... (Review)
Review
The neuroendocrinology of reproduction focuses on the neuromodulation of gonadotropin-releasing hormone (GnRH), the ontogeny of the hypothalamic-pituitary-gonadal axis, and common reproductive events and conditions, namely, puberty, the menstrual cycle, and disorders of reproductive function. The core concept underpinning the neuroendocrinology of reproduction is neuroregulation of hypothalamic GnRH drive. In both men and women, reproductive function requires that GnRH input elicit appropriate secretion of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary and that the gonads respond to such input appropriately. Moreover, insufficient GnRH drive causes hypothalamic hypogonadism and secondary insufficiency of gonadal sex steroid hormone synthesis and release in both sexes. Alterations in GnRH drive also reflect gonadal conditions such as dysgenesis, hyperandrogenism, gonadotropin mutations, and aging and loss or absence of oocytes or Sertoli cells. The most common cause of insufficient GnRH drive is functional, that is, due to the endocrine effects of psychologic or behavioral variables. Rarely does reduced GnRH drive reflect organic or congenital causes such as developmental defects, brain tumors, or celiac disease. Despite a common neuropathogenesis the heterogeneity of behavioral variables associated with reduced GnRH drive has resulted in a variety of names, including functional hypothalamic amenorrhea, stress-induced anovulation, and psychogenic amenorrhea.
Topics: Amenorrhea; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Reproduction
PubMed: 32736757
DOI: 10.1016/B978-0-444-64239-4.00001-1 -
Archives of Gynecology and Obstetrics Mar 2021Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian dysfunction, hyperandrogenaemia, infertility, hormonal imbalance and chronic anovulation. Experimental evidence infers that PCOS women are prone to cardiovascular problems and insulin resistance.
PURPOSE
To furnish the details about the association of inflammatory markers in PCOS.
DESIGN
An extensive literature search on PubMed, science direct and google scholar has been performed for articles about PCOS and inflammation in PCOS. A comprehensive analysis using original articles, reviews, systemic and meta-analysis was conducted for better understanding the relationship between inflammatory cytokines and PCOS.
RESULTS
The inflammatory markers perform a substantial part in managing the functions of the ovary. Any disturbances in their levels can lead to ovarian dysfunction. Inflammatory markers are associated with PCOS pathogenesis. The interplay between inflammatory cytokines in the PCOS ovary strongly implies that inflammation is one of the most potent risk factors of PCOS.
CONCLUSION
Inflammatory markers have a significant role in regulating the ovary. This manuscript highlights the significance of metabolic and inflammatory markers with PCOS. Since PCOS is always considered as a metabolic disorder, researchers can also consider focusing on the relationship between the inflammatory markers in PCOS to establish a new treatment or management of the disease and to improve women's health.
Topics: Anovulation; Biomarkers; Cytokines; Female; Humans; Hyperandrogenism; Infertility; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Metabolic Syndrome; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha
PubMed: 33439300
DOI: 10.1007/s00404-020-05951-2 -
International Journal of Molecular... Nov 2020Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and... (Review)
Review
Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and reports in the literature have suggested a negative correlation between circulating SHBG levels and markers of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Decreased SHBG levels increase the bioavailability of androgens, which in turn leads to progression of ovarian pathology, anovulation and the phenotypic characteristics of polycystic ovarian syndrome (PCOS). This review will use a case report to illustrate the inter-relationships between SHBG, NAFLD and PCOS. In particular, we will review the evidence that low hepatic SHBG production may be a key step in the pathogenesis of PCOS. Furthermore, there is emerging evidence that serum SHBG levels may be useful as a diagnostic biomarker and therapeutic target for managing women with PCOS.
Topics: Biomarkers; Female; Humans; Insulin Resistance; Molecular Targeted Therapy; Non-alcoholic Fatty Liver Disease; Polycystic Ovary Syndrome; Sensitivity and Specificity; Sex Hormone-Binding Globulin; Young Adult
PubMed: 33139661
DOI: 10.3390/ijms21218191 -
Frontiers in Pharmacology 2022Polycystic ovary syndrome (PCOS) is a very common, complex, and heterogeneous endocrine disorder of women that involves a combination of environmental and genetic... (Review)
Review
Polycystic ovary syndrome (PCOS) is a very common, complex, and heterogeneous endocrine disorder of women that involves a combination of environmental and genetic factors. PCOS affects women of growing age particularly at the early to late reproductive stage (15-35 years). Currently, PCOS affects 1 in every 10 women worldwide. It is characterized majorly by a raised level of androgens such as testosterone and a large number of ovarian cysts (more than 10) that cause anovulation, infertility, and irregular menstrual cycle. PCOS is also related to other endocrine and metabolic abnormalities, such as obesity, hirsutism, acne, diabetes, insulin resistance, and glucose impairment. PCOS can be treated with allopathic, ayurvedic, and natural or herbal medications along with lifestyle modifications. Herbal medicines remained in demand for numerous reasons such as high cost and side effects associated with the use of allopathic medicine and our traditional norms, which have helped humans to use more herbal products for their health benefits. Estrogenic and nonestrogenic phytochemicals present in various plant species such as L. [Fabaceae], (L.) Burm. f. [Asphodelaceae], (L.). Gaertn. [Asteraceae], (W.Bartram) Small [Arecaceae], L. [Ranunculaceae], and (Oliv.) Diels [] are effective and harmless. Herbal medicines are found to be cost-effective, efficacious, and a highly esteemed source of management/treatment for PCOS than allopathic medicines. In this literature review, diagnosis, signs, and symptoms of PCOS; causes of hormonal imbalance; and risk factors associated with PCOS and their management are discussed briefly, and the focus was to find out the role of herbal remedies in PCOS management.
PubMed: 35924049
DOI: 10.3389/fphar.2022.874914 -
ImmunoHorizons May 2023Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged individuals with ovaries. It is associated with anovulation and increased... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged individuals with ovaries. It is associated with anovulation and increased risk to fertility and metabolic, cardiovascular, and psychological health. The pathophysiology of PCOS is still inadequately understood, although there is evidence of persistent low-grade inflammation, which correlates with associated visceral obesity. Elevated proinflammatory cytokine markers and altered immune cells have been reported in PCOS and raise the possibility that immune factors contribute to ovulatory dysfunction. Because normal ovulation is modulated by immune cells and cytokines in the ovarian microenvironment, the endocrine and metabolic abnormalities associated with PCOS orchestrate the accompanying adverse effects on ovulation and implantation. This review evaluates the current literature on the relationship between PCOS and immune abnormalities, with a focus on emerging research in the field.
Topics: Female; Humans; Adult; Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Ovulation; Tumor Microenvironment
PubMed: 37195871
DOI: 10.4049/immunohorizons.2200033 -
Heliyon Oct 2022Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by menstrual irregularities, chronic anovulation, hirsutism, androgenic alopecia, and acne. At...
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by menstrual irregularities, chronic anovulation, hirsutism, androgenic alopecia, and acne. At diagnosis, patients can with different manifestations according to the disease phenotype, patient's age, and lifestyle. However, most patients pursue medical care because of the clinical symptoms of PCOS, such as hyperandrogenism, menstrual irregularities and infertility. Recent studies have shown that PCOS is associated with 80% of anovulatory infertility; however, the precise mechanism of PCOS-induced anovulation is still undetermined. The treatment strategies of PCOS are symptomatic depending mainly on the desired goals and clinical benefits. Life style intervention is still the first line treatment option for overweight females seeking pregnancy. In addition, there are many pharmacological agents that could be added to induce ovulation such as metformin, and clomiphene citrate. Nowadays, many patients preferred to use some herbal medicine that was proved to have potential therapeutic benefits in many studies in the management of PCOS. The purpose of this review was to discuss PCOS-induced infertility and the available therapeutic options as well as the impact of COVID-19 infection on the success of fertility attempts. To address this purpose, Pubmed, Scopus, EMBASE and Google databases were searched for studies discussing PCOS-induced infertility. The literature search revealed the proper therapeutic plans to treat PCOS-induced infertility, and that treatment should be modified according to patient's complaints, reproductive desires, and disease phenotypes. In conclusion, the use of specific therapeutic agents and patients' adherence to lifestyle interventions could help patients recover their reproductive and metabolic health.
PubMed: 36267367
DOI: 10.1016/j.heliyon.2022.e11010 -
Journal of Clinical Medicine Sep 2023Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo-... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new addition to the therapeutic arsenal for the metabolic management of PCOS. GLP-1 receptor agonists cause insulin release in a glucose-dependent manner, yielding clinical benefits such as heightened satiety, reduced appetite, and appetite regulation. GLP-1RAs have demonstrated efficacy in reducing glycated hemoglobin levels and promoting weight loss while ameliorating hyperlipidemia. Prior to initiating GLP-1RA therapy, patients should undergo screening for contraindications, including history of pancreatitis, diabetic retinopathy, or thyroid cancer. The effects of treatment should be monitored using laboratory testing and body weight measurements. Effective communication between clinician and patient should be maintained with regular check-in for a period of 6 to 12 months.
PubMed: 37762856
DOI: 10.3390/jcm12185915 -
Sports Medicine (Auckland, N.Z.) Oct 2023Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in...
BACKGROUND
Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in sports continues to increase, understanding the prevalence of a range of MC disorders and MC-related symptoms may guide preventive strategies to protect the health and optimise the performance of female athletes.
OBJECTIVE
To examine the prevalence of MC disorders and MC-related symptoms among female athletes who are not using hormonal contraceptives and evaluate the assessment methods used to identify MC disorders and MC-related symptoms.
METHODS
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Six databases were searched until September 2022 for all original research that reported the prevalence of MC disorders and/or MC-related symptoms in athletes not using hormonal contraceptives, which included the definitions of the MC disorders examined, and the assessment methods used. MC disorders included amenorrhoea, anovulation, dysmenorrhoea, heavy menstrual bleeding (HMB), luteal phase deficiency (LPD), oligomenorrhoea, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). MC-related symptoms included any affective and physical symptoms related to the MC that do not cause significant personal, interpersonal or functional impairment. The prevalence data across eligible studies were combined, and all studies were qualitatively synthesised to evaluate the assessment methods and tools used to identify MC disorders and MC-related symptoms. The methodological quality of studies was assessed using a modified Downs and Black checklist.
RESULTS
Sixty studies involving 6380 athletes were included. A wide range of prevalence was observed for all types of MC disorders, with a dearth of data on anovulation and LPD. Based on pooled data, dysmenorrhoea (32.3%; range 7.8-85.6%) was the most prevalent MC disorder. Studies reporting MC-related symptoms mostly examined the premenstrual and menstruation phases, where affective symptoms appeared more prevalent than physical symptoms. A larger proportion of athletes reported symptoms during the initial days of menstruation compared with the premenstrual phase. MC disorders and MC-related symptoms were retrospectively assessed using self-report methods in 90.0% of studies. Most studies (76.7%) in this review were graded as moderate quality.
DISCUSSION
MC disorders and MC-related symptoms are commonplace among female athletes, warranting further research examining their impact on performance and preventive/management strategies to optimise athlete health. To increase the quality of future studies, researchers should adopt standardised definitions of MC disorders and assessment methods such as a combination of calendar counting, urinary ovulation tests and a mid-luteal phase serum progesterone measurement when assessing menstrual function. Similarly, standardised diagnostic criteria should be used when examining MC disorders such as HMB, PMS and PMDD. Practically, implementing prospective cycle monitoring that includes ovulation testing, mid-luteal blood sampling (where feasible) and symptom logging throughout the MC could support athletes and practitioners to promptly identify and manage MC disorders and/or MC-related symptoms.
TRIAL REGISTRATION
This review has been registered in the PROSPERO database (CRD42021268757).
Topics: Female; Humans; Dysmenorrhea; Prevalence; Prospective Studies; Anovulation; Retrospective Studies; Menstrual Cycle; Premenstrual Syndrome; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Athletes; Contraceptive Agents
PubMed: 37389782
DOI: 10.1007/s40279-023-01871-8