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American Family Physician Jul 2019Menstrual patterns can be an indicator of overall health and self-perception of well-being. Primary amenorrhea, defined as the lifelong absence of menses, requires... (Review)
Review
Menstrual patterns can be an indicator of overall health and self-perception of well-being. Primary amenorrhea, defined as the lifelong absence of menses, requires evaluation if menarche has not occurred by 15 years of age or three years post-thelarche. Secondary amenorrhea is characterized by cessation of previously regular menses for three months or previously irregular menses for six months and warrants evaluation. Clinicians may consider etiologies of amenorrhea categorically as outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced. The history should include menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, galactorrhea, and chronic illness. Additional questions may target neurologic, vasomotor, hyperandrogenic, or thyroid-related symptoms. The physical examination should identify anthropometric and pubertal development trends. All patients should be offered a pregnancy test and assessment of serum follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone levels. Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized. Patients with primary ovarian insufficiency can maintain unpredictable ovary function and may require hormone replacement therapy, contraception, or infertility services. Functional hypothalamic amenorrhea may indicate disordered eating and low bone density. Treatment should address the underlying cause. Patients with polycystic ovary syndrome should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk. Amenorrhea can be associated with clinically challenging pathology and may require lifelong treatment. Patients will benefit from ample time with the clinician, sensitivity, and emotional support.
Topics: Amenorrhea; Diagnosis, Differential; Female; Humans; Medical History Taking; Physical Examination; Practice Guidelines as Topic
PubMed: 31259490
DOI: No ID Found -
Seminars in Reproductive Medicine May 2017The menstrual cycle is a reproductive vital sign and provides insight into hormonal imbalance as well as pregnancy. The significance of estrogen, however, extends beyond... (Review)
Review
The menstrual cycle is a reproductive vital sign and provides insight into hormonal imbalance as well as pregnancy. The significance of estrogen, however, extends beyond fertility and plays a role on tissues and organs throughout the body. Functional hypothalamic amenorrhea is a common form of secondary amenorrhea resulting in estrogen deficiency in young premenopausal women. While reversible, the cause of this disorder is related to psychological stress, excessive exercise, disordered eating or a combination of these factors resulting in suppression of the hypothalamic–pituitary–ovarian axis. The resulting loss of estrogen has profound effects on many systems throughout the body including cardiac, skeletal, psychological and reproductive. Often, these young women are the ‘walking well’ as they do not have bothersome symptoms of low estrogen and are unaware of the consequences of estrogen deficiency. This review focuses on the health consequences of hypothalamic amenorrhea, current research and available treatment options.
Topics: Amenorrhea; Animals; Cardiovascular Diseases; Estrogens; Female; Fertility; Health Status; Humans; Hypothalamus; Infertility, Female; Menstruation; Mental Disorders; Mental Health; Osteoporosis, Postmenopausal; Prognosis; Reproductive Health; Risk Factors; Sex Factors; Time Factors
PubMed: 28658709
DOI: 10.1055/s-0037-1603581 -
Revista Brasileira de Ginecologia E... May 2021In a healthy athlete, the caloric intake is sufficient for sports energy needs and body physiological functions, allowing a balance between energy availability, bone... (Review)
Review
In a healthy athlete, the caloric intake is sufficient for sports energy needs and body physiological functions, allowing a balance between energy availability, bone metabolism, and menstrual cycle. On the other hand, an imbalance caused by low energy availability due to a restrictive diet, eating disorders or long periods of energy expenditure leads to multisystemic deregulation favoring the essential functions of the body. This phenomenon, described as the female athlete triad, occurs in a considerable percentage of high-performance athletes, with harmful consequences for their future. The present review was carried out based on a critical analysis of the most recent publications available and aims to provide a global perception of the topic relative energy deficit in sport (RED-S). The objective is to promote the acquisition of more consolidated knowledge on an undervalued theme, enabling the acquisition of preventive strategies, early diagnosis and/or appropriate treatment.
Topics: Amenorrhea; Athletes; Athletic Performance; Energy Intake; Energy Metabolism; Feeding and Eating Disorders; Female; Female Athlete Triad Syndrome; Humans; Menstruation Disturbances; Relative Energy Deficiency in Sport
PubMed: 34077990
DOI: 10.1055/s-0041-1730289 -
Journal of Clinical Research in... Feb 2020Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea in adolescent girls. It is often seen in the setting of stress, weight loss, or excessive... (Review)
Review
Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea in adolescent girls. It is often seen in the setting of stress, weight loss, or excessive exercise. FHA is a diagnosis of exclusion. Patients with primary or secondary amenorrhea should be evaluated for other causes of amenorrhea before a diagnosis of FHA can be made. The evaluation typically consists of a thorough history and physical examination as well as endocrinological and radiological investigations. FHA, if prolonged, can have significant impacts on metabolic, bone, cardiovascular, mental, and reproductive health. Management often involves a multidisciplinary approach, with a focus on lifestyle modification. Depending on the severity, pharmacologic therapy may also be considered. The aim of this paper is to present a review on the pathophysiology, clinical findings, diagnosis, and management approaches of FHA in adolescent girls.
Topics: Adolescent; Amenorrhea; Female; Fertility; Humans; Hypothalamic Diseases; Life Style; Physical Examination; Psychotherapy
PubMed: 32041389
DOI: 10.4274/jcrpe.galenos.2019.2019.S0178 -
Nature Medicine Feb 2023Premature ovarian insufficiency (POI) is a major cause of female infertility due to early loss of ovarian function. POI is a heterogeneous condition, and its molecular...
Premature ovarian insufficiency (POI) is a major cause of female infertility due to early loss of ovarian function. POI is a heterogeneous condition, and its molecular etiology is unclear. To identify genetic variants associated with POI, here we performed whole-exome sequencing in a cohort of 1,030 patients with POI. We detected 195 pathogenic/likely pathogenic variants in 59 known POI-causative genes, accounting for 193 (18.7%) cases. Association analyses comparing the POI cohort with a control cohort of 5,000 individuals without POI identified 20 further POI-associated genes with a significantly higher burden of loss-of-function variants. Functional annotations of these novel 20 genes indicated their involvement in ovarian development and function, including gonadogenesis (LGR4 and PRDM1), meiosis (CPEB1, KASH5, MCMDC2, MEIOSIN, NUP43, RFWD3, SHOC1, SLX4 and STRA8) and folliculogenesis and ovulation (ALOX12, BMP6, H1-8, HMMR, HSD17B1, MST1R, PPM1B, ZAR1 and ZP3). Cumulatively, pathogenic and likely pathogenic variants in known POI-causative and novel POI-associated genes contributed to 242 (23.5%) cases. Further genotype-phenotype correlation analyses indicated that genetic contribution was higher in cases with primary amenorrhea compared to that in cases with secondary amenorrhea. This study expands understanding of the genetic landscape underlying POI and presents insights that have the potential to improve the utility of diagnostic genetic screenings.
Topics: Humans; Female; Amenorrhea; Primary Ovarian Insufficiency; Mutation; Genetic Testing; Genetic Association Studies; Ubiquitin-Protein Ligases
PubMed: 36732629
DOI: 10.1038/s41591-022-02194-3 -
Current Opinion in Pharmacology Dec 2022Functional hypothalamic amenorrhea (FHA) is the most common cause of secondary amenorrhea in women of reproductive age. FHA is predominantly caused by stress, decreased... (Review)
Review
Functional hypothalamic amenorrhea (FHA) is the most common cause of secondary amenorrhea in women of reproductive age. FHA is predominantly caused by stress, decreased caloric intake, excessive exercise, or a combination thereof. These physical, psychological, and metabolic stressors cause aberration in the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently impair function of the hypothalamic-pituitary-ovarian (HPO) axis. Various neurotransmitters acting in the central nervous system are involved in control of the HPO axis and of these, kisspeptin is one of the most important. Corticotropin-releasing hormone (CRH), also inhibits the pulsatile secretion of GnRH and also acts as an intermediary between stress factors and the reproductive system. One of the main ongoing concerns in patients with FHA is chronic hypoestrogenism, a condition, which is associated with sexual dysfunction and infertility. It may also lead to osteoporosis, and predispose to neurodegenerative and cardiovascular diseases. Treatment of FHA requires the elimination of causative factors, however, making the necessary lifestyle changes is not always easy to initiate and maintain. Broadening our knowledge of the complex neural mechanisms regulating reproductive function in which kisspeptin plays a key role can help in the development of new treatment options such as the potential of kisspeptin receptor agonists for patients with FHA.
Topics: Female; Humans; Kisspeptins; Amenorrhea; Luteinizing Hormone; Gonadotropin-Releasing Hormone; Reproduction
PubMed: 36103784
DOI: 10.1016/j.coph.2022.102288 -
Acta Paediatrica (Oslo, Norway : 1992) Dec 2015To evaluate the effect of breastfeeding on long-term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short-term (lactational... (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the effect of breastfeeding on long-term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal health outcomes.
METHODS
A systematic literature search was conducted in PubMed, Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity, subgroup analysis and meta-regression were explored.
RESULTS
Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37%, respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking.
CONCLUSION
This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However, an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident.
Topics: Adolescent; Adult; Amenorrhea; Breast Feeding; Breast Neoplasms; Depression, Postpartum; Diabetes Mellitus, Type 2; Female; Humans; Lactation; Maternal Health; Osteoporosis; Ovarian Neoplasms; Time Factors; Young Adult
PubMed: 26172878
DOI: 10.1111/apa.13102 -
Nutrients Aug 2021Functional hypothalamic amenorrhea (FHA) is a very common condition affecting women of procreative age. There are many reasons for this disorder, including a low... (Review)
Review
Functional hypothalamic amenorrhea (FHA) is a very common condition affecting women of procreative age. There are many reasons for this disorder, including a low availability of energy in the diet, low micro- and macronutrient intake, overly intensive physical activity, disturbed regeneration processes, sleep disorders, stress, and psychological disorders. The main determinant is long-term stress and an inability to handle the effects of that stress. FHA is a very complex disorder and often goes undiagnosed. Moreover, therapeutic interventions do not address all the causes of the disorder, which could have implications for women's health. As shown by scientific reports, this condition can be reversed by modifying its causes. This review of the literature aims to update the current knowledge of functional hypothalamic amenorrhea and underscores the complexity of the disorder, with particular emphasis on the nutritional aspects and potential interventions for restoring balance.
Topics: Amenorrhea; Energy Intake; Exercise; Feeding Behavior; Feeding and Eating Disorders; Female; Humans; Hypothalamus; Menstruation; Sleep; Stress, Physiological; Stress, Psychological
PubMed: 34444987
DOI: 10.3390/nu13082827 -
Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.International Journal of Molecular... Mar 2021Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40... (Review)
Review
Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4-30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave's disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto's type thyroid antibodies and has a prevalence of 10-40%. 21OH-Antibodies in Addison's disease (AD) can develop in association to APS-2.
Topics: Amenorrhea; Autoantibodies; Autoimmune Diseases; Female; Hashimoto Disease; Humans; Menopause, Premature; Ovary; Polyendocrinopathies, Autoimmune; Primary Ovarian Insufficiency
PubMed: 33807517
DOI: 10.3390/ijms22052594