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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 -
The Journal of Clinical Endocrinology... May 2017The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine...
COSPONSORING ASSOCIATIONS
The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society.
OBJECTIVE
To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA).
PARTICIPANTS
The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer.
EVIDENCE
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
CONSENSUS PROCESS
One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline.
CONCLUSIONS
FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.
Topics: Adolescent; Adult; Amenorrhea; Endocrinology; Evidence-Based Medicine; Female; Humans; Hypothalamic Diseases; Reproductive Medicine; Societies, Medical; Young Adult
PubMed: 28368518
DOI: 10.1210/jc.2017-00131 -
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 -
European Journal of Endocrinology May 2021Puberty is the period of transition from childhood to adulthood characterized by the attainment of adult height and body composition, accrual of bone strength and the... (Review)
Review
Puberty is the period of transition from childhood to adulthood characterized by the attainment of adult height and body composition, accrual of bone strength and the acquisition of secondary sexual characteristics, psychosocial maturation and reproductive capacity. In girls, menarche is a late marker of puberty. Primary amenorrhea is defined as the absence of menarche in ≥ 15-year-old females with developed secondary sexual characteristics and normal growth or in ≥13-year-old females without signs of pubertal development. Furthermore, evaluation for primary amenorrhea should be considered in the absence of menarche 3 years after thelarche (start of breast development) or 5 years after thelarche, if that occurred before the age of 10 years. A variety of disorders in the hypothalamus-pituitary-ovarian axis can lead to primary amenorrhea with delayed, arrested or normal pubertal development. Etiologies can be categorized as hypothalamic or pituitary disorders causing hypogonadotropic hypogonadism, gonadal disorders causing hypergonadotropic hypogonadism, disorders of other endocrine glands, and congenital utero-vaginal anomalies. This article gives a comprehensive review of the etiologies, diagnostics and management of primary amenorrhea from the perspective of pediatric endocrinologists and gynecologists. The goals of treatment vary depending on both the etiology and the patient; with timely etiological diagnostics fertility may be attained even in those situations where no curable treatment exists.
Topics: Amenorrhea; Female; Humans; Hypothalamo-Hypophyseal System; Ovary; Puberty; Puberty, Delayed
PubMed: 33687345
DOI: 10.1530/EJE-20-1487 -
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 -
Mayo Clinic Proceedings Sep 2023Functional hypothalamic amenorrhea is responsible for approximately a third of the cases of secondary amenorrhea. The condition is a result of disturbances in... (Review)
Review
Functional hypothalamic amenorrhea is responsible for approximately a third of the cases of secondary amenorrhea. The condition is a result of disturbances in gonadotropin-releasing hormone pulsatile secretion at the level of the hypothalamus, which in turn disrupts gonadotropin secretion. It is due to psychosocial stress, disordered eating, and/or excessive exercise. Often, however, it is a combination of more than one etiology, with a possible role for genetic or epigenetic predisposition. The dysfunctional gonadotropin-releasing hormone release leads to the cessation of ovarian function, resulting in amenorrhea, infertility, and a long-term impact on affected women's bone health, cardiovascular risk, cognition, and mental health. Functional hypothalamic amenorrhea is a diagnosis of exclusion, and treatment involves identifying and reversing the underlying cause(s). The aim of this concise review is to summarize the current knowledge of functional hypothalamic amenorrhea, review its pathophysiology and the adverse health consequences, and provide recommendations for diagnosis and management of this condition. Furthermore, this review will emphasize the gaps in research on this common condition impacting women of reproductive age all over the world.
Topics: Humans; Female; Amenorrhea; Cognition; Feeding and Eating Disorders; Genotype; Gonadotropin-Releasing Hormone
PubMed: 37661145
DOI: 10.1016/j.mayocp.2023.05.027 -
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 -
JAMA Nov 2021
Topics: Amenorrhea; Female; Humans; Medroxyprogesterone; Menstrual Cycle
PubMed: 34783850
DOI: 10.1001/jama.2021.13312 -
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