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Pediatric Annals Mar 2016Functional hypothalamic amenorrhea is a diagnosis of exclusion that is common in female athletes, particularly those participating in aesthetic sports (ballet, other...
Functional hypothalamic amenorrhea is a diagnosis of exclusion that is common in female athletes, particularly those participating in aesthetic sports (ballet, other dance genres, figure skating, and gymnastics) and endurance sports (cross-country running). Although common, it should be considered abnormal even in the high-level elite athlete. Amenorrhea in combination with low energy availability and low bone density is labeled "the Female Athlete Triad." Studies have demonstrated numerous long-term consequences of athletes suffering from all or a portion of this triad, including increased rate of musculoskeletal injuries, stress fractures, abnormal lipid profiles, endothelial dysfunction, potential irreversible bone loss, depression, anxiety, low self- esteem, and increased mortality. This article provides the clinician with the tools to evaluate an athlete with secondary amenorrhea, reviews the recommended treatment options for affected athletes, and discusses when to return to the activity in an effort to facilitate "healthy" participation.
Topics: Adolescent; Amenorrhea; Combined Modality Therapy; Female; Female Athlete Triad Syndrome; Humans; Return to Sport; Sports
PubMed: 27031318
DOI: 10.3928/00904481-20160210-03 -
International Journal of Environmental... Oct 2022The aim of this study was to rapidly review the literature on the prevalence of menstrual disorders in female athletes from different sports modalities. Articles were... (Review)
Review
The aim of this study was to rapidly review the literature on the prevalence of menstrual disorders in female athletes from different sports modalities. Articles were searched in the Web of Science and PubMed database in May 2022. A total of 1309 records were identified, and 48 studies were included in the final stage. The menstrual disorders described in the included studies were primary (in 33% of included studies) and secondary amenorrhea (in 73% of included studies) and oligomenorrhea (in 69% of included studies). The prevalence of menstrual disorders among the studies ranged from 0 to 61%. When data were pooled according to discipline (mean calculation), the highest prevalence of primary amenorrhea was found in rhythmic gymnastics (25%), soccer (20%) and swimming (19%); for secondary amenorrhea in cycling (56%), triathlon (40%) and rhythmic gymnastics (31%); and oligomenorrhea in boxing (55%), rhythmic gymnastics (44%) and artistic gymnastics (32%). Based on the results of this review, the study supports the literature of the higher prevalence of menstrual disorders in gymnastics and endurance disciplines. However, team sports modalities such as volleyball and soccer also presented a considerable percentage of menstrual disorders compared to the general population. It reinforces the importance of coaches and physicians paying attention to athletes' menstrual cycle as the occurrence of menstrual disorders can be associated with impairment on some health components.
Topics: Humans; Female; Amenorrhea; Oligomenorrhea; Prevalence; Athletes; Menstruation Disturbances; Gymnastics; Menstrual Cycle
PubMed: 36361122
DOI: 10.3390/ijerph192114243 -
Frontiers in Endocrinology 2022In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea... (Review)
Review
In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of skeletal fragility in this condition may appear self-explanatory. Actually, a growing body of evidence has clarified that estrogens are only part of the story. FHA occurs in eating disorders, overtraining, and during psychological or physical stress. Despite some specific characteristics which differentiate these conditions, relative energy deficiency is a common trigger that initiates the metabolic and endocrine derangements contributing to bone loss. Conversely, data on the impact of amenorrhoea on bone density or microarchitecture are controversial, and reduced bone mass is observed even in patients with preserved menstrual cycle. Consistently, oral estrogen-progestin combinations have not proven beneficial on bone density of amenorrheic women. Low bone density is a highly prevalent finding in these patients and entails an increased risk of stress or fragility fractures, and failure to achieve peak bone mass and target height in young girls. Pharmacological treatments have been studied, including androgens, insulin-like growth factor-1, bisphosphonates, denosumab, teriparatide, leptin, but none of them is currently approved for use in FHA. A timely screening for bone complications and a multidisciplinary, customized approach aiming to restore energy balance, ensure adequate protein, calcium and vitamin D intake, and reverse the detrimental metabolic-endocrine changes typical of this condition, should be the preferred approach until further studies are available.
Topics: Humans; Female; Amenorrhea; Bone Density; Hypothalamic Diseases; Endocrinologists; Bone Diseases, Metabolic; Estrogens
PubMed: 36303862
DOI: 10.3389/fendo.2022.946695 -
Human Reproduction Update May 2023The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman's circulating anti-Müllerian hormone (AMH)...
BACKGROUND
The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman's circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause.
OBJECTIVE AND RATIONALE
This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI).
SEARCH METHODS
A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded.
OUTCOMES
A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]).
WIDER IMPLICATIONS
The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis.
Topics: Female; Humans; Anti-Mullerian Hormone; Amenorrhea; Menopause; Primary Ovarian Insufficiency
PubMed: 36651193
DOI: 10.1093/humupd/dmac045 -
Frontiers in Endocrinology 2024
Topics: Humans; Female; Estradiol; Amenorrhea; Adolescent; Young Adult
PubMed: 38715794
DOI: 10.3389/fendo.2024.1397210 -
Endocrinology and Metabolism Clinics of... Jun 2024This review focuses on primary amenorrhea and primary/premature ovarian insufficiency due to hypergonadotropic hypogonadism. Following a thoughtful, thorough evaluation,... (Review)
Review
This review focuses on primary amenorrhea and primary/premature ovarian insufficiency due to hypergonadotropic hypogonadism. Following a thoughtful, thorough evaluation, a diagnosis can usually be discerned. Pubertal induction and ongoing estrogen replacement therapy are often necessary. Shared decision-making involving the patient, family, and health-care team can empower the young person and family to successfully thrive with these chronic conditions.
Topics: Humans; Primary Ovarian Insufficiency; Female; Amenorrhea; Hypogonadism; Estrogen Replacement Therapy
PubMed: 38677871
DOI: 10.1016/j.ecl.2024.01.009 -
The Journal of Clinical Endocrinology... Aug 2020Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population. (Review)
Review
CONTEXT
Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population.
DESIGN
The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic.
RESULTS
Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed.
CONCLUSION
The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.
Topics: Amenorrhea; Anabolic Agents; Anorexia Nervosa; Bone Density; Bone Density Conservation Agents; Bone Resorption; Celiac Disease; Estrogen Replacement Therapy; Female; Humans; Inflammatory Bowel Diseases; Osteoporosis; Osteoporotic Fractures; Premenopause; Treatment Outcome
PubMed: 32453819
DOI: 10.1210/clinem/dgaa306 -
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 -
BMC Complementary and Alternative... Dec 2014Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to... (Review)
Review
Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions.
METHODS
We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism.
RESULTS
A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin, fasting insulin and testosterone. There was evidence for the regulation of ovulation, improved metabolic hormone profile and improved fertility outcomes in PCOS. There was evidence for an equivalent effect of two herbal medicines and the pharmaceutical agents bromocriptine (and Vitex agnus-castus) and clomiphene citrate (and Cimicifuga racemosa). There was less robust evidence for the complementary combination of spirinolactone and Glycyrrhiza spp. for hyperandrogenism.
CONCLUSIONS
Preclinical and clinical studies provide evidence that six herbal medicines may have beneficial effects for women with oligo/amenorrhea, hyperandrogenism and PCOS. However the quantity of pre-clinical data was limited, and the quality of clinical evidence was variable. Further pre-clinical studies are needed to explain the effects of herbal medicines not included in this review with current clinical evidence but an absence of pre-clinical data.
Topics: Amenorrhea; Female; Humans; Hyperandrogenism; Oligomenorrhea; Phytotherapy; Plant Extracts; Polycystic Ovary Syndrome
PubMed: 25524718
DOI: 10.1186/1472-6882-14-511 -
Current Problems in Pediatric and... May 2022In this article, we will review the etiology and management of amenorrhea in adolescent and young adult women, beginning with the diagnostic work-up and followed by...
In this article, we will review the etiology and management of amenorrhea in adolescent and young adult women, beginning with the diagnostic work-up and followed by etiologies organized by system. Most cases of amenorrhea are caused by dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, which is the major regulator of the female reproductive hormones: estrogen and progesterone. We begin by reviewing hypothalamic etiologies, including eating disorders and relative energy deficiency in sport. Then, pituitary causes of amenorrhea are reviewed, including hyperprolactinemia, empty sella syndrome, Sheehan's syndrome and Cushing's syndrome. Next, ovarian causes of amenorrhea are reviewed, including polycystic ovarian syndrome and primary ovarian insufficiency. Finally, other etiologies of amenorrhea are discussed, including thyroid disease, adrenal disease and reproductive tract anomalies. In conclusion, there is a wide and diverse range of causes of amenorrhea in adolescents that originate from any level of the HPO axis, as well as anatomic and chromosomal etiologies. Treatment should be focused on the underlying cause. Preservation of bone density and risk of fractures should be discussed with amenorrheic patients since many causes of amenorrhea can result in decreased bone density and may be irreversible.
Topics: Adolescent; Amenorrhea; Female; Hormones; Humans; Young Adult
PubMed: 35525789
DOI: 10.1016/j.cppeds.2022.101184