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Fertility and Sterility Jul 1994To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal... (Review)
Review
OBJECTIVE
To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal therapeutic strategy to treat these conditions.
DATA IDENTIFICATION
Studies related to these topics were identified through literature and Medline searches.
STUDY SELECTION
Those studies that relate specifically to amenorrhea in women of reproductive age, including etiology, diagnosis, and the implications of replacement therapy or nontreatment of this state, were selected.
RESULTS
Amenorrhea, as defined by the absence of menses for > or = 6 months, may be found in up to 3% of women in the reproductive years. Classification of amenorrhea involves defining the exact cause for the cessation of menses, be it hypothalamic, pituitary, ovarian, or lower genital tract in origin. The majority of amenorrheic young women have very low levels of estrogens, and a minority will have subnormal noncyclic estrogen levels, unopposed by P, due to anovulation. This distinction is important in considering the long-term implications of amenorrhea. Hypoestrogenic amenorrhea is associated with a significant loss of bone mineral density and the associated risk of osteoporosis and fractures. Lipoprotein profiles are also adversely affected, and this is associated with an increased risk of cardiovascular events. Anovulatory amenorrhea due to "unopposed" estrogen is associated with an increased risk of endometrial hyperplasia and endometrial carcinoma even in young patients. Therapy should be aimed at treating the underlying cause of amenorrhea, if possible, or reconstitution of an estrogen-P biphasic monthly cycle if not.
CONCLUSIONS
Untreated amenorrhea is associated with significant long-term morbidity, especially in young women. Early recognition and institution of treatment will minimize late complications.
Topics: Aging; Amenorrhea; Estrogen Replacement Therapy; Estrogens; Female; Humans; Reproduction; Terminology as Topic
PubMed: 8005272
DOI: 10.1016/s0015-0282(16)56808-3 -
The Journal of Clinical Endocrinology... Jun 2018We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in participants with anorexia nervosa (AN) and normal-weight...
OBJECTIVE
We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in participants with anorexia nervosa (AN) and normal-weight oligoamenorrheic athletes (OAs). However, data directly comparing compartment-specific bone parameters in participants with AN, OAs, and controls are lacking.
DESIGN
A total of 468 female participants 14 to 21.9 years old were included: 269 with AN, 104 OAs, and 95 normal-weight eumenorrheic controls. Dual-energy x-ray absorptiometry was used to assess areal BMD (aBMD) of the whole body less head (WBLH), spine, and hip. High-resolution peripheral quantitative computed tomography was used to assess volumetric BMD (vBMD), bone geometry, and structure at the non-weight-bearing distal radius and weight-bearing distal tibia.
RESULTS
Participants with AN had lower WBLH and hip aBMD z scores than OAs and controls (P < 0.0001). Participants with AN and OAs had lower spine aBMD z scores than controls (P < 0.01). At the radius, total and cortical vBMD, percentage cortical area, and thickness were lower in the AN and OA groups than in controls (P ≤ 0.04); trabecular vBMD was lower in participants with AN than controls. At the tibia, participants with AN had lower measures for most parameters compared with OAs and controls (P < 0.05); OAs had lower cortical vBMD than controls (P = 0.002). Participants with AN and OAs had higher fracture rates than controls. Stress fracture prevalence was highest in OAs (P < 0.0001); nonstress fracture prevalence was highest in participants with AN (P < 0.05).
CONCLUSION
AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OAs, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.
Topics: Absorptiometry, Photon; Adolescent; Amenorrhea; Anorexia Nervosa; Athletes; Bone Density; Bone and Bones; Female; Fractures, Bone; Humans; Prevalence; Young Adult
PubMed: 29659886
DOI: 10.1210/jc.2018-00338 -
Eating and Weight Disorders : EWD Dec 2021In patients living with Anorexia Nervosa (AN), dehydration and haemoconcentration, may prevent a correct interpretation of laboratory nutritional parameters. Our study...
PURPOSE
In patients living with Anorexia Nervosa (AN), dehydration and haemoconcentration, may prevent a correct interpretation of laboratory nutritional parameters. Our study aims to evaluate if some indicators of disease severity, as body mass index (BMI), Phase Angle (PhA) and months of amenorrhea may be predictors of metabolic alterations (serum albumin, liver enzymes).
METHODS
In 154 outpatients with AN, case history was collected, and anthropometric and laboratory parameters measured. Patients were divided according to the following tertiles (T) of BMI, duration of amenorrhea and PhA: (1) BMI (T1 < 15.6; T2 15.6-16.8; T3 > 16.8 kg/m); (2) Amenorrhea duration (T1 < 7; T2 7-14; T3 > 14 months); (3) PhA value (T1 < 4.64; T2 4.64-5.35; T3: > 5.35°). ROC curves were used to determine which of these three indicators (BMI, PhA and amenorrhea duration) might better identify patients belonging to Group A or B (less than 3 or more metabolic abnormalities).
RESULTS
The most frequent registered metabolic alterations were for alkaline phosphatase (ALP), alanine aminotransferase, cholesterol and hemoglobin. Aspartate aminotransferase, ALP and gamma glutamyl transferase abnormalities were frequent in the first tertiles of all the three indicators. Albumin was low in the T1 of BMI and PhA. No differences in nutritional alterations emerged according to amenorrhea duration. PhA had the best performance (AUCs: 0.721) in identifying patients with 3 or more abnormalities, with the optimal cut-off value of 4.5°.
CONCLUSIONS
Our data confirmed PhA as the more reliable predictor of metabolic alterations, followed by BMI and amenorrhea duration, especially in the first tertile.
EVIDENCE-BASED MEDICINE
Level 2.
Topics: Amenorrhea; Anorexia Nervosa; Body Mass Index; Female; Humans; Outpatients; Retrospective Studies
PubMed: 33608860
DOI: 10.1007/s40519-021-01121-8 -
Journal of Korean Medical Science Jul 2022This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea.
BACKGROUND
This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea.
METHODS
This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis.
RESULTS
The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance.
CONCLUSION
The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.
Topics: 46, XX Disorders of Sex Development; Amenorrhea; Female; Humans; Hypogonadism; Mullerian Ducts; Prospective Studies
PubMed: 35880506
DOI: 10.3346/jkms.2022.37.e230 -
Frontiers in Endocrinology 2022Functional hypothalamic amenorrhea (FHA) is a clinical condition associated with high levels of physiological and psychological stress ranging from weight loss to...
INTRODUCTION
Functional hypothalamic amenorrhea (FHA) is a clinical condition associated with high levels of physiological and psychological stress ranging from weight loss to maladaptive behavior and coping skills. A reliable measure of the psychophysiological response to stress and the ability to cope with stimuli is heart rate variability (HRV). Through the sympathetic (SNS) and parasympathetic nervous system (PNS), the autonomic nervous system (ANS) promotes various changes in HRV that reflect the individual's psychophysiological response to stress. FHA patients are characterized by high levels of PNS activation during psychological load, suggesting that parasympathetic hyperactivation could be a pathology marker.
METHODS
In the present study, we examine changes in HRV during observation of erotic, neutral, and disgusting images in 10 patients with FHA [(mean ± S.D.) age: 26.8 ± 5.9] and in 9 controls (age: 25.4 ± 6.4; BMI: 22.47 ± 2.97) to assess the differential activation of PNS and SNS between FHA patients and controls matched for age and without other clinical conditions.
RESULTS
Our results showed that FHA patients had significantly higher HRV activation while observing high emotional value images and not during the observation of neutral images confirming a parasympathetic hyperactivation.
DISCUSSION
HRV and cognitive and psychological testing, could provide new insights into understanding such a clinically understudied condition and provide further tools for clinical diagnosis and treatment.
Topics: Female; Humans; Young Adult; Adult; Amenorrhea; Autonomic Nervous System; Parasympathetic Nervous System; Heart Rate; Emotions
PubMed: 36531461
DOI: 10.3389/fendo.2022.982845 -
Cleveland Clinic Journal of Medicine Apr 2018The female athlete triad is a syndrome consisting of low energy availability (ie, burning more calories than one is taking in), menstrual dysfunction, and low bone... (Review)
Review
The female athlete triad is a syndrome consisting of low energy availability (ie, burning more calories than one is taking in), menstrual dysfunction, and low bone mineral density, although all 3 components need not be present. Many providers, physical therapists, and coaches are unaware of it and thus do not screen for it. Early intervention using a team approach is essential in patients with any component of the female athlete triad to prevent long-term adverse health effects.
Topics: Adolescent; Adult; Amenorrhea; Bone Density; Energy Intake; Energy Metabolism; Female; Female Athlete Triad Syndrome; Humans; Osteoporosis; Young Adult
PubMed: 29634467
DOI: 10.3949/ccjm.85a.16137 -
Hormone Research 2009Women harbouring inactivating mutations in luteinizing hormone (LH) beta subunit (LHB) or LH receptor (LHCGR) genes have similar clinical manifestations characterized by... (Review)
Review
Women harbouring inactivating mutations in luteinizing hormone (LH) beta subunit (LHB) or LH receptor (LHCGR) genes have similar clinical manifestations characterized by female external genitalia, spontaneous breast and pubic hair development at puberty, and normal or late menarche followed by oligo-amenorrhea and infertility. Oestradiol and progesterone levels are normal for the early to midfollicular phase, but do not reach ovulatory or luteal phase levels, confirming lack of ovulation. Notably, serum LH levels are low in patients with LHB mutations and high in those with LHCGR mutations, whereas follicle-stimulating hormone levels are normal or only slightly increased. Pelvic ultrasound has demonstrated a small or normal uterus and normal or enlarged ovaries with cysts. Women with LHB mutations may be treated with hCG (human chorionic gonadotropin) or LH, whereas those with mutations in LHCGR are resistant. Lhb and Lhcgr knockout female mice are close phenocopies of the respective human mutations, and confirm that early follicular development, low levels of oestrogen production and theca cell development are independent of LH action, which is necessary for ovulation. Although inactivating mutations in LHB and LHCGR are rare in comparison to other genetic and non-genetic causes of hypogonadism, they should be considered in the differential diagnosis of oligo-amenorrhea and infertility.
Topics: Amenorrhea; Animals; Chorionic Gonadotropin; Female; Hormone Replacement Therapy; Humans; Infertility, Female; Luteinizing Hormone, beta Subunit; Menstrual Cycle; Mice; Mice, Knockout; Mutation; Receptors, LH
PubMed: 19129711
DOI: 10.1159/000183895 -
American Family Physician Jun 2000The female athlete triad is defined as the combination of disordered eating, amenorrhea and osteoporosis. This disorder often goes unrecognized. The consequences of lost... (Review)
Review
The female athlete triad is defined as the combination of disordered eating, amenorrhea and osteoporosis. This disorder often goes unrecognized. The consequences of lost bone mineral density can be devastating for the female athlete. Premature osteoporotic fractures can occur, and lost bone mineral density may never be regained. Early recognition of the female athlete triad can be accomplished by the family physician through risk factor assessment and screening questions. Instituting an appropriate diet and moderating the frequency of exercise may result in the natural return of menses. Hormone replacement therapy should be considered early to prevent the loss of bone density. A collaborative effort among coaches, athletic trainers, parents, athletes and physicians is optimal for the recognition and prevention of the triad. Increased education of parents, coaches and athletes in the health risks of the female athlete triad can prevent a potentially life-threatening illness.
Topics: Amenorrhea; Anorexia Nervosa; Bulimia; Diagnosis, Differential; Exercise; Female; Humans; Life Style; Patient Education as Topic; Prognosis; Risk Factors; Sports; Teaching Materials
PubMed: 10865930
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Aug 2021Granulosa cell tumor of the ovary (GCT) is a rare ovarian tumor with nonspecific symptoms. Studies reported that GCT are usually secreting estrogens and inhibins,... (Review)
Review
Granulosa cell tumor of the ovary (GCT) is a rare ovarian tumor with nonspecific symptoms. Studies reported that GCT are usually secreting estrogens and inhibins, especially inhibin B. It is considered that, in premenopausal women, irregular menses or secondary amenorrhea may be an early symptom of GCT and, in postmenopausal women, the most common manifestation is vaginal bleeding. Additionally, endometrial abnormalities can be associated due to estrogenic secretion. At reproductive age, high levels of inhibin, lead to low levels of FSH and secondary amenorrhea causing infertility. At times, increased levels of LH in women with GCT are observed and the pathogenesis is still unclear. Therefore, inhibin B level can differentiate GCT from other causes of secondary amenorrhea. We report the case of a 26-year-old nulliparous, women who presented in our clinic with secondary infertility lasting longer than 2 years, secondary amenorrhea, polycystic ovarian syndrome, and suspicion of right ovarian endometrioma on CT scan. The ultrasound examination revealed that the right ovary was transformed in an anechoic mass with increased peripheral vascularity having a volume of 10 cm. This patient had high serum levels of inhibin B and LH but normal levels of FSH and estradiol. The preliminary diagnosis of granulosa cell tumor of the ovary was made. After counseling, the informed consent for treatment was obtained and the patient agreed to undergo surgery. An uneventful laparoscopy was performed with right oophorectomy and multiple peritoneal sampling. The histological diagnosis confirmed adult GCT limited to right ovary, with negative peritoneal biopsies (FIGO IA). After surgery the patient recovered fully and had normal menstrual cycles with normal serum levels of hormones. Two months later she conceived spontaneously and had an uneventful pregnancy. In conclusion, for cases with secondary amenorrhea, the evaluation of inhibin B level is essential. Elevated inhibin B level may be a sign for the presence of an unsuspected tumor. With early diagnosis and treatment, the prognosis is generally good and the fertility may be preserved, especially in young patients with GCT.
Topics: Adult; Amenorrhea; Female; Granulosa Cell Tumor; Humans; Infertility; Inhibins; Luteinizing Hormone; Ovary; Pregnancy
PubMed: 34441035
DOI: 10.3390/medicina57080829 -
American Journal of Physiology.... Sep 2014The renin-angiotensin-aldosterone system (RAAS) is integrally involved in multiple cardiovascular physiological processes including arterial blood pressure (BP)... (Review)
Review
The renin-angiotensin-aldosterone system (RAAS) is integrally involved in multiple cardiovascular physiological processes including arterial blood pressure (BP) regulation. Over activity of the RAAS has been implicated in the pathogenesis of a number of cardiovascular disease entities, including hypertension. Several lines of evidence suggest estrogen favorably modulates the RAAS. Conversely, estrogen deficiency due to menopause may contribute to over activity of the RAAS. Of importance, estrogen deficiency in women is not exclusive to the postmenopausal period. Functional hypothalamic amenorrhea is a reversible cause of premenopausal hypoestrogenemia. In contrast to postmenopausal women (PMW), premenopausal women with exercise-associated functional hypothalamic amenorrhea demonstrate decreased, not increased, resting BP compared with their estrogen-replete eumenorrheic counterpart. In this review we briefly examine the effects of estrogen status on the RAAS and present the hypothesis that the RAAS is altered in physically active women with functional hypothalamic amenorrhea.
Topics: Amenorrhea; Animals; Blood Pressure; Estrogens; Female; Humans; Motor Activity; Premenopause; Renin-Angiotensin System
PubMed: 24944241
DOI: 10.1152/ajpregu.00182.2014