Fifteen-minute consultation: a structured approach to the child with primary amenorrhea.

Puberty is a life-changing time in the life of a young person, with physical, psychological and social considerations. Amenorrhea is derived from Latin: a-'not', men-'month' and rhein-'flow', meaning absence of monthly flow. In medical terms, it is a symptom describing absence of menstruation. It can be classified as either primary or secondary. This article will focus solely on primary amenorrhea. Primary amenorrhea can induce great anxiety in both the patient and the family and often presents to the general paediatrician. A thorough history and examination and judicious use of investigations is crucial to ensure timely diagnosis and management.

Idiopathic hyperprolactinemia - A challenge for primary care.

Hyperprolactinemia is a condition of elevated serum prolactin, which usually occurs in women as compared to men. Most patients present to primary care clinics with a history of galactorrhoea, oligomenorrhea, amenorrhoea or infertility. Literature search reveals that there were few idiopathic causes of hyperprolactinemia, which resolved by itself without specific pharmacological or surgical treatment. This case is of a 39-year-old woman presented with amenorrhea for four months after Implanon removal and concomitantly noted to have galactorrhoea for four years without any medical attention. The condition persisted after cessation of breastfeeding. After undergoing several investigations including imaging studies, the underlying cause of hyperprolactinemia was noted to be idiopathic. Due to the unclear cause of its aetiology, this case caused various challenges to the primary care. Exhaustive physiological and pathological causes of hyperprolactinemia have been ruled out. Nevertheless, with adequate treatment, she gained her normal menstrual and resolved galactorrhoea symptoms.

Can improvement in hormonal and energy balance reverse cardiovascular risk factors in athletes with amenorrhea?

Female athletes display a high prevalence of hypothalamic amenorrhea as a result of energy imbalance. In these athletes with amenorrhea, decreased luteinizing hormone/follicule-stimulating hormone secretion leads to deficiency in endogenous estrogen. The severe estrogen deficiency in these athletes may increase cardiovascular risk similar to that in postmenopausal women. This review discusses the potential cardiovascular risk factors in athletes with amenorrhea as a result of hypoestrogenism, which include endothelial dysfunction and unfavorable lipid profiles. We also consider the potential to reverse the cardiovascular risk by restoring energy or hormonal imbalance along the reproductive axis in athletes with amenorrhea.

The efficacy of using acupuncture in managing polycystic ovarian syndrome.

PURPOSE OF REVIEW: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder, which significantly impairs the fertility of 3-10% of women at reproductive age. It is getting very popular for women with PCOS to seek alternative therapies to treat PCOS, for example, acupuncture. This review examines the currently available evidence from the randomized controlled trial to guide future recommendation on using acupuncture to assist the treatment of PCOS. RECENT FINDINGS: PCOS is manifested by oligo-amenorrhoea, infertility, and hirsutism. The standard treatment of PCOS includes oral pharmacological agents, lifestyle changes, and surgical modalities. Pharmacologically based therapies are only effective in 60% of the patients, which are also associated with different side-effects. As such, acupuncture offered an alternative option. Acupuncture can affect ß-endorphin production, which may, in turn, affect gonadotropin-releasing hormone secretion and affecting ovulation and menstrual cycle. Therefore, it is postulated that acupuncture may induce ovulation and restore menstrual cycle via increasing ß-endorphin production. SUMMARY: Although modern medical science has discovered the action mechanisms underlying how acupuncture may manage the symptoms of PCOS, majority of the trials are small in sample size and lack of consistency in the choice of acupoints. Larger scale trials are needed to provide standardized protocols.

Amenorrhea: A Systematic Approach to Diagnosis and Management.

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.

Microwave endometrial ablation versus thermal balloon endometrial ablation (MEATBall): 5-year follow up of a randomised controlled trial.

OBJECTIVE: To compare long-term outcomes following microwave endometrial ablation (MEA™) and thermal balloon ablation (TBall). DESIGN: Follow up of a prospective, double-blind randomised controlled trial at 5 years. SETTING: A teaching hospital in the UK. POPULATION: A total of 320 women eligible for and requesting endometrial ablation. METHODS: Eligible women were randomised in a 1:1 ratio to undergo MEA or Tball. Postal questionnaires were sent to participants at a minimum of 5 years postoperatively to determine satisfaction with outcome, menstrual status, bleeding scores and quality of life measurement. Subsequent surgery was ascertained from the women and the hospital operative database. MAIN OUTCOME MEASURES: The primary outcome measure was overall satisfaction with treatment. Secondary outcomes included evaluation of menstrual loss, change in quality of life scores and subsequent surgery. RESULTS: Of the women originally randomised 217/314 (69.1%) returned questionnaires. Nonresponders were assumed to be treatment failures for data analysis. The primary outcome of satisfaction was similar in both groups (58% for MEA™ versus 53% for TBall, difference 5%; 95% CI -6 to 16%). Amenorrhoea rates were high following both techniques (51% versus 45%, difference 6%; 95% CI -5 to 17%). There was no significant difference in the hysterectomy rates between the two arms (9% versus 7%, difference 2%; 95% CI -5 to 9%). CONCLUSIONS: At 5 years post-treatment there were no significant clinical differences in patient satisfaction, menstrual status, quality of life scores or hysterectomy rates between MEA™ and Thermachoice 3, thermal balloon ablation.

Current evaluation of amenorrhea: a committee opinion.

The purpose of this American Society for Reproductive Medicine Practice Committee Opinion is to provide clinicians with principles and strategies for the diagnostic evaluation of patients presenting with primary or secondary amenorrhea. This revised document replaces the Practice Committee Document titled "Current evaluation of amenorrhea," last published in 2008 (Fertil Steril 2008;90:S219-25).

Dietary and Lifestyle Management of Functional Hypothalamic Amenorrhea: A Comprehensive Review.

Functional Hypothalamic Amenorrhea (FHA) is a condition characterized by the absence of menstruation, which is increasingly affecting young women. However, specific recommendations for treating and preventing this condition are lacking. Based on a review of the available literature, this article provides practical and feasible dietary management recommendations for healthcare professionals and researchers in women's health and nutrition. It answers the question of what interventions and nutritional recommendations are necessary to restore menstrual function in women struggling with FHA. Physicians recommend an energy availability threshold of 30 kcal/kg FFM/day to prevent FHA. Also, energy availability below and above this threshold can inhibit LH pulsation and cause menstrual disorders. In addition, the risk of menstrual disorders increases with a decrease in the caloric content of the diet and the duration of the energy deficit, and women with FHA have significantly lower energy availability than healthy women. It is essential to ensure that adequate kilocalories are provided throughout the day (regular meals that are a source of proper glucose) to avoid a negative energy balance, as glucose has been proven to affect LH pulses and T3 and cortisol concentrations in the body. Dietary intervention should focus on increasing the caloric content of the diet, thus increasing energy availability and restoring energy balance in the body. Treatment and diagnosis should also focus on body composition, not just body weight. An increase in body fat percentage above 22% may be required to restore menstrual function. In women with FHA, even an increase in body fat mass of one kilogram (kg) increases the likelihood of menstruation by 8%. It is advisable to reduce the intensity of physical activity or training volume, while it is not advisable to give up physical activity altogether. It is also important to ensure adequate intake of micronutrients, reduce stress, and incorporate cognitive-behavioral therapy.

Primary Amenorrhea and Premature Ovarian Insufficiency.

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.

Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential.

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin-releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss-often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.

Predictors of the resumption of menses in adolescent anorexia nervosa.

BACKGROUND: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. METHODS: A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. RESULTS: Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. CONCLUSIONS: The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.

Women with anorexia nervosa should not be treated with estrogen or birth control pills in a bone-sparing effect.

Eating disorders are prevalent, serious conditions that affect mainly young women. An early and enduring sign of anorexia is amenorrhea. There is no evidence for benefits of hormone therapy in patients with anorexia; however, hormone medication and oral contraceptives are frequently prescribed for young women with anorexia as a prevention against and treatment for low bone mineral density. The use of estrogens may create a false picture indicating that the skeleton is being protected against osteoporosis. Thus the motivation to regain weight, and adhere to treatment of the eating disorder in itself, may be reduced. The most important intervention is to restore the menstrual periods through increased nutrition. Hormone and oral contraceptive therapy should not be prescribed for young women with amenorrhea and concurrent eating disorders.

Amenorrhea: an approach to diagnosis and management.

Although amenorrhea may result from a number of different conditions, a systematic evaluation including a detailed history, physical examination, and laboratory assessment of selected serum hormone levels can usually identify the underlying cause. Primary amenorrhea, which by definition is failure to reach menarche, is often the result of chromosomal irregularities leading to primary ovarian insufficiency (e.g., Turner syndrome) or anatomic abnormalities (e.g., Müllerian agenesis). Secondary amenorrhea is defined as the cessation of regular menses for three months or the cessation of irregular menses for six months. Most cases of secondary amenorrhea can be attributed to polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, or primary ovarian insufficiency. Pregnancy should be excluded in all cases. Initial workup of primary and secondary amenorrhea includes a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone. Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile. Patients with hypothalamic amenorrhea should be evaluated for eating disorders and are at risk for decreased bone density. Patients with polycystic ovary syndrome are at risk for glucose intolerance, dyslipidemia, and other aspects of metabolic syndrome. Patients with Turner syndrome (or variant) should be treated by a physician familiar with the appropriate screening and treatment measures. Treatment goals for patients with amenorrhea may vary considerably, and depend on the patient and the specific diagnosis.

Diagnostic pitfalls in the evaluation and management of amenorrhea in adolescents.

Amenorrhea is a common menstrual problem seen in adolescents. Amenorrhea has been shown to have a negative impact on adolescents' quality of life. In this paper we discuss the various causes and investigations of amenorrhea in adolescents and address management dilemmas for specific conditions. Specific approaches in dealing with adolescents using the HEADSS (Home, Education, Activity, Drugs, Sexual activity, Suicidal) approach are discussed.

Recognition and rehabilitation of the female athlete triad/tetrad: a multidisciplinary approach.

While the benefits of physical activity are numerous, the female athlete triad poses a significant health risk to young athletes. Emerging research links the triad to endothelial dysfunction--a sentinel event in cardiovascular disease--suggesting that this complex interplay of metabolic and endocrine factors may be described more accurately as a tetrad. Effective treatment of the triad/tetrad requires a multidisciplinary approach. Emphasis must be placed on prevention, recognition, and treatment of triad for the promotion of healthy nutritional and activity profiles in female athletes across their lifespans.

Functional Hypothalamic Amenorrhea: Recognition and Management of a Challenging Diagnosis.

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.

My 28 Days - a global digital women's health initiative for evaluation and management of secondary amenorrhea: case report and literature review.

There is a need to close the gap between knowledge and action in health care. Effective care requires a convenient and reliable distribution process. As global internet and mobile communication increase capacity, innovative approaches to digital health education platforms and care delivery are feasible. We report the case of a young African woman who developed acute secondary amenorrhea at age 18. Subsequently, she experienced a 10-year delay in the diagnosis of the underlying cause. A global digital medical hub focused on women's health and secondary amenorrhea could reduce the chance of such mismanagement. Such a hub would establish more efficient information integration and exchange processes to better serve patients, family caregivers, health care providers, and investigators. Here, we show proof of concept for a global digital medical hub for women's health. First, we describe the physiological control systems that govern the normal menstrual cycle, and review the pathophysiology and management of secondary amenorrhea. The symptom may lead to broad and profound health implications for the patient and extended family members. In specific situations, there may be significant morbidity related to estradiol deficiency: (1) reduced bone mineral density, 2) cardiovascular disease, and 3) cognitive decline. Using primary ovarian insufficiency (POI) as the paradigm condition, the Mary Elizabeth Conover Foundation has been able to address the specific global educational needs of these women. The Foundation did this by creating a professionally managed Facebook group specifically for these women. POI most commonly presents with secondary amenorrhea. Here we demonstrate the feasibility of conducting a natural history study on secondary amenorrhea with international reach to be coordinated by a global digital medical hub. Such an approach takes full advantage of internet and mobile device communication systems. We refer to this global digital women's health initiative as My 28 Days®.

The management of menstrual suppression and uterine bleeding: a survey of current practices in the Pediatric Blood and Marrow Transplant Consortium.

BACKGROUND: Current guidelines recommend the use of combined hormonal contraceptive pills for menstrual suppression in pediatric blood and marrow transplant (BMT) recipients but recent research reveals that provider practice varies. This study was designed to describe the current practice for managing menstrual issues, that is, menstrual suppression and uterine bleeding, in pediatric BMT patients and to better understand health care providers' practices in the use of gonadotropin-releasing hormone agonists (GnRHa). PROCEDURE: A cross sectional survey consisting of 53 questions was distributed via email to principal investigators in the Pediatric Blood and Marrow Transplant Consortium (PBMTC). Responses were collected using www.surveymonkey.com. RESULTS: Menstrual suppression and uterine bleeding in pediatric BMT patients are primarily managed by pediatric oncologists (97%). The most frequently reported hormonal method used for induction of therapeutic amenorrhea was GnRHa (41%). The top three reasons for choosing a method were greater likelihood of amenorrhea, concerns about side effects, and possible gonadal protection. Continuous combined hormonal contraceptive pills were the most commonly used method for the management of clinically significant uterine bleeding regardless of primary method used for menstrual suppression. CONCLUSION: Despite the 2002 PBMTC guidelines, wide variation in menstrual suppression management practices still exists. Our data show that use of GnRHa is more common than previously reported. Additional research is needed to develop evidence-based practice guidelines in pediatric BMT patients.

Restoration of menses with nonpharmacologic therapy in college athletes with menstrual disturbances: a 5-year retrospective study.

BACKGROUND: Functional hypothalamic amenorrhea is common among female athletes and may be difficult to treat. Restoration of menses (ROM) is crucial to prevent deleterious effects to skeletal and reproductive health. OBJECTIVES: To determine the natural history of menstrual disturbances in female college athletes managed with nonpharmacologic therapies including increased dietary intake and/or decreased exercise expenditure and to identify factors associated with ROM. STUDY DESIGN: A 5-yr retrospective study of college athletes at a major Division I university. METHODS: 373 female athletes' charts were reviewed. For athletes with menstrual disturbances, morphometric variables were noted. Months to ROM were recorded for each athlete. RESULTS: Fifty-one female athletes (19.7%) had menstrual disturbances (14.7% oligomenorrheic, 5.0% amenorrheic). In all, 17.6% of oligo-/amenorrheic athletes experienced ROM with nonpharmacologic therapy. Mean time to ROM among all athletes with menstrual disturbances was 15.6 ± 2.6 mo. Total absolute (5.3 ± 1.1 kg vs. 1.3 ± 1.1 kg, p < .05) and percentage (9.3% ± 1.9% vs. 2.3% ± 1.9%, p < .05) weight gain and increase in body-mass index (BMI; 1.9 ± 0.4 kg/m2 vs. 0.5 ± 0.4 kg/m2, p < .05) emerged as the primary differentiating characteristics between athletes with ROM and those without ROM. Percent weight gain was identified as a significant positive predictor of ROM, OR (95% CI) = 1.25 (1.01, 1.56), p < .05. CONCLUSIONS: Nonpharmacologic intervention in college athletes with menstrual disturbances can restore regular menstrual cycles, although ROM may take more than 1 yr. Weight gain or an increase in BMI may be important predictors of ROM.