Has Menstruation Disappeared? Functional Hypothalamic Amenorrhea—What Is This Story about?

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.

Functional Hypothalamic Amenorrhea: A Stress-Based Disease

The aim of the study is to present the problem of functional hypothalamic amenorrhea, taking into account any disease and treatment, diagnosis, and consequences of this disease. We searched PubMed (MEDLINE) and included 38 original and review articles concerning functional hypothalamic amenorrhea. Functional hypothalamic amenorrhea is the most common cause of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences. The basis of functional hypothalamic amenorrhea is hormonal, based on impaired pulsatile GnRH secretion in the hypothalamus, then decreased secretion of gonadotropins, and, consequently, impaired hormonal function of the ovaries. This disorder leads to hypoestrogenism, manifested by a disturbance of the menstrual cycle in the form of amenorrhea, leading to anovulation. Prolonged state of hypoestrogenism can be very detrimental to general health, leading to many harmful short- and long-term consequences. Treatment of functional hypothalamic amenorrhea should be started as soon as possible, and it should primarily involve lifestyle modification. Only then should pharmacological treatment be applied. Importantly, treatment is most often long-term, but it results in recovery for the majority of patients. Effective therapy, based on multidirectional action, can protect patients from numerous negative impacts on fertility, cardiovascular system and bone health, as well as reducing mental morbidity.

Functional hypothalamic amenorrhea remission, with spontaneous pregnancy after behavioral modifications

Functional Hypothalamic Amenorrhea (FHA) is a disorder that generates a state of chronic anovulation due to a low calorie intake and high energy expenditure through intense physical activity. This energy deficit induce several hormonal changes that lead to decreased secretion of gonadotrophin releasing-hormone (GnRH) and luteinizing hormone (LH), resulting in a chronic state of hypoestrogenism and infertility. Loss of bone mineral content and delayed puberty may also arise from such condition depending on patient´s age. Herein we present a case of a patient with HFA that was reversible through behavioral modifications, resulting in spontaneous pregnancy

Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea

Purpose Functional hypothalamic amenorrhea (FHA) occurs in response to exaggerated stressors with or without body weight loss. Various hormones, neurotransmitters, and neuromodulators are involved in the control of GnRH and kisspeptin is one of them. Our study aimed to evaluate the putative temporal coupling between kisspeptin and GnRH-induced LH pulsatile secretion. Methods In total, 71 patients with FHA were selected for this study. All patients undergo to a pulsatility study for LH and kisspeptin evaluation (120 min, sampling every 10 min), and to an endocrine evaluation for prolactin (PRL), estradiol (E2), androstenedione (A), 17-hydroxy-progesterone (17OHP), TSH, fT3, fT4, insulin, cortisol and testosterone (T), glucose, total cholesterol, triglycerides. Results Our data demonstrated kisspeptin and LH pulsatile secretions and that both hormones are co-secreted and temporally coupled at time 0 (p < 0.05). When patients were subdivided in hypo-LH (≤3 mIU/ml, n = 58) and normo-LH (>3 mIU/ml, n = 13), more insights were observed on the specific correlations of metabolic and hormone profiles with pulsatility indexes of LH and kisspeptin. Conclusions Our study demonstrated the presence of a distinct kisspeptin episodic secretion in patients with FHA, and showed the temporally coupling of kisspeptin with LH secretory episodes thus supporting that though in amenorrhea, the reproductive axis is still relying on kisspeptin to drive GnRH discharge. In addition, correlations among hormonal data sustain the hypothesis that stress-induced compensatory events are the main direct and indirect promoters of the reproductive blockade in patients affected by FHA.

AKUPUNKTUR TERAPI UNTUK MENURUNKAN LEVEL ANSIETAS PADA WANITA DENGAN WEIGHT LOSS RELATED AMENORRHEA: A PILOT STUDY

ABSTRAKLatar Belakang: Weight loss related amenorrhea merupakan suatu kondisi amenorea yang disebabkan oleh disfungsi hypothalamus atau disebut juga dengan Functional Hypothalamic Amenorrhea (FHA). Ketika seorang wanita mengalami amenorea dalam jangka waktu yang relatif lama, tentunya kondisi ini akan mempengaruhi psikologis wanita tersebut. Oleh sebab itu, mengkaji kondisi psikis dari wanita yang menderita weight loss related amenorrhea dan membantu menurunkan level ansietasnya juga sangat di perlukan. Pilot study ini dilakukan untuk mengetahui efek dari akupunktur terapi untuk menurunkan level ansietas pada wanita dengan weight loss related amenorrhea.Metode: Sebanyak 15 orang wanita dengan diagnose weight loss related amenorrhea bersedia menjadi partisipan dalam pilot study ini. Seluruh partisipan mendapatkan 20 kali terapi yang dilakukan di Shanghai Research Institute of Acupuncture and Meridian, Shanghai-China. Zung Self-Rating Anxiety Scale (SAS) questionnaire digunakan dalam pilot study ini sebagai alat ukur terhadap level ansietas partisipan. Data yang didapatkan dalam study ini, dianalisa menggunakan paired-sample t-test dengan level signifikansi p≤0.05.Hasil: Terdapat penurunan yang signifikan pada hasil SAS partisipan dalam study ini. Sebelum terapi dilakukan, diperoleh hasil SAS sebesar 46.60±8.58 yang mengindikasikan ansietas sedang. Setelah menjalani 20 kali treatment, hasil SAS mengalami penurunan menjadi 41.80±3.07 (p<0.05), yang menunjukan ansietas dalam rentang normal.Kesimpulan: Hasil ini mengindikasikan bahwa akupunktur dapat dijadikan sebagai salah satu metode pengobatan untuk menurunkan level ansietas yang disebabkan oleh weight loss related amenorrhea.Kata kunci: Akupunktur, SAS, ansietas, weight loss related amenorrheaABSTRACTBackground: Weight loss related amenorrhea is a condition caused by dysfunction of the hypothalamic pituitary ovarian axis due to significant weight loss. Amenorrhea that caused by dysfunction of hypothalamic also known as Functional Hypothalamic Amenorrhea (FHA). When this amenorrhea last for long duration of time, it might involve our psychologist condition. This pilot study was conducted to investigate the effect of acupuncture to reduce anxiety level among women with weight loss related amenorrhea. Methods: Fifteen participants were enrolled in this pilot study. The participants received 20 sessions of acupuncture treatment and all of the treatment sessions was conducted in Shanghai Research Institute of Acupuncture and Meridian, Shanghai-China. Zung Self-Rating Anxiety Scale (SAS) questionnaire was used as a measurement tool to measure the anxiety level among participants. Paired-sample t-test was performed to analyze the data result, with significant p value ≤0.05. Results: Significant changes was found in mean score of SAS before and after treatment. It approximately 46.60 ± 8.58 before treatment and it decrease to 41.80 ± 3.07 after treatment (p<0.05). Conclusion: The result of this pilot study suggest that acupuncture is effective and it can be used as treatment method to reduce anxiety level among participants with weight loss related amenorrhea.Keywords: Acupuncture, SAS, anxiety, weight loss related amenorrhea

Administration of Very Low Doses of Estradiol Modulates the LH Response to a GnRH Bolus and the LH and Cortisol Responses to Naloxone Infusion in Patients with Functional Hypothalamic Amenorrhea (FHA): A Pilot Study

Background: Functional Hypothalamic Amenorrhea (FHA) is a stress-induced blockade of the reproductive axis. Such impairment is mainly due to altered control of GnRH-induced gonadotropin secretion as well as alterations of other endocrine functions. Methods: Seventeen patients with FHA participated in the study. Basal hormonal profiles and GnRH and Naloxone tests for LH (Luteinizing Hormone) and for LH and cortisol responses, respectively, were performed before and after two weeks of administration of a very low dose of estradiol (2.5 ng two times a day). Results: The treatment improved both gonadotropins, mainly LH. The LH response to the GnRH test improved in terms of the peak amplitude, as evaluated using Instantaneous Secretory Rates (ISR) computation. Moreover, when performing the Naloxone test after the treatment interval, FHA patients showed a quicker LH response and recovery of the cortisol response. Conclusions: Our study supports the relevance of very low dose estradiol priming to promote and restore impaired neuroendocrine function in patients with FHA.