How to treat anorexia nervosa? – case report

Anorexia nervosa is an eating disorder characterized by low body weight and body image distortion with obsessive fear of gaining weight. It is a complex condition involving psychological, neuroendocrine, hormonal and metabolic components. The following is a case report of a young patient diagnosed as anorexia nervosa and primary amenorrhea, without the development of secondary female characteristics. Hormonal examination confirmed hypothalamic origin of the described disorders. There was an important impairment in the mood sphere (Beck's Depression Inventory and Hamilton Depression Rating Scale) of this young woman. Densitometry of lumbar spine revealed significant bone loss (diagnozed as osteoporosis) in this patient. All of the abovementioned examinations were repeated after one and a half years of hormonal treatment (estrogen-progestins). A return of normal menstrual cycle (with ovulation function) and normal hormonal profile have been observed. After one and a half years of treatment the patient had regular feeding patterns and none of the anorexia nervosa symptons have been found. A significant improvement in Beck's Depression Inventory and Hamilton Depression Rating Scale was found after one and a half years of hormonal treatment. The patient was also characterized by important increase of bone mass density – osteopenia was described by the densitometry of the lumbar spine

Spontaneous endogenous pulsatile release of kisspeptin is temporally coupled with luteinizing hormone in healthy women

Objective To evaluate the presence of a spontaneous pulsatile release of kisspeptin and whether it is temporally coupled to LH pulses. Design Experimental study. Setting Academic medical center. Patient(s) Thirty young healthy eumenorrheic women aged 20-37 years were included in the study group. All subjects were white women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland. Intervention(s) Kisspeptin, FSH, LH, E2, PRL, and insulin were evaluated in all subjects at baseline. Main Outcome Measure(s) All women underwent a pulsatility study measuring LH and kisspeptin plasma concentrations to assess the spontaneous episodic secretion of both hormones, sampling every 10 minutes for 2 hours from 9:00 to 11:00 a.m. for a total of 12 blood samples. Detection and specific concordance (SC) algorithms were used to detect pulses and their concordance. Result(s) A significant endogenous secretory pattern was demonstrated for both LH and kisspeptin over the 2-hour duration of the study (2.4 ± 0.1 peaks/2 h). The computation of the SC index showed for the first time that kisspeptin and LH are cosecreted and temporally coupled at time "0," and their peaks occur at the same point in time. Conclusion(s) The present study provides evidence supporting the hypothesis that kisspeptin is highly relevant in the regulation and modulation of reproductive functions in humans

Serum Levels of Tryptophan, 5-Hydroxytryptophan and Serotonin in Patients Affected with Different Forms of Amenorrhea

Tryptophan (Trp) is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT) through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5-hydroxytryptophan (5-HTP) in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P ≤ 0.05) lower in the anorexic (11.64 ± 0.53 μg/ml, mean ± S.E.) than in the control (12.98 ± 0.37 μg/ml) groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed

Why kisspeptin is such important for reproduction?

Recently discovered neuropeptide called kisspeptin is thought to be an essential gatekeeper in control of reproduction. Kisspeptin, the product of KiSS-1 gene and its G protein-coupled receptor GPR54 play a master role in the puberty period and fertility. This 54 amino acid peptide known also as metastatin, because of its metastasis suppression ability is also implicated in tumour biology. Kisspeptin/GPR54 system activates the hypothalamus-pituitary-ovarian axis. Its mechanism is not clearly understood. Kisspeptin influence is found above more at the level of hypothalamus but also at the pituitary and ovaries level. Kisspeptin can directly stimulate GnRH secretion from arcuate nucleus of hypothalamus. It is thought that kisspeptin plays an essential role in the metabolic regulation of fertility. In negative energy balance conditions an expression of KiSS-1 gene is decreased. Inactivating GPR54 mutations cause hypogonadotropic hypogonadism in humans. Simultaneously, mutations which increase GPR54 signalling are connected with gonadotropin-dependent premature puberty. Lately, possible therapeutic role of kisspeptin administration has been discussed. It was stated that kisspeptin might be used to manipulate the hypothalamic-pituitary-gonadal axis in humans. However, further studies are essential to reveal the exact mechanism and role of GPR54 agonists and antagonists applications. Moreover, the role of kisspeptin in the aspect of detection and treatment of specific cancers should be discovered

Hypoestrogenism in young women and its influence on bone mass density

One of the most important hormonal factors responsible for bone health is estradiol. Genetic factors, adequacy of hormonal functioning, nutrition and physical activity may be the markers of bone status and development in young women. During adolescence, women reach peak bone acquisition and develop a skeletal mass. This process is largely regulated by endocrine factors mainly such as adequate levels of gonadal, adrenal and pituitary hormones. The crucial role played by estradiol and its impact on bones are very multiple. Estradiol induces growth factors' activation, receptor activator of nuclear factor kappa B ligand (RANKL) production inhibition and is mainly referred to antiresorptive activity. Clinical situations leading to hypoestrogenism has been linked to decreased bone mineral density leading to osteopenia and osteoporosis. This status both in fertile and perimenopausal women can increase the risk of pathological fractures. Such conditions as hypothalamic-pituitary insufficiency (functional hypothalamic amenorrhea, anorexia nervosa, Kallmann syndrome, hyperprolactinemia), ovarian failure (gonadal dysgenesis, premature ovarian failure) and iatrogenic treatment (surgery, chemotherapy, radiotherapy) can cause hypoestrogenism. The treatment of osteopenia and osteoporosis caused by hypoestrogenism is very essential and multidirectional. The crucial role of the therapy is the achievement of proper serum estradiol concentration and eliminate the causes of hypoestrogenism

Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA

Skeletal status and body composition in young women with functional hypothalamic amenorrhea.

Functional hypothalamic amenorrhea (FHA) related to hypoestrogenism and hormonal status may influence skeletal homeostasis and body composition. The study aimed to evaluate hormones concentrations, body composition and bone strength in FHA cases. PATIENTS AND METHODS: Total body scans using DXA method (DPX-L, GE Lunar) were performed in a group of 27 women aged 21.8 years ± 3.9 with FHA related to weight loss. References of healthy control subjects were used to calculate Z-scores (age and gender matched), SD-scores (height and gender matched), and SDs-scores (weight and gender matched). Whole skeleton bone mineral content (TBBMC, g) and density (TBBMD, g/cm(2)), lumbar spine (L2-L4) bone mineral density (SBMD; g/cm(2)), lean body mass (LBM, g) and fat mass (FM, g) were investigated. Relative bone strength index was calculated as the TBBMC/LBM ratio. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, and prolactin (PRL) concentrations were assayed to characterize hormonal profile of FHA cases. RESULTS: Hormonal evaluation in patients with FHA revealed significantly decreased serum concentrations of gonadotropins and estradiol. Serum LH concentrations were 1.47 ± 0.89 mIU/ml, FSH 4.44 ± 1.94 mIU/ml. Estradiol concentrations in serum were 27.08 ± 13.10 pg/ml. As evidenced by Z-scores, FHA cases had decreased SBMD, TBBMD and TBBMC Z-scores of -1.23 ± 0.90 (p < 0.0001), -0.72 ± 0.86 (p < 0.001), and -0.90 ± 1.40 (p < 0.01), respectively. Reduced FM, LBM and FM/LBM ratio Z-scores of -1.80 ± 2.28 (p < 0.001), -0.59 ± 1.49 (p < 0.05) and -0.74 ± 1.55 (p < 0.05), but not TBBMC/LBM Z-score of -0.54 ± 2.14 (ns) were noted in FHA cases compared with healthy control cases. TBBMC, TBBMD, TBBMC/LBM when BH- or BW-matched were normal as evidenced by SD-scores and SDs-scores. SBMD remained reduced when BH-matched (SD-score = -0.40 ± 0.86; p < 0.05) whereas FM and FM/LBM were lower than expected in healthy, both compared to BH- and BW-dependent references. The length of amenorrhea in months negatively correlated with SBMD Z-score (R = -0.39, p < 0.05), and SD-scores for SBMD (R = -0.48), TBBMD (R = -0.43), TBBMC (R = -0.46) (all p < 0.05) and positively with SDs-scores for FM (R = 0.44, p < 0.05). CONCLUSION: Patients with FHA were characterized by lower concentrations of serum FSH, LH and estradiol concentrations. Moreover, FHA cases had decreased FM and an imbalanced relationship between BW, FM, and LBM. Despite reduced BMD and BMC, bone strength was not significantly affected by FHA