Micronutrient deficiency in menstrual dysfunction among women of reproductive age

Objective. To determine whether inorganic menstrual dysfunction (MD) is associated with magnesium, iron and vitamin D deficiency in women of reproductive age. Materials and methods. The study group I consisted of 50 women with MD: dysmenorrhea (16 women), oligomenorrhea (12 women), functional hypothalamic amenorrhea (3 patients) and acyclic abnormal uterine bleeding (19 women), the comparison group II was composed of 30 patients with normal menstrual function. The methods of study included history taking using a questionnaire to detect the signs of magnesium deficiency, physical examination, echography of pelvic organs, full blood count, blood tests to determine the concentration of magnesium, vitamin D and ferritin as well as consulting a therapeutist. Results. Magnesium deficiency was registered significantly more often in patients with MD (93.0 3.6 %, 73.0 8.1 %, respectively; p 0.05). The most typical signs of magnesium deficiency were the central symptoms: headache (58.0 7.1 %, 22.0 7.6 %; p 0.001), irritability (53.0 7.1 %, 26.0 8.0 %; p 0.01), dyssomnia (45.0 7.0 %, 17.0 6.9 %; p 0.01), dizziness (42.5 7.0 %, 22.0 7.6 %; p 0.05), a decrease in libido (34.0 6.7 %, 13.0 6.1 %; p 0.05), as well as trophic disturbances including hair loss (38.0 6.9 %, 13.0 6.9 %; p 0.01). Similar findings were obtained when we studied the iron supply: the frequency of latent iron deficiency (according to ferritin concentration) was 77.0 5.9 and 35.7 8.4 % respectively; p 0.001. Deficiency or insufficient supply of 25(ОH)D was registered significantly more often in women with MD in comparison with healthy women (45.0 7.0 %, 20.0 7.3 %; p 0.05). Conclusions. In summary, determination of the level of micronutrients and adequate compensation of their deficiency can be important factors in physiological correction of endocrine imbalance leading to functional disorders in the reproductive system and a decrease in fertility.

In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse

A hypothalamic pulse generator located in the arcuate nucleus controls episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) and is essential for reproduction. Recent evidence suggests this generator is comprised of arcuate 'KNDy' cells, the abbreviation based on co-expression of kisspeptin, neurokinin B, and dynorphin. However, direct visual evidence of KNDy neuron activity at a single-cell level during a pulse is lacking. Here, we use in vivo calcium imaging in freely moving female mice to show that individual KNDy neurons are synchronously activated in an episodic manner, and these synchronized episodes always precede LH pulses. Furthermore, synchronization among KNDy cells occurs in a temporal order, with some subsets of KNDy cells serving as 'leaders' and others as 'followers' during each synchronized episode. These results reveal an unsuspected temporal organization of activation and synchronization within the GnRH pulse generator, suggesting that different subsets of KNDy neurons are activated at pulse onset than afterward during maintenance and eventual termination of each pulse. Further studies to distinguish KNDy leader from follower cells is likely to have important clinical significance, since regulation of pulsatile GnRH secretion is essential for normal reproduction and disrupted in pathological conditions such as polycystic ovary syndrome and hypothalamic amenorrhea.

Neuroendocrine Effects of Carnitines on Reproductive Impairments

Carnitines are quaternary amines involved in various cellular processes such as fatty acid uptake, β-oxidation and glucose metabolism regulation. Due to their neurotrophic activities, their integrative use has been studied in several different physio-pathological conditions such as anorexia nervosa, chronic fatigue, vascular diseases, Alzheimer’s disease and male infertility. Being metabolically active, carnitines have also been proposed to treat reproductive impairment such as functional hypothalamic amenorrhea (FHA) and polycystic ovary syndrome (PCOS) since they improve both hormonal and metabolic parameters modulating the neuroendocrine impairments of FHA. Moreover, they are capable of improving the lipid profile and the insulin sensitivity in patients with PCOS.

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.

P–601 Anovulatory patients with PCOS have lower euploidy rates compared to those with hypothalamic amenorrhea and to normo-ovulatory patients

Study question How do euploidy rates differ in anovulatory women with polycystic ovarian syndrome (PCOS) and hypothalamic hypogonadism (HH) compared to normo-ovulatory women undergoing IVF/ICSI? Summary answer Patients with PCOS have a significantly lower euploidy rate compared to patients with HH and patients with tubal factor infertility. What is known already Previous studies have demonstrated similar blastocyst conversion rates in women with PCOS and tubal factor infertility. Reported aneuploidy rates in preimplantation genetic testing cycles are similar in women with PCOS and tubal infertility. There are no data on blastocyst conversion or aneuploidy rates in women with HH. While PCOS and HH are different physiologic processes, patients with these disorders are reported together to SART and to the CDC National ART Surveillance System under the diagnosis of “ovulatory dysfunction”. Study design, size, duration: Retrospective cohort study of all autologous IVF and ICSI cycles for patients with oligo-anovulation (PCOS, n = 552 and HH, n = 48) and normo-ovulation (tubal factor infertility, n = 423) from 1/1/2012 to 6/30/2019. A total of 1023 cycles from 720 patients were analyzed. Participants/materials, setting, methods Cycle outcomes, including number of oocytes, mature oocytes, blastocysts and euploid blastocysts were assessed for each diagnosis. Adjusted relative risks (aRR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, AMH, and stimulation protocol. Poisson regression was used for counts and with an offset for ratios. Patients contributing multiple cycles were accounted for using general estimating equations. Main results and the role of chance PCOS patients were given a lower starting dose of gonadotropins and received less total gonadotropins compared to patients with tubal factor infertility or HH, but had similar stimulation durations as tubal-factor patients. Patients with HH received higher total doses of gonadotropins and had longer stimulation durations. PCOS patients had significantly more oocytes retrieved and a higher number of blastocysts than patients with tubal factor infertility (18.9 vs. 13.6 aRR 1.16 95% CI: 1.05–1.28 and 6.6 vs. 3.7 aRR 1.32 95% CI 1.10–1.57, respectively). Patients with HH had a similar number of oocytes retrieved and number of blastocysts compared to tubal factor patients. The blastocyst conversion rate was higher for PCOS than tubal (59.4% vs. 49.7%), but not significantly different (aRR 1.04 95% CI: 0.94–1.15). Blastocyst conversion and euploidy rates were similar for HH and tubal factor patients (51.9% vs. 49.7% and 39.1% vs. 44.9%, respectively, aRR 1.01 95% CI: 0.81–1.26 and aRR 1.05 95% CI: 0.85–1.31, respectively). In the adjusted model, patients with PCOS had a significantly lower euploidy rate than patients with tubal infertility (aRR 0.75 95% CI: 0.58–0.96). Patients with HH also had a significantly higher euploidy rate compared to women with PCOS (aRR 1.41 95% CI: 1.05–1.89). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Cycle outcomes differ for ovulatory dysfunction patients with PCOS as compared to those with HH. HH patients require higher total doses of gonadotropins and longer stimulations to achieve similar cycle outcomes as normo-ovulatory patients. While PCOS patients have more embryos, the percent of euploid blastocysts is lower. Trial registration number Not applicable

Menstrual Disorders Related to Eating Disorders

: Eating disorders (ED) are associated with multiple physical complications that strongly affect the physical health of these young and fragile patients and can also cause significant mortality, the highest among psychiatric pathologies. Among the various organic complications, albeit still little known, the gynecological implications, up to infertility, are very widespread. Among adolescent and adult patients, gynecological symptoms can be very widespread and range from menstrual irregularities to amenorrhea, from vaginitis to ovarian polycystosis, up to complications during the gestational phase and postpartum, in addition to the possible consequences on the unborn child. Among the most frequent and significant gynecological disorders in women with ED, there are menstrual irregularities that may occur with oligomenorrhea or even amenorrhea. , Although no longer part of the DSM-5 diagnostic criteria for defining anorexia nervosa (AN), this symptom must be considered a very relevant event in the overall evaluation of young women and adolescents with eating disorders. Functional hypothalamic amenorrhea in ED patients is related to psychological distress, excessive exercise, disordered eating, or a combination of these factors, which results in suppression of the hypothalamic-pituitary-ovarian axis, and consequently, hypoestrogenism. This paper has the objective to summarize the causes and the mechanism underlying menstrual disorders and provide a better understanding of the correlation between the reproductive system and the mechanisms that regulate food intake and eating habits. In addition, early recognition of risk factors for eating disorders for gynecological implications can help put more accurate assessments of patients to prevent potentially fatal complications. The importance of the involvement of specialist gynecologists in the multidisciplinary team that has to follow patients with eating disorders is also discussed.

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens

Reproductive hormones play a crucial role in the growth and maintenance of the mammalian skeleton. Indeed, the biological significance for this hormonal regulation of skeletal homeostasis is best illustrated by common clinical reproductive disorders, such as Primary Ovarian Insufficiency, Hypothalamic Amenorrhea, Congenital Hypogonadotropic Hypogonadism and Early Menopause, which contribute to the clinical burden of low bone mineral density and increased risk for fragility fracture. Emerging evidence relating to traditional reproductive hormones and the recent discovery of newer reproductive neuropeptides and hormones has deepened our understanding of the interaction between bone and the reproductive system. In this review, we provide a contemporary summary of the literature examining the relationship between bone biology and reproductive signals that extend beyond estrogens and androgens, and include kisspeptin, gonadotropin releasing hormone, follicle stimulating hormone, luteinizing hormone, prolactin, progesterone, inhibin, activin and relaxin. A comprehensive and up-to-date review of the recent basic and clinical research advances is essential given the prevalence of clinical reproductive disorders, the emerging roles of upstream reproductive hormones in bone physiology, as well as the urgent need to develop novel safe and effective therapies for bone fragility in a rapidly ageing population.