Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea.

BACKGROUND: Neurokinin B (NKB) belongs to the tachykinin family of proteins who's regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. AIM: To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. MATERIALS AND METHODS: A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. RESULTS: Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. CONCLUSIONS: Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

The influence of estro-progestin therapy on neurohormonal activity in functional hypothalamic amenorrhea.

Background: Functional hypothalamic amenorrhea (FHA) is a chronic endocrine disorder caused by the abnormal pulsatile secretion of neurohormones in the hypothalamus. Secretion of GnRH is regulated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons produce, among other neurohormones, neurokinin B (NKB) which regulates the coordinated stimulation or inhibition of GnRH secreting neurons. Aim of the study: Assessment and comparison of serum NKB in patients with FHA at baseline, and following 6 months of estrogen-progestagen therapy. Materials and methods: Fifty-five patients with functional hypothalamic amenorrhea were included in the study group. Serum concentrations of neurokinin B (NKB), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-ß-estradiol (E2), prolactin (PRL), cortisol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), fasting glucose and insulin, as well as lipid profile were measured at baseline. At the time of diagnosis, patients with FHA were prescribed a course of 2 mg 17-ß-estradiol and 10 mg dydrogesterone for duration of 6 months. Serum NKB was then reassessed following treatment at 6 months. Results: At baseline, the FHA group was found to have a decreased serum NKB concentration when compared to a healthy control group. Following 6 months of sequential estrogen-progestogen hormone therapy, this study did not find any statistically significant difference in serum NKB concentration in the treatment arm compared to baseline. Conclusions: For the first time, NKB secretion has been studied in patients with FHA. A significantly lower level of serum NKB was observed in these patients at baseline, when compared to a control group. After 6 months of combination estrogen-progesterone therapy, no significant changes in NKB levels were observed in these patients. These findings, for the first time in the literature, provide insight into the perceived benefit of HRT, calling into question its benefit in addressing the underlying etiopathogenetic contributors of FHA. These new findings may contribute to more targeted and appropriate treatment of such patients in the future.

Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea.

OBJECTIVE: Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). MATERIALS AND METHODS: One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. RESULTS: Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-ß-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. CONCLUSIONS: This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

From diagnosis to treatment of androgen-secreting ovarian tumors: a practical approach.

About 5% of all ovarian tumors develop some form of hormonal activity. Only 1% of ovarian tumors will secrete androgens causing clinical hyperandrogenism. Most androgen-secreting neoplasms (ASN) derive from sex cord or stroma cells of the ovary and may affect both premenopausal and postmenopausal women. Typically, a patient will present reporting symptoms of rapidly increasing hyperandrogenization such as: hirsutism, acne, frontal/male pattern balding, and in severe cases even virilization. Sertoli-Leydig Cell Tumors are the most frequent ASN and constitute about 0.5% of all ovarian neoplasms. Typically affecting women under 30 years of age, these tumors are usually unilateral and benign. They are also the most common tumor in postmenopausal women suffering with hyperandrogenism. Other tumors originating from the sex-cord stroma are also known to develop in this population, but the incidence of these is much lower. Approaching suspected hyperandrogenemia and its related symptoms in a clinical setting can be a significant diagnostic challenge. When evaluating a patient for hyperandrogenism, it is important to assess the severity of symptoms but most of all it is critical to assess the time of onset and dynamics of symptom progression. Diagnostic tools including laboratory tests and imaging studies should also be engaged. When deriving a differential diagnosis for androgen-secreting ovarian tumors, adrenal gland tumors should be considered as well as typical endocrine pathologies including polycystic ovary syndrome, congenital adrenal hyperplasia, Cushing's disease, and acromegaly. Treatment options for an androgen-secreting ovarian tumors is mainly surgical, but in exceptional cases can involve pharmacotherapy alone.

Hyperthyroidism associated with struma ovarii - a case report and review of literature.

BACKGROUND: Hyperthyroidism is a state characterized by elevated serum level of thyroid hormones: thyroxine (T4) and triiodothyronine (T3). This is mainly related to the condition and functioning of the thyroid gland. In 60-80% of cases elevation of these hormones are caused by Grave's disease. Thyrotoxicosis is an extreme presentation of hyperthyroidism which can, in rare cases, be caused by excessive synthesis of thyroxine by tumor cells. Struma ovarii is a rare ovarian teratoma composed of thyroid tissue in more than 50%. OBJECTIVE AND METHOD: To present a case of a 30-year-old female patient with a past history of Grave's disease treated by strumectomy 7 years prior; now presenting for the assessment of secondary amenorrhea. Pelvic ultrasound revealed bilateral solid tumors on the left and right ovary, respectively measuring 5 cm and 6 cm in diameter. Her clinical presentation was suggestive of overt hyperthyroidism, and she presented with a significantly elevated CA-125 (152.7 U/mL). RESULTS: The patient subsequently underwent a bilateral oophorectomy in which both masses were excised and histopathological examination confirmed teratoma maturum cysticum. Struma ovarii was noted as a component of the left ovary teratoma. CONCLUSION: Establishing a proper diagnosis of hyperthyroidism and elucidating its origin is often challenging. Struma ovarii is a rare cause of hyperthyroidism but should always be considered in case of treatment resistant hyperthyroidism. This case-report lends itself as an example of the value in maintaining gynecological-endocrinological knowledge in the setting if clinical gynecology.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

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.

Hormonal Effects on Hair Follicles.

The hair cycle and hair follicle structure are highly affected by various hormones. Androgens-such as testosterone (T); dihydrotestosterone (DHT); and their prohormones, dehydroepiandrosterone sulfate (DHEAS) and androstendione (A)-are the key factors in terminal hair growth. They act on sex-specific areas of the body, converting small, straight, fair vellus hairs into larger darker terminal hairs. They bind to intracellular androgen receptors in the dermal papilla cells of the hair follicle. The majority of hair follicles also require the intracellular enzyme 5-alpha reductase to convert testosterone into DHT. Apart from androgens, the role of other hormones is also currently being researched-e.g., estradiol can significantly alter the hair follicle growth and cycle by binding to estrogen receptors and influencing aromatase activity, which is responsible for converting androgen into estrogen (E2). Progesterone, at the level of the hair follicle, decreases the conversion of testosterone into DHT. The influence of prolactin (PRL) on hair growth has also been intensively investigated, and PRL and PRL receptors were detected in human scalp skin. Our review includes results from many analyses and provides a comprehensive up-to-date understanding of the subject of the effects of hormonal changes on the hair follicle.

CHEK2 Mutation in Patient with Multiple Endocrine Glands Tumors. Case Report.

BACKGROUND: Many studies show the occurrence of several multiple endocrine neoplasia syndromes caused by different mutations, for example, in MEN1 and RET genes. Nevertheless, there are less common mutations causing multiple endocrine glands tumors. Examples of such mutations are CHEK2 gene mutations, causing breast, kidney, gastric, colorectal, prostate, lung, ovarian, and thyroid cancers. CASE DESCRIPTION: In 2005, a 30-year-old woman was admitted to the hospital due to uncontrolled hypertension and obesity. Performed tests have shown ACTH (adrenocorticotropic hormone)-independent micronodular adrenal hyperplasia (AIMAH) as a cause. In 2010, the further diagnostic analysis revealed Cushing's disease caused by ACTH-secreting pituitary microadenoma. Additionally, in 2011, the patient underwent the strumectomy of multinodular struma. Papillary thyroid carcinoma was found in the excised tissue. In 2018, transvaginal ultrasonography revealed a tumor of the right ovary. After a performed hysterectomy with bilateral salpingo-oophorectomy, the histopathology result has shown female adnexal tumors of probable Wolffian origin (FATWO) located in the broad ligament of the uterus. Due to the history of multiglandular diseases, the patient was referred to genetic testing. We found a positive pathogenic mutation in CHEK2-suppressor gene involved in DNA repair, cell cycle arrest, and apoptosis in response to DNA damage. CONCLUSION: CHEK2 variants may predispose to a range of endocrine glands tumors, including those identified in our patient. Multiple endocrine glands tumors, as in the presented patient, are a serious problem of public health, due to numerous hospitalizations and necessary repeated surgical treatments. Moreover, the association between CHEK2 and ovarian cancer can be a serious problem with reproductive health.

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman.

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T - on admission 1.72 ng/ml and one month later 3.75 ng/ml (normal range 0.08-0.82 ng/ml) and A - 24.90 ng/ml (normal range 0.40-3.40 ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56 × 43 mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges - 0.74 ng/ml (normal range 0.08-0.82 ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.

A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management.

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS. Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed. Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests). Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.

Cardiovascular health in patients with premature ovarian insufficiency. Management of long-term consequences.

Cardiovascular diseases (CVDs) represent the world's leading cause of death among women. Women with premature ovarian insufficiency (POI) may be at higher risk of cardiovascular disease, such as myocardial infarction or stroke, than women with normal menopause. The increased burden may be mediated by a worsening of cardiovascular risk factors, such as lipid profiles, with accompanying loss of ovarian function. In contrast, the increased burden may be caused by factors that precede and potentially contribute to both CVD events and ovarian decline, such as smoking. Women with X chromosome-related POI like Turner syndrome (TS) are a distinct group with unique medical needs. Regardless of the cause, women with POI may serve as an important population to target for CVD screening and prevention strategies. These strategies should include the use of CVD risk stratification tools to identify women who may benefit from lifestyle modification and pharmacological therapy to prevent CVD.

[Serum kisspeptin levels in patients with anorexia nervosa]. / Stezenia kisspeptyny w surowicy u chorych z rozpoznanym jadlowstretem psychicznym.

Anorexia nervosa (AN) is a disorder characterized by extreme restriction of food intake and incorrect perception of patients' body, its weight and shape. Patients diagnosed with anorexia nervosa apart from an eating disorder are characterized also by hypothalamic amenorrhea. Many neuropeptides and neurotransmitters play an important role in physiological regulation of gonadoliberin (GnRH) secretion. AIM: The aim of the study is to assess the role of kisspeptin in the etiology of anorexia nervosa. MATERIALS AND METHODS: The study was classified as 55 women aged from 17 to 28 years old. Patients were classified into two groups: study group consisted of 15 patients diagnosed with AN and control group consisted of 40 healthy women. Examination of serum blood from patients was performed by ELISA-enzyme-linked immunosorbent assay. Concentrations of serum kisspeptin, FSH, LH, estradiol, prolactin, testosterone were analyzed in patients from study and control group. RESULTS: The average body weight of patients with AN was 45.0±7.56 kg and was statistically significantly lower compared to women in the control group (61.1±7.20 kg) (p=0.0001). The average serum concentration of kisspeptin in patients with AN was 0.20±0.07 ng/ml, in women in the control group was 0.3±0.36 ng/ml (p=0.712). Serum LH concentrations in patients with AN was 2.5±1.71 mIU/ml and was statistically significantly lower compared to women in the control group (13.5±9.73 mIU/ml) (p=0.0001). The mean serum estradiol concentrations in patients with AN were 31.0±15.3 pg/ml and were statistically significantly lower compared to the control group (129.0±107.7 pg/ml) (p=0.0001). CONCLUSIONS: There was not significant difference between serum kisspeptin levels in patients with AN and healthy women. Further research is needed on the role of kisspeptin in AN.

The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications.

Women during perimenopausal period experience a range of symptoms, which interfere with physical, sexual, and social life. About 65-75% of symptoms connected with postmenopausal period are vasomotor symptoms (VMS), such as hot flushes and night sweats. Hot flushes are subjective sensation of heat associated with cutaneous vasodilatation and drop in core temperature. It is suspected that VMS are strongly correlated with pulsatile oversecretion of gonadotropin-releasing hormone (GnRH) and subsequently luteinizing hormone (LH). Evidence has accumulated in parallel showing that lack of negative feedback of steroid hormones synthesized in ovary causes overactivation of hypertrophied kisspeptin/neurokinin B/dynorphin (KNDy) neurons, located in infundibular nucleus. Oversecretion of both kisspeptin (KISS1) and neurokinin B (NKB), as well as downregulation of dynorphin, plays dominant role in creation of GnRH pulses. This in turn causes VMS. Administration of senktide, highly potent and selective NK3R agonist, resulted in increase of serum LH concentration, induction of VMS, increase in heart rate, and skin temperature in postmenopausal women. These finding suggest that modulation of KNDy neurons may become new therapeutic approach in the treatment of VMS.

Kisspeptin and LH pulsatile temporal coupling in PCOS patients.

PURPOSE: To evaluate the temporal coupling between spontaneous kisspeptin and luteinizing hormone (LH) pulsatile releases in polycystic ovary syndrome (PCOS) patients. METHODS: We examined 71 patients diagnosed with PCOS. A 2 h pulsatility study was performed to evaluate serum kisspeptin and LH pulse frequency and concentration, sampled every 10 min; baseline follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), cortisol, 17-hydroksy-progesterone (17OHP), testosterone (T), free testosterone index (FTI, and insulin levels were also measured. Detect and Specific Concordance (SC) algorithms were used to evaluate the temporal coupling associations between spontaneous episodic secretion of kisspeptin and LH. RESULTS: All PCOS patients demonstrated LH and kisspeptin pulsatile secretions. When the SC index was calculated across the sample of PCOS patients (n = 71), no temporal coupling was observed between kisspeptin and LH pulses. When PCOS patients were subdivided according to their menstrual cyclicity, oligomenorrheic patients demonstrated elevated kisspeptin pulse frequency. Additionally, the SC index reveled a temporal coupling between kisspeptin and LH secretory peaks only in eumenorrheic patients (n = 30, intermenstrual interval < 45 days). Oligomenorrheic PCOS patients (intermenstrual interval > 45 days) did not demonstrate temporal coupling between kisspeptin and LH secretory peaks. CONCLUSIONS: The study of the endogenous kisspeptin and LH pulsatile release revealed the temporal coupling of kisspeptin with LH secretory pulses only in eumenorrheic. This data supports the hypothesis that neuroendocrine impairments in PCOS affect the coupling of kisspeptin with LH pulses and potentially worsen as the disease progresses, becoming unequivocally evident in oligomenorrheic PCOS patients.

Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA).

Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI).

Premature ovarian insufficiency (POI) is defined as a cessation of function of ovaries in women younger than 40 years old. Brain-derived neurotrophic factor (BDNF) is a protein critically involved in neuronal growth and metabolism. BDNF also has been shown to be important regulator of oocyte maturation. Recent data show that BDNF can be potentially involved in POI pathology. The aim of the study was to assess the BDNF plasma concentrations in patients diagnosed with idiopathic POI. 23 women diagnosed with POI (age 31 ± 7 years) and 18 (age 31 ± 3) controls were included to the study, matched according to age and body mass index. The BDNF concentrations were measured using competitive enzyme-linked immunosorbent assay (ELISA). Hormonal and metabolic parameters were measured in all individuals, in controls in late follicular phase. The POI group demonstrated lower mean plasma concentrations of BDNF (429.25 ± 65.52 pg/ml) in comparison to healthy controls (479.75 ± 34.75 pg/ml, p = 0.0345). The BDNF plasma concentration correlated negatively (R = -0.79, p < 0.001) with number of months since last menstrual period. There was a positive correlation between BDNF and progesterone in controls. In conclusion, POI patients show significantly lower BDNF plasma concentration and it correlates with the duration of amenorrhea. This observation brings important potential insights to the pathology of POI.

The role of progesterone therapy in early pregnancy: from physiological role to therapeutic utility.

Progesterone is a steroid hormone of essential role in reproduction. In early pregnancy, it is responsible for preparation of endometrium for implantation process and maintenance of gestational sac in uterus, also by modulation of maternal immune system. Even though, several indices has been proposed as markers of endogenous progesterone synthesis (progesterone or luteinizing hormone measurements, endometrial biopsy), none has been proved to be reliable in detecting luteal phase defect. Currently, several pharmaceutical formulations are available, but in clinical setting the non-oral formulations seems to be effective in therapy. Progesterone is effective in the treatment of patients undergoing assisted reproductive technology procedure, as a luteal phase support. Some studies showed also its efficacy in the treatment of threatening or recurrent miscarriage, but newer trials neglected this beneficial effect. Due to controversies regarding utility of progesterone supplementation in these conditions, further studies are needed to address this issue.