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.

Clinical and hormonal features of women with polycystic ovary syndrome living in rural and urban areas.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies among women at reproductive age, but its pathology remains unknown. From epidemiological studies it is known that endogenous, mainly genetic and exogenous, environmental factors are of importance. OBJECTIVE: The aim of the study was to compare the phenotype of women diagnosed with PCOS from urban and rural areas of Poland. According to the knowledge of the authors, this is first such study. MATERIAL AND METHODS: The retrospective study included 3,877 PCOS patients: 2511 women living in cities and 1,366 village inhabitants, aged between 18 - 45 years. Clinical data, including medical history, body mass, height and hirsutism severity was obtained from each patient. Hormones were also tested in each patient: follicle stimulating hormone, luteinizing hormone, prolactin, estradiol [E2], testosterone, dehydroepiandrosterone sulphate [DHEAS], thyroid stimulating hormone, free thyroxin, insulin [INS], 17 hydroxyprogesterone, cortisol [CORT]) and metabolic (75g oral glucose tolerance test, Chol - total cholesterol, HDL-C - high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, and the TG (triglicerides) profile. RESULTS: PCOS women from urban areas had a higher mean serum concentration of E2 in comparison to the inhabitants of rural areas. Women from cities had a lower mean level of DHEAS, CORT, and INS measured in the morning than rural residents. Insulin-resistance, using homeostasis model assessment, was more pronounced among women from villages. The prevalence of menstrual disorders, in general, was higher in PCOS women living in rural comparing to urban areas. CONCLUSIONS: The clinical and biochemical indices differed significantly between women diagnosed with PCOS living in cities and villages. In general in Poland, the PCOS phenotype is more severe in women living in rural areas. This study shows that different living conditions significantly affect the PCOS phenotype.

Pregnancy after oocyte donation in 45, X Turner syndrome women, complicated by gestational diabetes and polyhydramnios. Case report and mini-review of literature.

Patients suffering from Turner syndrome (TS) demonstrate characteristic clinical features, with a short stature and gonadal dysgenesis causing infertility in most patients. Spontaneous pregnancies in women with TS are quite rare and pregnancy outcomes involving an increased risk of miscarriage and stillbirths are observed. In this case report, we present a 28 years old pregnant woman with the diagnosis of TS. Due to hypergonadotrophic hypogonadism, she was proposed an in vitro fertilization (IVF) program with an oocyte donor from unrelated anonymous women. After the second transfer, implantation occurred. In the 24th week of gestation, gestational diabetes class 1 was diagnosed. In the 31st week of gestation, polyhydramnios was diagnosed, although other parameters were reassuring. Considering the polyhydramnios, along with the diagnosis of Turner syndrome in the mother, we decided to perform an elective cesarean section. Subsequently, a healthy term male was born. For most women with the diagnosis of TS, the only way to become pregnant is through oocyte donation. The aim of this work was to characterize the course of pregnancy in TS patient and review literature addressing this issue.

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.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

OBJECTIVE: To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). STUDY DESIGN: Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. INTERVENTION(S): Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 µg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. RESULT(S): After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. CONCLUSION(S): Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Recurrent endometrial hyperplasia as a presentation of estrogen-secreting thecoma - case report and minireview of the literature.

Thecoma is a rare ovarian tumor, presenting usually in postmenopausal women as unilateral, benign, solid lesion. About 15% of affected patients develop endometrial hyperplasia (EH) and 20% are diagnosed with endometrial cancer. In this case report, we present 60-year-old women admitted because of recurrent spotting of 5 years duration, which started 1 year after menopause. In history, the patient underwent three times curettage procedures and once (1 year before admission) had estradiol levels typical for reproductive-age women. At admission, we found elevated serum levels of estradiol (222.5 pg/ml) and a small mass in the right ovary. The markers of germ cell tumors were negative. After the initial diagnosis, the patient was qualified for total abdominal hysterectomy with bilateral salpingo-oophorectomy. The histopathological examination and immunohistochemical staining confirmed the thecoma diagnosis. In follow-up examination after 8 weeks, we found decreased serum estradiol levels and relief of the symptoms. In conclusion, we want to underline that in cases of EH, especially in patients with a history of recurrences, the special attention should be paid for differential diagnosis. In such cases, the estrogen-secreting tumors should be excluded.

Eating disorders in older women.

Eating disorders (EDs) are disturbances that seriously endanger the physical health and often the lives of sufferers and affect their psychosocial functioning. EDs are usually thought of as problems afflicting teenagers. However, the incidence in older women has increased in recent decades. These cases may represent either late-onset disease or, more likely, a continuation of a lifelong disorder. The DSM-5 classification differentiates 4 categories of eating disorder: anorexia nervosa, bulimia nervosa, binge-eating disorders and other specified feeding and eating disorders. The weight loss and malnutrition resulting from EDs have widespread negative consequences for physical, mental and social health. The main risk factors for developing long-term consequences are the degree of weight loss and the chronicity of the illness. Most of the cardiac, neurological, pulmonary, gastric, haematological and dermatological complications of EDs are reversible with weight restoration. EDs are serious illnesses and they should never be neglected or treated only as a manifestation of the fashion for dieting or a woman's wish to achieve an imposed standard feminine figure. Additionally, EDs are associated with high risk of morbidity and mortality. The literature concerning EDs in older, postmenopausal women is very limited. The main aim of this paper is to ascertain the epidemiology and prognosis of EDs in older women, and to review their diagnosis and management.

Mood disorders and quality of life in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects 5-10% of the population of women. The exact etiology of PCOS remains unclear, but it is believed to result from complex interactions between genetic, behavioral and environmental factors. The spectrum of its symptoms such as hirsutism, skin problems, obesity and finally infertility has a huge negative impact on the individuals' psychological and interpersonal functioning. PCOS symptoms can lead to significant deterioration in quality of life and be highly stressful negatively affecting psychological well-being and sexuality. Fear symptoms like palpitation, being out of breath and tension might be caused by many somatic diseases. Moreover, detection and continuous thinking about illness can lead to significant negative impact on individual functioning in society. PCOS may be a factor potentially favoring the occurrence of mood disorders and depression. Biological, social and psychological consequences of PCOS among women of reproductive age are opening a new perspective on management of women's health in these patients.

Pregnancy complications in polycystic ovary syndrome patients.

Infertility is a widely disputed problem affecting patients suffering from polycystic ovary syndrome (PCOS). As a serious dysfunction, it frequently occurs in PCOS patients. It is, therefore, important to devote more attention to pregnancy in PCOS sufferers. According to various data, the risk of miscarriage in PCOS women is three times higher than the risk of miscarriage in healthy women. Unfortunately, the risk of most frequent pregnancy pathologies is also higher for PCOS patients, as gestational diabetes (GD), pregnancy-induced hypertension and pre-eclampsia, and small for gestational age (SGA) children. Impaired glucose tolerance and GD in pregnant PCOS patients occur more frequently than in healthy women. A quadruple increase in the risk of pregnancy-induced hypertension linked to arterial wall stiffness has also been observed in PCOS patients. The risk of pre-eclampsia, the most severe of all complications, is also four times higher in those suffering from PCOS. Pre-eclampsia is also more frequent in patients presenting additional risk factors accompanying PCOS, such as obesity or GD. At that point, it should be mentioned that PCOS patients are under 2.5 higher risk of giving birth to SGA children than healthy women. It appears that SGA can be linked to insulin resistance and insulin-dependent growth dysfunction. Therefore, PCOS pregnant women are patients of special obstetrical care.

Health in older women athletes.

Physical activity has been identified as a protective factor against a wide spectrum of diseases, but little is known about the link between older women's health and their professional involvement in sport in the past. The aim of this narrative review is to characterize and summarize the available data concerning the influence of physical activity on morbidity and mortality in former female athletes. Concerning bone health, it seems that physical activity in the past can be protective against osteoporosis in postmenopausal women, but these data come from observational studies only. Also the cardiovascular system appears to benefit in older women from regular sport in the past. This refers mainly to better heart efficiency, and improved endothelial function and metabolic profile. The incidence of different types of neoplasms, especially breast cancer, is also decreased in former athletes. Professional sport, on the other hand, acts negatively on the pelvic floor and is a risk factor for urinary incontinence. The overall effect on mortality is difficult to assess, because of many parameters, such as the sport's intensity, variety of the sport and exposure to extreme danger in some disciplines. Also, caution should be kept in interpretation of the data because of the shortage of well-designed studies.

Long-term consequences of anorexia nervosa.

Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.

Kallmann syndrome in women: from genes to diagnosis and treatment.

Kallmann syndrome (KS) can be characterized as genetic disorder marked by hypogonadotropic hypogonadism and anosmia. Franz Jozef Kallmann was the first who described this disease in 1944. He suggested, that this disease has hereditary background. At present, six genes are regarded as causal genes of KS. These genes can be listed in chronological order: KAL1, FGFR1, FGF8, CHD7, PROKR2 and PROK2. The sensitivity of molecular testing of KS is only about 30%. Diagnosis based on clinical findings is therefore such important. Cardinal features of patients with KS include hypogonadotropic hypogonadism and anosmia or hyposmia. Some non-reproductive, non-olfactory symptoms can also be present, depending on the genetic form of disease. Some patients with KS present midline cranial anomalies (cleft lip, cleft palate and imperfect fusion). Sometimes patients can also suffer from missing teeth (dental agenesis). Optic problems, such as colour blindness or optic atrophy also can occur in KS patients. Very characteristic symptom in KS patients is mirror movements of the upper limbs (imitation synkinesis for contralateral limbs). The type of treatment in women with KS depends on the goal of therapy. After the diagnosis of syndrome, the main goal of the treatment is to induce and maintain secondary sex characteristic (estrogen-progestin therapy). The further goal in some patients can be related to enable fertility (gonadotropin, gonadotropin-releasing hormone therapy).

Hypothalamic amenorrhea in a Camurati-Engelmann disease--a case report.

OBJECTIVE: A case report of a patient diagnosed with Camurati-Engelmann Disease (CED) in association with the functional hypothalamic amenorrhea disturbances. CED is a very rare genetically determined disorder classified as a type of bone dysplasia. DESIGN: Case report. SETTING: Department of Gynecological Endocrinology, 3rd grade Medical University Hospital. PATIENT: Twenty-one years old female patient with CED admitted to the hospital because of primary amenorrhea. Her history revealed skeletal deformities and hearing impairment. METHODS: Clinical examination, ultrasound, laboratory evaluations (including serum gonadotropins (FSH, LH) at basal state and after stimulation with gonadotropin-releasing hormone, serum basal estradiol) radiological studies (X-ray of the head, the lumbar spine and lower extremities; a computed tomography of the head), G-banding karyotype, polymerase chain reaction and DNA sequencing. Hormonal serum evaluations were made using an enzyme-linked immunosorbent assay. The exon 4 of the transforming growth factor beta 1 gene was amplified by a polymerase chain reaction and the product was directly sequenced. RESULTS: The hormonal analysis was characteristic for the hypogonadotropic hypogonadism. Radiological and molecular analyses confirmed CED diagnosis. CONCLUSIONS: The hypothalamic amenorrhea in a patient with CED may be explained as a consequence of fat hypotrophy and very low body mass index. Therefore, impairment within hypothalamic-pituitary axis in patients with CED should be treated with special attention.

[The controversies in the diagnosis of polycystic ovary syndrome]. / Kontrowersje w rozpoznawaniu zespolu policystycznych jajników.

Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age. The main clinical features of PCOS include abnormal ovulation, clinical or laboratory indices of elevated androgen levels and polycystic morphology of the ovaries. Even though the PCOS was described primarily in the 1935 by Stein and Leventhal, to date we are lacking the commonly accepted agreement in the issue of diagnosis of this syndrome. Contemporary, greater part of clinicians worldwide accept and use the Rotterdam criteria published in 2003 for recognizing PCOS, although the National Institute of Health criteria (1990) are also popular. Recently, in 2009 Androgen Excess and PCOS Society published an upgraded guidelines for recognizing the syndrome. In spite the publication of those three statements, interpretation of the three main groups of symptoms of the PCOS remain in many aspects controversial. The assessment of hyperandrogenisation is highly subjective and can be performed using different scoring systems. The matter of measuring androgen levels is complicated by the lack of easy accessible and, at the same time, precise laboratory method. The ovulation evaluation is also not standardized. The evaluation of ovarian morphology, made by ultrasound is problematic, since the methods proposed by Rotterdam criteria are very difficult and time-consuming. As an result of existing controversies in field of diagnosis of the PCOS, women with different phenotypes can be recognized with PCOS by different clinicians. This in turn, complicates the treatment and follow-up of those women. In conclusion, there is need for a large scientific and clinical research concerning this syndrome, to settle improved and more reliable diagnosing criteria.

[Natural history of polycyclic ovary syndrome]. / Historia naturalna zespolu policystycznych jajników.

Polycystic Ovary Syndrome (PCOS) occurs in 3-6% women of reproductive age. The Rotterdam 2003 criteria for PCOS diagnosis include: oligo or anovulation, hyperandrogenism and a typical clinical picture of polycystic ovaries in the USG image when other causes of hypoestrogenism are excluded. The etiology of the syndrome remains largely unknown. In 30-60% cases of women with PCOS, obesity is observed. The aim of the present study was to track the natural history of PCOS by observing the disorders in different stages of the female patient's life starting with infancy through childhood and adolescence, then full sexual maturity period, which is the best known one and up to around menopause period. Each of these life stages is characterized by different specificity of disorders. In the fetal and infant period the focus should be placed on the influence of hormonal disorders in mother on PCOS induction. Childhood is the period when the observation is focused on fenotypical features that may indicate the risk of PCOS development. In the reproductive period, which is the most widely known, the focus is understandably on fertility disorders, however metabolic disorders are also quite often manifested. In PCOS patients around menopause, metabolic disorders are of primary focus for exemple mostly the risk of the development of diabetes type 2 as well ascardiovascular system diseases. Such versatility of coexistent disorders in one syndrome and variability depending on a woman's age call for closer examination of these relations and dependencies.