Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)-well-studied functional variants involved in one-carbon metabolism-and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49-7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

The role of factors associated with the course of pregnancy and childbirth in attention deficit hyperactivity disorder (ADHD). / Rola czynników zwiazanych z przebiegiem ciazy i porodu w zespole nadpobudliwosci psychoruchowej z deficytem uwagi.

OBJECTIVES: Assessment of the prevalence of risk factors associated with the course of pregnancy and childbirth and the condition of the child after birth in agroup of children and adolescents with ADHD and a control group. METHODS: 205 unrelated children and adolescents diagnosed with ADHD and 106 primary and secondary school students aged 7-17. Method. Mothers of children and adolescents diagnosed with ADHD, and those from the control group, were asked to provide a medical history in order to obtain data to supplement the Pregnancy and perinatal history questionnaire. RESULTS: Statistically significant differences (p < 0.05) were demonstrated for the incidence rates of factors related to the course of pregnancy and childbirth such as: the occurrence of maternal diseases during pregnancy, especially in the I/II trimester, and other problems during pregnancy; exposure to stress and taking medication during pregnancy; smoking during pregnancy; mother's age at childbirth, i.e., < 25 years or > 35 years; use of pain reducing substances during labor and problems with the child during the delivery;an APGAR score in the range of 5-7 points; the occurrence of neonatal jaundice necessitating treatment, especially replacement transfusion; physical anomalies or other congenital problems in the newborn, as well as adaptive problems necessitating neonatal oxygen administration or placement in an incubator. CONCLUSIONS: Significantly more frequent occurrence of risk factors related to the course of pregnancy, childbirth and the child's condition after birth in the ADHD group may indicate their potential role in the etiology of ADHD.

Steroid Hormone Sensitivity in Reproductive Mood Disorders: On the Role of the GABAA Receptor Complex and Stress During Hormonal Transitions.

Women worldwide are two to three times more likely to suffer from depression in their lifetime than are men. Female risk for depressive symptoms is particularly high during the reproductive years between menarche and menopause. The term "Reproductive Mood Disorders" refers to depressive disorders triggered by hormonal fluctuations during reproductive transitions including the perimenarchal phase, the pre-menstrual phase, pregnancy, the peripartum period and the perimenopausal transition. Here we focus on reproductive mood disorders manifesting in adult life. We propose a research agenda that draws together several reproductive mood disorders and investigates which genetic, endocrinological, neural, and psychosocial factors can explain depressive symptoms during phases of hormonal transitions in women. Based on current research it is assumed that some women experience an increased sensitivity to not only fluctuations in reproductive steroids (estrogen and progesterone), but also stress-related steroids. We integrate both dynamics into the concept of "steroid hormone sensitivity," expanding on the concept of "reproductive hormone sensitivity." We suggest that a differential response of the stress steroid system including corticosteroids, neurosteroids, like allopregnanolone and the GABA-A Receptor complex, as well as a differential (epi)genetic risk in serotonergic and GABAergic signaling, are moderators or mediators between changes in the reproductive steroid system and the physiological, affective, and cognitive outcomes manifesting in reproductive mood disorders. We point to the lack of research on the role of psychosocial factors in increasing a woman's stress level and at some point also the sensitivity of her stress steroid system within the etiology of Reproductive Mood Disorders. Drawing together the evidence on various reproductive mood disorders we seek to present a basis for the development of more effective pharmacological, social, and psychological treatment interventions and prevention strategies for women susceptible to these disorders. This could pave the way for new research as well as medical and psychological teaching and practice- such as a new type of Practice for Gynecological Psychoneuroendocrinology- with the aim of working on and ultimately offering more integrative forms of support not yet available to women suffering from depression during hormonal transitions. In medical history women have been left alone with this integrative challenge.

The impact of surgical treatment of obesity on the female fertility.

As obesity is considered to be a pandemic of the twenty-first century, the bariatric surgery becomes more common through the global population. The adverse effects of obesity on fertility can be reversed through the bariatric surgery procedures. In this review, we presented the effects of bariatric surgery on hypothalamic-pituitary-ovarian axis and fertility, ovarian reserve, and contraception efficacy.

Menopause and diabetes: EMAS clinical guide.

INTRODUCTION: Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. AIMS: To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. MATERIALS AND METHODS: Literature review and consensus of experts' opinions. RESULTS AND CONCLUSION: Metabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17ß-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient's specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.

Mood disorders in women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) and related oestrogen deficiency is a cause of many psychological symptoms, including: depression, psychological tension, anxiety, mood lability, loss of libido, feelings of loss of femininity and attractiveness, and decreased self- and sexual esteem. Distress related to POI diagnosis may be even more confusing when POI is diagnosed in relation to serious health complications such as cancer, due to surgery or chemotherapy. Every case of POI requires coordinated medical advice with special attendance of a gynaecological endocrinologist, psychotherapist, and sometimes even a psychiatrist.

Neurological health and premature ovarian insufficiency - pathogenesis and clinical management.

Premature ovarian insufficiency (POI) is related to neurological problems through neurological symptoms of oestrogen deficiency, diseases caused by oestrogen deficiency, and neurological genetic diseases. Neurological symptoms of oestrogen deficiency are usually reported as climacteric symptoms. Diseases caused by oestrogen deficiency are dementia, cognitive decline, and Parkinsonism. Among genetic neurological disorders, ovarioleukodystrophy and fragile X-associated tremor/ataxia syndrome (FXTAS) are reported.

Use of oral contraceptives for management of acne vulgaris and hirsutism in women of reproductive and late reproductive age.

Hormonal contraception in both reproductive and late reproductive age, as well as contraceptive action, is used also for other indications like dysmenorrhoea, menstrual disorders, endometriosis, acne vulgaris, and hirsutism. Acne vulgaris and hirsutism are important signs related to hyperandrogenaemia and present a serious medical problem for the patients and a challenge for medical doctors in terms of effective treatment. The application of hormonal contraception to treat acne vulgaris and hirsutism requires knowledge of the mechanism of antiandrogenic actions and the possible contraindications and complications. These data are presented in this review.

Correlation between allopregnanolone levels and depressive symptoms during late menopausal transition and early postmenopause.

OBJECTIVES: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and allopregnanolone levels in women during late menopausal transition and early postmenopause. METHODS: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17ß-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and allopregnanolone levels. RESULTS: We found that serum allopregnanolone concentration was lower in early postmenopausal women compared to women in late menopausal transition; that there was a correlation between serum allopregnanolone levels in early postmenopausal women and time since last menstruation, intensity of climacteric symptoms, and intensity of depression symptoms and that there was a correlation between serum allopregnanolone levels and several depression symptoms presence (shallow sleep and symptoms of the digestive tract in women during late menopause transition; feelings of guilt, sleep disorders and general somatic symptoms in early postmenopausal women). CONCLUSION: We concluded that reproductive aging is characterized by a reduction of allopregnanolone circulating levels that correlate to Hamilton depression index in early postmenopause and presence of specific depressive symptoms during late menopausal transition and early postmenopause.

Overweight in Boys With ADHD Is Related to Candidate Genes and Not to Deficits in Cognitive Functions.

OBJECTIVE: The aim of the study was to assess the relationship of overweight, the polymorphisms of selected candidate genes, and deficits in the executive functions among children with ADHD. METHOD: We examined 109 boys with ADHD aged between 7 and 17 years. The study indicated variants of 14 polymorphisms in eight candidate genes. We applied seven neuropsychological tests to evaluate the executive functions. Overweight was diagnosed on the basis of the guidelines of the International Obesity Task Force. RESULTS: Analyses revealed significant association between DRD4 rs1800955, SNAP25 rs363039 and rs363043, 5HTR2A rs17288723, and overweight in boys with ADHD. There were no significant differences in the level of neuropsychological test results between patients with overweight and without overweight. CONCLUSION: Overweight in boys with ADHD is associated with polymorphisms in three candidate genes: DRD4, SNAP25, and 5HTR2A, but not through conditioning deficits in cognitive functions.

Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy.

Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer-associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first-line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum-based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first-line treatment. Therefore, it is crucial to develop a novel drug that effectively affects ovarian cancer, particularly tumors that are resistant to current chemotherapy. The aim of the present study was to identify genes whose expression may be used to predict survival time or prognosis in ovarian cancer patients treated with chemotherapy. Gene or protein expression is an important issue in chemoresistance and survival prediction in ovarian cancer. In the present study, the research group consisted of patients treated at the Surgical Clinic of the Gynecology and Obstetrics Gynecological Clinical Hospital, Poznan University of Medical Sciences (Poznan, Poland) between May 2006 and November 2014. Additional eligibility criteria were a similar severity (International Federation of Gynecolgy and Obstetrics stage III) at the time of diagnosis, treatment undertaken in accordance with the same schedule, and an extremely good response to treatment or a lack of response to treatment. The performance of the OncoScan® assay was evaluated by running the assay on samples obtained from the four patients and by following the recommended protocol outlined in the OncoScan assay manual. The genomic screening using Affymetrix OncoScan Arrays resulted in the identification of large genomic rearrangements across all cancer tissues. In general, chromosome number changes were detected in all examined tissues. The OncoScan arrays enabled the identification of ~100 common somatic mutations. Chemotherapy response in ovarian cancer is extremely complex and challenging to study. The present study identified specific genetic alterations associated with ovarian cancer, but not with response for treatment.

Denosumab - a new medication in the treatment of postmenopausal osteoporosis.

Osteoporosis is a chronic, systemic skeletal disorder characterised by decreased bone density. It leads to an increased risk of bone fractures - one of the major causes of disability in modern societies. Bisphosphonates are the most commonly used medications in the treatment of postmenopausal osteoporosis. Denosumab, a new approach to fracture prevention, is a fully human monoclonal antibody that targets nuclear factor-κB ligand (RANKL), an important cytokine regulating formation and function of osteoclasts. Generally, denosumab is not used as initial therapy; however, in some cases it should be considered. It concerns patients at high risk of fracture, such as older patients who have difficulty with the dosing requirements of oral bisphosphonates or who have markedly impaired renal function. Denosumab can be also considered in patients who present intolerance or unresponsiveness to other therapies. Clinical studies have shown that denosumab is highly effective in increasing bone mineral density (BMD) in postmenopausal women regardless of the site analysed, as well as reducing the risk of bone fractures. The risk of developing antiresorptive, agent-induced osteonecrosis of the jaw related to denosumab therapy is low.

Aromatase inhibitors in the treatment of endometriosis.

Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body's oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis.

The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women.

OBJECTIVE: The aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women. METHODS: A total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42-67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis. RESULTS: After correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C>T (SNP 1137070), COMT c.472G>A (SNP 4680), MTHFR c.677C>T (SNP 1801133) and ESR1 454(-351) A>G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT+TT (OR=1.83; pcorr=0.009 and OR=1.85; pcorr=0.003, resp.), and of the MTHFR c.677 TT and c.677 CT+TT (OR=3.52; pcorr=0.00009 and OR=2.06; pcorr=0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA+AA genotypes (OR=2.23; pcorr=0.03 and OR=2.17; pcorr=0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454(-351) AG and 454(-351) AG+GG genotypes were associated with lower risk of depression in postmenopausal women (OR=0.48; pcorr=0.012, and OR=0.52; pcorr=0.015, resp.). CONCLUSIONS: Our study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women.

Disturbances of sleep continuity in women during the menopausal transition.

OBJECTIVES: The objective of the study was to evaluate the prevalence of sleep continuity disorders in women during menopausal transition, to evaluate the relationship between disturbances of sleep continuity and the severity of menopausal syndrome and the occurrence of various symptoms of this syndrome, as well as to evaluate the association between the presence of sleep disturbances and serum concentrations of gonadotropins, prolactin and sex hormones. METHODS: Consecutive 140 women (mean age 54.4 ± 4.7 years) searching for the treatment in the Clinic for Gynaecological Endocrinology who reported symptoms of menopausal syndrome were investigated. The type and severity of disturbances of sleep continuity were evaluated using a survey based on the sleep related questions from Hamilton Depression Rating Scale. The severity of symptoms of menopausal syndrome was assessed using the Kupperman Index. The concentration of the following hormones in blood serum was tested: FSH, LH, 17ß-estradiol, PRL, total testosterone, DHEAS and SHBG. RESULTS: Disturbances of sleep continuity were a prevalent complaint in the studied group of women. Difficulties in falling asleep were found in 57.8% of women, difficulties in maintaining sleep in 70%, waking up too early in 60.7%. The severity of all three types of sleep continuity disturbances was related to the severity of menopausal syndrome as measured with Kupperman Index (Spearman correlation coefficient r = 0.63, r = 0.61, r = 0.52, respectively; p < 0.001). Difficulties in maintaining sleep were negatively correlated with the concentration of FSH (r = - 0.19; p < 0.05), 17ß-estradiol (r = - 0.19; p < 0.05) and SHBG (r = - 0.18; p < 0.05), difficulties in falling asleep negatively correlated with the concentration of 17ß-estradiol in the blood serum (r = - 0.19; p < 0.05). CONCLUSIONS: Sleep continuity disturbances are frequently reported by women during the menopausal transition. Interventions aimed at reducing the symptoms of menopausal syndrome should be considered as important action to improve sleep quality in this population of patients.

Serum levels of 3alpha-androstanediol glucuronide in young women with polycystic ovary syndrome, idiopathic hirsutism and in normal subjects.

OBJECTIVE: The study objective was to assess the role of 3alpha-androstanediol glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in patients with idiopathic hirsutism (IH) and in normal non-hirsute women. STUDY DESIGN: Fifty-nine young women with mean age 21.90+/-3.52 years suffered from hirsutism were included in the study. Among these 59 hirsute women 31 women with mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age 22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven normal women, age-matched (mean age 22.60+/-2.90 years), without signs of hirsutism and with normal menstrual cycle served as control for this study. Serum was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha-diolG), main androgens such as: testosterone, free testosterone, dehydroepiandrosterone (DHEAS) and also others hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA) method in the study and control group. Hirutism was assessed using modified Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were significantly higher than in controls. RESULTS: There were no significant differences between serum 3alpha-diolG levels in PCOS group and IH group. Similarly, there were significant differences between serum 3alpha-diolG levels in IH group and control subjects. CONCLUSION: We conclude that 3alpha-diolG is not useful as the marker for peripheral androgen metabolism and for differentiation between idiopathic hirsutism and PCO-related hirsutism.

[Genetic aspects of premature ovarian failure]. / Genetyczne podloze przedwczesnego wygasania czynnosci jajników.

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

[Relationship between climacteric symptoms and serum neuropeptide Y level in postmenopausal women]. / Wystepowanie objawów zespolu klimakterycznego a stezenie neuropeptydu Y w surowicy u kobiet po menopauzie.

UNLABELLED: The aim of this study was to determine circulating levels of neuropeptide Y (NPY) in postmenopausal women with climacteric symptoms in comparison with regularly menstruating women in reproductive age and to assess the relationship between serum NPY levels and the presence of climacteric symptoms in postmenopausal women. MATERIALS AND METHODS: We studied 41 postmenopausal patients attending the Clinic of Gynecological Endocrinology, University of Medical Sciences, Poznan because of climacteric complaints. The controls were 20 regularly menstruating women in reproductive age. In the study group the severity of climacteric symptoms was assessed using the Kupperman index. Serum 17 beta-estradiol, follicle stimulating hormone (FSH) and NPY concentrations were measured by radioimmunoassay in both groups. RESULTS: The mean value of the Kupperman index in the study group was 23.4 points (SD +/- 10.4 points); 17 beta-estradiol serum concentration was lower than 0.014 ng/ml in 30 women from the study group and the mean serum estradiol level for the remaining group was 0.023 ng/ml (SD +/- 0.03 ng/ml); the mean serum FSH concentration in the study group was 98.2 Ul/l (SD +/- 11.8 IU/l), the mean serum NPY concentration in the study group was 18.4 ng/ml (SD +/- 8.3 ng/ml). The mean serum NPY concentration in the control group was 12.9 ng/ml (SD +/- 6.3 ng/ml) and was lower than in the study group (t-test: p < 0.05). The difference between serum NPY concentration in patients with a particular climacteric symptom and patients without was not statistically significant for any symptom (t-test: p > 0.05). CONCLUSION: Serum NPY level is higher in postmenopausal women than regularly menstruating women in reproductive age an may be responsible for climacteric symptoms presence.

Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women.

OBJECTIVES: The aim of this study was evaluation of the influence of hormonal replacement therapy (HRT) on the regional cerebral blood flow in postmenopausal women. METHODS: The study group were 20 postmenopausal women, mean age 48.7 years (S.D. +/- 4.9 years). The control group were ten regularly menstruating women, mean age 32.6 years (S.D. +/- 13.2 years). In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17beta-estradiol level with the use of radioimmunological method. Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography (SPECT). Tracer accumulation evaluation was performed in three slices defined as: cerebellar slice, thalamic slice and ventricular slice, the reference region was delineated in the cerebellum. In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT. RESULTS: Before HRT mean value of the Kupperman index in the study group was 29.8 points (S.D. +/- 7.1 points); 17beta-estradiol 27 pg/ml (S.D. +/- 2 pg/ml); FSH 56 IU/l (S.D. +/- 49.5 IU/l); SPECT study revealed cerebral blood flow impairment in ten women. In all the studied slices cerebral blood flow was lower in the study group than in the controls. After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points (S.D. +/- 2.1 points) (P < 0.05); 17beta-estradiol 44 pg/ml (S.D. +/- 25 pg/ml); FSH 36.4 IU/l (S.D. +/- 57.3 ng/ml); we found cerebral blood flow increase in all studied slices: right cerebellar slice: 5.2%; left cerebellar slice: 4.1%; right thalamic slice: 3.8%; left thalamic slice: 3.3%; right ventricular slice: 7.5%*; left ventricular slice: 6.7%* (* P < 0.05). CONCLUSIONS: Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women. HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17beta-estradiol level.