Clinical, hormonal and metabolic parameters in women with PCOS with different combined oral contraceptives (containing chlormadinone acetate versus drospirenone).

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10% of women of reproductive age. It is characterized by chronic anovulation leading to menstrual disorders, and increased infertility. The syndrome can also manifest as hirsutism and acne. AIM OF THE STUDY: The aim of the study was to compare, over a duration of 6 months, the effects of drospirenone (DRSP) versus chlormadinone acetate (CMA) containing oral contraceptives (OCs) on clinical, hormonal, and metabolic parameters in 120 PCOS women. MATERIALS AND METHODS: 120 women with the diagnosis of PCOS according to the Rotterdam 2003 criteria were recruited to the study. All patients were divided to two treatment groups of OCs, containing: 3 mg DRSP/30 mcg EE (ethinylestradiol) (60 patients) and 2 mg CMA/30 mcg EE (60 patients). Clinical parameters such as hirsutismus and acne were evaluated. Metabolic parameters such as serum insulin, glucose concentration, homeostatic model assessment of insulin resistance, body mass index, systolic and diastolic blood pressures were also measured. Among hormonal parameters, serum estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, and free thyroxine were measured. RESULTS: The use of both DRSP- or CMA-containing OCs provided similar positive therapeutic effects with regard to clinical, metabolic, and hormonal parameters. Among clinical parameters, like hirsutismus, after 6 months of continuous OC treatment, a statistically significant improvement was observed in both groups: DRSP (p < 0.0001) and CMA OC treatment (p < 0.0001). In addition, significant improvement was showed according to acne lesions both after DRSP (p < 0.0001) and CMA treatments (p < 0.0001). Among glucose, insulin levels and HOMA-IR, there were statistically significant higher levels in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.05) and CMA OC treatment (p < 0.02, p < 0.0001, p < 0.0001). Hormonal parameters such as LH, FSH, prolactin, testosterone and DHEA-S were statistically significant lower in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.01, p < 0,002, and p < 0.0001) and CMA OC treatment (p < 0.0001, p < 0.0001, p < 0.04, p < 0.002, and p < 0.0001). CONCLUSIONS: Further research, however, is needed not only to define optimal duration, and to clarify the effects of treatment on long-term metabolic outcomes, but also to explore different treatment options and possible combined therapies.

Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Genes involved in the pathogenesis of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is defined by the presence of primary or secondary amenorrhea, for at least 4 months, before the age of 40 years associated with follicle stimulating homone levels in menopausal range, exciding 40 UI/L. The diagnosis is confirmed by two blood sample at least 1 month to measure the level of FSH (over 40 UI/L) and level of estradiol (below 50 pmol/L). Ovarian follicular dysfunction and/or depletion of functional primordial follicles characterized this pathology. Abnormal bleeding patterns also include oligomenrrhea and polimenorrhea; because of these irregular menstrual cycles during adolescence, diagnosis could be difficult in young women. Excluding the cases in which an etiopathogenetic agent could be identified, such as in case of chemio- and radiotherapy or extensive surgery, women with autoimmune diseases and/or infections, the etiology of POI remains idiopathic. An important genetic component exists, supported by both a frequent recurring familiar event (20-30%) and the association with other different genetic disorders in particular the X chromosome defects and the implication of some different genes with significant functions in ovarian development. For most of the women the diagnosis of POI is unexpected because of there are no obvious signs or symptoms that precede the cessation of periods with a normal menstrual history, age of menarche and fertility prior to the onset of menopause. The diagnosis of POI has a deleterious psychological impact on the emotional sphere of the women affected: anger, depression, anxiety and sadness are common and the fact that the diagnosis coincides with infertility needs a psychological support. Oral hormonal replacement therapy (HRT) administration is not recommended as first choice of treatment because of the higher hormones concentration with respect to the real hormones necessity of the patients and transdermal HRT may be preferred in women with coagulation disturbances to relief symptoms and to improve to quality of life and the sexuality of these women until the age of 50 years old which is the median age of physiological menopause. Moreover it should be considered the associate comorbidities of POI such as bone loss, cardiovascular disease and endocrine disease.

Transvaginal sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis: association with symptoms.

OBJECTIVES: To investigate whether there are sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding. METHODS: This was a prospective observational study including women referred from a gynecology outpatient center to our university hospital for ultrasound examination. Inclusion criteria were age between 18 and 30 years, regular menstrual cycle and nulligravid status. Exclusion criteria were a past or current history of endometriosis, fibroids, ovarian cysts or lesions, endometrial pathology, current use of hormonal treatments or medications that would affect the menstrual cycle, previous uterine surgery and history of infertility. Women underwent a detailed clinical assessment and a two- (2D) and three-dimensional (3D) transvaginal ultrasound (TVS) examination. 2D-TVS features associated with diffuse adenomyosis were predefined as: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls with the presence of straight vessels, extending into the hypertrophic myometrium, on power Doppler examination. On 3D-TVS, endomyometrial junctional zone (JZ) was measured as the distance from the basal endometrium to the internal layer of the outer myometrium on coronal section at any level of the uterus, and the smallest (JZmin) and largest (JZmax) JZ thicknesses and their difference (JZdiff) were recorded. 3D-TVS evaluation was considered suggestive for adenomyosis when JZmax ≥ 8 mm and/or JZdiff ≥ 4 mm. The presence of associated symptomatology represented our main outcome: the amount of menstrual loss was assessed by a pictorial blood loss analysis chart (PBAC) and painful symptoms were evaluated using a visual analog scale (VAS). RESULTS: During the observation period, 205 women (median age, 24 (interquartile range, 23-27) years) were enrolled into the study and 156 met the inclusion criteria. According to the 2D-TVS criteria, diffuse adenomyosis was found in 53 (34.0%) women and asymmetrical myometrial thickening of the uterine walls was the most common sonographic feature observed. ANOVA showed a significant relationship between the number of 2D-TVS features of diffuse adenomyosis and VAS score for dysmenorrhea (P = 0.005) as well as PBAC score for menstrual loss (P = 0.03). 3D-TVS showed that women with 2D-TVS features of diffuse adenomyosis had a significantly higher value of JZmax (6.38 ± 2.30 mm, P < 0.001), JZmin (2.07 ± 0.43 mm, P = 0.002) and JZdiff (4.33 ± 1.99 mm, P < 0.001) than did women without these features. Women with sonographic features of diffuse adenomyosis were symptomatic in 83% of cases, reported dysmenorrhea in 79.2% and showed a higher incidence of heavy bleeding than did those without these features (18.9% vs 2.9%; P = 0.001). CONCLUSIONS: Sonographic features suggestive of diffuse adenomyosis may develop earlier in reproductive life than previously thought, and may occur in association with dysmenorrhea and abnormal uterine bleeding in nulligravid women. Their observation in these women should therefore warrant further gynecological investigation.

Premature ovarian insufficiency: from pathogenesis to clinical management.

Premature ovarian insufficiency (POI) represents a condition characterized by the absence of normal ovarian function due to an incipient (by 3-10 years) ovarian aging. In most of the women affected there are no signs or symptoms that precede the interruption of menstruation and the onset of POI and the majority of women have a normal history of menarche, regular menstrual cycles and normal fertility. The possible genetic role in the development of POI has been largely demonstrated and many genes have been involved; on the other hand, ovary is not protected immunologically and the detection of autoantibodies directed against various ovarian targets strongly support the hypothesis of an autoimmune etiology. In approximately 5-10% of women with a diagnosis of POI with a normal karyotype, a spontaneous pregnancy could occur even if the recovery of ovarian function is temporary and poorly predictable. Embryo donation and adoption are other alternatives that should be considered. POI and subsequent loss of reproductive capacity is a devastating condition and a difficult diagnosis for women to accept so it requires an individualized and a multidisciplinary approach. Hormonal replacement therapy (HRT) should be commenced as soon as possible to prevent and to contrast the onset of the symptoms related to hypoestrogenism and to improve the quality of life for these women.

Hormone replacement therapy in menopause and in premature ovarian insufficiency.

Menopause is defined by world health organization (WHO) as the permanent cessation of menstruating resulting from a loss of ovarian follicular activity, after one year of amenorrhea. It signifies the last menstrual cycle and the end of women's fertile and reproductive life. The average age for a women to undergo menopause is 51 years; unlike menarche, whose average age has decreased over the past decades, the age of menopause has remained unchanged. We can distinguish: 1) premenopause, the time interval leading up to menopause; 2) climacteric, the time interval between the reproductive e non-reproductive life; 3) premature menopause, that occurs in 1% of women. Menopause can also be induced iatrogenically as a result of surgery, medical therapy, chemotherapy and radiotherapy. Beyond the life the number of oocytes falls until there are no more suitable follicles for reproduction and the menopause ensues. At the same time, the ability of the ovary to produce hormones falls, leading to an increasing pulsatile release of FSH in order to stimulate the ovary to produce oestrogens. Menopause is characterized by different symptoms such as hot flushes, night sweats, dispareunia, prolapse, vulval itching due to vaginal atrophy and dryness, urinary incontinence, dysuria, and also the psychological aspects don't should be underestimated because of many women suffer of depression, mood instability, insomnia, fatigue and decreased libido. Long term symptoms include osteoporosis, cardiovascular and neuro-degenerative diseases. The main aim of different treatments was symptoms relief. Pharmacological agents and psychological support represent the goal for menopause treatment.

Evaluation of brain-derived neurotrophic factor in menstrual blood and its identification in human endometrium.

The presence of high-affinity brain-derived neurotrophic factor receptor Trk B in mouse and in human fetal oocytes, together with the presence of neurotrophins in human follicular fluid suggests a paracrine role for brain-derived neurotrophic factor (BDNF) in female biology. This study aims to evaluate if BDNF is present and quantitatively determined in human menstrual blood and endometrium. Twenty-one women were studied and subdivided in two groups: A, 11 fertile women (27 ± 2 days cycle length) and B, 10 anovulatory women and/or women with inadequate luteal phase (36 ± 2 days cycle length). In fertile women menstrual BDNF levels was higher than plasma (679.3 ± 92.2 vs 301.9 ± 46.7 pg/ml p <0.001). Similarly, in Group B, BDNF in menstrual blood was higher than plasma (386.1 ± 85.2 vs 166.8 ± 24.1 pg/ml p < 0.001). Moreover, both menstrual and plasma BDNF concentrations in Group A were significantly higher respect to Group B (679.3 ± 92.2 vs 386.1 ± 85.2 pg/ml p < 0.001; 301.9 ± 46.7 vs 166.8 ± 24.1 pg/ml p < 0.001). Immunohistochemistry evidence of BDNF in endometrium, during follicular and luteal phase, was also shown. The detection of BDNF in the human menstrual blood and endometrium further supports the role of this neurotrophin in female reproductive function.

Plasma brain-derived neurotrophic factor concentrations in children and adolescents.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity influencing learning, memory and cognitive behavior. The aim of this study is to assess plasma BDNF variations according to pubertal status. METHODS: A total of 110 subjects were included in the study. Blood samples were collected after overnight fasting. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. Gonadotrophins, sex steroids, and IGF-1 were also assessed. RESULTS: BDNF was positively correlated with platelet count and negatively associated with both BMI and age. BDNF levels in pubertal males were significantly lower than prepubertal males and both prepubertal and pubertal females. CONCLUSIONS: Plasma BDNF levels seem to be influenced by hormonal status. We demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF blood levels and platelets remain the most important predictor of their concentration. Further studies are necessary to better understand the role of this neurotrophin in pubertal development.

Allopregnanolone levels decrease after gonadotropin-releasing hormone analog stimulation test in girls with central precocious puberty.

BACKGROUND: Allopregnanolone, a neuroactive steroid mainly secreted by adrenals and gonads, is a hormone that seems to play a role in precocious puberty, as demonstrated by its high baseline levels found in girls with central precocious puberty (CPP). Allopregnanolone concentrations significantly increase after GnRH and ACTH stimulation test suggesting both its ovarian and adrenal production. AIM: Aim of this study was to evaluate allopregnanolone concentrations after GnRH and GnRH agonist analog stimulation test in girls with CPP to better establish its secretion source. SUBJECTS AND METHODS: Gonadotropins and steroid hormones were evaluated in different days after GnRH and triptorelin stimulation test in 15 CPP girls. RESULTS: After GnRH stimulation, LH, FSH, and allopregnanolone concentrations significantly increased (p<0.05). After triptorelin administration LH, FSH, estradiol and DHEAS levels significantly increased (p<0.05), while allopregnanolone concentrations significantly decreased (1.08±0.24 vs 0.87±0.28 nmol/l; p=0.003). CONCLUSIONS: The different response of allopregnanolone to GnRH and GnRH agonist analog might reflect the agonist and antagonist action exerted by these secretagogues. Our data suggest the prevalent gonadal allopregnanolone production in CPP subjects and the usefulness of its measurement in the diagnosis of CPP.

Serum levels of tryptophan, 5-hydroxytryptophan and serotonin in patients affected with different forms of amenorrhea.

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

Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity and influences learning, memory and cognitive behaviour. The aim of this study is to assess plasma BDNF variations according to hormonal status. METHODS: A total of 60 subjects were included: 20 fertile ovulatory women, 15 amenorrhoeic women and 25 postmenopausal women. Blood samples were collected after overnight fasting. For 5 out of the 20 fertile women, samples were collected every 2 days throughout the whole menstrual cycle. Following basal evaluation, 10 out of 25 postmenopausal women were administered a hormone replacement therapy (HRT) and reevaluated after 6 months of treatment. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. In fertile women, estradiol (E(2)), progesterone and gonadotrophins were also assessed. RESULTS: In fertile women, luteal phase levels of plasma BDNF were significantly higher than follicular phase levels (P < 0.001). BDNF increased from early follicular phase up to Day 14 of the cycle, reaching a pre-ovulatory peak, similar to E(2). A second rise took place during mid-luteal phase, with a peak on Day 24. Amenorrhoeic subjects, as well as postmenopausal women, showed significantly lower plasma BDNF levels compared with fertile females (P < 0.001). BDNF was positively correlated with E(2) and progesterone and negatively correlated with menopausal age. HRT restored BDNF levels to those present in fertile women during the follicular phase. CONCLUSIONS: Plasma BDNF levels are influenced by hormonal status. Modifications in BDNF circulating levels during the menstrual cycle suggest a potential role for gonadal sex hormones (E(2) and progesterone) in regulating neurotrophin expression.

High basal serum allopregnanolone levels in overweight girls.

OBJECTIVE: Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3alpha-hydroxy-5alpha-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children. SUBJECTS AND MEASUREMENTS: We studied 27 normal weight (NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients. RESULTS: Basal AP concentrations in OW girls were significantly higher than in NW controls (P=0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones (P=0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients (P=0.025). AP and DHEAS were significantly directly related to weight (r=0.31 and r=0.54, respectively) and body mass index (r=0.29 and r=0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS (r=0.60), A (r=0.72) and luteinizing hormone (r=0.64) levels was demonstrated. CONCLUSION: The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects.

Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation.

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.

Activin, inhibin and the human breast.

Activins and inhibins are growth factors involved in cell differentiation and proliferation. Human breast tissues such as normal mammary tissue, fibroadenoma, and breast cancer express inhibin and activin mRNA and proteins. Activin A and its binding protein, follistatin, are also present in human milk during the first week of lactation. Using immunohistochemistry, we have observed that the inhibin/activin alpha, betaA, and betaB subunits are present in normal breast tissue regardless of menstrual cycle phase or menopause, as well as in fibrocystic disease, and breast tumors. The mRNAs encoding all three activin/inhibin subunits are expressed in breast carcinoma, fibroadenoma, and normal mammary tissue. The betaA subunit gene expression is higher in either local or metastatic breast carcinoma than in normal tissue. In addition, dimeric activin A is detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic adjoining tissue. Recent evidence suggests that some of the activin A produced by breast carcinoma is released into systemic circulation. In women with breast cancer, serum activin A levels are often elevated, and a significant decrease is observed in the first and second days following tumor excision. The role of activin and inhibin as endocrine and/or paracrine factors in the breast is still uncertain. Activin has complex effects on cell growth during branching morphogenesis, but it is generally considered as an inhibitor of cell proliferation as in vitro studies have shown that activin A treatment of breast cancer cells arrests cell growth. Inhibin is generally considered as a tumor suppressor, but its possible role in the breast is less understood.

Inhibins and activins in pregnancy.

Human placenta, decidua, and fetal membranes are the major sites of production and secretion of inhibin A and activin A in maternal serum, amniotic fluid, and umbilical cord blood. These tissues also express follistatin-related gene and betaglycan, the binding proteins of activin A and inhibin A, respectively, recently identified. They show a different expression throughout pregnancy, suggesting new functional roles into gestational tissues. The availability of suitable assays for measuring inhibin A and activin A lead us the possibility to investigate their secretion in healthy pregnancy. In addition, several evidences underline the potential role and the clinical usefulness of their measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as: threatened abortion, placental tumors, hypertensive disorders of pregnancy, intrauterine growth restriction, fetal hypoxia. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future further possibilities in early diagnosis, prediction, and monitoring pregnancy diseases.

Adrenal response to adrenocorticotropic hormone stimulation in patients with premenstrual syndrome.

Several studies have been performed during recent years to investigate the existence of a possible endocrine cause for premenstrual syndrome (PMS); the results reported are often discordant. Great interest has been raised around allopregnanolone, which could be involved in the determination of mood disorders reported by PMS patients. During the luteal phase, lower levels of this hormone have been detected in PMS patients. The aim of our study was to evaluate estradiol, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, total and free testosterone, cortisol, pregnenolone and allopregnanolone levels in 20 patients suffering from PMS and to compare them with those found in 20 fertile healthy women in the follicular and the luteal phases. Adrenocorticotropic hormone (ACTH) tests after dexamethasone suppression were performed in 10 patients of each group during the follicular and the luteal phases. In the PMS group, significantly lower allopregnolone levels were found in the luteal phase, while progesterone was lower in the PMS group in both phases. In the PMS group, higher free testosterone levels were found during the luteal phase and higher DHEA levels in both the follicular and the luteal phases. The present data confirm reduced allopregnanolone levels in the luteal phase in PMS patients, together with higher levels of DHEA and free testosterone. It is possible to conclude that, in addition to the previously described reduced luteal secretion of allopregnanolone, the adrenal gland production of this steroid in PMS sufferers is also impaired in the luteal phase. Considering the specific actions of these hormones on the control of mood and behavior, this specific hormonal milieu may contribute to the cyclic occurrence of anxiety, aggressiveness and irritability reported by PMS patients.

Abnormal umbilical artery Doppler waveforms and cord blood inhibin a and inhibin B levels.

Inhibin A and inhibin B are glycoprotein hormones produced by human placenta and by several fetal organs during pregnancy. They are secreted in maternal circulation in increasing amounts from early until term pregnancy, and in umbilical cord blood levels are significantly lower than in maternal serum and do not differ from mid-pregnancy to term gestation. In the present study, we aimed to determine whether secretion of inhibin A and inhibin B into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. A group of women (n = 13) with abnormal Doppler umbilical artery flow velocimetry and a group of control women (n = 11) with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms were studied. In each woman, inhibin A and inhibin B concentrations were estimated in umbilical cord artery and vein. In the two groups of women, mean inhibin A levels did not differ between umbilical cord artery and vein. In addition, no difference was retrieved both in umbilical cord artery and vein values between healthy controls and patients with abnormal Doppler umbilical artery flow velocimetry. On the contrary, inhibin B levels were significantly higher in samples from umbilical cord vein than artery, in both groups of pregnant women (both p < 0.001). However, women with abnormal Doppler umbilical artery flow velocimetry had inhibin B levels significantly higher than healthy controls (p = 0.005) only in the umbilical cord artery, but not in the vein. In the presence of abnormal Doppler umbilical artery flow velocity, the concentrations of inhibin B are increased in the arterial umbilical circulation, suggesting that inhibin B is released from multiple fetal sources as a response to hypoxemic stress. As inhibins may affect the hypothalamus-pituitary-adrenal axis which plays an important role in the mechanisms of adaptations to the post-natal life, inhibin B in fetal circulation might then be beneficial to a fetus whose intrauterine survival is threatened by impaired umbilical-placental blood flow.

Increased serum inhibin B levels in postmenopausal women with altered thyroid function.

Hyper- and hypothyroidism have significant effects on the female reproductive system. However, little in the way of data is available on the relationship between ovarian paracrine control and thyroid function. This study was aimed at characterising the serum levels of inhibin B in relation to altered thyroid function. Serum inhibin B and FSH levels were measured in 91 women (51 regularly cycling and 40 postmenopausal). The mean serum concentration of inhibin B in euthyroid cycling women (0.025 +/- 0.018 microg/l) was similar to that observed in hyper- and hypothyroid patients (0.022 +/- 0.015 and 0.018 +/- 0.014 microg/l, respectively, p=ns). Inhibin B levels were obviously reduced (-72%) in euthyroid postmenopausal women. In contrast, in hyper- and hypothyroid postmenopausal women, inhibin B levels remained substantially at the premenopausal level. So far, serum inhibin B appeared to be significantly increased in both hyperthyroid patients (0.025 +/- 0.014 microg/l; p<0.0001) and in hypothyroid patients (0.016 +/- 0.006 microg/l; p=0.0006). Altered thyroid function did not affect FSH levels at fertile age. However, a significant decrease of FSH levels was observed in hyper- and hypothyroid (-52% and -43%, respectively) postmenopausal women. Nevertheless, these FSH levels remained in the postmenopausal range. These results indicate that an altered thyroid function affects serum inhibin B levels in postmenopausal women.

Inhibin A, inhibin B and activin A concentrations in umbilical cord artery and vein.

Activin A and inhibins (A and B) are growth factors expressed during pregnancy by the human placenta, decidua and fetal membranes, and by several fetal organs. They are secreted in both the maternal and the fetal circulations, but the net contribution of the fetus to inhibins/activin A production is still unclear. In the present study we determined whether there was a difference in the serum concentration of activin A, inhibin A and inhibin B between the artery and vein of the umbilical cord. Arterial and venous umbilical cord blood was obtained immediately before elective Cesarean section of 16 term infants from uncomplicated pregnancies. Inhibins and activin A levels were assayed by specific enzyme-linked immunosorbent assays. The paired t-test and linear regression analysis were used to calculate statistical significance. Inhibin A levels did not differ between the artery and vein of the umbilical cord. In contrast, arterial inhibin B levels were significantly (p < 0.001) lower, and activin A concentrations significantly (p < 0.05) higher than the respective venous concentrations. A significant correlation between arterial and venous levels of inhibin A (r = 0.591; p < 0.05), inhibin B (r = 0.749; p < 0.0001) and activin A (r = 0.571; p < 0.05) was found. The present findings suggest that the human placenta is the main source of inhibin B, and the fetus of activin A, in the umbilical cord. In light of the possible roles played by inhibin and activin in erythroid differentiation, protection of neurons against brain injury and modulation of adrenal and pancreatic hormone release, the present data may be of help in evaluating their changes in the umbilical cord when gestational diseases occur.