160 research outputs found

    Inositol as putative integrative treatment for PCOS

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    Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols. Such compounds are mainly represented in humans by two inositol stereoisomers: myo-inositol (MYO) and d-chiro-inositol (DCI). MYO is the precursor of inositol triphosphate, a second messenger that regulates thyroid-stimulating hormone (TSH) and FSH as well as insulin. DCI derives from the conversion of myo-inositol via an insulin-dependent pathway. Several preliminary studies have indicated possible benefits of inositol therapy in PCOS patients, but to date no meta-analysis has been performed. This review aims to give clinical insights for the clinical use of inositol in PCOS

    Thyroid, Adrenal, PRL Impairments and Ovarian Function

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    Endocrine axes (prolactin, thyroid and adrenal axes) directly and indirectly modulate and drive human female central functions, mainly behavior and reproduction. Though having distinct abilities, they greatly act both at peripheral as well as at neuroendocrine levels, so as to participate in the control of reproduction. Any event that changes these balanced activities produces specific peripheral signals that induce abnormal functions centrally, thus triggering menstrual disorders such as oligomenorrhea or amenorrhea. It is clear that the knowledge of the relationships that exist between the different endocrine axes becomes essential for the choice of therapeutical approach. This review aims to focus on the main aspects of the physiopathology of the endocrine diseases that might be at the basis of that interference with female reproductive capacity

    Might DHEA be Considered a Beneficial Replacement Therapy in the Elderly ?

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    Dehydroepiandrosterone (DHEA) [prasterone] is typically secreted by the adrenal glands and its secretory rate changes throughout the human lifespan.When human development is completed and adulthood is reached, DHEA and DHEA sulphate (DHEAS) [PB-008] levels start to decline so that at 70–80 years of age, peak DHEAS concentrations are only 10–20% of those in young adults.This age-associated decrease has been termed ‘adrenopause’, and since many agerelated disturbances have been reported to begin with the decline of DHEA/DHEAS levels, this provides a potential opportunity for use of DHEA as replacementtherapy.For these reasons, use of DHEA as a replacement therapy in aging men and women has been proposed and this paper outlines the reported beneficial effects ofsuch treatment in humans. Many interesting results have been obtained in experimental animals suggesting that DHEA positively modulates most age-related disturbances. However, renewed interest in DHEA has arisen as a result of recentstudies suggesting that DHEA appears to be beneficial in hypoandrogenic men as well as in postmenopausal and aging women. Menopause is the event in awoman’s life that induces a dramatic change in the steroid milieu, and use of DHEA as ‘replacement treatment’ has been reported to restore both the androgenic and estrogenic environment and reduce most of the symptoms of this change.As menopause is the beginning of the biological transition of women towards senescence, it is of great interest to better understand how DHEA might help to solve and/or overcome the problems of this complex stage of life. In men withadrenal insufficiency and hypogonadism without androgen replacement, DHEA administration results in a significant increase in circulating androgens.Though most data are suggestive for use of DHEA as hormonal replacement treatment, more defined and specific clinical trials are needed to uncover all of the ‘secrets’ and features of this steroid before it can be used as a standard treatment.Furthermore, DHEA is perceived differently around the world, being considered only a ‘dietary supplement’ in the US, while in many European countries it isconsidered a ‘true hormone’ that has not been approved for use as a hormonal treatment by the European health authorities. This overview offers some points of view on use of DHEA as an experimental hormonal replacement therapy

    Specific concordance index defines the physiological lag between LH and progesterone in women during the midluteal phase of the menstrual cycle

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    Using a recently developed statistically based method for assessment of the degree of concordance, we evaluated the degree of specific concordance (SC) between luteinizing hormone (LH) and progesterone secretory patterns. Eight healthy women volunteered for this study, undergoing a 12-h pulsatility study, sampling every 10 min. LH and progesterone pulse frequencies were estimated with the program DETECT (9.75 +/- 1 and 11.5 +/- 0.9 pulses/12 h, respectively; mean +/- SEM). The temporal relationship between LH and progesterone secretions was evaluated with cross-correlation analysis and with the computation of the SC index. Cross-correlation showed concordance between LH and progesterone (p less than 0.05) at a range of lag between 0 and 40 min, while the SC index indicated that LH and progesterone pulses were significantly (p less than 0.05) and maximally correlated at 10-min lag. In conclusion, our data demonstrated that the specific concordance confirms the statistically significant concordance of LH and progesterone secretory events in women during the midluteal phase. In addition, the use of this new, objective, statistically based approach permits, compared to traditional cross-correlation analysis, a more precise definition of the physiological time lag for temporal coupling of secretory events between the two hormones

    Contraception as prevention and therapy: sex steroids and the brain

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    The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. Specific receptors for gonadal steroids have been identified in the amygdala, hippocampus, basal forebrain cortex, cerebellum, locus ceruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central gray matter.At the hypothalamic level, the principal target for sex steroids is those neurons producing the pulsatile release of the gonadotropin releasing hormone (GnRH), localized in the mediobasal hypothalamus and the arcuate nucleus.The GnRH release depends on the complex and co-ordinated interrelationships among gonadal steroids, pituitary gonadotropins and neuroactive transmitters, such as the noradrenaline, dopamine, opioid peptides (β-endorphin), acetylcholine, serotonin, γ-aminobutyrric acid, corticotropin releasing hormone and neuropeptide Y.The interplay of these control mechanisms is governed by peripheral feedback signals; as well as the input from higher brain centers they may modify the GnRH secretion. The anterior pituitary lobe is the best known target tissue for endogenous or exogenous sex steroid hormones, because it is possible to detect luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in blood, as the expression of the pituitary cells' activity. The synthesis and release of FSH and LH by the gonadotropic cells depend upon the peripheral control of gonadal hormones and the GnRH hypothalamic release. In summary, during a woman's reproductive life, the interaction between neurotransmitters, neuropeptides and gonadal hormones modulates the hypothalamo-pituitary-gonadal axis by acting selectively on the synthesis and release of GnRH and of pituitary gonadotropic hormones.The increased use of oral contraceptives in the last 30 years and, in general, of sex steroid hormone derivative therapies, has led to the study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies by focusing attention on the interactions between estrogens and progestins in the modulation of the hypothalamo-pituitary-gonadal axis.The different kinds of estrogen and progestin molecules used in oral contraceptives inhibit the ovulatory process and may interfere with other sex steroid hormone receptors, thus exerting multiple effects in each target tissue

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

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    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

    Polycystic Ovary Syndrome: From Contraception to Hormone Replacement Therapy

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    Polycystic ovary syndrome (PCOS) is a common disease based on a combination of various endocrine impairments. The use of hormonal treatments permits the aesthetic disturbances to be counteracted (acne, hirsutism, alopecia), but greater attention has to be given to insulin resistance, which may induce more severe diseases, such as diabetes. The use of oral contraceptives is helpful, but a lifestyle change is considered essential so as to improve the natural ability to resist disease affecting the circulation and metabolism. When the menopausal transition starts, greater attention is given to those PCOS patients who demonstrated insulin resistance during their fertile life. The use of hormone replacement therapy is often suggested as it has been proven to be beneficial

    Estimation of instantaneous secretory rate of luteinizing hormone in women during the menstrual cycle and in men

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    In both men and women the pulsatile secretory pattern of LH has been extensively characterized. In the present study we used the algorithm for computation of instantaneous secretory rate (ISR) incorporated into the DETECT program to evaluate the secretory activity of gonadotrophs in vivo. We studied the pulsatile release of LH in four healthy women during four phases of the same menstrual cycle (early and late follicular and luteal phases) and in five healthy men. Computation of ISR permitted us to estimate the frequency and the duration of the secretory events from the gonadotrophs. Samples were collected every 10 min for 6 h. The apparent LH pulsatile frequency during the menstrual cycle varied from 5.0 +/- 0.8 (mean +/- SD) during the early follicular phase (EFP) to 5.3 +/- 1.2 peaks/6h during the late follicular phase (LFP), to 3.3 +/- 1.0 during early luteal phase (ELP) and to 5.3 +/- 0.4 peaks/6h during the late luteal phase (LLP). The mean pulse duration also changed throughout the phases of the cycle (EFP 47.4 +/- 13.2 min; LFP 55.4 +/- 21.6 min; ELP 100 +/- 50.4 min; LLP 48.1 +/- 11 min). In healthy men the LH pulse frequency was 3.8 +/- 1.6 peaks/6h and the duration was 71.5 +/- 35.7 min. When time series were analysed for ISR determination no significant changes were observed between the LH pulse frequency detected on ISR and that observed on plasma concentrations. Conversely, a significant reduction of the duration of the pulses was found when using ISR instead of plasma concentration.(ABSTRACT TRUNCATED AT 250 WORDS
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