Therapeutic approach for metabolic disorders and infertility in women with PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental. The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.

Genetic, hormonal and metabolic aspects of PCOS: an update.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.

Role of nutrients in modulating microbiota and immunity in COVID-19 disease.

COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages.

Arterial involvement in Fabry disease: state of the art and future diagnostic purposes.

Anderson-Fabry disease (FD) is a rare genetic, progressive, and multi-systemic condition, with X-linked inheritance. This is caused by pathogenic variants in the GLA gene, coding for the lysosomal enzyme called alpha-galactosidase A (aGLA), responsible for the cleavage of globotriaosylceramide (Gb3). The reduced or absent activity of aGLA causes the intracellular accumulation of Gb3, particularly in smooth and endothelial muscle cells, which causes cellular dysfunction. The main organs involved are the central nervous system, heart, and kidneys. However, being a ubiquitous enzyme, FD disease must be considered a systemic disease involving the peripheral nervous system, ocular and audio-vestibular systems. Also, the vascular district is damaged but the pathophysiology of vasculopathy in FD is not yet entirely understood. In literature, many vascular diagnostic tests were used to evaluate this specific involvement in FD, i.e., carotid intima media thickness (cIMT), arterial stiffness (AS), flow-mediated dilation (FMD) and atherosclerotic plaques; evaluation of vascular calcifications in FD patients is not presently available. In this review, we examined the current available literature on vascular aspects in FD. Moreover, we presented our global vascular evaluation, based on Radio Frequency Duplex Ultrasound (RF-DU), plaques, and vascular calcifications, to apply to FD patients.

Therapeutic management of idiopathic recurrent serositis: a retrospective study.

OBJECTIVE: Idiopathic recurrent serositis (IRS) is the most frequent serositis encountered in real-life medical sceneries, and its management represents a therapeutic challenge. There are few epidemiologic data related to IRS, though most studies have focused on recurrent pericarditis, revealing that 70% of all forms of pericarditis are idiopathic and caused by innate immunity abnormalities. The aim of this study was to evaluate outcome and recurrence rates of patients with IRS, assessing management modalities used in our Periodic Fever Centre of the Gemelli Hospital, Rome, Italy, in comparison with previous treatments in other centres. PATIENTS AND METHODS: Retrospectively, we analyzed the medical charts of 57 unselected patients with history of IRS managed during the period 1998-2017. RESULTS: A strong heterogeneity emerged by evaluating treatments of this cohort. In particular, in our Centre there was a larger use of combined therapies: 14 patients out of 27 (52%) were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, compared to only 2 patients (7.4%) previously treated with combined treatments. We used corticosteroid monotherapy only in 1 case, against 7 from other centres. The mean duration of NSAID treatment in other hospitals was 43.8 days (SD ±27.40) and 191.25 days (SD ±42.23) in our Centre; the mean duration of corticosteroid treatment in other hospitals was 101.5 days (SD ±56.40) and 180.7 days (SD ±84.87) in our Centre. Colchicine was administered in other hospitals for the same duration of NSAIDs, and corticosteroids with an average duration of 111 days (SD ±30); conversely, we administered colchicine for an average duration of 250.12 days (SD ±80.7). Relapses of IRS were reported in 1/3 of cases who had discontinued therapies. CONCLUSIONS: The overall duration of treatments to manage IRS has a weight in terms of patients' outcome. A reduced duration of therapy with corticosteroids and a longer duration of therapy with NSAIDs determine a longer disease-free interval. A significant discriminating effect in terms of risk of IRS recurrence relies in an earlier combination therapy with colchicine independently from the start with either NSAIDs or corticosteroids. Finally, the evaluation of genes causing autoinflammatory diseases has not revealed any pathogenetic variants in a subcohort of 20/57 patients with IRS.

Metformin doses and body mass index: clinical outcomes in insulin resistant polycystic ovary syndrome women.

OBJECTIVE: PCOS is the most common endocrinopathy among reproductive age women. Approximately 60% of PCOS women have insulin resistance. While the efficacy of metformin in reducing insulin resistance and decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used. PATIENTS AND METHODS: Prospective non-randomized cohort study of 108 insulin resistant, overweight and obese PCOS women, aged between 22 and 35 years. All patients received 1500 mg of metformin (500 mg x 3 times/day) for the first 6 months. At the end of this period, the patients' HOMA index was evaluated. In subjects, who did not demonstrate normalization of the HOMA index, the dose was increased to 2500 mg/day (500 mg at breakfast and 1000 mg at lunch and dinner) for additional 6 months. The hormonal blood profile, fasting insulin and fasting glucose levels, HOMA index, anthropometric assessment, pelvic ultrasound, FAI index and cholesterol were evaluated. RESULTS: Overall results showed a good response to metformin therapy in insulin-resistant PCOS patients with BMI >25, while in patients with higher BMI (31.15 ± 0.40), no normalization of HOMA was found. At the higher dose of metformin, obese patients achieved a good response to therapy, with improvement in BMI, menstrual pattern, cholesterol levels and hyperandrogenism. CONCLUSIONS: Our results demonstrate a correlation between the required dose of metformin, BMI and hyperandrogenism. The dose of metformin should be adjusted to patients' BMI in order to obtain significant results in terms of clinical, metabolic and hormonal responses.

Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association.

AIM: Polycystic ovary syndrome (PCOS) affects 5-10% of women of childbearing age and manifests itself through oligomenorrhea, anovulation, hirsutism, micro-polycystic ovaries. Insulin resistance is a characteristic of PCOS patients and is more pronounced in obese patients. Insulin resistance and consequent hyperinsulinemia are related to many aspects of the syndrome such as hyperandrogenism, reproductive disorders, acne and hirsutism. In the long-term it may increase the risk of cardiovascular disease and negatively affect lipid profile and blood pressure. Changes in lifestyle and diet can partially improve these aspects. The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies. New molecules have recently been marketed, that produce the same results, but without the side-effects. One of these is myo-inositol, a new insulin-sensitizing molecule which has been successfully administered to women suffering from PCOS. Associations between inositol and other compounds that can increase the therapeutic effect have been proposed. Of these, we found to be interesting the association with monacolin K, a natural statin that reduces cholesterol levels starting point of the synthesis of steroids, including androgens, and lipoic acid, known for its anti-inflammatory, antioxidant and insulin-sensitizing activity. We decided to assess the efficacy of the product. METHODS: We recruited 30 women aged between 24 and 32 years suffering from PCOS with insulin resistance, HOMA index>2.5 and no other endocrine diseases. The following were assessed: Body Mass Index (BMI), characteristics of menstrual cycles, lipid profile (total cholesterol, and HDL), androgens (total testosterone and androstenedione). The patients were also assessed for the degree of hirsutism using the Ferriman-Gallwey Score>8. The subjects were divided into two groups: Group A, treated with an association of 1 g myo-inositol, 5 mg monacolin K and 400 mg lipoic acid for 6 months; Group B, treated with a double dosage of 2 g myo-inositol, 10 mg monacolin K, 800 mg lipoic acid for 6 months. RESULTS: The results have shown good efficacy of both dosages, although women treated with a double dosage of myo-inositol, monacolin K and lipoic acid showed a significantly greater improvement in terms of lipid parameters and those connected with hyperandrogenism. CONCLUSION: This new myo-inositol, monacolin K and lipoic acid association contains appropriate substances to contrast various etiopathogenic elements responsible for the onset of PCOS and the symptoms of hyperandrogenism and dyslipidemia related to it.

[Evaluation of the efficacy of a new nutraceutical product in the treatment of postmenopausal symptoms]. / Valutazione dell'efficacia di un nuovo preparato nutraceutico nel trattamento dei disturbi delle donne in postmenopausal.

The onset of vasomotor symptoms in postmenopausal women represents the beginning of a hard period from the emotional point of view which involves some of the most important neurotransmitters. Hot flushes and insomnia associated with a state of anxiety that affect postmenopausal women are included in an index known as the Kupperman Index. The use of nutraceuticals in Italy is increasingly widespread, and only 6-8% of women currently choose to take hormone replacement therapy. The action of these natural supplements primarily depends on the selection of substances and the dose of each single ingredient. Moreover, it also depends on the range of vasomotor symptoms (from mild to moderate/severe). The aim of this study was to test the action of a new product without phytoestrogens containing Cimicifuga racemosa, chasteberry (Vitex agnus-castus), hyaluronic acid, zinc and ginger (ElleN®) in two different groups of women: one with mild and the other with moderate/severe menopausal symptoms. All women received a dose of one tablet per day of ElleN® for three months. Results showed a significant reduction in the Kupperman Index in both groups. The treatment was particularly effective against hot flushes associated with night insomnia and anxiety. The product was well tolerated, did not cause any side effects, and none of the subjects dropped out of the study. In conclusion, it can be stated that the supplement evaluated in the present study is able to reduce moderate/severe menopause symptoms.