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.

A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF.

The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive ß-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

[Evaluation of the myo-inositol-monacolin K association on hyperandrogenism and on the lipidic metabolism parameters in PCOS women]. / Valutazione dell'associazione myo-inositolo-monacolina K sull'iperandrogenismo e sui parametri del metabolismo lipidico in donne con PCOS.

AIM: Polycystic ovary syndrome (PCOS) is a multifactorial pathology affecting 5-10% of the female population. Usually occurs with oligo/amenorrhea, anovulation, hirsutism, polycystic ovaries. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome. It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients. METHODS: A new molecule with insulin-sensitizing properties, myo-inositol, has recently been successfully administered in women with PCOS. New associations between natural substances like myo-inositol and other components have been proposed to improve the therapeutical efficacy. Among these substances, the monacolin K, a natural statin appeared to have important actions in cholesterol synthesis. In this article we study the effect of inositol alone and the association between myo-inositol and monacolinin K in the treatment of PCOS with insulin resistance, menstrual irregularities and hirsutism. RESULTS AND CONCLUSION: The results of this study demonstrated a good efficacy of both treatments, although in the group treated with the combination of myo-inositol/monacolin K improvement in lipids and hyperandrogenism were significantly better.

[Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia]. / Il trattamento con carnitina, acetilcarnitina, L-arginina e ginseng migliora la motilità spermatica e la salute sessuale negli uomini con astenozoospermia.

AIM: Among the factors contributing to male infertility, asthenospermia constitutes both a health and a social problem frequently associated with alterations in sexual function. Studies have shown that acetyl carnitine and L-arginine improve sperm motility and that ginseng enhances libido and sexual performance. This study examined the effect of treatment with carnitine, acetyl carnitine, L-arginine and ginseng in men with idiopathic asthenospermia and altered sexual function. METHODS: The study population was 180 patients with asthenospermia randomly assigned to two groups: group A (90 men) received treatment and group B (90 men) did not. The sperm count was 16.6 ± 3.2 x 106/mL and the total sperm motility was 26.5 ± 3.4%. RESULTS AND CONCLUSION: Sexual satisfaction was measured using the sexual satisfaction index (SSI). At the end of therapy, a significant improvement was observed in progressive sperm motility on spermiogram evaluation and in SSI scores in the treatment group.

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.

[Association of antioxidants and natural immune activators in the treatment of astheno-teratospermia and abacterial leukocytosis]. / Ruolo di un'associazione tra antiossidanti e stiomlanti immunitari naturali nel trattamento dell'astenoteratospermia con leucocitosi.

AIM: Leukocytes are often present in human seminal plasma and more frequently in infertile men. Leukocytospermia is associated with sperm morphological and functional alterations. Immune cell activation leads to an increase of free radical production, without any antioxidant defence activation. Leukocyte presence during sperm maturation and migration through male genital tract and consequently exposure to reactive oxygen species led to sperm alteration: axonemal, acrosomal and nuclear structure damage, associated with necrosis. In order to evaluate the immune-modulating and antioxidative activity of beta-glucan, fermented papaya and lactoferrin associated with vitamins C and E, we analysed sperm characteristics of selected infertile male with astheno-teratospermia and abacterial leukocytosis. METHODS: We selected 20 patients referred to our Sterility Centre for semen analysis with leukocyte concentration higher than 1x106 cell/mL. Seminal quality evaluation was performed according to WHO guidelines (1999) using Papanicolau and eosin staining, before and after three months of treatment with beta-glucan, papaya, lactoferrin, vitamin C and E. RESULTS: After therapy, seminal analysis showed a significant reduction of leukocyte concentration and an increase of sperm motility and normal sperm morphology. CONCLUSION: Our results suggest that a combined immunomodulating and antioxidant treatment protect sperm cells during maturation and migration through the male genital tract, resulting in a functional rescue demonstrated by the improvement of semen quality.

Natural molecules for the therapy of hyperandrogenism and metabolic disorders in PCOS.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women of reproductive age and a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology. However, PCOS is also associated with other metabolic abnormalities such as insulin resistance, impaired glucose tolerance, and diabetes. There are few medications that are approved for the most common symptoms of PCOS, leading to the off-label use of medications that were approved for other indications. One of the most common medications being used off label for PCOS is metformin. Research of other effective therapeutic options has included the utility of inositol. PATIENTS AND METHODS: A systematic literature search of PubMed was performed using the following combination of terms: 'PCOS', 'hyperandrogenism' 'inositol', 'natural molecules'. Only papers published between 2000 and 2016 were included in our analysis. The present review analyzes all aspects of the choice of natural molecules in the treatment of hyperandrogenism and metabolic disorders in PCOS women. RESULTS: The rationale underlying the use of inositols as a therapeutic application in PCOS derives from their activities as insulin mimetic agents and their salutary effects on metabolism and hyperandrogenism without side effects. CONCLUSIONS: In this review will discuss the role of a number of natural associations between inositol and different substances in the treatment of hyperandrogenic symptoms in PCOS women.

[Effectiveness of oral administration of Lactobacillus paracasei subsp. paracasei F19 in association with vaginal suppositories of Lactobacillus acidofilus in the treatment of vaginosis and in the prevention of recurrent vaginitis]. / Efficacia dell' utilizzo del Lactobacilllus paracasei subsp. paracasei F19 nella vaginosi e nella prevenzione delle recidive di vaginite somministrato per via orale contemporaneamente ad un Lactobacillus acidofilusper via vaginale.

AIM: The aim of this paper was to estimate the effectiveness of the contemporary oral administration of Lactobacilllus paracasei subsp paracasei F19 in association with vaginal suppositories containing Lactobacilllus acidofilus in the treatment of bacterial vaginosis and in the prevention of recurrent vaginitis. METHODS: We have recruited 60 women in good health, aged between 18 and 40 years with suspect or confirmed diagnosis of bacterial vaginosis. The women were randomized in 2 groups: Group A treated with vaginal suppositories containing Lactobacillus acidofilus (Calagin, SIFFRA, Florence); Group B treated with the same vaginal suppositories + probiotic containing Lactobacilllus paracasei subsp paracasei F 19 for oral administration (Gene-filus F19, SIFFRA, Florence). The patients were examined at the end of therapy (3 months) and then after 3 months from the end of treatment. RESULTS: In both groups at end of therapy there was a significant reduction of vaginal pH, an improvement of sniff test and of the subjective symptomatology after 3 months of treatment which still decreased during follow-up (3 months). In Group B there was a meaningful reduction of vaginal pH and of sniff test at the end of therapy and a maintenance of positive effect also after 3 months. CONCLUSIONS: The results obtained in this study show that the therapy with vaginal Lactobacillus in the treatment of bacterial vaginosis is successful. The association of oral administration is useful to balance the vaginal environment with the intestinal microflora with improvement of long-term results. The use of probiotics was determinant in the treatment of a pathology like bacterial vaginosis and as an alternative to the conventional local antibiotic therapies.

[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.