Inositols in the ovaries: activities and potential therapeutic applications.

INTRODUCTION: Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones. AREAS COVERED: This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility. EXPERT OPINION: Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients' specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.

Inositols in Polycystic Ovary Syndrome: An Overview on the Advances.

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.

Experts' opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond.

Introduction: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

Peroxiredoxin 4 levels in patients with PCOS and/or obesity.

BACKGROUND: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in increased oxidative stress conditions. It is found to be positively associated with cardiovascular risk. The aim of the study was to investigate peroxiredoxin 4 levels in women with polycystic ovarian syndrome (PCOS) and/or obesity. METHODS: In this cros-sesctional study were included 80 patients. Anthropometric measurements and biochemical tests, including peroxiredoxin 4 measurement, were performed. RESULTS: There was a tendency towards lower peroxiredoxin 4 levels in non-obese PCOS subjects (5674.8 ± 3822.4 pg/ml), higher in obese PCOS (6588.9 ± 3731.0 pg/ml) and even higher in obese patients without PCOS (7724.6 ± 4840.4 pg/ml). Patients with abdominal obesity according to waist circumference and waist-to-hip ratio had significantly higher levels of peroxiredoxin compared to those without (7108.2 ± 4568.0 vs. 5079.8 ± 2555.4 pg/ml; p = 0.015 and 7310.6 ± 2646.2 vs. 4785.0 ± 2646.2 pg/ml; p = 0.013). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, hypertension, dislipidemia, hyperandrogenemia, metabolic syndrome. Peroxiredoxin 4 showed weak positive correlation to weight (r = 0.228; p = 0.044) and visceral adiposity index (r = 0.278; p = 0.031) and higher to erythrocyte sedimentation rate (r = 0.4; p < 0.01), but not to hormonal parameters and insulin sensitivity indexes. CONCLUSIONS: Non-obese patients with PCOS have a tendency towards lower peroxiredoxin 4 levels compared to obese patients with and without PCOS. Patients with abdominal obesity have significantly higher peroxiredoxin 4 levels than those without. We were not able to prove correlation between peroxiredoxin 4 levels and hormonal and carbohydrate status of the PCOS patients.

Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).

25(OH) vitamin D levels in premenopausal women with polycystic ovary syndrome and/or obesity.

BACKGROUND: Insulin resistance, hyperinsulinemia, and obesity play an important role in development of polycystic ovary syndrome (PCOS). Current evidence suggests that vitamin D (VitD) deficiency may contribute to the disturbance in insulin metabolism and the development of the metabolic syndrome. The aim of this study was to investigate VitD levels, measured as 25(OH)D, in Bulgarian women with PCOS and/or obesity. MATERIALS AND METHODS: The study included 103 women, divided into three groups - group 1 Obese (n = 33); group 2 Nonobese PCOS (n = 50), and group 3 Obese PCOS (n = 20). 25(OH)D levels were measured by electrochemiluminescence immunoassay. RESULTS: Almost 2/3 of the women with PCOS and/or obesity appeared to be VitD-deficient. Women with obesity, especially visceral (with or without PCOS), had significantly lower levels of 25(OH)D compared to lean PCOS subjects. Women with and without metabolic syndrome however did not differ significantly in 25(OH)D levels. Women with normal body mass index (BMI) had higher 25(OH)D levels compared to overweight and obese (p = 0.028). There was no correlation between 25(OH)D levels and indices of glucose metabolism - fasting blood glucose and immunoreactive insulin (IRI) and after OGTT and HOMA index.

Effect of short-term standard therapeutic regimens on neuropeptide Y and adipose tissue hormones in overweight insulin-resistant women with polycystic ovary syndrome.

AIM: The study was aimed at elucidating the influence of a 3-month treatment with routine therapeutic regimens--oral hormonal contraceptives (OHC) with antiandrogenic activity (a standard combination of ethynil estradiol 35 microg plus cyproterone acetate 2 mg) in combination with insulin sensitizing agents--metformin (Group I) and rosiglitazone (Group II) on adipose tissue hormones and hypothalamic neuropeptide Y (NPY) in women with polycystic ovary syndrome. PATIENTS AND METHODS: The study included 66 overweight insulin resistant women with PCOS according to the recent ESHRE-ASRM criteria randomized into 2 age-matched therapeutic groups. RESULTS: Significant decrease of leptin (P < 0.01; P = 0.001, resp.), resistin (P < 0.01; P < 0.01, resp.), tumour necrosis factor alpha (TNF alpha) (P = 0.001; P < 0.001, resp.), and NPY (P < 0.05; P < 0.001, resp.) was observed in both groups after treatment. These findings were in parallel with a significant decrease in the anthropometric parameters of body weight in the metformin group only. No significant changes in hormonal characteristics of the groups were found except for a significant decrease in androstenedione and DHEA-S (P < 0.05) in the metformin group and in 17-OH-progesterone (P < 0.05) in the rosiglitazone group. HDL-cholesterol rose and diastolic blood pressure fell significantly (P < 0.05) in the metformin group. CONCLUSION: Our data suggest beneficial effects of the treatment on potential cardiovascular risk in insulin resistant PCOS women.

Ultrasound-guided fine-needle aspiration biopsy in unselected consecutive patients with thyroid nodules.

The objective was to analyze the results of UG-FNAB, performed in unselected consecutive patients with thyroid nodules. Methods. The UG-FNAB records were analyzed in this retrospective study. Indication for biopsy was the presence of at least one nodule detected by ultrasound. Results. 330 patients at mean age ± SD 48.4 ± 11.2 years; women/men = 12.8/1 were analyzed. From the total 596 nodules found 546 (91.6%) were investigated with 1231 punctures (2.3 per nodule and 3.7 per patient). Benign solitary nodules had 42.7%, multinodular goiter (MNG) 44.8%, inconclusive 4.8%, and others 2.1% and malignant nodules 5.5% of the patients (6.6% of solitary and 5.1% of MNG patients). The risk for a separate nodule in MNG to be malignant was 2.7%. Conclusions. UG-FNAB is a safe and reliable diagnostic approach for thyroid nodules. It is the method of choice for hypo- and isoechoic not purely cystic solitary nodules, regardless of the nodule size. In MNG, its positive predictive value and diagnostic accuracy are lower. The final decision for regular US monitoring, UG-FNAB of the dominant nodule, multipuncture UG-FNAB or surgical exploration is one of complex appraisal. We consider UG-FNAB appropriate for most nodules in MNG, according to the above mentioned criteria.

Effect of tibolone on sexual function in late postmenopausal women.

BACKGROUND: Sexual dysfunction may significantly affect quality of life and marital relations in the postmenopausal period. The aim of the study was to assess the effect of tibolone on climacteric symptoms and sexuality in late postmenopausal but still symptomatic women. PATIENTS AND METHODS: A six-month prospective study was conducted of two groups of clinically healthy postmenopausal women: a control group (n = 18; mean age 57.8 +/- 4.1 yrs; menopause at 49.7 +/- 2.5; years of amenorrhea 8.1 +/- 4.0 yrs) and a tibolone group (n = 22; mean age 57 +/- 4.5 yrs; menopause at 47.7 +/- 3.9; years of amenorrhea 9.2 +/- 4.6 yrs), who received 2.5 mg tibolone daily for six months. The Kupperman menopausal index (KI) was calculated for both groups at baseline and at six months. Sexual function was assessed by the Female Sexual Function Index (FSFI) questionnaire at the beginning and at the end of the study. The FSFI comprised five main domains: desire, arousal, lubrication, orgasm and pain. Satisfaction and a total score were also recorded. RESULTS: The results showed that during the observation period KI decreased significantly in the tibolone group (15.7 +/- 9.2 vs 11.3 +/- 6.8, p < 0.001), while in the control group no difference was observed. There was a significant improvement of sexual function in the tibolone group in all domains: desire -- from 2.6 +/- 1.0 to 3.1 +/- 1.0 (p < 0.001); arousal -- from 2.3 +/- 1.8 to 3.4 +/- 1.1 (p < 0.001); lubrication - 2.6 +/- 2.1 and 3.5 +/- 1.4 (p < 0.05). The ability to reach orgasm increased (p < 0.001) and pain and discomfort during and after sexual intercourse significantly decreased (p < 0.01). The overall satisfaction and the total score in the treated group changed favourably in a statistically significant manner, while these parameters did not change in the control group. CONCLUSIONS: Treatment with tibolone had a beneficial effect on the climacteric symptoms and sexual function of late postmenopausal women. Moreover, tibolone seems to have an advantage over conventional hormone replacement therapy (HRT) in improving desire and arousal.

Metabolic disturbances in women with polycystic ovary syndrome.

The AIM of the study was to characterize the metabolic syndrome in lean and overweight women with polycystic ovary syndrome (PCOS). The study included 142 premenopausal women distributed into 2 subgroups according to the body mass index: Group 1 with normal weight (n = 39) and Group 2 with overweight (n = 103). The following parameters were measured: basal and oral glucose tolerance test (oGTT)-induced glucose, insulin and triglycerides (TG1), glycated hemoglobin, total, HDL- and LDL-cholesterol; HOMA index and 2 indices of atherogenic risk (total/HDL-cholesterol and atherogenic index) were calculated. The results were compared with those of 35 clinically healthy women allocated also to 2 subgroups: Group 3 with normal weight (n = 18) and Group 4 with overweight (n = 17). Group 1 differed from group 3 in significantly higher fasting, 120-minute insulin, 180-minute insulin during the oGTT, fasting and stimulated TG1, and atherogenic index. Group 2 did not differ from group 4 in the lipid parameters, but 60-minute, and 120-minute glucose, the area under the curve (AUC) of glucose, and stimulated insulin were significantly higher at similar levels of fasting insulin, homeostasis model assessment (HOMA) index and glucose-to-insulin ratio. Fasting glucose did not differ between the two subgroups of PCOS women, but 60-minute, and 120-minute glucose, AUC glu, fasting, 60-minute, and 180-minute insulin, AUC ins and HOMA index were significantly higher in group 2 where the lipid parameters were significantly unfavourable. Our data confirmed the presence of insulin resistance of various degree and an increased lipid atherogenic risk in PCOS while obesity appeared as an additional factor aggravating the metabolic disturbances.