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Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance
Gynecological Endocrinology
Abstract and Figures
Background:
Insulin resistance plays a key role in the pathogenesis of polycystic ovarian syndrome (PCOS). One of the methods for correcting insulin resistance is using myo-inositol.
Aim:
The aim of the present study is to evaluate the effectiveness of myo-inositol alone or in combination with clomiphene citrate for (1) induction of ovulation and (2) pregnancy rate in anovulatory women with PCOS and proven insulin resistance.
Patients and methods:
This study included 50 anovulatory PCOS patients with insulin resistance. All of them received myo-inositolduring three spontaneous cycles. If patients remained anovulatory and/or no pregnancy was achieved, combination of myo-inositol and clomiphene citrate was used in the next three cycles. Ovulation and pregnancy rate, changes in body mass index (BMI) and homeostatic model assessment (HOMA) index and the rate of adverse events were assessed.
Results:
After myo-inositol treatment, ovulation was present in 29 women (61.7%) and 18 (38.3%) were resistant. Of the ovulatory women, 11 became pregnant (37.9%). Of the 18 myo-inositol resistant patients after clomiphene treatment, 13 (72.2%) ovulated. Of the 13 ovulatory women, 6 (42.6%) became pregnant. During follow-up, a reduction of body mass index and HOMA index was also observed.
Conclusion:
Myo-inositol treatment ameliorates insulin resistance and body weight, and improves ovarian activity in PCOS patients.
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... Так, по данным S. Gerli и соавт., использование мио-инозитола в течение 14 мес приводило к развитию резистентности у 30% пациенток [55]. Также, согласно результатам исследования Z. Kamenov и соавт., резистентность к мио-инозитолу затрагивала более 38% женщин [56]. В заключение необходимо отметить результаты исследования M. Iuorno и соавт., согласно которым использование D-хиро-инозитола в течение 6-8 нед приводило к развитию резистентности у 40% пациенток [57]. ...
... Данный биологически активный агент кроме усиления абсорбции обладает рядом других позитивных эффектов, включая иммуномодулирующий, антистрессовый, антибактериальный и противоязвенный [62]. Вместе с тем, по результатам имеющихся исследований, было показано, что использование альфа-лактальбумина позволяет повысить биодоступность мио-инозитола и его концентрацию в сыворотке крови на 32% и 30% соответственно [56,62]. В исследовании другой степени доказательности также было установлено, что добавление альфа-лактальбумина к мио-инозитолу позволяет повысить сывороточную концентрацию последнего более чем в 2 раза, что способствует более эффективной регуляции овуляторной функции пациенток с СПЯ [63]. ...
Polycystic ovary syndrome is a proven risk factor for both endometrial hyperplasia and cancer. The article reflects the current paradigm of etiology, pathogenesis and management of patients with endometrial hyperplasia on the background of polycystic ovary syndrome, according to the data of domestic and foreign literature.
... En un estudio de 12 semanas con 50 mujeres con sobrepeso y SOP, el uso de 2 g/día de MI (junto con 200 mcg de ácido fólico) resultó en reducciones significativas en varias hormonas, incluyendo la hormona luteinizante (LH), prolactina, testosterona e insulina, así como una mejora en la sensibilidad a la insulina [32]. También se observó mejoras en la tasa de parto y el restablecimiento del ciclo menstrual en mujeres con amenorrea u oligomenorrea [33,34]. ...
Los inositoles son hexahidroxiciclohexanos conformados por nueve estereoisómeros, la mayoría biológicamente activos. La presente revisión pretende recapitular los principales efectos del mioinositol (MI) sobre las características patológicas del síndrome de ovario poliquístico (SOP) y su papel como regulador en la respuesta hormonal y bioquímica femenina. Las pacientes con SOP presentan trastornos clínicos, hormonales, metabólicos y fisiológicos que requieren tratamiento especializado a largo plazo. Por su parte, el inositol ha demostrado ser efectivo para reducir la severidad de los síntomas, regular la función menstrual y mejorar el perfil hormonal controlando parámetros metabólicos, por lo que su administración representa una opción efectiva para el manejo de los síntomas del SOP. A pesar de esto, existen limitaciones para los estudios como el hecho de que, al tratarse de un síndrome, el SOP es una condición heterogénea con una amplia variedad de síntomas y manifestaciones clínicas, por lo que también implica variedad de respuesta en las pacientes al MI. En los últimos años, su investigación ha generado evidencia terapéutica prometedora, pero aún falta abarcar más estudios controlados y doble ciego para definir su efecto según los fenotipos del SOP, así como investigaciones a largo plazo que evalúen la seguridad y eficacia del tratamiento en períodos prolongados. De manera general, el MI representa una alternativa efectiva y segura para el tratamiento del SOP, mostrando resultados similares a los presentados por otros tratamientos sin la presencia de los efectos secundarios conocidos.
... This consistency across studies strengthens the evidence supporting the efficacy of the combination therapy in inducing ovulation compared to myo-inositol alone in women with polycystic ovarian syndrome. In research led by Zdravko Kamenov et al. (15), it was found that following myo-inositol treatment, ovulation occurred in 29 women (61.7%), while 18 (38.3%) showed resistance to the treatment. ...
... 16 Similarly, a pregnancy rate of (15.1%) is testified in myo-inositol and folic acid users in one study. 17 Quite a few studies compared metformin with clomiphene citrate in polycystic infertile women. In one study, 626 women were administered six cycles of three randomised medical treatments, including metformin 1gm twice daily combined with placebo, clomiphene citrate combined with placebo, or metformin with clomiphene citrate. ...
Objective: To compare Clomiphene Citrate, ovulation induction efficacy following using insulin sensitises, Metformin versus Myo-inositol in subfertile women with polycystic ovary syndrome. Study Design: Prospective comparative study. Place and Duration of Study: Department of Obstetrics and Gynaecology, Combined Military Hospital, Kharian Pakistan, from Jun to Nov 2021. Methodology: A total of 316 patients with polycystic ovary syndrome and infertility who were included in the study. Group-A was administered Metformin, whereas Group-B as given Myo-inositol. Both groups were given clomiphene citrate for ovulation induction and were followed for six months. Results: There were 316 patients (158 in each Group). The mean age was 29.2±0.5 years, and the BMI of 23.2±1.7 Kg/m2 in both. Ovulation recorded in Group-A (Metformin) was 141(44.6%) versus Group-B (Myo-inositol), 103(32.6%). The pregnancy test was positive 33(21.1%) patients of Group-A versus 29(18.4%) of Group-B. The common complaints seen in both groups were nausea and vomiting 2(0.6%), while headache 1(0.3%) and dizziness 2(0.6%) occurred only in Group-B. Conclusion: Clomiphene citrate with Metformin, as first-line therapy for sub-fertile women with polycystic ovary syndrome, improved ovulation and had fewer side effects than Myo-inositol.
... It is key to note that approximately 38% of patients may be resistant to myo-inositol, but studies in which alphalactalbulmin was supplemented noted reduction in this resistance. However, these studies were not randomized trials and did not involve patients undergoing IVF thus severely limiting general applicability [34][35][36]. Overall myo-inositol especially when combined with folic acid and melatonin may be a promising adjuvant for any patient with PCOS planning IVF. ...
Polycystic ovarian syndrome (PCOS) is a widespread syndrome that poses unique challenges and constraints to the field of assisted reproductive technology. This condition is the most common cause of anovulation among infertile couples. Debate exists over the best therapeutic course of action when patients with PCOS proceed to IVF. In this review, we evaluate the best-performing and safest methods of IVF preparation, ovarian stimulation, trigger method for maturation of stimulated egg growth, and planning for embryo transfer. Pre-IVF considerations include being aware of individual AMH and vitamin D levels as well as BMI prior to selecting an ovarian stimulation protocol. Numerous supplements such as myo-inositol complement the benefits of lifestyle change and may enhance IVF performance including oocyte yield and pregnancy rate. Concerning stimulation protocols, antagonist cycles with the judicious use of GnRH agonist trigger, pre-treatment with metformin and vitamin D repletion may help mitigate the accompanied risk of ovarian hyperstimulation syndrome (OHSS). Following ovarian stimulation, PCOS patients typically undergo programmed frozen embryo transfer (FET) cycles which are more conducive for women with irregular cycles, but likely carry a higher risk of hypertensive disorders of pregnancy. However, newer stimulated FET protocols using Letrozole may offer improved outcomes. Overall, patients with PCOS require careful individual tailoring of their IVF cycle to achieve optimal results.
To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process.
A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes.
A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM.
This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.
Abstract
One of the most common chronic inflammatory pediatric disorders is bronchial asthma, it
constitutes a major health problem affecting both genders, their prevalence worldwide varies,
and different risk factors may predispose to develop of asthma in children. The present study
aimed to evaluate the clinical profile of pediatric patients with chronic bronchial asthma.
Patients and Methods: a retrospective study was carried out and analyzed the data of 118
children aged 6-14years who attended the Pediatric Allergy Clinic, at Al-Bayda medical center
(AMC), Al-Bayda, Libya, who were clinically diagnosed with persistent asthma over one-year
period. (2020) Results: A total of 118 children who were clinically diagnosed with asthma
were enrolled: 25.4% mild persistent, 59.3 % moderate persistent and 15.3% severe persistent
asthma of semi-equal sex distribution, most of them not exclusively breast feeding 54.2% and
51.7%had positive family history of asthma, the most commonly used medications were
inhaled glucocorticosteroids and long acting b2-agonist(50%), overall cases the mean value of
duration till disease control was 5.7±2.6 months, with longest duration till achievement of
control is consumed by sever case. Loss of patient’s adherence occurred in 20.3% of cases. No
significance correlation between the age of patients, family history of atopy or breast-feeding
history and the degree of asthma severity and duration till disease control. Conclusion:
Moderate persistent asthma is the commonest pattern of severity, most of cases had positive
family history of atopy and current asthma control was good with adjustment of a treatment
according to the guidelines.
Keywords: Bronchial asthma, clinical profile, pediatric, Al-Bayda.
Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.
Women with Polycystic Ovarian Syndrome (PCOS) present several factors that increase the cardiovascular risk, such as insulin resistance and dyslipidemia. Myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. However, their effects on dyslipidemia are less clear. The aim of the present study was to evaluate whether the combined therapy myo-inositol plus D-chiro-inositol (in a in a physiological ratio of 40:1) improve the metabolic profile, therefore, reducing cardiovascular risk in PCOS patients.
Twenty obese PCOS patients [BMI 33.7 ± 6 kg/m2 (mean ± SD)] were recruited. The lipid profile was assessed by measuring total cholesterol, LDL, HDL and triglycerides before and after 6 months treatment with the combined therapy. Secondary end points included changes in BMI, waist-hip ratio, percentage of body fat, HOMA-IR and blood pressure.
The combined therapy myo-inositol and D-chiro-inositol improved LDL levels (3.50 ± 0.8 mmol/L versus, 3 ±1.2 mmol/L p < 0.05), HDL (1.1 mmol/L ± 0.3 versus 1.6 mmol/L ± 0.4 p < 0.05) and triglycerides (2.3 ± 1.5 mmol/L versus 1.75 ± 1.9 mmol/L p < 0.05). Furthermore, significant improvements in HOMA-IR were also observed.
The combined therapy myo-inositol plus D-chiro-inositol is able to improve the metabolic profile of PCOS women, therefore, reducing the cardiovascular risk.
BACKGROUND: Polycystic ovary syndrome (PCOS) could be associated with a variety of signs of metabolic syndrome. The aim of
our study was to compare the cardiovascular risk factors in PCOS women and in a control group selected from a random population
sample. METHODS AND RESULTS: 50 PCOS women with a mean (±SD) age of 30.7 ± 4.2 years, and 335 controls with a mean age of
29.9 ± 3.1 years selected from a random population sample of nine districts of the Czech Republic were compared for basic
anthropometric characteristics, blood pressure, plasma lipids and fasting glucose. PCOS women had a significantly higher body
mass index (BMI). After adjusting for BMI, PCOS women had higher blood pressure and LDL‐cholesterol, and lower HDL and HDL‐cholesterol/total
ratio. Arterial hypertension was more prevalent in PCOS women than in controls. There was no difference in the prevalence
of impaired fasting glucose between both groups. Impaired glucose tolerance was found in 11.8% of PCOS women. Diabetes mellitus
was more frequent in PCOS families. CONCLUSIONS: Czech PCOS women, even in their thirties, show a significantly worse cardiovascular
risk profile than a control group selected from a random population sample. The differences cannot be explained by obesity.
It is unknown whether hyperinsulinemia plays a role in the pathogenesis of polycystic ovary syndrome (PCOS) in normal weight or thin women. Evidence indicates that these women are insulin resistant and hyperinsulinemic, and this study was conducted to test the hypothesis that hyperinsulinemia stimulates ovarian cytochrome P450c17 alpha activity in nonobese women with PCOS, thereby increasing serum androgen concentrations. We assessed ovarian P450c17 alpha activity (by measuring the response of 17 alpha-hydroxyprogesterone to a GnRH agonist), fasting serum steroids, and oral glucose tolerance before and after oral administration of either metformin (500 mg) or placebo three times daily for 4-6 weeks in 31 nonobese women with PCOS. In the 19 women given metformin, the mean (+/-SE) area under the serum insulin curve after oral glucose administration decreased from 44 +/- 5 to 24 +/- 3 nmol/L.min (P = 0.003). Basal serum 17 alpha-hydroxyprogesterone decreased from 3.4 +/- 0.3 to 2.5 +/- 0.4 nmol/L (P = 0.05), and GnRH-stimulated peak serum 17 alpha-hydroxyprogesterone decreased from 12.2 +/- 1.6 to 7.5 +/- 0.7 nmol/L (P = 0.005). Serum 17 alpha-hydroxyprogesterone values did not change in the placebo group. In the metformin group, serum free testosterone decreased by 70% from 18.2 +/- 3.1 to 5.5 +/- 0.7 pmol/L (P < 0.001), and serum sex hormone-binding globulin increased from 84 +/- 6 to 134 +/- 15 nmol/L (P = 0.002). None of these values changed in the placebo group. These findings suggest that hyperinsulinemia stimulates ovarian P450c17 alpha activity in nonobese women with PCOS. They also indicate that decreasing serum insulin with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates the hyperandrogenism of these women.
Normal women produce small amounts of active androgens. When androgen levels are elevated, such as for example in the polycystic ovary syndrome, this is followed by the development of male physical characteristics of muscle mass, structure and function as well as android adipose tissue distribution and function. Psychological features and stress reactions also seem similar to those of men. Such women have an increased risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular disease. Recent data have shown that these physical, and psychological characteristics, as well as risk of ill health, are also found in the population of women selected at random. Women in the lowest quintiles of levels of sex-hormone-binding globulin - an indicator inversely related to active androgens - are at risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular mortality. The mechanism probably includes muscular insulin resistance, following a relative androgen excess.It is thus apparent that androgens, even within the highest levels of the nonselected population of women, are powerful predictors of serious disease development. The population at risk might be as large as about 20% of middle-aged women. This is an area of female disease risk which requires more attention in screening and intervention procedures.