Contraception with estradiol valerate and dienogest: adherence to the method

Purpose: The aim of the study was to examine the discontinuation rate of hormonal contraception with estradiol valerate (E2V) and dienogest (DNG). Patients and methods: We collected data at the Family Planning Clinics of the Departments of Obstetrics and Gynecology of Pisa and Cagliari. We included in the analysis 354 consecutive women using oral contraceptive pills containing E2V and DNG. We analyzed the rate and the reason for discontinuation, classifying the reasons in 5 categories: 1) minor side effects, 2) adverse events, 3) other events not directly caused by the drug or conditions for which the pill could represent a risk factor, 4) no compliance with the method and 5) no further need. Results: Of the 354 women examined, 50.8% had discontinued E2V/DNG pill. Excluding women who stopped the pill because of no further need (10.5%), 27.4% discontinued because of minor side effects, 1.7% discontinued for adverse events, 9.9% because of other events not directly caused by the drug or conditions for which the pill could represent a risk factor and 1.4% because of difficulties with compliance. Irregular bleedings were the main reasons reported for discontinuation. The time to discontinuation for irregular bleedings was significantly (p<0.02) longer in adults than in adolescents and slightly but not significantly longer in women who received information about this possible effect. Conclusion: Unacceptable cycle control was the principal cause of discontinuation of pill with E2V and DNG. An appropriate information about this possible effect may improve adherence to this combined oral contraceptive

Effetti della somministrazione di una combinazione di mio-inositolo e acido alfa-lipoico su parametri metabolico-ormonali in pazienti con sindrome dell'ovaio policistico. Studio retrospettivo longitudinale.

La Sindrome dell’Ovaio Policistico (PolyCystic Ovary Syndrome, PCOS) è una patologia con prevalenza elevata nella popolazione femminile in età fertile ed è associata a condizioni ad alto rischio cardiovascolare, quali l'insulino-resistenza e la sindrome metabolica; questo comporta un aumento del rischio individuale per patologie cardiovascolari in età post-menopausale. Visto che evidenze scientifiche dimostrano che nella patogenesi dell'insulino-resistenza di pazienti con PCOS è implicata anche un'alterazione del normale equilibrio degli inositoli, queste molecole, dotate di proprietà insulino-sensibilizzanti, sono ad oggi sempre più adoperate nella normale pratica clinica, pur non essendone tuttora compresa la totalità dei loro meccanismi d'azione e quindi dei loro potenziali effetti. Nel nostro lavoro proponiamo l'utilizzo di una combinazione di mio-inositolo ed acido alfa-lipoico, molecola dal potere antiossidante e antinfiammatorio, con l'obiettivo di valutarne la capacità di ripristinare un normale ciclo mestruale, di favorire il calo ponderale e di migliorare i parametri glico-metabolici in una popolazione di donne in età fertile affette da PCOS. Infine, confrontiamo i nostri risultati con quelli ottenuti in una popolazione analoga sottoposta a trattamento con D-chiro-inositolo e acido alfa-lipoico. In questo studio retrospettivo longitudinale abbiamo reclutato 43 pazienti con PCOS sottoposte ad una terapia con mio-inositolo e acido alfa-lipoico e abbiamo valutato nel tempo la durata del ciclo e il BMI, la secrezione insulinica dopo OGTT e l'indice HOMA-IR, osservando un'efficacia sulla normalizzazione del ciclo delle pazienti indipendente dall'effetto sul BMI. Abbiamo inoltre osservato risultati interessanti sul BMI e sulla secrezione insulinica, che suggeriscono un potenziale effetto positivo sul calo ponderale e sulla performance delle cellule beta pancreatiche. Confrontandole con la seconda popolazione di 35 pazienti sottoposte a trattamento con D-chiro-inositolo e acido alfa-lipoico abbiamo osservato effetti paragonabili per la durata del ciclo e il BMI, con la principale differenza in termini di risposta insulinica: solo il mio-inositolo associato all'acido alfa-lipoico, infatti, è efficace sull'intera popolazione a prescindere dall'insulino-resistenza

Clinical and Metabolic Effects of Alpha-Lipoic Acid Associated with Two Different Doses of Myo-Inositol in Women with Polycystic Ovary Syndrome

The aim of this retrospective study was to evaluate the effects of a treatment with α-lipoic acid (ALA) associated with two different doses of myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Eighty-eight women received the treatment, and 71 among them had complete clinical charts and were considered eligible for this study. All women were treated with 800 mg of ALA per day: 43 patients received 2000 mg of MI and 28 received 1000 mg of MI per day. Menstrual cyclicity, BMI, FSH, LH, estradiol, testosterone, androstenedione, fasting insulin, HOMA-IR, and insulin response to a 2 h OGTT were evaluated before and after 6 months of treatment. The presence of diabetic relatives (DRs) was investigated. Cycle regularity was improved in 71.2% of women. The improvement of menstrual cyclicity occurred regardless of the state of IR and the presence of DRs of the patients. Women with IR mainly showed a significant improvement of metabolic parameters, while those without IR had significant changes of reproductive hormones. Patients with DRs did not show significant changes after the treatment. 85.7% of women taking 2000 mg of MI reported a higher improvement of menstrual regularity than those taking 1000 mg of MI (50%; p<0.01). In conclusion, ALA + MI positively affects the menstrual regularity of women with PCOS, regardless of their metabolic phenotype, with a more evident effect with a higher dose of MI. This effect seems to be insulin independent. The presence of IR seems to be a predictor of responsivity to the treatment in terms of an improvement of the metabolic profile

Estetrol: A New Choice for Contraception

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ER&alpha;) and ER&beta;, with a preference for ER&alpha;. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP

COVID-19, gender and estroprogestins, what do we know?

The new coronavirus disease-19 (COVID-19) pandemic has rapidly spread all around the world, eliciting many questions and doubts about the pathogenesis of the disease and treatment. Mortality has been related to a prothrombotic state. Risk factors for the infection and for severe forms of COVID-19 have still to be defined. According to data collected, women appear to be less prone to severe forms of the disease and their mortality was lower than for men. The role of female hormones in the modulation of inflammation may be the reason behind this gender gap. Considering the prothrombotic state activated by the virus, hormone therapies have been placed under investigation as possible increasing risk factors for severe forms. Moreover, new vaccines and their rare thrombotic side effects have increased the concern about this issue. The goal of this review is to go over the mechanisms that lead up to thrombosis during COVID-19, trying to explain the possible reasons why women seem to be naturally protected. The expert opinions about whether to continue/discontinue hormonal therapies are reviewed. Moreover, available data about the so-called 'vaccine induced immune thrombotic thrombocytopaenia' caused by vaccines against COVID-19 are discussed

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins\u2019s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson\u2013Golabi\u2013Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17\u3b2-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases