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

Novità, problemi e recenti sviluppi nel campo della contraccezione

Negli ultimi 40 anni la contraccezione ormonale è stata oggetto di numerosi cambiamenti nell’ottica di fornire alle donne una maggiore possibilità di scelta e compliance nell’utilizzazione. È stata modificata la dose, sono state introdotte nuove molecole progestiniche, si sono aggiunte nuove vie di somministrazione come la via sottocutanea, transdermica, transvaginale ed intrauterina ed è stato ridotto o abolito l’intervallo di sospensione. L’attenzione odierna è soprattutto rivolta all’intervallo di sospensione o tablets-free period e alla necessità della sospensione mensile. La modificazione del primo da 7 a 4 giorni è stata una necessità nei regimi a bassissimo dosaggio (15 μg/die) per assicurare l’efficacia contraccettiva. Per quello che riguarda la sospensione sono stati proposti regimi continuativi da 3 mesi ad un anno: numerose condizioni potrebbero trarre vantaggio dall’amenorrea come i sintomi premestruali, il controllo di patologie come le anemie ferro-prive e le patologie della coagulazione, la cefalea, l’endometriosi. Nonostante gli ottimi risultati nelle prime sperimentazioni negli USA, il regime continuativo non è ancora entrato nella pratica clinica per i retaggi culturali legati all’amenorrea che ne consegue: la mestruazione infatti rappresenta la verifica mensile dell’efficacia contraccettiva, il flusso mestruale pare più fisiologico della sua mancanza, la paura di effetti collaterali da eccesso di farmaco o di turbe sulla futura fertilità. In conclusione ciò che suggeriamo è condurre un appropriato counseling e, tenendo conto di tutte le possibilità a nostra disposizione, scegliere la terapia giusta per la paziente appropriata

Review of clinical experience with estradiol in combined oral contraceptives

Previous attempts to replace ethinylestradiol (EE) with 17beta-estradiol (E2) in combined oral contraceptives (COCs) have proved unsatisfactory in terms of bleeding outcomes. A review of previous studies of E2-based COCs has shown that, despite good ovulation inhibition, bleeding irregularities affected up to 100% of women, often resulting in high rates of discontinuation (up to 42%). Suggested reasons for the bleeding irregularities observed with these predominantly monophasic estradiol-progestin preparations included suboptimal doses of E2 and an inappropriate estrogen/progestin ratio. The progestin used in the investigated formulations (e.g., norethisterone acetate, desogestrel and cyproterone acetate) may also have affected the overall bleeding profile. More recent studies of a multiphasic COC containing estradiol valerate (E2V) and dienogest (DNG) indicate efficient ovulation inhibition and acceptable cycle control. In a randomized, double-blind trial that compared E2V/DNG with a monophasic COC comprising EE/levonorgestrel (LNG), the occurrence of scheduled withdrawal bleeding per cycle with E2V/DNG and EE/LNG was 77.7-83.2% and 89.5-93.8%, respectively. The intensity and duration of withdrawal bleeding was reduced with E2V/DNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5-18.6%) and EE/LNG (9.9-17.1%). This review shows that after several unsatisfactory attempts to develop E2-based COCs, more recent studies employing endometrial-focused progestins, e.g., DNG, and multiphasic dosing regimens appear to be a promising approach for an E2-based COC that provides efficient ovulation inhibition and acceptable cycle control

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

Unilateral adnexal agenesis and dermoid cyst: Fertility implications

We report the loss of potential fertility in a 23-year-old nulliparous woman who attended the outpatient gynaecological endocrinology clinic for amenorrhea and hot flushes started after a laparoscopic surgery for dermoid cyst. During surgery an unilateral ovarian and fallopian tube agenesis were found. The hormonal evaluation was performed. The results evidenced high plasma levels of LH and FSH. Their values were 56.6 and 121.3 mUI/ml, respectively. The concentrations of plasma E2 were < 20 pg/ml and of AMH were <0.08 ng/ml. Genetic analysis showed normal karyotype (46, XX). We think that if an embryological defect is suspected, an appropriate counselling about fertility preservation along with the assessment of hormonal levels before ovarian surgery should be recommended to all women in the reproductive age in order to offer future reproductive chances. © 2015 Informa UK Ltd. All rights reserved

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