Update on the combination of myo-inositol/d-chiro-inositol for the treatment of polycystic ovary syndrome.

In this article, we present a narrative review on the use of inositol in the treatment of polycystic ovary syndrome (PCOS). Of the different inositols that exist, only myo-inositol (MYO) and D-chiro inositol (DCI) have been studied in the treatment of PCOS. The results of the studies show that there is insufficient or controversial evidence to recommend the use of DCI alone, while MYO alone shows positive results and, above all, the MYO/DCI combination is effective when used at a ratio of at least 40:1, but there is enough rationale to further study ratios such as 66:1 to 100:1 as other possible effective combinations.

The views of women and pharmacists on the desirability of a progestogen-only pill over the counter. Results of a survey in Germany, Italy and Spain.

PURPOSE: To explore the perceived need and enthusiasm for over the counter (OTC) progestogen-only pills (POP). MATERIALS AND METHODS: A web-based survey of 1000 sexually active women (16-45) and 100 pharmacists in Germany, Italy and Spain. RESULTS: Despite not wanting to conceive, 5-6% of women in each country were not using contraception and 8-20% were using methods less effective than condoms. At least 74% of respondents felt knowledgeable about the different contraceptives available but at least 1/3 had experienced difficulty accessing oral contraceptive (OCs) in the past two years. The cost of contraceptives, the need to see a doctor and long waits for appointments were cited as barriers for not using OCs. The majority agreed they would discuss with their doctor the decision to buy the POP, consult about side effects and other reproductive health issues. Over 2/3 of pharmacists in each country would be very, or fairly, likely to recommend the POP, agreeing that the benefits included improved access for women, and offered them more independence. CONCLUSIONS: Asked directly, women in Germany, Spain and Italy currently using contraception are positive about a POP OTC. Pharmacists are also positive, with the overwhelming majority in favour of providing POPs.

Combined hormonal contraception and COVID-19.

Aim: This article reviews the possibility of using combined hormonal contraception during the COVID-19 pandemic. Methods: narrative reviewResults: The factors that protect women from the severity of the disease are analysed, as well as the risk factors for the use of this type of contraception, especially related to the increased risk of a thrombotic event in patients affected by the disease. Finally, the information available on the guidelines for action in patients with COVID-19 using combined hormonal contraception is collected.Conclusions: We can continue to prescribe and use hormonal methods with EE.

Prevention of unintended pregnancies by using emergency contraception: the differences between levonorgestrel and ulipristal acetate. A theoretical model using data from a survey on the use of emergency contraception in Spain, 2017.

Objective: To estimate the differences in unintended pregnancies avoided using either levonorgestrel (LNG) or ulipristal acetate (UPA) emergency contraception (EC). Design: Cross-sectional study. Setting: Survey carried out in Spain. Participants: 1000 Spanish women reporting unprotected sex in 2017. Main measurements: EC use, reasons for not using EC, calculation of the number of unintended pregnancies avoided. Results: 39% of Spanish women having had unprotected sex used EC. 61% of those women did not use EC and 11% did not know the existence of this resource. In 2017 the use of EC prevented 101,271 unintended pregnancies. If instead of using LNG every woman had used UPA another 15,979 additional pregnancies could have been prevented. Conclusions: If all Spanish women having unprotected sex used EC we could expect a significant decrease in the number of unintended pregnancies and abortions. Using UPA instead of LNG would have a greater impact on that reduction with the corresponding benefit for women and society as a whole.

Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey.

BACKGROUND: The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported. METHODS: Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18-50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7 "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale©), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates). RESULTS: Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values < 0.05). There were no other significant differences between groups. CONCLUSIONS: This real-world observational study supports extended-cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

Cross-sectional evaluation of the impact of information on flexible extended regimens of oral contraceptives in the choices made by women seeking contraceptive counselling: the FLEXO study.

OBJECTIVE: Oral combined hormonal contraceptives (CHCs) are available that limit the number of menses when used in a flexible extended regimen. Our aim was to investigate the decision-making processes of women presented with a flexible extended CHC option. METHODS: The FLEXO study is an epidemiological, cross-sectional, multicentre study conducted under typical clinical practice conditions to determine women's acceptance of a flexible continuous CHC regimen versus a cyclical 21/7 day regimen, after receiving standardised information during contraceptive counselling. RESULTS: A total of 1350 women were invited to participate, of whom 1156 were enrolled. Of these, 47.2% chose the flexible extended CHC regimen. Their main reason for choosing this regimen was to reduce the number of menses (25.7%), followed by the desire to avoid symptoms related to menstruation (21.6%). The reasons given for rejecting this regimen were the desire to have monthly menstrual cycles (24.9%) and the fear of becoming pregnant and not being aware of it due to the absence of menstruation (18.1%). CONCLUSION: Many women chose the extended flexible regimen when they received information about this option. Women primarily chose this pattern to relieve or eliminate discomfort related to menstruation.

Male perception about the inconveniences associated with monthly bleeding for their partner - an international survey.

OBJECTIVE: To assess men's perceptions about monthly bleeding and associated inconveniences for their partner, as well as men's attitudes regarding the desired menstruation frequency for their partner and knowledge about hormonal contraceptives. METHODS: A 15 min quantitative online survey was conducted among 5044 men aged 18-45 years, who had been in a relationship for more than 6 months, across 13 European countries (Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, Latvia, The Netherlands, Poland, Portugal, Spain and Switzerland). Responses were compared to those obtained in a similar study among European women. RESULTS: Most men perceived that their partner considered her menstrual flow as moderate, lasting an average of 5.2 d, slightly longer than previously reported by women. Almost all men reported that their partners experience menstruation-related symptoms. However, prevalence of mood-related symptoms was perceived to be more frequent and physical symptoms less frequent, relative to women's self-reported symptoms. Given the option, 71% of men would choose longer intervals between their partner's periods. Maintaining the couple's sex life, social life and relationship quality were key factors cited in their preference. Overall, 42% of respondents stated that women taking hormonal contraceptives needed to have monthly periods. CONCLUSIONS: Men's perception regarding their partner's periods was generally consistent with that previously reported by women. Most men would prefer less frequent bleeding episodes for their partners. Although, the present data suggest that couples are discussing periods, knowledge about contraception could be improved. Health care professionals should intensify counselling to better inform both partners about their contraceptive options.

Efficacy and side-effects profile of the ethinylestradiol and etonogestrel contraceptive vaginal ring: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and tolerability (side-effects profile), and compliance of the combined contraceptive vaginal ring (CCVR) compared with combined oral hormonal contraceptives (COC). DATA SOURCES: The PubMed, Embase, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, ClinicalTrials.gov, Clinical Trials Registry Platform (ICTRP) and CINAHL databases were searched. METHODS OF STUDY SELECTION: Electronic databases were searched for randomised clinical trials comparing the CCVR with COC with a duration of at least 3 months between 01 December and 15 December 2015. The primary outcome was efficacy. The secondary outcomes were compliance, absence of withdrawal bleeding, breakthrough bleeding, nausea and headache. Heterogeneity was assessed using I2 statistic and Cochran's Q statistic. Results were expressed as odds ratios (OR) with 95% confidence intervals (CIs) using random-effects models or fixed-effects models depending on the heterogeneity. RESULTS: 4368 records were identified, 2844 of which were removed after duplicates and 1524 records were screened. Of these, 1503 were excluded and 21 full text articles were assessed for eligibility. After removing another 7 articles, 14 records were finally included in the qualitative and quantitative analysis. The results show a trend to higher efficacy for the CCVR in preventing pregnancy (Peto OR: 0.52 [95% CI: 0.26-1.04]) and a significantly lower presence of nausea (Peto OR: 0.66 [95% CI: 0.46-0.93]). More cycles were compliant in the CCVR group (Peto OR: 1.22 [95% CI: 1.12-1.32]) and fewer women reported breakthrough bleeding (Peto OR: 0.68 [95% CI: 0.51-0.91]). CONCLUSIONS: Our findings demonstrate that the CCVR is as effective and tolerable as the COC but with a better bleeding profile.

Missed pills: frequency, reasons, consequences and solutions.

OBJECTIVES: Oral hormonal contraception is an effective contraceptive method as long as regular daily intake is maintained. However, a daily routine is a constraint for many women and can lead to missed pills, pill discontinuation and/or unintended pregnancy. This article describes the frequency of inconsistent use, the consequences, the risk factors and the possible solutions. METHODS: The article comprises a narrative review of the literature. RESULTS: Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, generally adolescents. The reasons for this are age, inability to establish a routine, pill unavailability, side effects, loss of motivation and lack of involvement in the initial decision to use oral contraceptives. The consequences are 'escape ovulations' and, possibly, unintended pregnancy. Solutions are either to use a long-acting method or, for women who prefer to take oral contraceptives, use a continuous or long-cycle regimen to reduce the risks of follicular development and thus the likelihood of ovulation and unintended pregnancy. A progestogen with a long half-life can increase ovarian suppression. CONCLUSIONS: For women deciding to use oral contraceptives, a shortened or eliminated hormone-free interval and a progestogen with a long half-life may be an option to reduce the negative consequences of missed oral contraceptive pills.

The inconvenience due to women's monthly bleeding (ISY) survey: a study of premenstrual symptoms among 5728 women in Europe.

OBJECTIVES: The aim of the ISY study was to investigate the prevalence of menstrual-related symptoms prior to and/or during menstrual or withdrawal bleeding among women from 12 European countries. METHODS: A 15-min quantitative online survey was conducted in two waves from February to September 2015 among 5728 women aged between 18 and 45 years, with an equal distribution of women using a combined hormonal contraceptive, including regular combined oral contraceptives (COCs) (CHC group, n = 2739) and women using a non-hormonal contraceptive or no contraceptive (non-HC group, n = 2989). RESULTS: The prevalence of at least one menstrual-related symptom was high in CHC users (93%) and in non-HC users (95%) (p < .0001) and the average number of symptoms reported was 5.3 vs. 5.9, respectively, (p < .0001). Pelvic pain, bloating/swelling, irritability and mood swing were reported in more than half of the women in both groups. Although generally modest, symptom severity was higher in non-HC users, except for headache. Overall, during the last four cycles, 60-75% of women did not require a treatment for most symptoms but headaches and pelvic pain. Mood swings/irritability, water retention/weight gain, lack of energy/mood swings and lack of energy/irritability were common symptoms that frequently co-occurred. No associations were reported between symptoms and age, educational qualifications or women's desire to reduce the frequency of menstruation. CONCLUSIONS: Premenstrual and menstrual symptomatology was less frequent, less numerous and less severe (except for headache) in women using CHCs; however, it remains a common concern. Reducing the frequency of menstrual periods could reduce withdrawal-related symptoms.

Women's preferences for menstrual bleeding frequency in 12 European countries: the Inconvenience Due to Women's Monthly Bleeding (ISY) survey.

OBJECTIVES: Our aim was to assess the level of inconvenience associated with menstrual bleeding and determine how many women across 12 European countries would prefer a bleeding frequency of less than once a month and what would motivate their choice. METHODS: A 15-min quantitative online survey was conducted in two waves among 5728 women aged between 18 and 45 years, with an equal distribution of women using a combined hormonal contraceptive (CHC group, n = 2739) and women using a non-hormonal contraceptive or no contraceptive (non-HC group, n = 2989). The first wave was carried out in Austria, Belgium, France, Italy, Poland and Spain, in February 2015, and the results have been published. The second wave was conducted in the Czech Republic, Germany, Hungary, Portugal, Latvia and the Netherlands, between August and September 2015. RESULTS: The menstrual period was significantly longer (5.0 versus 4.6 days) and heavier (15 versus 7%) in non-HC users than in CHC users (p < .0001). Given the choice, ∼60% of women would like less frequent menstrual bleeding. There was heterogeneity in the preference across countries. Sexuality, social life, work and sporting activities were key factors affecting women's preference. CONCLUSION: The majority of women in the 12 European countries would prefer to reduce the frequency of menstrual periods. Quality of life was the main factor affecting their preference.

Women's preferences for menstrual bleeding frequency: results of the Inconvenience Due to Women's Monthly Bleeding (ISY) survey.

OBJECTIVES: Our aim was to assess the level of inconvenience associated with monthly bleeding, determine how many women would prefer a bleeding frequency of less than once a month, and what would motivate their choice. METHODS: A 15-min quantitative online survey was carried out among 2883 women aged between 18 and 45 years in six European countries (Austria, Belgium, France, Italy, Poland and Spain). RESULTS: Of those surveyed, 1319 women used a combined hormonal contraceptive (CHC group) and 1564 used a non-hormonal contraceptive or no contraceptive (non-HC group). The menstrual period was significantly longer (5 vs. 4.5 days), heavier (16% vs. 8% heavy menstrual flow) and associated with more symptoms (6.1 vs. 5.6) in non-HC users than in CHC users (p < 0.0001). More than half of the women in each group reported pelvic pain, bloating/swelling, mood swings and irritability, but the rate was significantly higher in the non-HC group. Given the choice, 57% of women in both groups said they would opt for longer intervals between periods. Sexuality, social life, work and sporting activities were key factors affecting their decision. CONCLUSIONS: The majority of women would prefer to have menstrual periods less than once a month, with a frequency ranging from once every 3 months to no periods at all. This can be explained by the desire to avoid the unpleasant aspects of menstruation and its negative impact on private and professional life.

Effect on quality of life of switching to combined oral contraception based on natural estrogen: an observational, multicentre, prospective phase IV study (ZOCAL Study).

OBJECTIVES: This observational, multicentre, prospective phase IV study examined change in health-related quality of life (QOL) from baseline to 6 months in women initiating combined oral contraception (COC) based on natural estrogen. METHODS: Eligible women attending a baseline and 6-month gynaecology appointment belonged to one of three groups: group 1 used barrier contraception (condoms) and elected to continue this method; group 2 used condoms and elected to switch to COC based on natural estrogen; group 3 used COC based on ethinylestradiol and elected to switch to COC based on natural estrogen. The Spanish Society of Contraception (SEC)-QOL scale assessed health-related QOL. Secondary outcomes included symptoms of premenstrual syndrome, intermenstrual bleeding, duration and intensity of menstrual bleeding, contraception continuation rate, and tolerability. RESULTS: A total of 857 women were enrolled and 785 completed the study. Group 2 (n = 224 completed) had significantly lower SEC-QOL global and dimension scores at baseline and significantly greater increases in SEC-QOL from baseline to 6 months compared with groups 1 (n = 72) and 3 (n = 489). Group 3 reported a similar SEC-QOL score to that of group 1 at baseline but showed significantly greater improvement in SEC-QOL global and psychological scores from baseline to 6 months. Among women receiving COC based on natural estrogen, the contraception continuation rate was 713/780 (91.4%); treatment-related adverse events were reported by 13/780 (1.7%). CONCLUSIONS: Improved SEC-QOL after 6 months was found in women who were dissatisfied with their current contraception at baseline and chose to switch to COC based on natural estrogen.

Direct costs of unintended pregnancy in Spain.

OBJECTIVE: The aim of the study was to estimate the burden and direct medical costs of unintended pregnancy to the public payer in Spain. METHODS: An economic model evaluating the costs and outcomes of contraceptive use over a 1-year period was constructed for women in Spain aged 15 to 44 years at risk of pregnancy. Model inputs were derived from published literature and national survey data. Outcomes evaluated included: (i) the annual number of unintended pregnancy events and their cost; (ii) the proportion of unintended pregnancy events and their cost due to non-adherence; and (iii) the use and cost of contraceptive methods in Spain. RESULTS: Of the total number of pregnancies, 35% are estimated to be unintended and are associated with a direct cost burden of €292.8 million per year. Most unintended pregnancies (26%) occur in women aged 30 to 34 years, whilst 69% of the total cost burden is estimated to be attributable to poor adherence to contraceptive methods. CONCLUSIONS: The cost associated with unintended pregnancy is high. The major proportion of the burden is estimated to be attributable to imperfect adherence and is likely avoidable. Shifts in patterns of contraceptive use, combined with measures to improve adherence, could have a substantial and positive impact on this burden.

Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review.

OBJECTIVE: Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. METHODS: A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. RESULTS: The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. CONCLUSION: E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Alcohol and drug abuse and risky sexual behaviours in young adult women.

OBJECTIVE: To assess alcohol abuse as a predictor of risky sexual behavior among adolescents and young adult women, a high-risk population for unintended pregnancies. SUBJECTS: Totally 3163 adolescent and young adult women, 18-29 years, were assessed on sociodemographics, alcohol and drug use and risky sexual behaviors. INTERVENTIONS: Participants answered a structured questionnaire on their leisure habits, drug and alcohol consumption, contraception and sexual behaviors. RESULTS: Most of the young adult women perceive that sexuality is an important part of their life but not a main concern (77.6%) and that alcohol removes the barriers to have sex (62.3%). Additionally, 77.0% claimed that contraception had "a lot" (53.4%) and "quite" (23.6%) influence on the quality of their sexuality. However, up to a 38.4% of the interviewed women had had sex without using any contraception and 29.6% of them acknowledged that had taken alcohol and of these, 40.7% said that alcohol was responsible for not using contraception. Alcohol abuse predicted an increase in risky sexual behaviours (4.45 CI: 2.01-9.75, p < 0.0001). The effect of alcohol was independent of age. CONCLUSIONS: These findings suggest that contraception-related behavioural interventions for young adult women should discuss the link between alcohol and sexual risk behavior.

Differences in contraceptive use between Spanish female healthcare providers and Spanish women in the general population aged 23 to 49 years: the HABITS Study.

OBJECTIVE: To compare the contraceptive modalities used in the general female population with those of female healthcare providers (HCPs) in Spain. METHODS: A nationwide survey of a representative sample of Spanish women and female Spanish HCPs aged 23 to 49 years (total sample size: 3200). RESULTS: The condom was the most widely used contraceptive method in both groups (30% and 23% in the general population and among HCPs, respectively). The reasons cited for relying on this method were ease of use (19% and 13%, respectively; p = 0.2), effectiveness (16% and 22%, respectively; p = 0.2), absence of side effects (14% and 22%, respectively; p = 0.1), and fear of side effects associated with oral contraception (13% and 2%, respectively; p < 0.0001). After the condom, oral contraceptives, the intrauterine device and the vaginal ring were the most widely used methods among HCPs (13% each). CONCLUSIONS: The spectrum of contraceptive methods used by female HCPs differs from that of women in the general Spanish population. HCPs opt more often for long-acting reversible contraceptives because of their effectiveness and safety whereas women in the general population rely more frequently on the condom and surgical methods.

Effects of SARS-COVID-19 lockdown on menstrual patterns: A transversal large sample survey.

OBJECTIVE: To elucidate the presence, importance, and characteristics of menstrual changes related to stressful circumstances during the COVID-19 lockdown in Spain. STUDY DESIGN: An online survey was administered in Spain to menstruating women aged 15-55 who had not contracted COVID-19. It collected information on activities during the lockdown, sexual activity, perceptions of emotional status, any changes in menstrual characteristics, and impact on quality of life. The analysis of menstrual changes was limited to responders who did not use hormonal contraception. RESULTS: A total of 6449 women answered the survey, and 4989 surveys were valid for the final analysis. 92.3% of women had at least one menstruation period during the lockdown, while 7.7% had amenorrhea. Quality of life (QoL) associated with menstruation worsened in 19% of women, did not change in 71.7%, and improved in 1.6%. For 50.1% of the women, global QoL worsened during the lockdown; 41.3% remained about the same and 8.7% reported improvement. Sexual activity during the lockdown decreased in 49.8% of the respondents, remained unchanged in 40.7%, and increased in 9.5%. As far the menstrual changes are concerned, there were no statistically significant differences in amenorrhea incidence, regularity of the menstrual cycle, or the amount or duration of menstrual bleeding in non-hormonal contraceptive users when evaluated by the length and characteristics of isolation, the perception of exposure to COVID-19 and the economic or employment situation. Conversely, we found statistically significant differences according to the intensity of changes in emotional status due to lockdown stressors and changes in regularity, duration, and heaviness of menstruation. CONCLUSION: Changes in emotional status, but not the length and intensity of the isolation or exposure to the disease, significantly influenced menstrual disturbances during the COVID-19 lockdown.

A review of the pharmacology, clinical outcomes, and real-world effectiveness, safety, and non-contraceptive effects of NOMAC/E2.

Selecting an appropriate oral contraceptive can be challenging for healthcare professionals due to the abundance of marketed contraceptive options with different clinical and real-world effectiveness and safety profiles. Nomegestrol acetate + 17ß-estradiol (NOMAC/E2) is a combined oral contraceptive (COC) that inhibits ovulation by suppressing ovarian function by a 17-hydroxy-progesterone derivative and an estrogen identical to that endogenously produced by the ovaries. This narrative review examines clinical and real-world studies of NOMAC/E2 based on a background literature search using PubMed and Google Scholar. The review outlines the pharmacology of NOMAC/E2, including its progestational activity, pharmacokinetics, and effects on carbohydrate metabolism, lipid metabolism, and coagulation parameters, and summarizes key clinical efficacy and safety data that led to the approval of NOMAC/E2 in Europe, Brazil, and Australia. To help elucidate how NOMAC/E2 clinical trial data translate into a real-world setting, this review describes the effectiveness and safety of NOMAC/E2 in prospective studies that include over 90,000 users (half of whom received NOMAC/E2), outlining its effects on risk of thrombosis, menstrual bleeding patterns, weight, mood, acne, bone health, and patient quality of life. Non-contraceptive benefits of NOMAC/E2 for women with endometriosis, dysmenorrhea, or pre-menstrual dysphoric disorder are also discussed. These data demonstrate that NOMAC/E2 has a long half-life and rapid absorption, is effective at preventing unwanted pregnancies, and exhibits a favorable safety profile in both clinical trials and real-world settings. Importantly, NOMAC/E2 is not associated with increased risk of venous thromboembolism, a major safety concern of healthcare professionals for women receiving hormonal contraceptives. This review highlights NOMAC/E2 as a differentiated option among COCs and could help inform oral contraceptive choice to ultimately improve patient management and outcomes in real-world settings.

Toward a new concept of "natural balance" in oral estroprogestin contraception.

The Pill has undergone many changes since its first appearance some 50 years ago. Key developments included the reduction of ethinylestradiol doses and the synthesis of new progestins in order to increase safety, compliance and efficiency. Low-dose combined oral contraceptives (COCs) are currently the preferred option for millions of women. Due to this widespread use, it has been argued that the safety of COCs should be even better, raising the threshold for excellence. Yet in spite of major improvements, there is still an associated risk of venous thromboembolism (VTE). The next step in COCs' evolution should take total estrogenicity and hepatic estro-androgenic balance into account. The focus on the estrogen component--which has not changed in 50 years--has yielded a new class of natural estrogen pills. Following the introduction of a first quadriphasic pill, a monophasic estradiol pill based on the concept of "natural balance" was subsequently made available. These recent achievements could represent a step forward in the evolution of COCs and pave the way for better safety.