Paloma Lobo

Position of the Spanish Menopause Society regarding the management of perimenopause

Perimenopause is an imprecise period in woman over 40 years of age, which comprises the time between the moment that the first changes in the menstrual cycle appear and the year following the definitive cessation of the menses. Besides irregular bleeding, many women also complain of hot flashes and other characteristic symptoms of postmenopause. Moreover, most of them are concerned about the future impact that these events may have on their health, such as needing health exams or continuing to use contraceptive methods. A panel of experts from the Spanish Menopause Society has met to establish diagnostic and therapeutic guidelines for this period based on the best available evidence.

Extended regimens of combined hormonal contraception to reduce symptoms related to withdrawal bleeding and the hormone-free interval: A systematic review of randomised and observational studies

Abstract Objective To assess whether continuous and extended regimens (CRs/ERs) of combined hormonal contraceptives (CHCs) improve symptoms related to withdrawal bleeding or the hormone-free interval and to compare the efficacy, safety, and cost of CRs/ERs to those of conventional 28-day regimens. Study design A literature search of the PubMed database was conducted for randomised clinical trials (RCTs) and observational studies published in any language between 2006 and 2013. Results Sixteen RCTs and 14 observational studies evaluated issues related to our objectives. CRs/ERs, whose efficacy and safety were comparable to those described for conventional regimens, were preferred due to their improvement of symptoms related to withdrawal bleeding or the hormone-free interval and the lower costs resulting from the reduced incidence of these symptoms. Conclusion The contraceptive efficacy and safety of CR/ER use of CHCs is at least equal to that of 28-days conventional regimens, and this use may have some cost savings. CRs/ERs are recommended for women willing to take a CHC for treatment of symptoms related to withdrawal bleeding or the hormone-free interval. Chinese Abstract 摘要 目的 评估复方激素类避孕药（CHCs）连续与扩展周期给药方案能否改善撤 退性出血或停药期间的相关症状，并且与常规28天治疗方案相比较 其有效性、安全性及花费情况。 实验设计 对2006年-2013年间以任何语言发表在Pubmed数据库的随机临 床实验（RCTs）和观察性研究进行文献检索。 结果 针对研究目标，我们对16组随机临床实验和14组观察性研究进行 了评估。在有效性和安全性方面，连续/扩展周期给药方案优于常规方 案，主要是由于撤退性出血或是停药期间相关症状的改善以及由 此导致的成本降低。 结论 复方激素避孕药连续/扩展周期给药方案，其避孕的有效性和安全性至 少与28天常规给药方案等同，并可能节约一定的成本。

Continuation Rate of Combined Hormonal Contraception: A Prospective Multicenter Study

BACKGROUND Data from clinical trials regarding continuation of use and contraceptive efficacy do not always apply to the general public. Therefore, a study among typical users was conducted to assess the continuation rate at the end of 12 cycles of combined hormonal contraceptive methods, reasons for discontinuation, and the Pearl index. METHODS Prospective, observational, and multicenter study of 3443 women aged 18 to 49 years starting one of the three combined hormonal contraception methods available in Spain (the vaginal ring, the contraceptive pill, and the transdermal skin patch). RESULTS The study population (intention-to-treat analysis) included 3443 women, of whom 45.4% were included in the vaginal ring group, 42.6% the pill group, and 12.1% the skin patch group. The continuation rate at 12 cycles was 45.9% for the pill, 42.3% for the vaginal ring, and 26.0% for the skin patch. The Pearl index was 0.61 (95% confidence interval [CI] 0-1.2) for the pill, 0.61 (95% CI 0-1.1) for the vaginal ring, and 2.34 (95% CI 0.3-9) for the skin patch (p<0.001). CONCLUSION At 12 cycles, the vaginal ring and the pill showed similar continuation rates and effectiveness, which were significantly higher than the skin patch.

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

Abstract 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. Chinese Abstract 摘要 目的 自50年前推出以来,口服避孕药不断降低与其使用相关的静脉血栓栓塞(VTE)的风险。但是，增加的静脉血栓栓塞风险仍然存在。其他担忧，如对脂质和碳水化合物代谢的影响也有报道。这项研究中，我们将含炔雌醇（EE）/左炔诺孕酮（LNG）和含炔雌醇/屈螺酮（DRSP）的2个参照复方口服避孕药(COCs)与含雌二醇（E2）（戊酸雌二醇[E2V] /地诺孕素[DNG]和雌二醇/醋酸诺美孕酮[NOMAC]）的复方口服避孕药进行比较。根据它们对已确定的止血和代谢指标的影响来评估。 方法使用MEDLINE/PubMed数据库文献检索进行头对头研究。选择炔雌醇/左炔诺孕酮作为对照组。 结果相比于炔雌醇/屈螺酮和炔雌醇/左炔诺孕酮的止血影响，雌二醇片和炔雌醇/左炔诺孕酮的止血影响被广泛比较。炔雌醇/左炔诺孕酮与戊酸雌二醇/地诺孕素之间的止血和代谢指标的变化则不具统计学意义。与炔雌醇/左炔诺孕酮相比，雌二醇/醋酸诺美孕酮对止血指标具有明显有利的结果，对碳水化合物和脂质代谢则是中性效应。 结论相比于含炔雌醇/左炔诺孕酮口服避孕药及其他口服避孕药，含雌二醇/醋酸诺美孕酮口服避孕药具有更少的止血和代谢影响，这表明它可能是降低与口服避孕药相关的静脉血栓栓塞风险的一种有希望的候选药品。然而，这仍需要良好的前瞻性临床试验来验证。 关键词 复合口服避孕药，雌二醇，炔雌醇，止血指标，脂质和碳水化合物代谢指标，孕激素，静脉血栓栓塞

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

Abstract 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.

Toward a new concept of “natural balance” in oral estroprogestin contraception

Abstract 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.

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

Abstract 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.

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

Abstract 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.

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

Abstract 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.

Missed pills: frequency, reasons, consequences and solutions

Abstract 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.