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.

Development and conceptual validation of a questionnaire to help contraceptive choice: CHLOE (Contraception: HeLping for wOmen's choicE).

OBJECTIVE: The aim of this research was to develop a questionnaire to facilitate choice of the most appropriate contraceptive method for individual women. METHODS: A literature review was conducted to identify key aspects influencing contraceptive choice and inform development of a questionnaire for online completion. Questionnaire development was overseen by a steering committee consisting of eight gynaecologists from across Europe. The initial draft underwent conceptual validation through cognitive debriefing interviews with six native English-speaking women. A qualitative content analysis was conducted to accurately identify potential issues and areas for questionnaire improvement. A revised version of the questionnaire then underwent face-to-face and online evaluation by 115 international gynaecologists/obstetricians with expertise in contraception, prior to development of a final version. RESULTS: The final conceptually validated Contraception: HeLping for wOmen's choicE (CHLOE) questionnaire takes ≤10 min to complete and includes three sections to elicit general information about the individual, the health conditions that might influence contraceptive choice, and the woman's needs and preferences that might influence contraceptive choice. The questionnaire captures the core aspects of personalisation, efficacy and safety, identified as key attributes influencing contraceptive choice, and consists of 24 closed-ended questions for online completion prior to a health care provider (HCP) consultation. The HCP receives a summary of the responses. CONCLUSION: The CHLOE questionnaire has been developed to help women choose the contraception that best suits their needs and situation while optimising the HCP's time.

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.

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.

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.

Elective abortion: Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF).

The number of elective abortions has been stable for several decades. Many factors explain women's choice of abortion in cases of unplanned pregnancies. Early initiation of contraceptive use and a choice of contraceptive choices appropriate to the woman's life are associated with lower rates of unplanned pregnancies. Reversible long-acting contraceptives should be favored as first-line methods for adolescents because of their effectiveness (grade C). Ultrasound scan before an elective abortion must be encouraged but should not be obligatory (professional consensus). As soon as the embryo appears on the ultrasound scan, the date of pregnancy is estimated by measuring the crown-rump length (CRL) or, from 11 weeks on, by measuring the biparietal diameter (BPD) (grade A). Because reliability of these parameters is ±5 days, the abortion may be done if measurements are respectively less than 90 mm for CRL and less than 30 mm for BPD (professional consensus). A medically induced abortion, performed with a dose of 200 mg mifepristone combined with misoprostol, is effective at any gestational age (Level of Evidence (LE) 1). Before 7 weeks, mifepristone should be followed 24-48 h later by misoprostol, administered orally, buccally, sublingually, or even vaginally followed if needed by a further dose of 400 µg after 3 h, to be renewed if needed after 3 h (LE 1, grade A). After 7 weeks, administration of misoprostol by the vaginal, sublingual, or buccal routes is more effective and better tolerated than by the oral route (LE 1). Cervical preparation is recommended for systematic use in surgical abortions (professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 µg (grade A). Vacuum aspiration is preferable to curettage (grade B). A uterus perforated during surgical aspiration should not routinely be considered to be scarred (professional consensus). An elective abortion is not associated with a higher risk of subsequent infertility or ectopic pregnancy (LE 2). The medical consultation before an elective abortion generally does not affect the decision to end or continue the pregnancy, and most women are sufficiently certain about their choice at this time. Women appear to find the method used most acceptable and to be most satisfied when they were able to choose the method (grade B). Elective abortions are not associated with an increased rate of psychiatric disorders (LE 2). However, women with psychiatric histories are at a higher risk of psychological disorders after the occurrence of an unplanned pregnancy than women with such a history (LE 2). For surgical abortions, combined hormonal contraceptives - oral or transdermal - should be started on the day of the abortion, while the vaginal ring should be inserted 5 days afterwards (grade B). For medical abortions, the vaginal ring should be inserted in the week after mifepristone administration, while the combined contraceptives should begin the same day as the misoprostol or the day after (grade C). Contraceptive implants should be inserted on the same day as a surgical abortion, and may be inserted the day the mifepristone is administered for medical abortions (grade B and C respectively). In case of medical abortion, the implant can be inserted the same day the mifepristone is administered (grade C). Both the copper IUDs and levonorgestrel intrauterine system should be inserted on the day of the surgical abortion (grade A). After medical abortions, an IUD can be inserted in 10 days after mifepristone administration, after ultrasound scan verification of the absence of an intrauterine pregnancy (grade C).

[Tibolone]. / La tibolone.

INDIRECT MECHANISM OF ACTION: Tibolone (OD 14) is the precursor of its active principles that are its metabolites: 3 alpha and 3 beta hydroxylated derivatives. In vivo, the latter behave like estrogens. Certain tissues (liver, endometrium) may metabolize the 3 beta ol derivative into the delta 4 isomer with progestagenic and androgenic activity. The metabolism of the product in other tissues such as the breast and brain is unknown. ACTIVITY: At the dose of 2.5 mg/day, the product expresses an estrogen activity equivalent to that observed with classical doses of estrogens in the brain, genito-urinary tract, vascular endothelium and bone. In the brain and muscle, it also has a slightly androgenic effect and in the breast an antiestrogenic effect. ON METABOLIC LEVEL: The product acts like a minor androgen (lowering triglycerides and HDL cholesterol without interfering in the cholesterol cell flow) and it stimulates fibrinolysis. ON CLINICAL LEVEL: Tibolone treats the symptoms of estrogen privation and protects against bone loss, without inducing bleeding or mastodynia. There is a lack of large epidemiological studies on prevention of fracture risks, cardiovascular effects and breast. Tolerance in the population studied was excellent (healthy population). However, tolerance remains to be assessed in particular sub-groups (populations at risk of certains pathologies).

[Investigation, treatment and surveillance of late-onset hypogonadism in males: the official guidelines of the International Society for the Study of the Aging Male (ISSAM) with comments]. / Diagnostic, traitement et surveillance de l'hypogonadisme de survenue tardive chez l'homme : recommandations officielles de l'International Society for the Study of the Aging Male (ISSAM) et commentaires.

There is growing interest in the hormonal changes of the ageing male, particularly in view of the expected growth of the population of males over the age of 50. Current research topics essentially concern androgen decline in the aging male (ADAM), or partial androgen deficiency of the aging male (PADAM), commonly called "andropause" in France. Although progress has been made in our knowledge concerning androgen deficiency of the aging male, it is still incomplete, sometimes confused, and some aspects of androgen replacement therapy remain controversial. The International Society for the Study of the Aging Male (ISSAM) therefore considered it appropriate to propose a series of practical and official guidelines concerning the investigation, treatment and surveillance of late-onset hypogonadism in males. The French translation of these recent international guidelines is presented and discussed in this article.

Effects of tibolone and combined 17beta-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial.

BACKGROUND: Serum C-reactive protein (CRP) is an independent risk factor for the development of cardiovascular diseases in healthy post-menopausal women. Oral unopposed and progestin-combined 17beta-estradiol (E(2)) increase serum CRP in post-menopausal women. The aim of this study was to compare the effects of tibolone, a steroid with estrogenic, androgenic or progestogenic properties, with a combination of E(2) and norethisterone acetate (E(2) + NETA) on serum CRP levels in healthy post-menopausal women. METHODS: A total of 139 post-menopausal women (mean age: 55 years, range 44-48) was randomly assigned to receive tibolone 1.25 mg/day (n = 52), tibolone 2.5 mg/day (n = 39) or E(2) 2 mg/day plus NETA 1 mg/day (n = 48) for 2 years. Serum CRP was measured at baseline and at 6, 12 and 24 months. RESULTS: Both doses of tibolone and E(2) + NETA increased serum CRP by a similar extent as soon as 6 months with a sustained effect over the 24 month treatment period. For example, after 6 months of treatment, serum CRP increased by a median of +106% (P < 0.001), +89% (P < 0.05) and +139% (P < 0.001) for tibolone 1.25 mg/day, tibolone 2.5 mg/day and E(2) + NETA respectively. CONCLUSIONS: Tibolone and E(2) + NETA significantly increase serum CRP levels in healthy post-menopausal women to a comparable extent. Relationships between induced elevated CRP levels with tibolone and E(2) + NETA and cardiovascular events require further studies.