Efficacy, safety and acceptability of a benzalkonium chloride spermicide cream in women aged 40 years and over needing contraception: A prospective multicentre study.

OBJECTIVE: This multicenter prospective study (BZK40+) aims to determine the efficacy and tolerance of a benzalkonium chloride-containing spermicide as contraceptive among women aged 40 and over. PROCEDURE: Fertile women enrolled in this open single-arm study were instructed to systematically use the benzalkonium chloride spermicide before each intercourse. At the end of a 6-month mandatory period, participants were given the option of continuing the study for a further 6 months. The primary endpoint for contraceptive efficacy was the Pearl Index (PI) up to 12 months of typical use. MAIN FINDINGS: A total of 151 women (mean age: 45.9 years) were enrolled, 144 (95.4%) completed the initial 6-month period and 63 (41.7%) completed the optional 6-month period. The median number of intercourses ranged from 3 to 5 per month. The spermicide was applied before 96.3% of the 5,895 sexual intercourses. The PI up to 12 months of typical use was 0 pregnancies (95% confidence interval: 0-2.88). The cumulative treatment exposure was 1249.7 women-months. CONCLUSION: This first study in women aged 40 years and over shows that benzalkonium chloride spermicide (Pharmatex®) is effective, well tolerated and well accepted in this population. Although very interesting, these results with a PI equal to zero are surprising and not in accordance with the low efficacy of spermicides in the overall population according to the WHO. So, our results should be interpreted with caution and confirmed by future research. Clinical trial registration number (EudraCT): 2016-004,188-38.

Contraceptive use in Latin America and the Caribbean with a focus on long-acting reversible contraceptives: prevalence and inequalities in 23 countries.

BACKGROUND: The rise in contraceptive use has largely been driven by short-acting methods of contraception, despite the high effectiveness of long-acting reversible contraceptives. Several countries in Latin America and the Caribbean have made important progress increasing the use of modern contraceptives, but important inequalities remain. We assessed the prevalence and demand for modern contraceptive use in Latin America and the Caribbean with data from national health surveys. METHODS: Our data sources included demographic and health surveys, multiple indicator cluster surveys, and reproductive health surveys carried out since 2004 in 23 countries of Latin America and the Caribbean. Analyses were based on sexually active women aged 15-49 years irrespective of marital status, except in Argentina and Brazil, where analyses were restricted to women who were married or in a union. We calculated contraceptive prevalence and demand for family planning satisfied. Contraceptive prevalence was defined as the percentage of sexually active women aged 15-49 years who (or whose partners) were using a contraceptive method at the time of the survey. Demand for family planning satisfied was defined as the proportion of women in need of contraception who were using a contraceptive method at the time of the survey. We separated survey data for modern contraceptive use by type of contraception used (long-acting, short-acting, or permanent). We also stratified survey data by wealth, area of residence, education, ethnicity, age, and a combination of wealth and area of residence. Wealth-related absolute and relative inequalities were estimated both for contraceptive prevalence and demand for family planning satisfied. FINDINGS: We report on surveys from 23 countries in Latin America and the Caribbean, analysing a sample of 212 573 women. The lowest modern contraceptive prevalence was observed in Haiti (31·3%) and Bolivia (34·6%); inequalities were wide in Bolivia, but almost non-existent in Haiti. Brazil, Colombia, Costa Rica, Cuba, and Paraguay had over 70% of modern contraceptive prevalence with low absolute inequalities. Use of long-acting reversible contraceptives was below 10% in 17 of the 23 countries. Only Cuba, Colombia, Mexico, Ecuador, Paraguay, and Trinidad and Tobago had more than 10% of women adopting long-acting contraceptive methods. Mexico was the only country in which long-acting contraceptive methods were more frequently used than short-acting methods. Young women aged 15-17 years, indigenous women, those in lower wealth quintiles, those living in rural areas, and those without education showed particularly low use of long-acting reversible contraceptives. INTERPRETATION: Long-acting reversible contraceptives are seldom used in Latin America and the Caribbean. Because of their high effectiveness, convenience, and ease of continuation, availability of long-acting reversible contraceptives should be expanded and their use promoted, including among young and nulliparous women. In addition to suitable family planning services, information and counselling should be provided to women on a personal basis. FUNDING: Wellcome Trust, Pan American Health Organization.

Non-use of Contraception by Canadian Youth Aged 15 to 24: Findings From the 2009-2010 Canadian Community Health Survey.

OBJECTIVES: Non-use of contraception is an important contributor to unintended pregnancy. This study assessed non-use of contraception and its determinants among Canadian youth aged 15 to 24. METHODS: Data from the 2009-2010 Canadian Community Health Survey respondents aged 15 to 24 were used to identify non-users of contraception among heterosexual youth who had had intercourse within the previous 12 months, were not pregnant or sterilized, and felt it was important to avoid pregnancy. Sociodemographic, behavioural, and geographic factors were compared for non-users and users of contraception. RESULTS: Among youth at risk for unintended pregnancy, 15.5% were non-users of contraception. There were no differences between sexes. Across regions of Canada, Quebéc had the highest proportion of at-risk youth, but at-risk Quebéc youth were the least likely to be non-users (7.4%; CI 5.7%-9.0%) compared with at-risk youth in the Territories (28.3%; CI 21.6%-35.0%). In the multivariable analysis, aside from residence outside of Quebéc, younger age, lower income, Aboriginal identification (adjusted OR [aOR] 1.67; CI 1.18-2.37), and smoking (aOR 1.55; CI 1.24-1.92) were associated with non-use. Canadian-born youth (aOR 0.61; CI 0.39-0.96) and those enrolled in school (aOR 0.63; CI 0.50-0.81) were less likely to be non-users. CONCLUSION: The 15.5% of Canadian youth at risk for unintended pregnancy who were non-users of contraception represent an estimated 300 000 Canadian youth. Policies and programs to promote and support access to sexual health services and effective contraception with specific attention to supporting the needs of younger teens, Aboriginal youth, newcomers, low-income youth, and youth who are not in school are needed.

[Contraception during perimenopause: The spermicides option]. / Contraception des femmes en périménopause : place des spermicides.

AIM: In perimenopause, the increased cardiovascular and cancer risk and the increased incidence of gynaecologic disorders have a major impact on the choice of an appropriate contraceptive method. The aim of this review is to assess the potential benefit of spermicides at this stage of woman's life. MATERIALS AND METHODS: This review presents the eligibility criteria of the different contraceptive methods according to national and international guidelines, together with a literature review of the efficacy and side-effects of the two major spermicidal preparations, benzalkonium chloride and nonoxynol-9, with specific focus on the over-40 age group. RESULTS: The guidelines do not contraindicate any contraceptive method in women after 40. The efficacy data of spermicides show high variation between publications, with no age-specific differences. A special group suitable for spermicide use for contraception is perimenopausal women, particularly those with contraindications to other contraceptive methods or unwilling to use them. An additional benefit of some spermicides could be their lubricant effect. CONCLUSION: The spermicide option should be included into contraceptive counselling for women aged over 40, with evidence-based information about their mechanism of action, efficacy and safety. There is, however, a need for efficacy and acceptability studies on spermicides, with special reference to this age group.

A self-assessment efficacy tool for spermicide contraceptive users.

BACKGROUND: Easily accessible contraceptive methods, such as chemical and barrier methods, are used currently by approximately 1 in 6 women who use contraception in the United States. Even in the face of suboptimal effectiveness, coitally dependent methods likely will always have a role in fertility management. Because most contraceptive efficacy stratifications use population-based data, for women to make informed decisions about the individual fit of a contraceptive method, better evidence-based, user-friendly tools are needed. OBJECTIVES: Spermicides are a readily available, over-the counter, woman-controlled contraceptive method, but their effectiveness is user-dependent. Patient-decision aids for spermicides and other barrier methods are not well-developed, and overall failure rates could be improved by aids that account for individual characteristics. We sought to derive a prediction rule for successful use of spermicides for pregnancy prevention and to convert those data to a point-of-care instrument that women can use when they are considering spermicide use during contraceptive decision-making. STUDY DESIGN: We pooled local data from 3 randomized clinical trials that were published in 2004, 2007, and 2010 that tested spermicide efficacy. We constructed a prediction rule for unintended pregnancy using bootstrap validation and developed a scoring system. RESULTS: Data from 621 women showed a mean age of 29 years; 49% of the women were African American, and 43% were white. The overall pregnancy rate was 10.3% (95% confidence interval, 7.9-12.7) over 6 months. In adjusted logistic regression, age >35 years was protective against pregnancy (odds ratio, 0.19; 95% confidence interval, 0.06-0.58; P = .003), and multigravidity was associated with high failure rates (odds ratio, 7.24; 95% confidence interval, 3.04-17.3; P < .001). These risk factors (together with frequency of unprotected sex) were used in a model that maximized sensitivity for pregnancy prediction to compute the predicted probability of unintended pregnancy for each woman. This model was 97% accurate in predicting women who had a <5% pregnancy risk while using spermicides. CONCLUSION: Using prospectively collected data, we built a simple risk calculator for contraceptive failure that women can consult when considering spermicide use. This instrument could support patient-centered contraceptive decision-making.

[Contraception in breastfeeding women: place for spermicides]. / Contraception des femmes allaitantes: place des spermicides.

Any contraceptive method prescribed to a breastfeeding woman should be not only adapted to her physiological condition after delivery and to the health of her newborn, but should also meet her expectations. According to the French guidelines, combined hormonal contraception is prohibited up to 6 weeks after delivery in breastfeeding women and is not recommended within 6 months. Intrauterine devices and oral progestin alone may be utilized only from the fourth week after delivery. Spermicides have a privileged indication in breastfeeding women. Indeed, they have no restriction in national and international guidelines. In France, spermicides primarily include myristalkonium chloride and benzalkonium chloride that does not pass into maternal milk according Liebert. In addition to their safe use, the lubricant effect of some specialties can be useful. Spermicides can be used in combination with a condom as well as with the lactational amenorrhea method. The acceptability and success of spermicides in breastfeeding woman depends largely on the information of users, their motivation and understanding of the conditions of use.

Pregnancy in HIV clinical trials in Sub Saharan Africa: failure of consent or contraception?

OBJECTIVE: Higher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa. METHODS: Female and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP); and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use. RESULTS: All respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel) would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.

[Sexually transmitted infections and spermicides]. / Sexuálne prenosné infekce a spermicidy.

Incidence of sexually transmitted infections (diseases) has been already increasing again for more than one decade; the world number of 125-340 millions of new cases a year is estimated. Fifteen thousands of new HIV-positive persons daily present a substantial contribution to the total amount. Besides an increasing number of unplanned pregnancies, the huge spreading of sexually transmitted infections predominantly of the second generation is the main reason for a renewed interest in search of local contraceptives, i.e. spermicides. An urgent need for a new, non-detergent, synthetic or natural spermicide emerged to replace the traditional nonoxynol-9. New preparation of microbicidal spermicide should offer dual protection against both unplanned conception and sexually transmitted infections.

Recurrent urinary tract infections in women: diagnosis and management.

Recurrent urinary tract infections, presenting as dysuria or irritative voiding symptoms, are most commonly caused by reinfection with the original bacterial isolate in young, otherwise healthy women with no anatomic or functional abnormalities of the urinary tract. Frequency of sexual intercourse is the strongest predictor of recurrent urinary tract infections in patients presenting with recurrent dysuria. In those who have comorbid conditions or other predisposing factors, recurrent complicated urinary tract infections represent a risk for ascending infection or urosepsis. Escherichia coli is the most common organism in all patient groups, but Klebsiella, Pseudomonas, Proteus, and other organisms are more common in patients with certain risk factors for complicated urinary tract infections. A positive urine culture with greater than 102 colony-forming units per mL is the standard for diagnosing urinary tract infections in symptomatic patients, although culture is often unnecessary for diagnosing typical symptomatic infection. Women with recurrent symptomatic urinary tract infections can be treated with continuous or postcoital prophylactic antibiotics; other treatment options include self-started antibiotics, cranberry products, and behavioral modification. Patients at risk of complicated urinary tract infections are best managed with broad-spectrum antibiotics initially, urine culture to guide subsequent therapy, and renal imaging studies if structural abnormalities are suspected.

[Evolution and future of contraception]. / Evoluzione e futuro della contraccezione.

In order to meet the need for efficacious and safe contraception, contraceptives are in continuous evolution. Among oral contraceptives evolution has brought reduction of ethynylestradiol doses, up to change the estrogenic molecule to natural estradiol. In order to individualize contraception, numerous different progestin molecules have been developed and are being tested. Individualization has also brought at developing new schedules for contraceptive administration, and different routes of administration. Important developments have appeared on parenteral hormonal contraception, such as the intravaginal, subdermal, transdermal or injectable contraception. Intrauterine devices are being developed, becoming smaller, easier to insert, and sometimes capable to locally release progestins. New spermicides, that are capable to protect from sexually transmitted disease, are also being developed. Emergency contraception has evolved in a safer and more acceptable hormonal contraception. Recent introduction of molecules modulating progesterone receptors, seem to bring additional advantages by increasing the efficacy and extending the window of efficacy of emergency contraception.

Dermaseptins and magainins: antimicrobial peptides from frogs' skin-new sources for a promising spermicides microbicides-a mini review.

Sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), the causative agents of acquired immunodeficiency syndrome (AIDS), are two great concerns in the reproductive health of women. Thus, the challenge is to find products with a double activity, on the one hand having antimicrobial/antiviral properties with a role in the reduction of STI, and on the other hand having spermicidal action to be used as a contraceptive. In the absence of an effective microbicide along with the disadvantages of the most commonly used spermicidal contraceptive worldwide, nonoxynol-9, new emphasis has been focused on the development of more potential intravaginal microbicidal agents. Topical microbicides spermicides would ideally provide a female-controlled method of self-protection against HIV as well as preventing pregnancies. Nonoxynol-9, the only recommended microbicide spermicide, damages cervicovaginal epithelium because of its membrane-disruptive properties. Clearly, there is an urgent need to identify new compounds with dual potential microbicidal properties; antimicrobial peptides should be candidates for such investigations. Dermaseptins and magainins are two classes of cationic, amphipathic alpha-helical peptides that have been identified in the skin extracts of frogs Phyllomedusa sauvagei and Xenopus laevis. Regarding their contraceptive activities and their effect against various STI-causing pathogens, we believe that these two peptides are appropriate candidates in the evaluation of newer and safer microbicides spermicides in the future.

Potential acceptability of microbicides in HIV prevention in stable marital relationships in Malawi.

BACKGROUND: The XVII International Conference on AIDS held in Mexico City in August 2008 emphasised the importance of dual prevention using both vaccines and microbicides in the fight against HIV and AIDS. Microbicides are important because they constitute one of the potentially important female-controlled methods of HIV and sexually transmitted infection prevention, especially in Malawi where the use of the female condom has not yet been fully embraced. METHODS: A qualitative study utilising focus group discussions was used to assess the acceptability of the microbicide nonoxynol-9 (N-9) as part of the ongoing Preparatory AIDS Vaccine Evaluation (PAVE) studies. RESULTS: The study observed that men oppose the use of N-9, and that although women consider themselves at risk for HIV they caution against the unintended consequence of altering the vaginal environment with the use of microbicides, which can interfere with the men's preference for dry sex. DISCUSSION AND CONCLUSIONS: Although N-9 did not produce the desired results, these can inform the development of other promising microbicide candidates. The study concludes that it is important to pay attention to how new microbicides are formulated rather than just concentrating solely on an individual product's effectiveness.

A little bit pregnant: modeling how the accurate detection of pregnancy can improve HIV prevention trials.

The prevalence of unplanned pregnancies contributes to the methodological challenges of human immunodeficiency virus (HIV) prevention trials. In this paper, the authors discuss the incidence of pregnancy, including chemical pregnancy, and how the different methods of pregnancy diagnosis could affect the statistical power and calculated outcomes of HIV prevention trials. Study sample size inflation factors are estimated to aid in the design of clinical trials.The authors used published data of women attempting pregnancy as well as data from HPTN 055 (www.HPTN.org/research_studies/hptn055.asp) to estimate the percentage of early study discontinuation that would be associated with 3 diagnostic methods for pregnancy in a hypothetical clinical trial. They classified chemical pregnancies as false-positive pregnancy tests and showed the sample size adjustment that would be necessary in clinical trial design because of the early discontinuations associated with pregnancy. There is a greater than 3-fold difference in the number of falsely positive pregnancy tests that will be detected, depending upon the diagnostic method used. The number of incident pregnancies may render HIV prevention trial sample sizes inadequate by as much as 50%. Pregnancy prevention and precise pregnancy diagnosis are critical to the statistical power and integrity of HIV prevention trials.

Bridging the gap between male and female fertility control; contraception-on-demand.

Contraception-on-demand refers to contraceptive methods that are only employed when needed, such as barrier or postcoital methods, as opposed to technologies, such as the IUD or pill, where the exposure is continuous irrespective of the risk of pregnancy. The development of women-centered approaches to contraception-on-demand is a high priority in current contraceptive research, with emphasis on the 15- to 25-year-old demographic. Since this cohort of potential users is also at high risk of contracting sexually transmitted disease, topical methods that would provide simultaneous protection against both fertility and infection are of particular interest. This review examines the current strategies that are being pursued to achieve this objective.

Attitudes of men in an Australian male tolerance study towards microbicide use.

BACKGROUND: Vaginal microbicides are in development to provide new options for the prevention of sexually transmissible infections. Although promoted as a female-initiated product, men may influence the decision to use a microbicide and the way that it is used, so it is important to explore their views. METHODS: Men (n = 36) enrolled in a 7-day, phase 1 clinical safety trial of SPL7013 Gel were interviewed pre- and post-use of the gel. The trial did not include use of the gel during sex. Interviews were digitally-recorded and transcribed verbatim, and analysed using a framework approach. RESULTS: The men (mean age 37 years) were interested in the idea of vaginal microbicides, had little knowledge about them, and varied beliefs about how they work. They tended to assess microbicide use in relation to condoms and lubricants. Many would want a microbicide to be as effective as condoms. Participants did not anticipate difficulties discussing use with their partners. Many thought that a microbicide would be less intrusive than condoms; some anticipated that the lubricating properties might enhance sexual pleasure. Some anticipated using a microbicide with a condom or with a lubricant, and a few raised questions about the timing of use and use during different types of sexual activity. CONCLUSIONS: No major barriers to microbicide use were found in this sample of Australian men, who anticipated being willing to use them if they are shown to be safe and effective. Our findings should help to inform the design of further studies as well as future information materials and anticipatory guidance.

SILCS diaphragm: postcoital testing of a new single-size contraceptive device.

BACKGROUND: This study was conducted to compare the effectiveness of a new, single-size silicone contraceptive diaphragm used with either spermicide [2% nonoxynol-9 (N-9)] or lubricant in preventing sperm from penetrating midcycle cervical mucus. STUDY DESIGN: A crossover postcoital test (PCT) in healthy, sexually active women not at risk for pregnancy due to tubal occlusion was conducted. Couples had a baseline PCT without a device to verify normal fertility parameters. Qualified couples underwent up to two test cycles using the SILCS diaphragm with a metal spring. A subgroup of couples underwent a third test cycle with the SILCS polymer spring diaphragm used with N-9 gel. RESULTS: Fifteen couples completed a baseline cycle and were randomized to order of study gel. Of these, 14 couples completed a baseline cycle and at least one test cycle, 12 couples completed a baseline cycle and two test cycles and 8 couples completed a third test cycle with the polymer spring prototype. Sperm was detected in the vaginal pool in all completed test cycles. The SILCS metal spring diaphragms used with N-9 gel reduced the average number of progressively motile sperm per high power field in the cervical mucus from a baseline of 12.5 to 0, while use of this device with lubricant reduced the number to 0.5. The SILCS polymer spring diaphragm used with N-9 performed the same as the metal spring used with N-9. CONCLUSION: The SILCS diaphragm used with N-9 gel performed well. It is likely that the SILCS diaphragm will give acceptable results in a contraceptive effectiveness study but that adjunctive use of a chemical barrier such as N-9 gel will be necessary for it to be most effective.

Microbicide acceptability: insights for future directions from providers and policy makers.

To help fill the gap concerning health care providers' and policy makers' knowledge of and views concerning microbicides, we compared data from one U.S. study and two South African studies that explored these issues. Frontline providers in South Africa were enthusiastic about any method that would have the potential to slow the HIV/AIDS epidemic, whereas providers in New York City and policy makers in South Africa balanced their enthusiasm with more concerns. Across all studies, participants wanted timely and accurate scientific information, and they raised issues about safety, "messiness," and cost. Many had difficulty understanding that promoting a partially effective method can reduce risk if a client uses it more often than a highly effective method. Microbicide advocates need to effectively communicate to providers the evidence-based findings from microbicide trials and find approaches to introduce concepts such as "harm reduction" and "prevention equation" perspectives in client counseling. Developing these approaches will maximize the positive influence that providers can exert on user acceptability of microbicides once they become available.

Update on nonoxynol-9 as vaginal spermicide.

Nonoxynol-9 (N-9) is a typical surfactant. For more than 30 years that very property of N-9 has been successfully exploited for its spermicidal action. It is available as an over-the-counter, locally acting vaginal spermicide. The suitability of N-9 as a spermicide is elaborated in this article. The reasons why N-9 may fail as a contraceptive are discussed. In spite of many drawbacks, which are mentioned in the article, N-9 is still often resorted to as a locally acting contraceptive. The review ends with suggestions to alter the molecular structure of N-9 and to adjust the dosages.