Advance provision of emergency contraception to young men: An exploratory study in a clinic setting.

PURPOSE: To explore the acceptability of advance provision of emergency contraceptive pills (ECPs) to young men seeking health care. METHODS: For this exploratory study in a clinic setting, we approached young men aged 16-35 to participate in a survey eliciting socio-demographics, sexual and contraceptive history, and knowledge about ECPs. We offered young men advance provision of ECPs and compared characteristics of 126 young men who did and did not accept the ECPs. RESULTS: Most (76%) of the participants accepted advance provision and left with an ECP pack, with even higher proportions among males whose sexual histories were suggestive of increased risk of involvement in an unintended pregnancy. CONCLUSIONS: This study holds promise to inform scale up of advance provision of ECPs among young men.

Continuous dosing of a novel contraceptive vaginal ring releasing Nestorone® and estradiol: pharmacokinetics from a dose-finding study.

BACKGROUND: As part of a program to develop a novel estradiol-releasing contraceptive vaginal ring (CVR), we evaluated the pharmacokinetic (PK) profile of CVRs releasing segesterone acetate (Nestorone® (NES)) combined with one of three different estradiol (E2) doses. STUDY DESIGN: A prospective, double-blind, randomized, multi-centered study to evaluate a 90-day CVR releasing NES [200mcg/day] plus E2, either 10mcg/day, 20mcg/day, or 40mcg/day in healthy reproductive-age women with regular cycles. Participants provided blood samples twice weekly for NES and E2 levels during the first 60 days (ring 1) and the last 30 days (ring 2) of use. A subset underwent formal PK assessments at ring initiation, ring exchange (limited PK), and study completion. RESULTS: The main study enrolled 197 women; 22 participated in the PK substudy. Baseline characteristics between the main and PK participants were comparable, with an average BMI of 25.8 kg/m2 (SD 4.3). In the PK substudy, all three rings showed similar NES PK: mean area under the curve (AUC(0-72)) 34,181 pg*day/mL; concentration maximum (Cmax) 918 pg/mL; time to maximum concentration (Tmax) 3.5 h. For E2, the Cmax occurred at 2 h, and was significantly higher with the 20 mcg/day ring (mean 390 pg/mL); 10 mcg/day, 189 pg/mL, p=.003; 40 mcg/day, 189 pg/mL, p<.001), and declined rapidly to≤50 pg/mL for all doses by 24 h. For all subjects, the median E2 levels remained under 35 pg/mL during treatment. CONCLUSION: PK parameters of NES were not affected when paired with different doses of E2, but E2 levels from all three doses were lower than anticipated and no dose response was observed. IMPLICATIONS: While these novel estradiol-releasing combination contraceptive vaginal rings provided sustained release of contraceptive levels of Nestorone over 90 days, the E2 levels achieved were not consistent with bone protection, and a dose-response was not observed.

Vaginal birth after cesarean: a meta-analysis of morbidity and mortality.

The cesarean birth rate has continued to climb despite efforts to counteract it. A major reason for this rise is the practice of elective repeat cesarean. We conducted a meta-analysis that included 31 studies with a total of 11,417 trials of labor to evaluate the association between birth route after a cesarean and morbidity and mortality for the mother and infant. Summary odds ratios were calculated. Maternal febrile morbidity was significantly lower after a trial of labor than after an elective repeat cesarean. The intended birth route made no difference in the rates of uterine dehiscence or rupture. The use of oxytocin, presence of a recurrent indication for the previous cesarean, and presence of an unknown uterine scar were also unassociated with dehiscence or rupture. After excluding antepartum deaths, fetuses weighing less than 750 g, and congenital anomalies incompatible with life, we found no difference in perinatal death rates. The proportion of 5-minute Apgar scores of 6 or lower was higher after a trial of labor, but we were unable to exclude very low birth weight fetuses or those with congenital anomalies from this analysis. Our findings argue for trials of labor for more women after a cesarean birth.

Oral contraceptives and venous thromboembolism: should epidemiologic associations drive clinical decision making?

PIP: New studies linking use of oral contraceptives (OCs) containing a third generation progestogen with venous thromboembolism (VTE) have stirred controversy. Epidemiologists face the task of separating a direct effect of the OC from the confounding effect of a pre-existing factor (e.g., smoking). Only 1-2% of VTE cases are fatal. The percentage of VTE cases that are diagnosed and treated in the hospital is low and falling. A major challenge in the epidemiologic study of non-fatal conditions is that clinical and social factors will also affect whether or when or where the diagnosis is made. The newest studies of OCs and VTE were based on cases diagnosed and treated in the hospital. They found the risks for non-fatal VTE among OC users to be about 2-4 times higher than those for non-users and 1.5-2 times higher for those using levonorgestrel-containing OCs. In the past, laboratory and epidemiologic studies have pointed to the estrogen dose as the main risk factor for VTE and thus the lower estrogen dose OCs are less likely to contribute to VTE than the older higher estrogen dose OCs. Yet the new studies found an increased risk of VTE with lower doses of estrogen. There has been consistency in the findings, leading some to conclude that causation explains the findings. A re-analysis of the data from these studies found that the highest relative risks occurred with the recently introduced desogestrel-containing OC that has only 20 mcg ethinyl estradiol. Yet it would have been expected to be safer than the other OCs. The authors concluded that clinicians may have assumed that each new OC should be safer, and thus they have been selectively prescribing them to higher risk women. Since the association between the third generation OCs and VTE risk is weak and there is no biologic explanation for the association, one should not consider the association causal. Physicians should consider all the evidence before changing OC prescription practices. Clinical actions based on weak associations undermine their credibility and that of epidemiologists.^ieng

Breast cancer risk: perception versus reality.

Evidence that breast cancer is hormonally mediated has fueled women's concern that use of oral contraceptives (OC) will increase their risk of developing the disease. A recent reanalysis of combined worldwide epidemiologic evidence regarding the relationship between breast cancer risk and use of combination OC provides reassurance that there is little or no association between OC use and breast cancer. Ten or more years after discontinuation of OC use, there is no difference in cumulative risk of breast cancer among OC ever-users and never-users. The risk of breast cancer diagnosis is slightly elevated in current OC users and remains slightly elevated until about 10 years after OC discontinuation. Once recency of use is taken into account, other characteristics have little additional effect. There is no increase in breast cancer risk with increasing dose or duration of OC use and no difference in risk related to type of estrogen or progestin used. Moreover, those breast cancers diagnosed in OC ever-users were found to be significantly more likely to be localized than those diagnosed in same-age never-users.

PIP: A recent survey of US women 40-50 years old with no history of breast cancer found that women's perceptions of their risk of developing and dying of breast cancer exceeded the actual risk. Evidence that breast cancer is hormonally mediated has raised concerns that oral contraceptive (OC) use increases a woman's risk of developing the disease. This concern has been fueled by the observation that the increasing diagnosis of breast cancer in many countries has occurred in tandem with widespread OC use. However, a reanalysis by the UK Imperial Cancer Research Fund Epidemiology Unit of worldwide epidemiologic data revealed little or no evidence of a link between OC use and breast cancer. 10 or more years after discontinuation of OCs, there is no difference in cumulative breast cancer risk between OC ever-users and nonusers. Breast cancer risk among ever-users was not affected by duration of OC use, age at first use, parity, family history, or the dose or type of OC. Moreover, breast cancers diagnosed in OC ever-users are significantly less advanced and more likely to be localized to the breast than those in never-users. It may be that current or recent OC users are receiving more breast examinations and therefore have the opportunity for early diagnosis and improved prognosis.

Primary dysmenorrhea in adolescent girls and treatment with oral contraceptives.

This review examines the prevalence, associated morbidity, and treatment of primary dysmenorrhea in adolescent girls. Relevant literature was examined by systematic, evidence-based review using MEDLINE and Cochrane Collaboration databases. Dysmenorrhea is highly prevalent during adolescence. Despite differences in measurement methods, 20%-90% of adolescent girls report dysmenorrhea and about 15% of adolescents describe their dysmenorrhea as severe. During adolescence, dysmenorrhea leads to high rates of school absence and activity nonparticipation. Most adolescents with dysmenorrhea self-medicate with over-the-counter preparations; few consult healthcare providers. Combined oral contraceptives (COC) are an accepted treatment for dysmenorrhea in nonadolescent women. However, data supporting the efficacy of COC is limited. Very small studies show decreased prostaglandin in menstrual fluid associated with high-dose COC use. Larger studies are limited to cross-sectional comparisons showing lower prevalence of dysmenorrhea in low-dose COC users compared to non-COC users. One small, randomized controlled trial including some adolescents demonstrated an improvement in dysmenorrhea with high-dose COC treatment compared to placebo. The efficacy of low-dose COC in the treatment of adolescent dysmenorrhea has yet to be determined. If effective, well-established safety and noncontraceptive health benefits may make COC an ideal treatment for dysmenorrhea in adolescent girls.

Women's preferences for testing and management of sexually transmitted infections among low-income New York City family planning clients.

High prevalence of chlamydia in the USA persists despite efforts to annually screen women under the age of 26. Tailoring sexually transmitted infection (STI) services to client preferences may strengthen existing programmes. We report women's preferences for STI services from a family planning clinic in New York City serving low-income women. Seventy-eight percent (995/1275) of eligible women participated, with a mean age of 26 (SD±7). Ninety-one percent self-identified as Latina. Nineteen percent reported a past STI. Women preferred self-collection (65%) for testing to a speculum exam (20%); 15% had no preference. Women with a previous STI were more likely to prefer a pelvic exam to women with no previous STI (50% versus 32%, P < 0.01). Nearly all women (94%) preferred informing a sex partner about a positive STI test themselves, but 88% were willing to bring expedited partner therapy to a partner. Women were more likely to prefer third party partner notification if their last partner was casual rather than a main partner (14% versus 3%, respectively, P < 0.01). Forty-four percent of participants worried about physical violence after partner notification. Self-collecting specimens for screening was widely acceptable. Partner notification strategies should be based on understanding partnership status, including fears of violence.

Managing chlamydia infections in young men: results from an audit of a public men's clinic in New York City.

Research on management of Chlamydia trachomatis (CT) among men has largely been neglected. Findings from an audit of 284 CT-infected men from 2004 to 2005 attending a young men's clinic primarily serving Latino men in New York City, NY, USA, are presented. Ninety-nine percent received treatment, with 81% treated within 14 days of a positive test. Three percent reported no partner in the last three months, 17% were referred by a CT-positive partner and 24% were missing partner information. Among the rest, 18% received expedited partner therapy, 4% directly observed therapy, 12% partner referral and 65% did not receive documented partner management. Of the 34% who had a post-treatment visit at least three months after their index visit, only 36% received a test for re-infection. Among primarily Latino men in an urban clinic in New York City, a high proportion of CT cases were treated in a timely manner. However, documentation of partner management was often lacking and few CT cases received tests for re-infection.

Epidemiologic studies: pitfalls in interpretation.

PIP: Researchers should design epidemiologic studies in such a way as to avoid or minimize known or suspected biases. They should acknowledge unavoidable biases and explain how they may affect results. Careful selection of the control group can minimize or avoid biases in case control studies. Forms of selection bias include self-selection bias, diagnostic suspicion bias, and assembly (susceptibility) bias. The process of acquiring needed data can produce information bias. Forms of information bias are recall bias caused by selective memory and surveillance bias. Confounding occurs when two exposures or processes occur simultaneously and the effect of one is obscured by or distorted by the effect of the other. The confounding variable may misconstrue the apparent relationship between the exposure under study and the outcome of interest. If the research has measured the confounding variable, its effects can be disentangled. Age is the most common and important confounding variable. Since age tends to be related to both exposures and outcomes, researchers need to match subjects by age or to control for age in the analysis. Age may be a confounding variable in some case control studies between oral contraceptives (OCs) and cervical cancer. The risk of disease is reported as the odds ratio in case control studies, while it is the relative risk for cohort studies. It is best to use well-designed studies and large sample sizes to find statistically significant strengths of association. Meta-analysis is used more and more to increase sample sizes but the individual study populations and the variables are often very different. In fact, the studies in the meta-analysis tend to be confounders. Clinicians should consider the aforementioned concerns when interpreting the results of epidemiologic studies. They must be prepared to address validity and clinical relevance. To do so, they need to be familiar with basic study designs and associated issues to provide appropriate counseling and informed clinical decision making.^ieng

A perspective on the concept of "risk".

PIP: Compared to the risks inherent in pregnancy and daily activities of living, the increased risk of nonfatal venous thromboembolism (VTE) among users of oral contraceptives (OCs) containing desogestrel and gestodene is relatively benign. About 20-30 cases of nonfatal VTE per 100,000 users of third-generation OCs containing these progestins can be expected compared to 10-15 cases per 100,000 users of levonorgestrel-containing OCs. Pregnancy, on the other hand, confers an increased risk of about 60 cases of nonfatal VTE per 100,000 women. Since OCs remain the most popular reversible method of birth control, their discontinuation because of VTE concerns would have serious public health consequences in terms of unwanted pregnancy prevention. Moreover, OCs confer a number of noncontraceptive health benefits, including protection against ovarian and endometrial cancer, osteoporosis, benign breast disease, ovarian cysts, and pelvic inflammatory disease. The lives saved by OCs should be considered in any analysis of the small VTE risk they may impart.^ieng

Oral contraceptives and thrombosis: an overview of study methods and recent results.

Studies of the associations between oral contraceptives and cardiovascular disease are limited by the extreme rarity of these problems among young women. There are no randomized, controlled trials, and the large, prospective cohort studies only have data regarding older oral contraceptive formulations that are now little used. Historical cohort studies that use record-linkage techniques to analyze data from computerized databases represent a new approach to assessing oral contraceptive use and thrombosis. The largest new studies, with the most sophisticated analyses, use the case-control design. A surprising result of the new studies was a difference in risk of thrombosis according to progestin type. Because these are observational rather than randomized studies, clinical factors influence the choice of oral contraceptive and may bias the study results. Controversy about the surprising results has stimulated additional analyses and critical reviews in an attempt to explain the associations.

PIP: This article discusses methodologic aspects of recent studies on oral contraceptive (OC) use and thrombosis. Because of the extreme rarity of cardiovascular disease among young women, no studies of cardiovascular outcomes have employed a randomized, controlled trial design. Rather, all knowledge of OC risks comes from observational studies. Although case-control studies have suggested a difference in thrombosis risk according to progestin type, clinical factors that influence the choice of OC may bias the results. Historical cohort studies based on record-linkage techniques to analyze data from computerized databases represent a promising new approach for assessing the thrombosis risk of OCs. Overall, epidemiologic studies are less useful for subtle, weak associations where the relative risk is close to 1--the case with the most recent round of studies on the OC-thrombosis association. A balanced assessment of the differential values of various combination OCs would require that all the risks and benefits be considered on a formulation-by-formulation basis.

Current assessment of the use of intrauterine devices.

The need for effective, long-term contraception remains a significant issue. Intrauterine devices (IUDs) have evolved to the point where currently available devices are comparable, in safety and efficacy, to oral contraceptives. Due to concerns regarding previous devices, available IUDs remain largely underused by midwives and all other providers of reproductive health care. Recent medical data refute many of the medical-legal misconceptions. Currently available IUDs are safe and effective and represent a suitable contraceptive alternative for the appropriate patient.

PIP: Modern use of the intrauterine device (IUD) dates back to the early 1900s, when gynecologists in Germany began using contraceptive stem pessaries which extended into the uterus. IUDs then continued to evolve throughout the century. Introduced for use in the 1960s and 1970s, the Dalkon Shield was promoted as suitable for use in nulliparous women. By 1973, however, cases of septic abortion were reported to be associated with its use. The design of the Dalkon Shield was found to facilitate the ascension of bacteria from the vagina into the uterine cavity, leading to the development of pelvic infection. Dalkon Shield sales were discontinued in 1974, but the removal of inserted devices was not called for until the early 1980s. Many women who developed pelvic infections while using a Dalkon Shield joined in a class-action lawsuit against the manufacturer. The resultant negative media attention, as well as increased trepidation over liability by clinicians, contributed significantly to a sharp decrease in the use of all IUDs. The author explains that modern IUDs are now comparable in safety and efficacy to oral contraceptives, and that recent medical data refute many of the medical-legal misconceptions. Available IUDs are still largely underused by midwives and all other providers of reproductive health care due to concerns regarding earlier devices. The mechanism of IUD action; efficacy; pelvic inflammatory disease (PID), infection, and ectopic pregnancy; and product liability and malpractice are discussed.

Bleeding patterns after vaginal misoprostol for treatment of early pregnancy failure.

BACKGROUND: Dilatation and curettage (D&C) has been the usual treatment for early pregnancy failure (EPF). Medical management with misoprostol may be an effective alternative. Bleeding patterns during and after medical management of EPF are unknown. METHODS: A prospective cohort study was conducted at University-based clinics and physician offices. Eighty women <11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled. Treatment consisted of either 800 micro g of moistened (2 ml of saline) or dry vaginal misoprostol. Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary. Haemoglobin was assessed at enrollment and 2 weeks later. RESULTS: After misoprostol treatment, patients reported bleeding or spotting every day for the 14 days observed. Self-assessed heavy bleeding days were few (median 3) and usually occurred immediately after treatment. Sanitary pad use was highly variable (mean 30.5, range 2-125 pads over the 2 week period) and not related to changes in haemoglobin. The mean decrease in haemoglobin was 0.5 g/dl (SD 1.2). Complete expulsion without D&C occurred in 85% of subjects. CONCLUSIONS: Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common. Heavy bleeding is usually limited to a few days after treatment. Clinically important changes in haemoglobin are rare.