Contraception - Articles in Press

Community pharmacists providing emergency contraception give little advice about future contraceptive use: a mystery shopper study - Corrected Proof

Anna Glasier, Rachel Manners, Joanna C. Loudon, Aileen Muir — 2010-07-23

Abstract: Background: UK women increasingly prefer to attend a pharmacy for emergency contraception (EC) rather than a doctor. Most women who use EC do not conceive and remain at risk of pregnancy unless they start regular contraception. We undertook a study to evaluate the quality of service provision in community pharmacies in Lothian, Scotland, and to determine what advice is given about contraception after EC use.Study Design: Mystery shopper study.Results: EC was unobtainable from 5/40 pharmacies (12.5%), refused because of “contraindications” in 7 (17.5%) and offered in 28 (70%). Most pharmacists appeared nonjudgemental, over 75% asked appropriate questions about eligibility, and over 90% gave appropriate advice about use. EC was universally refused beyond 72 h after sex but universally provided when the date of the last menstrual period was uncertain. Ongoing contraception after EC use was discussed in only 32.5% of all pharmacies and only 43% of those issuing EC.Conclusions: The quality of consultations for EC in pharmacies is generally good but only a minority discuss ongoing contraception after EC use. The implications for contraceptive use and unintended pregnancy rates are worrying.

Effects of the levonorgestrel-releasing intrauterine system on cervical mucus quality and sperm penetrability - Corrected Proof

2010-07-23

Abstract: Background: In levonorgestrel intrauterine system (LNG-IUS) users, the prevention of sperm penetration through cervical mucus has not been demonstrated.Study Design: Subjects were enrolled in an investigator-blinded study to compare quality and sperm penetrability of mid-cycle cervical mucus between LNG-IUS users and hormone-free controls. Cervical mucus was microscopically examined using World Health Organization (WHO) cervical mucus analysis (CMA). CMA score ≥10 of 15 points indicated cervical mucus favoring sperm penetration. Mucus was incubated with sperm using the WHO simplified slide test (SST) and Kremer sperm cervical mucus penetration test (SCMPT).Results: Data from 14 LNG-IUS users and 16 controls showed 14% of LNG-IUS users had CMA score ≥10% vs. 69% of controls (p=.004). SST showed no sperm penetration for LNG-IUS users, significantly less than controls (0% vs. 64.3%, p<.001). SCMPT demonstrated no sperm mucus penetration for LNG-IUS users at 2 and 6 h (0% vs. 85% in controls with 2-h score ≥6, p<.001; 6 h 0% vs. 79% in controls, p<.001).Conclusions: Mid-cycle cervical mucus of LNG-IUS users is poor quality and prevents endocervical sperm transport in vitro.

Happy anniversary mifepristone: a decade of promise and challenges - Corrected Proof

Beth Jordan, Wayne C. Shields — 2010-07-21

September 29, 2010, marks the 10th anniversary of Food and Drug Administration's approval of Mifeprex (mifepristone) in the United States. That moment 10 years ago brought women the promise of increased access to early, safe, noninvasive abortion and the potential mainstreaming of abortion services into the larger scope of routine comprehensive women's health care . The arduous 12-year path to approval required an intensive level of collaboration among key professional, advocacy and research organizations, working closely to navigate abortion-related politics and meet the natural challenges of introducing a new medical option to women and their health care providers.

Contraceptive sterilization use among married men in the United States: results from the male sample of the National Survey of Family Growth - Corrected Proof

2010-07-20

Abstract: Background: Surgical sterilization has many advantages. Previous information on prevalence and correlates was based on surveys of women.Study Design: We estimated the prevalence of vasectomy and tubal ligation of partners for male participants in the 2002 National Survey of Family Growth, a nationally representative survey of US residents aged 15–44 years. We identified factors associated with sterilizations using bivariate and multivariate techniques.Results: The findings revealed that 13.3% of married men reported having had a vasectomy and 13.8% reported tubal sterilization in their partners. Vasectomy increased with older age and greater number of biological children, non-Hispanic white ethnicity, having ever gone to a family planning clinic. Tubal sterilization use was more likely among men who had not attended college, those of older age and those with live births.Discussion: One in eight married men reported having vasectomies. Men who rely on vasectomies have a somewhat different profile than those whose partners have had tubal sterilizations.

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome - Corrected Proof

2010-07-20

Abstract: Background: This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS).Study Design: Forty women with PCOS (age 16–35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS).Results: In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20–50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD.Conclusions: Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism.

Obstetrician–gynecologist physicians' beliefs about emergency contraception: a national survey - Corrected Proof

Ryan E. Lawrence, Kenneth A. Rasinski, John D. Yoon, Farr A. Curlin — 2010-07-20

Abstract: Background: Although emergency contraception (EC) is available without a prescription, women still rely on doctors' advice about its safety and effectiveness. Yet little is known about doctors' beliefs and practices in this area.Study Design: We surveyed 1800 US obstetrician–gynecologists. Criterion variables were doctors' beliefs about EC's effects on pregnancy rates, and patients' sexual practices. We also asked which women are offered EC. Predictors were demographic, clinical and religious characteristics.Results: Response rate was 66% (1154/1760). Most (89%) believe EC access lowers unintended pregnancy rates. Some believe women use other contraceptives less (27%), initiate sex at younger ages (12%) and have more sexual partners (15%). Half of physicians offer EC to all women (51%), while others offer it never (6%) or only after sexual assault (6%). Physicians critical of EC, males and religious physicians were more likely to offer it never or only after sexual assault (odds ratios 2.1–12).Conclusion: Gender, religion and divergent beliefs about EC's effects shape physicians' beliefs and practices.

A pilot study of the Copper T380A IUD and oral levonorgestrel for emergency contraception - Corrected Proof

2010-07-20

Abstract: Background: This study evaluates the willingness of women presenting for emergency contraception (EC) to enroll in a study offering the copper intrauterine device (IUD) or oral levonorgestrel (LNG) and follows up the two groups for 6 months after EC administration to compare use of an effective method of contraception.Study Design: This prospective observational study offered these two methods to women presenting for EC. The primary outcome was use of an effective method of contraception 6 months after presenting for EC.Results: Thirty-four women (60%) chose oral LNG and 23 (40%) chose the copper IUD. One month after presenting for EC, 21 (96%) of 22 in the IUD group were still using the IUD and all 22 were using an effective method of contraception (efficacy ≥92%). In the LNG group, 13 (52%) of 25 were using an effective method of contraception (p<.001). At 6 months, 9 (69%) of 13 IUD users and 11 (52%) of 21 oral LNG EC users were using an effective method (p=NS).Conclusion: Women presenting for EC were willing to enroll in a study offering the copper IUD or oral LNG.

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada - Corrected Proof

2010-07-20

Abstract: Background: The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg.Study Design: Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events.Results: Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively.Conclusions: Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting.

Pharmacy access to the emergency contraceptive pill: a national survey of a random sample of Australian women - Corrected Proof

2010-07-20

Abstract: Background: The emergency contraceptive pill (ECP) has the potential to assist in reducing unintended pregnancy and abortion rates. Since its rescheduling to pharmacy availability without prescription in Australia in January 2004, there is little information about Australian women's knowledge, attitudes and use of the ECP. The aim of this study was to measure the knowledge about the ECP and sociodemographic patterns of and barriers to use of the ECP.Study Design: A cross-sectional study, using a computer-assisted telephone interview (CATI) survey conducted with a national random sample of 632 Australian women aged 16–35 years.Results: Most women had heard of the ECP (95%) and 26% had used it. The majority of women agreed with pharmacy availability of the ECP (72%); however, only 48% were aware that it was available from pharmacies without a prescription. About a third (32%) believed the ECP to be an abortion pill. The most common reason for not using the ECP was that women did not think they were at risk of getting pregnant (57%). Logistic regression showed that women aged 20–29 years (OR 2.58; CI: 1.29–5.19) and 30–35 years (OR 3.16; CI: 1.47–6.80) were more likely to have used the ECP than those aged 16–19 years. Women with poor knowledge of the ECP were significantly less likely to have used it than those with very good knowledge (OR 0.28; CI: 0.09–0.77). Those in a de facto relationship (OR 2.21; CI: 1.27–3.85), in a relationship but not living with the partner (OR 2.46; 95% CI 1.31–4.63) or single women (OR 2.40; CI: 1.33–4.34) were more likely to have used the ECP than married women.Conclusions: Women in Australia have a high level of awareness of the ECP, but more information and education about how to use it and where to obtain it are still needed.

A randomized, double-blind, noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria - Corrected Proof

2010-07-20

Abstract: Background: Unplanned pregnancies are common in Nigeria. Much of the unplanned pregnancies is due to low contraceptive prevalence and high contraceptive user failure rates. High user failure rates suggest the important role of emergency contraception to prevent unplanned pregnancy.Study Design: Randomized, controlled, double-blind, multicenter, noninferiority trial comparing efficacy and side effects of two emergency contraceptive regimens up to 5 days after unprotected intercourse among 3022 Nigerian women: levonorgestrel administered in two doses of 0.75 mg given 12 h apart and levonorgestrel administered in a single dose of 1.5 mg.Results: Efficacy was similar between the treatment groups; post-treatment pregnancy proportions were 0.57% in the two-dose regimen vs. 0.64% in the single-dose regimen (risk difference 0.07% (95% CI −0.50 to 0.64). The majority of women menstruated the first day of expected menses and the groups did not differ regarding reported side effects.Conclusions: This study shows the simplified emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen among Nigerian women.

College student knowledge and attitudes toward emergency contraception - Corrected Proof

Laura M. Miller — 2010-07-20

Abstract: Background: This study explored male and female college students' knowledge of and attitudes toward emergency contraception pills (ECPs).Study Design: A survey of 692 undergraduate college students (338 male and 358 female) was conducted at a mid-size university in northwest Pennsylvania during the Spring 2008 semester.Results: Eighty-three percent of the participants had experienced sexual intercourse, and 52% of them had feared a pregnancy at least once. Only 17% of the participants indicated prior use of ECP. Seventy-four percent of the students had heard of emergency contraception (EC); however, less than one-third knew the prescription status, common side effects or mechanisms of ECP. Only 16% of the participants knew that ECP was available at their college health center. Fifty percent of the students reported that they would feel comfortable using ECP, and 58% felt that ECP should be available without a prescription.Conclusions: College students' knowledge level about EC is poor. There is a clear need for ECP as a pregnancy prevention method among college students and for better education about it.

Endometrial safety of a novel monophasic combined oral contraceptive containing 0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 24/4-day regimen over six cycles - Corrected Proof

Thomas Rabe, Elena Hartschuh, Torsten Wahlstrom, Kornelia Höschen, Simone König — 2010-07-12

Abstract: Background: This study was conducted to examine whether small doses of ethinylestradiol (EE, 0.02 mg) and chlormadinone acetate (CMA, 2 mg) administered in a novel 24/4-day regimen during six cycles would suffice to suppress proliferation and to cause secretory changes in the endometrium.Study Design: This Phase II, randomized (two assessment groups), single-center, open, uncontrolled, multiple-dosing study treated 59 female subjects. The subjects underwent three endometrial biopsies: one pretreatment, one during medication (either at Cycle 3 or Cycle 6) and one during the first post-treatment cycle.Results: The study revealed that 0.02 mg EE/2 mg CMA effectively transformed the endometrium from a proliferative state into a secretory or inactive state after three (90% of subjects) and six (76% of subjects) medication cycles. The mean endometrial thickness decreased markedly from 10.2 (SD±3.0) mm (pretreatment) to an unfavorable level for the nidation of a blastocyst [5.3 (SD±2.1) and 4.1 (SD±2.2) mm in Medication Cycles 3 and 6, respectively]. Correspondingly, estradiol and progesterone levels decreased during treatment.In the post-treatment cycle, endometrial biopsy and ultrasound evaluation as well as sex hormone levels suggested a quick return to fertility. There were no signs of hyperplasia, endometrial polyps, neoplasia or other detrimental histopathological changes at any time during the trial. Treatment-related adverse events (AEs) were reported by 22 (37%) of 59 subjects and were reported most commonly in Cycle 1, decreasing continuously thereafter. No AEs led to discontinuation of the trial medication and there were no serious AEs.Conclusions: The 24/4-day regimen of 0.02 mg EE/2 mg CMA provided effective and reversible endometrial effects with secretory transformation or suppression without inducing pathological changes.

Mechanism of action of emergency contraception - Corrected Proof

Kristina Gemzell-Danielsson — 2010-07-12

Abstract: A major barrier to the widespread acceptability and use of emergency contraception (EC) are concerns regarding the mechanisms of action of EC methods. Today, levonorgestrel (LNG) in a single dose of 1.5 mg taken within 120 h of an unprotected intercourse is the most widely used EC method worldwide. It has been demonstrated that LNG-EC acts through an effect on follicular development to delay or inhibit ovulation but has no effect once luteinizing hormone has started to increase. Thereafter, LNG-EC cannot prevent ovulation and it does not prevent fertilization or affect the human fallopian tube. LNG-EC has no effect on endometrial development or function. In an in vitro model, it was demonstrated that LNG did not interfere with blastocyst function or implantation.

Non-contraceptive health benefits of intrauterine hormonal systems - Corrected Proof

Ian S. Fraser — 2010-07-12

Abstract: Non-contraceptive health benefits are now recognized as an important aspect of the overall impact of all hormonal contraceptives. The levonorgestrel-releasing intrauterine systems (LNG IUS) are particularly effective at producing a number of health benefits for women using the LNG IUS as a contraceptive (reduced menstrual bleeding; reduced dysmenorrhea and the potential for prevention of a number of gynecological conditions in the longer term, such as iron-deficiency anemia, endometrial hyperplasia, uterine fibroids, acute episodes of pelvic inflammatory disease, endometriosis and perhaps others). The LNG IUS also has the potential to specifically treat a range of pre-existing gynecological conditions such as heavy menstrual bleeding due to a wide range of underlying causes, endometrial hyperplasia, uterine fibroids, adenomyosis, and endometriosis.These health benefits should be recognized as a key component in the decision-making process for individual women in choosing a specific type of hormonal or other contraceptive. Investment in research into the very substantial health benefits of hormonal contraceptives, such as the LNG IUS, has generally been ignored in comparison with the massive investment into understanding the often subtle or rare complications of hormonal contraceptive use. Both are important, but there is a real need to define more accurately those women who will benefit most from these health benefits.

IUD use in HIV-positive women - Corrected Proof

Sheila M. Quinn, Courtney M. Schreiber — 2010-07-12

The levonorgestrel-releasing intrauterine system (LNG-IUS) is WHO Category 3 (risks outweigh benefits) for HIV-positive patients based on theoretical concerns regarding promotion of sexually transmitted infection (STI)/pelvic inflammatory disease (PID) and increased risk of transmission. We are aware of a prospective study done in Kenya that did not show increased risk of complications between HIV-positive and HIV-negative women getting copper T IUDs, although this study only had a 4-month follow-up and was not powered to detect differences . We have a motivated HIV-positive patient with a good CD4 count who really wants LNG-IUS. She uses condoms regularly with her partner. We are curious what other physicians have done in the past with such patients and want to know whether anyone would not be comfortable inserting the IUD.

Progesterone vaginal ring for contraceptive use during lactation - Corrected Proof

Anita Nath, Regine Sitruk-Ware — 2010-07-12

Abstract: The progesterone vaginal ring (PVR) has been shown to be effective as a contraceptive in breastfeeding women who need a better method of spacing pregnancies, and previous clinical trials of 1-year duration demonstrated its efficacy to be similar to that of the IUD during lactation. The duration of lactational amenorrhea is significantly prolonged in PVR users in comparison to IUD users with fewer median numbers of bleeding/spotting (B/S) episodes and B/S days. This long-acting delivery system designed for 3-month use needs to be renewed every 3 months as long as breastfeeding continues. The system designed as a matrix ring delivers 10 mg/day of the physiological hormone progesterone. Various factors such as comfort, ease of use, user control, rather than provider-dependent, and the fact that it contains a natural hormone have contributed to a high acceptability of the PVR method by breastfeeding women. The frequency of breastfeeding, breast milk volume and infant growth were not different in PVR users or IUD users, and the safety of this new method has been well documented. This article describes the available information and the results of the studies that led to approval of this method in several countries in Latin America so far. Further evaluation of the PVR acceptability in different populations where breastfeeding is popular and highly recommended for the infant's benefit is warranted.

Potent spermicidal effect of oleanolic acid 3-beta-d-glucuronide, an active principle isolated from the plant Sesbania sesban Merrill - Corrected Proof

Nilanjana Das, Poornima Chandran, Smritinath Chakraborty — 2010-06-25

Abstract: Background: The spermicidal activity of oleanolic acid 3-β-d-glucuronide (OAG), an active principle isolated from root extracts of Sesbania sesban, was evaluated.Study Design: Under the Sander–Cramer test criteria, the sperm-immobilizing activity of OAG was studied using highly motile rat sperm. Sperm mortality and membrane integrity were assessed by supravital staining, hypo-osmotic swelling (HOS), transmission electron microscopy (TEM) and sperm membrane lipid peroxidation (LPO). In vitro microbicidal potential and hemolytic index of OAG were examined in Lactobacillus culture and rat red blood corpuscles (RBCs), respectively. Post-intravaginal OAG application, the in vivo contraceptive efficacy was evaluated in rats. Ames test determined the carcinogenic potential of OAG.Results: The minimum effective concentration (MEC) of OAG was 50 mcg/mL. More than 97% of the OAG-treated sperm lost their HOS responsiveness in a dose-dependent manner. TEM and LPO revealed that OAG affected the sperm membrane integrity. OAG declined fertility to zero, was nonmutagenic and was not harmful to lactobacillus.Conclusion: OAG has significant spermicidal activity that may be explored further.

Comparison of 400 mcg buccal and 400 mcg sublingual misoprostol after mifepristone medical abortion through 63 days' LMP: a randomized controlled trial - Corrected Proof

2010-06-25

Abstract: Background: Buccal misoprostol 800 mcg and sublingual misoprostol 400 mcg demonstrate high efficacy and few adverse effects when used with 200 mg mifepristone for medical abortion through 63 days since the last menstrual period (LMP). Little is known about a 400-mcg buccal dose. This study compares two in-the-mouth routes of misoprostol using the same dose.Study Design: Eligible and consenting women (n=550) were randomized to 400 mcg of misoprostol buccally or sublingually 24 h after ingestion of 200 mg of mifepristone. Abortion status was assessed 2 weeks later.Results: Complete abortion occurred in 97.1% of the buccal group and 97.4% of the sublingual group (p=.97, RR: 1.00, 95% CI=0.97–1.03). Adverse effects were similar in both groups. Over 90% of women in both arms expressed high satisfaction with the method.Conclusions: Both 400 mcg buccal misoprostol and 400 mcg sublingual misoprostol after mifepristone appear to be good options for medical abortion through 63 days' LMP.

A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days - Corrected Proof

2010-06-24

Abstract: Background: Letrozole is a third-generation selective aromatase inhibitor. Animal data suggested that it might be useful in medical abortion. We performed two pilot studies to assess the feasibility of using letrozole in combination with either mifepristone or misoprostol for termination of pregnancy up to 63 days.Study Design: We recruited 40 subjects who requested legal termination of pregnancies up to 63 days. Medical abortion was performed with letrozole 7.5 mg daily for 2 days followed by 800 mcg vaginal misoprostol in 20 subjects and letrozole 7.5 mg combined with 200 mg mifepristone in another 20 subjects.Results: The mean induction-to-abortion interval of the regimen of letrozole and misoprostol was 9.1 h (median 7.9 h, range 2.7–23.6 h). The complete abortion rate was 80% (95% CI: 56.3–94.3%). For those with gestation of ≤49 days, the complete abortion rate was 87.5% (14/16; 95% CI: 61.7–98.5%). The mean induction-to-abortion interval of letrozole combined with mifepristone was 90.1 h (median 93.4 h, range 66.0–121.2 h). The complete abortion rate was 71.4% (95% CI: 47.8–88.7%).Conclusion: These preliminary results suggest that a regimen of letrozole and misoprostol may be useful in medical abortion, but the combination with mifepristone is less effective and takes longer. Randomized studies comparing letrozole and misoprostol to misoprostol alone are warranted.

BMI, pharmacokinetics, and OCP failure - Corrected Proof

Ganesh Cherala, Alison Edelman — 2010-06-21

Due to the intensity of pharmacokinetic studies, the sample sizes are often small. Thus, we were excited to have the opportunity to compare results from our prior publication with the recent paper by Westhoff et al. . Both studies found significant differences in the pharmacokinetic (PK) parameters between obese and normal-body mass index (BMI) women using oral contraceptives (OCP), but the differences varied. This could be due to the use of a low (30 mcg ethinyl estradiol [EE]/150 mcg levonorgestrel [LNG]) versus a very-low (20 mcg EE/100 mcg LNG) OC. However, we are concerned that the differences lie with the computed PK parameters and that a re-analysis, if possible, may change the study's conclusions.

Translational research with progesterone receptor modulator motivated by the use of levonorgestrel-releasing intrauterine system - Corrected Proof

2010-06-21

Abstract: The use of levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for management of menorrhagic women with uterine myomas because of reduction in menorrhagia. However, the size of myomas during use of LNG-IUS increased in some but decreased in other instances. This prompted us to characterize the effects of progesterone (P4) on cultured leiomyoma cell growth. Treatment with P4 resulted in increase in epidermal growth factor (EGF) expression in cultured leiomyoma cells, whereas treatment with E2 augmented EGF-R expression in those cells. This indicates that P4 and E2 act in combination to stimulate myoma growth through induction of EGF/EGF-R expression. Bcl-2 expression in leiomyoma cells was up-regulated by P4. Furthermore, P4 augmented proliferating cell nuclear antigen expression in cultured leiomyoma cells but not in cultured normal myometrial cells. This fact let us to examine the effects of progesterone receptor modulator (PRM) on leiomyoma cell proliferation and apoptosis in comparison with normal myometrial cells. Our studies revealed that CDB-2914 inhibits the proliferation, stimulates apoptosis of cultured leiomyoma cells, and inhibits the expression of angiogenic factors (vascular endothelial growth factor and adrenomedullin) and their receptors in cultured leimyoma cells, without affecting those in cultured normal myometrial cells. We then evaluated the effects of CDB-2914 on extracellular matrix (ECM) components in cultured leiomyoma cells. CDB-2914 increased ECM metalloproteinase inducer, matrix metalloproteinase (MMP)-1, MMP-8 contents and decreased tissue inhibitors of MMP (TIMP)-1, TIMP-2 contents as well as type I and type III collagen contents in cultured leiomyoma cells, without comparable effects on cultured normal myometrial cells. These findings demonstrate that PRM not only inhibits the proliferation and stimulates apoptosis of cultured leiomyoma cells but also suppresses collagen synthesis in a cell-type specific manner. This is meaningful for understanding the molecular mechanism of the usefulness of PRM in the treatment of uterine fibroids.

Spermatotoxicity of a protein isolated from the root of Achyranthes aspera: a comparative study with gossypol - Corrected Proof

2010-06-18

Abstract: Background: A previous study showed that 50% ethanolic extracts of the roots of Achyranthes aspera possess spermatotoxic effects.Study Design: A 58-kDa protein (Ap) was isolated, and its spermatotoxic effects were studied in comparison with gossypol. Ap (25 mg/kg body weight a day) and gossypol (40 mg/kg body weight a day) were administered orally to Swiss male albino mice for 35 days. Sperm motility, sperm count, sperm abnormality, toxicity markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) in the liver and serum, testicular activities of hydroxyl methyl glutaryl CoA reductase (HMG CoA reductase), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase(17β-HSD), glucose-6-phosphate dehydrogenase, cholesterol level and serum testosterone were assayed. Spermicidal action of the proteolytic digests of Ap was also studied in vitro.Results: Treated mice showed significant spermatotoxicity. Significant differences were also observed in the testicular activities of HMG CoA reductase, 3β-HSD, 17β-HSD and glucose-6-phosphate dehydrogenase and in the levels of cholesterol and serum testosterone. The nontoxic nature of Ap was indicated by the insignificant alterations in the activities of AST and ALT. Ap possessed spermicidal activity even after proteolysis.Conclusion: The 58-kDa protein isolated from A. aspera possesses spermatotoxic effects comparable to gossypol.

Operative management of intrauterine device complications: a case series report - Corrected Proof

2010-06-18

Abstract: Background: There is limited information about the number of intrauterine device (IUD) users requiring operative intervention for device-related complications. This is an evaluation of cases requiring in-hospital operative intervention for IUD perforations, removals and pregnancy-related complications.Study Design: Large retrospective case series of patients who received operative management of IUD complications.Results: Charts of patients from 15 hospitals in two health care systems from 2000 to 2007 were reviewed and outcomes of 276 women are reported. There were 95 operative IUD removals for perforations (including 60 levonorgestrel-releasing intrauterine systems), 157 operative procedures for inability to remove an IUD in the office, and 42 pregnancy-related complications that were managed in the operating room. Ectopic pregnancy was the most common diagnosis among pregnant women (23 of 42 pregnant women, 54.8%).Conclusion: The majority of operative procedures were performed for intrauterine IUDs, most of which were appropriately positioned IUDs with missing or short strings. In-office techniques for obtaining analgesia and dilation as well as appropriate devices for removal of T-shaped IUDs should make this practice rare.

Pharmacokinetics of a combined oral contraceptive in obese and three normal-weight women - Corrected Proof

Carolyn Westhoff, Malcolm Pike — 2010-06-18

Drs. Cherala and Edelman raise a number of issues that we are pleased to answer. Drs. Cherala and Edelman are critical of the duration of our pharmacokinetic (PK) assessment, i.e., 24 h after ingestion of the pill , rather than the 48 h after ingestion that they used . They used their data to estimate area under the curve (AUC)0–∞; we did not attempt to do this as we consider AUC0–24 to be the relevant statistic when describing the PK of an oral contraceptive since the next oral contraceptive (OC) will be taken after 24 h. The value of AUC0-∞ is of course relevant to the last active pill of the cycle although even then it is likely that the AUC24-48 and subsequent 24-h AUCs are most relevant to the continuing efficacy of the OC.

Evaluation of the effect of a patient decision aid about vasectomy on the decision-making process: a randomized trial - Corrected Proof

Michel Labrecque, Cristina Paunescu, Ioana Plesu, Dawn Stacey, France Légaré — 2010-06-18

Abstract: Background: Between 7% and 10% of men who choose vasectomy as a contraceptive method regret their decision. This study evaluates the effect of a patient decision aid (PtDA) designed to help men decide whether or not to have a vasectomy.Study Design: Men considering vasectomy were randomized to an experimental group that received a full PtDA containing information and values guidance (n=32) or to a control group that received an abridged PtDA containing information only (n=31).Results: Mean Decisional Conflict Scale (DCS) scores before and after the intervention were 2.6±0.4 and 1.9±0.4 in the experimental group and 2.5±0.4 and 1.8±0.4 in the control group (p=.94), respectively. Mean knowledge of vasectomy scores before and after the intervention were 50%±16% and 72%±18% in the experimental group and 55%±18% and 71%±15% in the control group (p=.40), respectively. At baseline, all participants were undecided as to whether to have a vasectomy. After the intervention, 60% of experimental group participants and 53% of control group participants had made a definite decision (p=.58).Conclusion: In men considering vasectomy, both versions of the PtDAs improved the quality of decision-making process to a similar extent. Information alone may be sufficient to support good decision making in these patients.

Type of contraception method used at last intercourse and associations with health risk behaviors among US adolescents - Corrected Proof

2010-06-18

Abstract: Background: This study was conducted to examine associations with contraception methods used at last sexual intercourse among US adolescents.Study Design: Data consisted of sexually active adolescents (9th–12th grade, weighted n=24,638) from the 1999–2007 Youth Risk Behavior Surveillance System (YRBSS). We performed multinomial multivariable logistic regression analyses with condom users at last sexual intercourse as the reference group.Results: Males who used alcohol, cigarettes, marijuana and cocaine were more likely to use no method/unsure of method (OR=2.4, CI=1.7–3.4) or rely on withdrawal (OR=2.6, CI=1.5–4.3). Females with six or more sexual partners were more likely to rely on withdrawal (OR=2.9, CI=2.1–3.9) or contraception methods that offer no STI protection [i.e., birth control pills: OR=1.9, CI=1.4–2.5; and depot medroxyprogesterone acetate (DMPA, marketed as Depo-Provera): OR=2.6, CI=1.6–4.2]. Earlier age of sexual debut was also associated with nonuse.Conclusion: Prevention efforts should focus on at-risk adolescents including substance-using males, females with six or more sexual partners, and those who initiate sexual intercourse at an early age.

Trends in the use of contraceptive methods and voluntary interruption of pregnancy in the Spanish population during 1997–2007 - Corrected Proof

2010-06-18

Abstract: Background: This study was designed to acquire information about the use of contraceptive methods in order to reduce the number of elective abortions.Study Design: Since 1997, representative samples of Spanish women of childbearing potential (15–49 years) have been surveyed by the Daphne Team every 2 years to gather data of contraceptive methods used.Results: During the study period, 1997 to 2007, the overall use of contraceptive methods increased from 49.1% to 79.9%. The most commonly used method was the condom (an increase from 21% to 38.8%), followed by the pill (an increase from 14.2% to 20.3%). Female sterilization and IUDs decreased slightly and were used by less than 5% of women in 2007. The elective abortion rate increased from 5.52 to 11.49 per 1000 women.Conclusions: The factors responsible for the increased rate of elective abortion need further investigation.

Cultural adaptation among Hispanic women as related to awareness and acquisition of emergency contraception - Corrected Proof

Kristy K. Ward, Angelica M. Roncancio, Abbey B. Berenson — 2010-06-18

Abstract: Background: The study was conducted to examine the relationship between cultural adaptation (acculturation), contraceptive use, personal history of induced abortion, and emergency contraceptive (EC) awareness and acquisition among a sample of young sexually active Hispanic women.Study Design: A total of 959 Hispanic women between 16 and 24 years of age (mean±SD 20.71±2.42 years) completed a survey containing questions on EC acquisition and awareness, acculturation, contraceptive used at last intercourse and history of induced abortion. Data were analyzed using logistic regression analyses.Results: Acculturation (p=.017), income (p=.024) and education (p<.001) were positively associated with awareness of EC. Additionally, acculturation (p=.003) and a history of an induced abortion (p=.026) were positively associated with acquisition of EC.Conclusions: Educational programs should make an effort to include Hispanic women with lower acculturation levels as increasing their knowledge about EC use and its mechanism of action may greatly reduce the number of unplanned pregnancies in this population.

Capturing the sexual side effects of hormonal contraception - Corrected Proof

Ellen Wiebe — 2010-06-04

I am responding to the article, “The EVAPIL scale” . The sexual question in EVAPIL does not capture the sexual side effects which women complain of from hormonal contraception. “Enjoying intercourse” is mostly related to the quality of a relationship while hormones cause effects in sexual desire, fantasies, sexual thoughts and arousability. In the study by Sanders et al. , “decreased frequency of sexual thoughts, and decreased psychosexual arousability” predicted changing or quitting hormonal contraception. In a study by Sabatini et al. , “disturbance of sexual intercourse due to vaginal dryness and loss of desire” predicted discontinuation of hormonal contraception. The Sexual Interest and Desire Inventory-Female uses the words “level of sexual interest/sexual desire” to capture this issue.

Inhibition of vascular endothelial growth factor during the postovulatory period prevents pregnancy in the marmoset - Corrected Proof

Hamish M. Fraser, Keith D. Morris, Stanley J. Wiegand, Helen Wilson — 2010-06-04

Abstract: Background: This study investigated the effects of inhibition of vascular endothelial growth factor (VEGF) during the first postpartum cycle in marmosets housed with a fertile male where a 90% fertility rate is normal.Methods: On resumption of mating, females were treated with either 25 mg/kg aflibercept, a potent VEGF inhibitor, or control Fc protein (n=6 per group) at the time of ovulation. Effects on timing of pregnancy were monitored by measuring plasma progesterone, chorionic gonadotropin (CG) and uterine palpation.Results: In five of six Fc-treated controls, the postpartum rise in progesterone was maintained and followed by a sustained rise in CG by Day 30 posttreatment indicating pregnancy. In all six aflibercept-treated animals, progesterone secretion was suppressed in the treatment cycle and a CG rise did not occur by Day 30. Pregnancy was delayed to the next cycle, significantly extending interbirth interval compared to controls. Posttreatment deliveries and infant development were normal.Conclusion: These results show that stringent pharmacological inhibition of VEGF suppresses luteal progesterone and prevents the successful establishment of pregnancy.

Finding the right face for advanced supply of emergency contraception - Corrected Proof

Courtney A. Schreiber, Sarah Ratcliffe, Kurt T. Barnhart — 2010-06-01

We appreciate the comments from Polis et al. with regard to the controversy surrounding advanced supply of emergency contraception (EC) use, and the part our article plays in the current body of literature. It appears that our interpretation of the state of the evidence is similar, however different our opinions are about future research directions.

Facing the facts on advance provision of emergency contraception - Corrected Proof

Chelsea B. Polis, Elizabeth G. Raymond, James Trussell — 2010-06-01

For over a decade, studies have assessed the effect of advance provision of emergency contraception (EC) on pregnancy rates. This research has shown uniformly disappointing results. A Cochrane review of 11 randomized trials updated in 2010 found no evidence of reduced pregnancy rates due to advance provision of EC, either in individual trials or in a meta-analysis of the pooled data of over 7000 women. A systematic literature review which also included observational studies reached the same conclusion .

Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review - Corrected Proof

Alison B. Edelman, Ganesh Cherala, Frank Z. Stanczyk — 2010-06-01

Abstract: The effect of obesity on drug metabolism and pharmacokinetics is poorly understood, and this is particularly true in regard to contraceptive steroids. This article will review the known and theoretical physiologic and pharmacologic interactions between obesity and contraceptive steroids.

Corrected Proof

Olivier Graesslin, Pierre Clerson — 2010-06-01

We would like to thank Dr. Wiebe for her interesting comments on our article “The EVAPIL scale” recently published in this journal . Dr. Wiebe suggests that the sexual question in EVAPIL does not capture the relevant characteristics of sexual side effects arguing that a question focusing on sexual desire would be more relevant than a question evaluating “enjoyment during intercourse,” which involves the quality in the relationship more than adverse effects of hormonal contraception. We agree with this remark. During the EVAPIL scale building process, sexual side effects were firstly evaluated by two separate questions regarding sexual desire and sexual pleasure. However, validation steps conducted in a population of oral contraception users demonstrated that there was a very strong correlation (r=0.92, p<.0001) between the answers obtained to these two questions and that the difference between desire and pleasure was not evident for most women. In order to limit the number of questions and not to oversize the weight of the sexual side effects, we decided to delete the question on sexual desire and to maintain the only question on sexual pleasure which clearly included information on sexual desire, at least for our sample of French women. In addition, the EVAPIL scale was written and validated in French, and the English translation of this question might have been confusing. The literal translation of the French term is:

Expanded safety and acceptability of the candidate vaginal microbicide Carraguard® in South Africa - Corrected Proof

The Carraguard Phase II South Africa Study Team — 2010-06-01

Abstract: Background: Carraguard's safety and acceptability was assessed among women in Gugulethu and Ga-Rankuwa, South Africa.Study Design: A randomized, placebo-controlled, triple-blind trial was conducted in HIV-negative, nonpregnant women who inserted Carraguard or placebo at least three times a week, including before vaginal sex, for 6 to 12 months. Monthly visits included pelvic examination, sexually transmitted infection (STI) testing/treatment and HIV counseling/testing. Acceptability was assessed quarterly.Results: Of 400 women (205 Carraguard, 195 placebo) enrolled, 328 (77%) completed at least 6 months. Incidence of genital epithelial disruption was similar between the Carraguard (13.6 per 100 woman-years) and placebo (21.3 per 100 woman-years) groups (relative risk, 0.64; 95% confidence interval, 0.37–1.10); there were no significant differences in rates of HIV/STI, though the study was not powered to determine effectiveness. Only 2% of adverse events were judged possibly related to (either) gel. More than 94% of women reported at least once liking the gel very much.Conclusions: Carraguard was not associated with more vaginal, cervical or external genital irritation than placebo, and it was acceptable when used approximately 3.5 times per week, including during sex.

Uptake and adherence to long-acting reversible contraception post-abortion - Corrected Proof

Sally B. Rose, Beverley A. Lawton, Selina A. Brown — 2010-06-01

Abstract: Background: This study aimed to increase use of long-acting reversible contraceptive (LARC) methods by women post-abortion.Study Design: Ten-week intervention at a public abortion clinic involving free access to three LARC methods (DMPA, LNG-IUS, Multiload Cu375); posters promoting LARC; updated information for clinic staff. Outcome measures: change in the proportion of women choosing LARC prior to and during the intervention; rate of follow-up and method retention at 6 weeks and at 6 months post-abortion.Results: Use of post-abortion LARC increased significantly from 44% at baseline (226/510) to 61% (310/510) during the intervention (p<.001). Use of LNG-IUS increased almost sixfold from 6% to 36%. Follow-up rates were 71% at 6 weeks (221/310) and 74% at 6 months (184/249). Method retention was 89% at 6 weeks (197/221) and 86% at 6 months (159/184).Conclusion: Uptake of LARC by women post-abortion can be achieved by increasing access to these methods — by eliminating cost and raising awareness and benefits of long-acting methods among both clinicians and patients.

Biopsychosocial variables associated with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate in adolescents: adolescents who lost 5% or more from baseline vs. those who lost less than 5% - Corrected Proof

2010-06-01

Abstract: Background: It is unclear why some adolescents experience substantial bone mineral density (BMD) loss, while others experience a minimal decrease during depot medroxyprogesterone acetate (DMPA) use. We examined biopsychosocial factors in adolescents who experienced ≥5% BMD loss from baseline compared with adolescents who experienced <5% BMD loss during DMPA use.Study Design: A multicenter, prospective, nonrandomized study of 181 female adolescents who initiated DMPA for contraception was conducted. BMD (by dual-energy X-ray absorptiometry) and serum estradiol were measured at initiation and every 6 months for 240 weeks of DMPA use.Results: Half of participants experienced BMD loss of ≥5% from baseline at the hip, and a quarter experienced BMD loss of ≥5% at the lumbar spine (BMD substantial losers, SL). Hip and lumbar spine BMD-SL received a significantly greater number of DMPA injections than non-SL (p<.001). Decreased estradiol levels did not statistically differ between BMD loss subgroups. Hip BMD-SL had significantly lower baseline body mass index (BMI) than non-SL (p=.002), and there was an inverse relationship between weight gain and degree of BMD loss. Mean calcium intake was significantly lower (p<.05) in hip BMD-SL, and reported alcohol use was significantly higher (p<.05) in lumbar spine BMD-SL compared with non-SL.Conclusions: BMD loss of ≥5% was more common at the hip than at the lumbar spine among adolescents using DMPA. Decreased serum estradiol levels did not correlate with magnitude of BMD loss. Lower BMI and calcium intake and greater alcohol use were associated with greater BMD loss in adolescents using DMPA.

The effects of mifepristone on the expressions of osteopontin, interleukin-6 and leukemia inhibitory factor in the villi of early pregnant women - Corrected Proof

Kaiyan Pei, Cuihua Yu, Xinquan Shi, Mengchun Jia — 2010-05-26

Abstract: Background: The autocrine, paracrine and hormonal effects of osteopontin (OPN), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) suggest that these cytokines may play key roles at the maternal–fetal interface. This study was performed to determine the effects of mifepristone on OPN, LIF and IL-6 mRNA and protein expressions in the villi in early pregnancy.Study Design: Twenty-nine healthy women seeking termination of pregnancy up to 40 days' gestation were recruited. The study group (n=14) was given 150 mg mifepristone 24 h before vacuum aspiration. The control group (n=15) was not given any treatment prior to vacuum aspiration. Villi were collected, and immunohistochemical analysis and real-time reverse transcription PCR (RT-PCR) were used to detect the locations and the expression levels of OPN, IL-6 and LIF mRNA.Results: In the study group, the expression level of OPN protein in the villous trophoblast and stoma cells was significantly lower (p<.01), while the expression levels of IL-6 and LIF protein were significantly higher than those in the control group (p<.01, p<.05, respectively). Compared with the control group, the relative expression of OPN mRNA was significantly lower (p=.001) and the IL-6 and LIF mRNA expression levels were significantly higher in the study group (p=.003 and p<.001, respectively).Conclusion: OPN, IL-6 and LIF may have critical roles in human pregnancy maintenance. These three factors may be involved in the immunological reaction initiated by mifepristone.

Contraceptive vaginal rings: a review - Corrected Proof

Vivian Brache, Anibal Faundes — 2010-05-21

Abstract: Development efforts on contraceptive vaginal rings were initiated over 40 years ago based on two principles: the capacity of the vaginal epithelium to absorb steroids and the capacity of elastomers to release these hormones at a nearly constant rate. Numerous models of contraceptive vaginal rings (CVRs) have been studied, but only two have reached the market: NuvaRing, a combined ring that releases etonogestrel (ENG) and ethinylestradiol (EE), and Progering, a progesterone-releasing ring for use in lactating women. The main advantages of CVRs are their effectiveness (similar to or slightly better than the pill), ease of use without the need of remembering a daily routine, user's ability to control initiation and discontinuation, nearly constant release rate allowing for lower doses, greater bioavailability and good cycle control with the combined ring. The main disadvantages are related to the mode of delivery; CVRs may cause vaginal discharge and complaints, ring expulsion is not uncommon, the ring may be felt during coitus and vaginal insertion may be unpleasant for some women. The studies reviewed in this article provide evidence that CVRs are safe, effective and highly acceptable to women. There is no doubt that CVRs offer a new, effective contraceptive option to women, expanding their available choices of hormonal contraception.

Recent methodological advances in male hormonal contraception - Corrected Proof

Peter Y. Liu, Ronald S. Swerdloff, Christina Wang — 2010-05-20

Abstract: Landmark WHO-sponsored trials showed decades ago that male hormonal contraception (MHC) is an effective male-directed contraceptive approach. Considerable progress has been made particularly in the last 5 years, establishing for the first time the reversibility of MHC and its short-term safety. Methodological advances in recent years include the pooling of information and individual-level integrated analysis; the first-time use of centralized semen analysis and fluorescence to detect low sperm concentrations; the establishment of sperm quality reference ranges in fertile men; the measurement of blood steroid concentrations by gas chromatography/mass spectrometry; and the inclusion of placebo groups to delineate clearly possible adverse effects of androgens and progestins in men. We report integrated analyses of factors that are important in predicting suppression and recovery of spermatogenesis after MHC clinical trials for the past 15 years. These are the best data available and will provide guidance and reassurance for the larger-scale Phase III specific regimen efficacy studies that will be required to bring MHC to the population (market).

How commonly do US abortion clinics offer contraceptive services? - Corrected Proof

Megan L. Kavanaugh, Rachel K. Jones, Lawrence B. Finer — 2010-05-20

Abstract: Background: About half of US women having abortions have already had at least one prior abortion. Facilitating access to contraception may help these women avoid subsequent unintended pregnancies. Information is needed to document the availability of contraceptive services in abortion care settings in the United States.Study Design: Data for this cross-sectional mixed-methods study were collected between December 2008 and September 2009 and come from two sources: 15 semistructured telephone interviews and 173 structured questionnaires administered to a nationally representative sample of eligible facilities. Respondents were administrators at large (400+ abortions per year), nonhospital facilities that provide abortion services in the United States.Results: Virtually all (96%) abortion clinics incorporate contraceptive education into abortion care, and the three most common methods reported to be distributed are the birth control pill (99%), the vaginal ring (61%) and Depo-Provera (58%). Almost one-third reported being able to offer post-abortion intrauterine device insertion. Most facilities (82%) accept some form of insurance for either contraceptive or abortion services, and those with a broader family planning focus are significantly more likely to do so. Administrators at the majority of facilities (56%) report that patients most commonly do not pay additional fees for contraceptive services because they are included in the cost of abortion services.Conclusion: Although almost all large, non-hospital abortion providers in the United States are able to provide some level of contraceptive care to their abortion patients, the degree to which they are able to do so is influenced by a wide range of factors.

Introduction to Population Council Symposium articles - Corrected Proof

Regine Sitruk-Ware, Daniel R. Mishell — 2010-05-19

The contents of this issue include several manuscripts of papers presented at a Symposium organized by the International Committee for Contraception Research (ICCR) of the Population Council, as a tribute to C. Wayne Bardin, M.D., Ph.D., who has inspired and led the research and development of new contraceptives in his role of Vice President of the Center of Biomedical Research of the Population Council and as a chairperson of the ICCR from 1978 to 1996. His vision and leadership led to the initiation of comprehensive research in male contraception, a neglected field and an obvious unmet need for couples of reproductive age. He trained a new generation of scientists in the field of Reproductive Endocrinology who have pursued the mission of the Population Council both in the United States and abroad in developed and less developed countries. He has also developed and achieved Food and Drug Administration approval for Paragard®, Norplant® and Jadelle®, major long-acting methods of contraception as well as mifepristone, a unique molecule with several indications in the field of gynecology.

Factors affecting mortality in a large cohort study with special reference to oral contraceptive use - Corrected Proof

Martin Vessey, David Yeates, Susan Flynn — 2010-05-19

Abstract: Background: This analysis updates mortality in the Oxford-Family Planning Association (Oxford-FPA) contraceptive study, with emphasis on oral contraceptive (OC) use.Study design: The Oxford-FPA study includes 17,032 women recruited from 1968–1974 at contraceptive clinics, aged 25–39 years, using OCs a diaphragm or an intrauterine device. Follow-up has been to March 2009; by then, 1715 women had died.Results: The rate ratio (RR) for overall mortality was 0.87 (CI 0.79–0.96), comparing ever-users of OCs with never-users. The RR for fatal cervical cancer was increased (7.3), but the CIs were very wide (1.2–305). There was no association between ever-use of OCs and mortality from breast cancer (RR 1.0, CI 0.8–1.2), nor was fatal breast cancer related to duration of OC use. OC use strongly protected against death from other uterine cancer and ovarian cancer; RRs for ever-use of OCs were 0.3 (CI 0.1–0.8) and 0.4 (CI 0.3–0.6), respectively. Protection increased with duration of OC use and persisted more than 20 years after cessation. Circulatory disease mortality was not increased, the RR for ever-use of OCs being 0.9 (CI 0.7–1.1). The overall mortality RR for all women smoking 15+ cigarettes daily was 2.25 (CI 1.99–2.53) and, for all women with a body mass index of 28+ kg/m2, was 1.33 (CI 1.07–1.64).Conclusions: Long-term follow-up strongly suggests that OC use slightly reduces all cause mortality.

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial - Corrected Proof

2010-05-19

Abstract: Background: The etonogestrel (ENG) implant Implanon® is a progestin-only contraceptive that provides effective contraception for up to 3 years. A new radiopaque ENG implant has been developed to extend the diagnostic modalities of Implanon and a next-generation applicator (NGA) was designed to facilitate correct subdermal insertion of Implanon.Study Design: In this open-label study, 23 investigators, experienced and inexperienced with Implanon, performed 301 insertions of the new radiopaque implant using the NGA. Primary outcome measurements were obtained from clinician satisfaction questionnaires completed after the 4th, 8th and 12th insertions. Additionally, insertion characteristics and X-ray visibility were assessed.Results: Almost all investigators were satisfied with the NGA from the first insertion onward, and all were satisfied or very satisfied after 12 insertions. The most frequently reported advantages included ease of use, one-handed action and fast insertion time; 2% of insertions were considered difficult in skin puncturing and/or sliding the needle subdermally. Three incorrect insertions occurred due to noncompliance with instructions. All assessed implants were visible on plain X-ray imaging.Conclusions: The NGA was well accepted by investigators with or without prior experience with Implanon. The results stressed the importance of correctly following implant insertion instructions.

Update on the cost-effectiveness of contraceptives in the United States - Corrected Proof

James Trussell — 2010-05-19

In , we update our results on the cost-effectiveness of contraceptives in the United States to reflect the recent steep increase in the average wholesale price of the Mirena intrauterine system to $843 (an increase of 43% over the average wholesale price of $586 in the original article).

Clinical trials in male hormonal contraception - Corrected Proof

Eberhard Nieschlag — 2010-05-17

Abstract: Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers.

Vaginal estrogen supplementation during Depo-Provera initiation: a randomized controlled trial - Corrected Proof

Angela Dempsey, Claudia Roca, Carolyn Westhoff — 2010-05-12

Abstract: Background: Irregular bleeding is often cited as the reason for discontinuation of depot-medroxyprogesterone acetate (DMPA) after the first injection. Estrogen supplementation during DMPA initiation may decrease bleeding and improve continuation.Study Design: This prospective, randomized, controlled trial evaluated estrogen supplementation during DMPA initiation. Women initiating DMPA were randomized to receive an estradiol vaginal ring for 3 months versus DMPA alone. Bleeding diaries and questionnaires at three and 6 months assessed bleeding, continuation and ring acceptability.Results: Seventy-one participants enrolled; 49 completed the first follow-up period. The median number of bleeding or spotting days was 16 in the estrogen ring group (n=26) versus 28 in the DMPA alone group (n=23) (p=.19). Seventy-seven percent of the intervention group received a second injection compared with 70% in the DMPA alone group (p=.56). For each additional day of bleeding and/or spotting reported, women were 3% less likely to receive a second injection (OR 0.97, 95% CI 0.94–0.99). Acceptability of the vaginal ring was high among those in the intervention group.Conclusions: Vaginal estrogen supplementation during DMPA initiation is acceptable to women and may decrease total bleeding.

The use of newer progestins for contraception - Corrected Proof

Regine Sitruk-Ware, Anita Nath — 2010-05-12

Abstract: The synthetic progestins used for contraception so far are structurally related either to testosterone (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor (GR) interactions. Dienogest (DNG) and drospirenone (DRSP) exhibit a partial antiandrogenic action, and DRSP has predominant anti-mineralocorticoid properties. The 19-norpregnanes include Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG), and possess a high specificity for binding to the progesterone receptor (PR) with no or little interaction with other steroid receptors. DRSP has been developed as combination oral pills with ethinyl estradiol (EE); DNG has been combined both with EE and, more recently, with estradiol valerate (E2V). NOMAc has been used as a progestin-only method and more recently combined with estradiol (E2). Nestorone is not active orally but proved to be the most active antiovulatory progestin when used parenterally. It has been developed in various formulations such as implants, vaginal rings or transdermal gel or spray. Risks and benefits of the new progestins depend upon the type of molecular structure, the type of estrogen associated in a combination and the route of administration.

Author response to the commentary “Evaluating research on abortion and mental health” - Corrected Proof

Vignetta Eugenia Charles, Chelsea Polis, Srinivas Sridhara, Robert Wm. Blum — 2010-05-07

Regarding the commentary in Contraception, “Evaluating research on abortion and mental health” , we would like to clarify any misunderstanding of our recent review, “Abortion and long-term mental health outcomes: a systematic review of the evidence” . A recent editorial in Contraception by Steinberg et al. cited our conclusions as sound science, and we would like to avoid further muddying the waters on evaluating this contentious body of literature by addressing the criticisms included in the commentary.

New frontiers in nonhormonal male contraception - Corrected Proof

C. Yan Cheng, Dolores D. Mruk — 2010-05-07

Abstract: The world's population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male's reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive.