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Objective: This study aimed to determine the effect of oophorectomy on baseline serum levels of androgens and estrogens in premenopausal and postmenopausal women., Methods: Fourteen premenopausal and 10 postmenopausal women underwent total hysterectomy and bilateral oophorectomy for benign disease of the uterus. Serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol-17β-glucuronide (3α-diol G), estrone (E 1 ), estradiol (E 2 ), and sex hormone-binding globulin (SHBG) were measured by highly specific immunoassays prior to surgery and 2 weeks afterward. Free T and free E 2 were calculated. Differences were determined between preoperative (preop) and postoperative (postop) samples, and between premenopausal and postmenopausal women., Results: In premenopausal women, postop levels of total and free T, DHT, and total and free E 2 decreased significantly from preop. Postop levels of DHEAS, A, 3α-diol G, and SHBG were decreased, but not significantly different from preop. In postmenopausal women, postop levels of total and free T and total and free E 2 decreased significantly from preop, but there was little change in the other compounds. Significant differences in the mean change from baseline between premenopausal and postmenopausal women were observed only for E 1 and total and free E 2 ., Conclusion: The significant decrease in serum T in postmenopausal women following oophorectomy adds to the evidence that the postmenopausal ovary continues to produce T.

Although vaccination against the Human Papilloma Virus (HPV) reduces the risk of related morbidities, the vaccine uptake remains low in adolescents. This has been attributed to limited parental knowledge and misconceptions. In this cross sectional study, we assessed the (1) clarity of educational material informing Hispanic mothers about HPV, cervical cancer and the HPV vaccine, (2) determined vaccination acceptability and (3) identified predictors of vaccine acceptance in an underserved health setting. 418 Hispanic mothers received the educational material and completed an anonymous survey. 91 % of participants understood most or all of the information provided. 77 % of participants reported vaccine acceptance for their children; this increased to 84 % when only those with children eligible to receive vaccination were included. Significant positive predictors of maternal acceptance of the HPV vaccine for their children were understanding most or all of the provided information, older age and acceptance of the HPV vaccine for themselves. Concerns about safety and general dislike of vaccines were negatively associated with HPV vaccine acceptance. Prior knowledge, level of education, previous relevant gynecologic history, general willingness to vaccinate and other general beliefs about vaccines were not significantly associated with HPV vaccine acceptance. The majority of participants reported understanding of the provided educational material. Vaccine acceptability was fairly high, but was even higher among those who understood the information. This study documents a cost-effective way to provide Hispanic mothers with easy-to-understand HPV-related information that could increase parental vaccine acceptability and future vaccine uptake among their children.

Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed.

Objective: The safety and tolerability of a new low-dose levonorgestrel/ethinyl estradiol (LNG/EE) contraceptive patch was compared with 2 combination oral contraceptives in 2 clinical studies in which approximately 30% of enrolled participants were obese., Study Design: Two phase 3, open-label, randomized, parallel-group, multicenter trials compared the LNG/EE contraceptive patch (n = 1579) with combination oral contraceptives (n = 581) in healthy women 17-40 years of age. Combination oral contraceptives were LNG 100 μg per EE 20 μg (combination oral contraceptive 20; n = 375) or LNG 150 μg per EE 30 μg (combination oral contraceptive 30; n = 206). Safety and tolerability data from the 2 trials were evaluated in integrated safety analyses., Results: Treatment-emergent adverse events of 2% or greater in the LNG/EE contraceptive patch were nasopharyngitis (5.2%), nausea (4.1%), upper respiratory infection (3.5%), headache (3.4%), sinusitis (2.9%), cervical dysplasia (2.3%), and urinary tract infection (2.1%). Including skin reaction-related treatment-emergent adverse events, the proportion of women who experienced any treatment-emergent adverse event was similar among women randomized to the contraceptive patch (47.5%), the combination oral contraceptive 20 (47.4%), or the combination oral contraceptive 30 (46.8%). The incidence of treatment-emergent adverse events was similar in obese vs nonobese participants in all groups. Serious adverse events occurred in less than 1% of participants in any of the treatment groups., Conclusion: The LNG/EE contraceptive patch and combination oral contraceptives were well tolerated and associated with similar treatment-emergent adverse event incidences in obese and nonobese women., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate skin irritation and patch adhesiveness of a new weekly low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (LNG/EE patch)., Study Design: This analysis was part of an open-label, parallel-group, multicenter, phase 3 study that randomized healthy women to the LNG/EE patch (one patch weekly for three consecutive weeks, followed by a patch-free week for 13 cycles) or to an oral contraceptive for six cycles followed by seven LNG/EE patch cycles. Participants selected patch application sites of abdomen, buttock or upper torso. Investigators rated patch adhesiveness and skin irritation using standardized scales. Participants rated skin irritation and itching daily using standardized scales and recorded patch fall-off on daily diary cards., Results: A total of 32,508 patches were applied (n=1273). At the five clinic visits in which investigators rated the patches, they rated adhesiveness=0 (no lift) for ≥84% of participants and skin irritation=absent/mild for 97% of patches. Participants reported that 2-3.7% of patches fell off and rated skin irritation as absent or mild for 92- 95% of patches, according to site., Conclusion: Investigator- and participant-rated assessments of LNG/EE patch adhesiveness and irritation demonstrated a low incidence of patch detachment, skin irritation and pruritus., Implications Statement: This secondary analysis of a phase 3 clinical trial of a new weekly low-dose LNG and EE contraceptive patch, which used assessment by both investigators and participants, observed a low incidence of skin irritation, pruritus and patch detachment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Pregnancy rates in US contraceptive clinical trials are increasing due to decreased treatment compliance. This study compared compliance with a new low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (CP, Twirla™) with that of a low-dose combination oral contraceptive (COC) in a demographically diverse population., Study Design: This analysis was part of an open-label, parallel-group, multicenter phase 3 study that randomized healthy sexually active women (17-40years) to 13cycles of LNG/EE CP or 6cycles of COC, then 7cycles of LNG/EE CP. We defined self-reported compliance as cycles that, according to diaries, show 21days of patch wear without missed days or any patch worn >7days or 21days of pill-taking without missed pill days. We verified compliance by detectable plasma presence of LNG and EE at cycles 2, 6, and 13., Results: Of the intention-to-treat population with diary information (N=1328, mean age 26.4years, 46% minorities, 33% obese), 10.0% of the CP (n=998) versus 21.2% of the COC group (n=330) self-reported noncompliance after 6cycles (p<.001). Laboratory assessments verified 10-14% of participants in both groups as noncompliant. Self-reported perfect use did not vary between obese [body mass index (BMI) ≥30kg/m(2)] versus nonobese (BMI <30kg/m(2)) participants in both groups or when stratified by age, education, or race/ethnicity in the CP group., Conclusions: Self-reported compliance was significantly greater in the CP than COC group and did not vary by obesity status. Discrepancies between self-reported and verified compliance question reliability of patient diaries., Implications Statement: This paper, based on an analysis of a phase 3 trial, shows that compliance was significantly greater with a new weekly transdermal CP than with a once-daily COC in obese as well as nonobese participants. Discrepancies between self-reported compliance and laboratory-verified compliance raise questions regarding the reliability of patient diaries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding., Methods: Women (17-40 years; body mass index 16-60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy., Results: Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1-6) were 4.45 (2.34-6.57) for Patch and 4.02 (0.50-7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98-4.67) for Patch and 3.80 (0.08-7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference)., Conclusions: Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479., Level of Evidence: I.

Objective: Pharmacokinetic interactions exist between combined oral contraceptives and protease inhibitors (PI). However, such information is lacking for progestin-only oral contraception. We sought to define the steady-state pharmacokinetic interaction between norethindrone (NET) and PI in HIV-infected women., Methods and Design: We conducted an open-label, prospective, nonrandomized trial to characterize the steady-state pharmacokinetics of serum NET in HIV-infected women receiving PI compared with a control group of HIV-infected women receiving other noninteracting drugs. After 21 days of 0.35 mg of NET ingestion once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours. The area under the curve between 0 and 72 hours after ingestion was calculated by trapezoidal approximation., Results: Thirty-five women were enrolled, 2 withdrew. Sixteen women in the PI group and 17 controls completed the study. NET half-life and maximum concentration were not significantly different between the 2 groups. Minimum concentration of NET was significantly higher in the PI group (P = 0.01). The ratio of the geometric mean NET area under the curve in the PI group compared with controls was 1.5 (90% confidence interval: 1.21 to 1.86). NET serum concentrations were significantly higher in HIV-infected women taking a PI compared with controls (P = 0.004)., Conclusions: Coadministration of PI inhibits NET metabolism as shown by higher serum NET area under the curve levels, a surrogate marker for therapeutic contraceptive efficacy. This study supports the increased utilization of progestin-only pills in HIV-infected women receiving certain PI regimens.

Background: The metabolic effects of progestin-only long-acting reversible contraception [levonorgestrel-releasing intrauterine system (LNG-IUS) and etonogestrel implant (ENG-I)] have been studied in normal-weight women but not in obese [body mass index≥30kg/m(2)] women., Study Design: A nonrandomized open-label prospective trial of healthy obese, reproductive-age women desiring to use long-acting reversible contraception (LARC) or nonhormonal contraception (NHC). At baseline, 3 months and 6 months, homeostasis model assessment insulin resistant (HOMA-IR) score, insulin sensitivity (HOMA-%S) and β-cell function (HOMA-%B) were calculated based on fasting insulin and glucose values. In addition, components of metabolic syndrome [fasting glucose (FG), high density lipoprotein cholesterol and triglycerides, systolic and diastolic blood pressure, abdominal circumference] were measured. Twenty-four subjects total (8 in each arm) were needed to detect a 1.0 difference in HOMA-IR with 80% power and a two-sided alpha of 0.05., Results: We present data on eight NHC, eight ENG-I and nine levonorgestrel intrauterine system (LNG-IUS) users. FG increased, and insulin sensitivity decreased over time among ENG-I users to a greater extent than among LNG-IUS users when compared to women using a nonhormonal method [FG change over 6 months=9.4mg/dL, 4.6mg/dL and -2.1mg/dL, respectively; p=.01); (HOMA-%S change over 6 months=-29.9%, -14.8% and 19.3%, respectively; p=.02)], while β-cell function and insulin resistance did not change significantly (p>.05)., Conclusion: While changes in FG and insulin sensitivity were seen in the present study among obese progestin-only contraceptive users, either progestin-only LARC method may be safely used clinically., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To measure infants' breast milk intake and infant growth when their mothers initiated either combined oral contraceptive (COC), levonorgestrel-releasing intrauterine system, or etonogestrel-releasing implant, or copper intrauterine device (IUD) as a reference group., Design: Prospective trial., Setting: University-based hospital., Patient(s): On postpartum day 42, 40 women initiated a contraceptive method according to their choice., Intervention(s): Deuterium (D2O; 0.5 g/kg mother's weight) was ingested by mothers on postpartum days 42, 52, and 63 as a marker of total body fluid., Main Outcome Measure(s): Infants' milk intake from 42 to 63 postpartum days was assessed by measurement of D2O levels in infants' saliva and infant growth by measuring their body weight, height, and tibia length. Women recorded all infant feed and changes of diapers wet with urine. Breastfeeding continuation was assessed at 6 months postpartum., Result(s): Infant mean milk intake, mean growth increase, mean number of breastfeeding episodes, daily wet diaper changes, and mean duration of exclusively breastfeeding (~5 months) were similar in the four groups., Conclusion(s): Use of a COC, the two progestin-only contraceptives, or copper IUD did not affect the amount of infant milk intake and growth up to 9 weeks of age. The incidence of full breastfeeding and breastfeeding continuation was similar with contraceptive hormonal use and no use., Clinical Trials Registration Number: NCT01388582., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens., Study Design: This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI., Results: From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01)., Conclusion: This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The safety of progestogens as a class has come under increased scrutiny after the publication of data from the Women's Health Initiative trial, particularly with respect to breast cancer and cardiovascular disease risk, despite the fact that only one progestogen, medroxyprogesterone acetate, was used in this study. Inconsistency in nomenclature has also caused confusion between synthetic progestogens, defined here by the term progestin, and natural progesterone. Although all progestogens by definition have progestational activity, they also have a divergent range of other properties that can translate to very different clinical effects. Endometrial protection is the primary reason for prescribing a progestogen concomitantly with postmenopausal estrogen therapy in women with a uterus, but several progestogens are known to have a range of other potentially beneficial effects, for example on the nervous and cardiovascular systems. Because women remain suspicious of the progestogen component of postmenopausal hormone therapy in the light of the Women's Health Initiative trial, practitioners should not ignore the potential benefits to their patients of some progestogens by considering them to be a single pharmacological class. There is a lack of understanding of the differences between progestins and progesterone and between individual progestins differing in their effects on the cardiovascular and nervous systems, the breast, and bone. This review elucidates the differences between the substantial number of individual progestogens employed in postmenopausal hormone therapy, including both progestins and progesterone. We conclude that these differences in chemical structure, metabolism, pharmacokinetics, affinity, potency, and efficacy via steroid receptors, intracellular action, and biological and clinical effects confirm the absence of a class effect of progestogens.

Background: The major contraceptive action of the levonorgestrel-releasing intrauterine system (LNG-IUS) is cervical mucus (CM) thickening, which prevents sperm penetration. No study to date has examined the temporal relationship between the insertion of the LNG-IUS and changes in CM quality and sperm penetration., Study Design: Participants were enrolled in a clinically descriptive study to compare the quality of CM and three parameters of sperm penetration prior to insertion of the LNG-IUS and on Days 1, 3 and 5 after insertion. Measurements of estradiol, progesterone and levonorgestrel (LNG) in serum and LNG in CM were also carried out at these times. CM was analyzed using the World Health Organization CM grading criteria. Sperm penetration was determined using an in vitro sperm-CM penetration test., Results: All 10 participants underwent LNG-IUS insertion during midcycle when CM quality was good and sperm penetration was excellent. On Day 1 after LNG-IUS insertion, the majority of participants demonstrated poor CM quality and poor sperm penetration. On Day 3, all participants had poor CM quality, and all but one subject had poor sperm penetration. By Day 5, all participants had poor CM quality and poor sperm penetration. LNG levels in CM peaked on the day after LNG-IUS insertion., Conclusion: Significant changes in quality of CM and sperm penetration were observed shortly after LNG-IUS insertion; however, CM can remain penetrable for up to 5 days when the LNG-IUS is inserted midcycle., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Steady progress in contraception research has been achieved over the past 50 years. Hormonal and nonhormonal modern contraceptives have improved women's lives by reducing different health conditions that contributed to considerable morbidity. However, the contraceptives available today are not suitable to all users, and the need to expand contraceptive choices still exists. Novel products such as new implants, contraceptive vaginal rings, transdermal patches and newer combinations of oral contraceptives have recently been introduced in family planning programs, and hormonal contraception is widely used for spacing and limiting births. Concerns over the adverse effects of hormonal contraceptives have led to research and development of new combinations with improved metabolic profile. Recent developments include use of natural compounds such as estradiol and estradiol valerate with the hope to decrease thrombotic risk, in combination with newer progestins derived from the progesterone structure or from spirolactone, in order to avoid the androgenic effects. Progesterone antagonists and progesterone receptor modulators are highly effective in blocking ovulation and preventing follicular rupture and are undergoing investigations in the form of oral pills and in semi-long-acting delivery systems. Future developments also include the combination of a contraceptive with an antiretroviral agent for dual contraception and protection against sexually transmitted diseases, to be used before intercourse or on demand, as well as for continuous use in dual-protection rings. Although clinical trials of male contraception have reflected promising results, limited involvement of industry in that area of research has decreased the likelihood of having a male method available in the current decade. Development of nonhormonal methods is still at an early stage of research, with the identification of specific targets within the reproductive system in ovaries and testes, as well as interactions between spermatozoa and ova. It is hoped that the introduction of new methods with additional health benefits would help women and couples with unmet needs to obtain access to a wider range of contraceptives with improved acceptability., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The effect of obesity on ovarian follicular suppression in women using low-estrogen dose contraceptive patches has not been determined., Study Design: A Phase II, parallel-group, multicenter, three-cycle study evaluated three patches containing different ethinyl estradiol (EE) and levonorgestrel (LNG) doses. Serum levels of EE, LNG, sex hormone-binding globulin and progesterone were compared in 41 obese [body mass index (BMI) ≥30] and 75 nonobese (BMI <30) women., Results: Suppression of ovulation during the luteal phase was dose dependent, with the highest dose (AG200-15) preventing progesterone increases in all women (cycles 2-3). In the follicular phase, the lowest-dose patch had the highest rate of increased progesterone in nonobese subjects. Progesterone levels ≥3.0 ng/mL in the follicular phase were more common in obese than nonobese women., Conclusions: AG200-15 suppresses ovulation in obese and nonobese women. All three patches found increased progesterone in the follicular phase, albeit more in obese versus nonobese women., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Few studies have examined the action of combined oral contraceptives (COCs) on cervical mucus. We hypothesized that midcycle cervical mucus of women taking COCs is of poor quality when compared to their own midcycle mucus prior to initiating COCs. We sought to compare the effect upon quality and sperm penetration of the cervical mucus on the last hormone-free day with a 24/4 regimen to a 21/7 regimen., Methods: This is an open-label, investigator-blinded, randomized, controlled, crossover equivalency study. All subjects received, in random order, 2 months of a 21/7 regimen and 2 months of a 24/4 regimen, each containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Analysis of cervical mucus quality (CMQ) and sperm penetration took place midcycle and on the last day of the hormone-free interval during the second month of each COC treatment., Results: From April 2010 to November 2011, 18 subjects completed all study visits. Mean midcycle CMQ was poor (mean CMQ=1) and did not differ between 24/4 and 21/7 regimens (p=.92). On the last day of the pill-free interval, the quality and sperm penetration were poor with both regimens., Conclusion: This study indicates that thickening of cervical mucus is a major mechanism of contraceptive action of COCs and that both 21/7 and 24/4 regimens result in poor quality and impenetrable mucus on the last day of the pill-free interval., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To review the clinical experience with the contraceptive vaginal ring (CVR, NuvaRing(®)) since its introduction over ten years ago., Methods: The literature was searched on efficacy, cycle control, safety, user preference and satisfaction of the CVR in comparison with combined oral contraceptives (COCs) and the patch, with special attention to recent developments., Results: The ring has the same working mechanism and contraindications as COCs. Serum levels of steroids are steadier, whereas oestrogenic exposure is lower. Contraceptive efficacy is similar, as are metabolic changes. Cycle control is better, and compliance and continuation rates are equal or higher. Oestrogen-related adverse symptoms appear to be fewer, but reports on the incidence of venous thrombosis are conflicting. Expulsion of the ring is reported by 4% to 20% of women. Local adverse events are the main reason for discontinuation. Acceptability is as high as with COCs and, after structured counselling, the ring is preferred by many women to the pill or the patch., Conclusions: Efficacy of the CVR, and the metabolic changes and adverse events it elicits, are generally comparable to those of COCs, yet oestrogenic exposure is lower and cycle control superior. After counselling, the ring is preferred to the pill by many women.

Background: Subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) has not been studied in the extremely obese population (BMI >or=40 kg/m(2)). The purpose of this 26-week prospective experimental study was to determine incidence of ovulation and follicular development among women with Class 1, 2 and 3 obesity after receiving DMPA-SC., Methods: Five normal-weight, five Class 1-2 obese, and five Class 3 obese women received subcutaneous injections of 104 mg DMPA-SC at baseline and 12 weeks later. Weekly progesterone levels, bimonthly estradiol (E(2)), and monthly medroxyprogesterone acetate (MPA) levels were measured by immunoassay methods for a total of 26 weeks in each subject., Results: Ovulation did not occur in any subject more than 1 week after the first injection. There was large intersubject and intrasubject variability in E(2) levels, and fluctuating E(2) levels were more frequent among obese women than normal-weight women. Median MPA levels remained above the level needed to prevent ovulation but, compared with normal-weight subjects, were lower among Class 1-2 obese and lowest among Class 3 obese subjects., Conclusion: Fluctuating E(2) levels reflective of follicular development occurred more often among Class 1, 2 and 3 obese women than normal-weight women after DMPA-SC injections. Median MPA levels were consistently lowest among Class 3 obese women but remained above the level needed to inhibit ovulation. Further studies should more fully address the pharmacokinetics of DMPA-SC in extremely obese women.

Objective: To examine breastfeeding and contraceptive use after the lactational amenorrhea method (LAM) criteria were no longer met., Methods: Two hundred and thirty-three parous Egyptian women with unplanned pregnancies less than 2 years after delivery completed a questionnaire examining breastfeeding practice and contraceptive use., Results: The majority of women (81.5%) with unplanned pregnancies within 2 years of delivery were breastfeeding at conception. Of these women, 36.3% had used a method of contraception other than LAM compared with 60.5% of women who had weaned (P<0.05). Among the breastfeeding women, 61.2% failed to use contraception because they believed breastfeeding would prevent pregnancy., Conclusion: Breastfeeding women with unplanned pregnancies were less likely to have used contraception than women who had weaned, suggesting that prolonged breastfeeding contributes to unmet contraceptive need.

Background: Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate., Study Design: Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7., Results: Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mm diameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups., Conclusion: In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC.

Chronic pelvic pain (CPP) affects about 15% of female adults in the United States. The source of this pain in many women is the bladder, specifically interstitial cystitis/painful bladder syndrome (IC/PBS). Despite the frequent occurrence of IC/PBS as a cause of CPP, there currently are no universally accepted guidelines for diagnosis and treatment of this disorder, and, consequently, many patients do not receive appropriate treatment in a timely manner. In an effort to develop a rational way to diagnose and treat patients with CPP, a panel of leaders in urology, gynecology, urogynecology and general women's health met to review recent literature, reach consensus and formulate 2 algorithms, one for diagnosing and the other for managing IC/PBS. This article reflects the results of that meeting.

Drospirenone is a novel progestin that is structurally related to 17 alpha-spirolactone and has antimineralocorticoid and antiandrogenic activity. A 3-mg dose of drospirenone was first used in combination with ethinyl estradiol (EE) 30 microg in a combination oral contraceptive (COC) that is administered for 21 days, followed by a 7-day hormone-free interval (HFI) (drospirenone/30EE, or Yasmin). The 21/7 regimen is considered to be the standard regimen for COC delivery. A formulation with the metabolic benefit of COCs containing a lower estrogen dose has been developed combining drospirenone 3 mg with EE 20 microg and using a regimen of 24 days of active pills, followed by a 4-day HFI (drospirenone/20EE-24/4), or YAZ (Bayer HealthCare Pharmaceuticals Inc., Wayne, New Jersey). Since drospirenone has a half-life of > 30 hours, its activity extends for a prolonged time into the shortened HFI. This new COC has been shown to provide effective contraception and to have a good safety profile. Two large noninterventional studies have recently evaluated the safety of drospirenone/30EE in 2 areas of special interest: hyperkalemia and thromboembolic events. Use of a drospirenone-containing COC was not associated with an increased risk of either type of disorder in comparison with COCs containing other progestins. Drospirenone/20EE-24/4 provides a low dose of EE in combination with drospirenone in an effective and safe COC that is administered using a regimen with a shortened HFI. Drospirenone/20EE-24/4 is the only COC with 3 indications: contraception and the treatment of premenstrual dysphoric disorder in women who wish to use a COC for birth control, and the treatment of moderate acne in women who are at least 14-years-old, have achieved menarche and wish to use a COC for birth control.

Objective: To provide an overview of interstitial cystitis (IC), including the presentation of patients with the disorder, and to explore diagnostic and treatment options., Study Design: Current literature concerning the history, etiology, diagnosis and treatment of IC was used to support expert recommendations regarding patient management. Experts discussed the literature surrounding IC, focusing on diagnostic tools and currently available treatment modalities., Results: Diagnosis of IC may often be delayed or missed due to the similarity of symptoms with a number of other conditions. A detailed medical history and careful physical examination are key for diagnosis, and a variety of screening and diagnostic tools are also available. Once a patient is diagnosed with IC, multimodal treatment through pharmacological and nonpharmacological approaches is recommended., Conclusion: The involvement of both the patient and physician in determining the therapeutic approach, the use of multimodal therapies, regular follow-up and staff involvement in care can bring relief to a substantial number of patients with this condition.

A study was conducted to describe the rate of obstetrical anal sphincter laceration in a large cohort of women and to identify the characteristics associated with this complication. Data from all vaginal deliveries occurring between January 1996 and December 2004 at one institution were used to compare women with and without anal sphincter lacerations. Among 16,667 vaginal deliveries, 1,703 (10.2%) anal sphincter lacerations occurred. Regression models suggested that episiotomy (OR 1.36; 95% CI 1.16, 1.58), vacuum delivery (OR 3.19; 95% CI 2.69, 3.79), and forceps delivery (OR 2.79; 95% CI 1.94, 4.02) were each associated with the increased risk of anal sphincter laceration. Year of delivery was associated with a decreased risk of anal sphincter laceration (OR 0.94; 95% CI 0.92, 0.96) with the rate of laceration decreasing from 11.2% to 7.9% during the study period. Episiotomy and operative vaginal delivery are significant, modifiable risk factors. Changes in obstetric practice may have contributed to the dramatic reduction in anal sphincter laceration during the study period.

Objective: To review a series of women with endometriomas developing in the scar of the skin incision performed for cesarean section., Study Design: A total of 37 patients diagnosed with incisional endometrioma at the time of surgical excision from 1975 to 2005 were identified from the comprehensive surgical database, which includes all operative procedures performed at this institution. The medical records of 33 of the 37 patients were available for review., Results: The endometriomas ranged in size from a diameter of 1-12 cm and were initially observed to be present 6 months to 9 years (mean, 3.2) after the surgical procedure. Diagnosis was best made by needle aspiration of chocolate colored fluid from the mass. Medical therapy with a gonadotropin releasing hormone agonist, medroxyprogesterone acetate or combination oral contraceptives had been attempted in 14 patients without a change in lesion size. All patients were cured by surgical excision of the endometrioma., Conclusion: The overall incidence of incisional endometriomas following cesarean section during the 30-year period was 0.08%. Optimal treatment is by surgical excision. It is hypothesized that failure to close the parietal and visceral peritoneum with sutures at the time of cesarean section may markedly increase the postoperative occurrence of an endometrioma in the skin incision scar.

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

This is the second of a two-article series describing the outcomes of the Hormonal Contraceptives Trial Methodology Consensus Conference held in Philadelphia, PA, on September 23, 2005. The first manuscript, "Hormonal Contraceptive Trials: Variable Data Collection and Bleeding Assessment Methodologies Influence Study Outcome and Physician Perception," provided a description of methodologies applied in the US Food and Drug Administration medical officer's review of clinical trial data as contained in the Summary Basis of Approvals of New Drug Applications, results of the review and general conclusions. This manuscript provides recommendations regarding best practices in trial design, data collection and analysis regarding bleeding data in combined hormone contraception trials.

Many women of childbearing age experience a variety of symptoms related to the menstrual cycle that may be limited to mild discomfort or extend to premenstrual syndrome or, depending on the degree of emotional and somatic impairment, to the most severe premenstrual dysphoric disorder (PMDD). With PMDD, women experience markedly compromised quality of life and ability to function in several settings, leading to higher direct medical costs for increased physician visits and laboratory tests, and higher indirect costs to employers through lower productivity at work. Diagnostic criteria established for premenstrual disorders may now enable physicians to evaluate their patients' complex symptoms more precisely and recommend a form of treatment that can alleviate the original complaint and improve healthcare for women.

Objectives: To estimate the prevalence of interstitial cystitis in women with detrusor overactivity refractory to anticholinergic medication using the potassium sensitivity test (PST)., Methods: Women with complaints of urinary frequency, urgency, and/or urge incontinence of 3 months' duration or longer were referred to the urogynecology clinic. Between October 2003 and June 2004, 47 consecutive women were diagnosed with phasic, idiopathic detrusor overactivity after evaluation by history, physical examination, urinalysis, urine culture, urodynamic testing, and cystoscopy. Refractory detrusor overactivity was defined as a 50% or less improvement in urinary urgency, frequency, and/or urge incontinence episodes while taking anticholinergic medications. All women were offered the PST., Results: All 47 women were included in the study; 18 (38.3%) had only detrusor overactivity incontinence and 29 (61.7%) also had concomitant urodynamic stress incontinence. Additionally, 19 women (40.4%) had pelvic pain. Of the 47 women, 31 agreed to undergo the PST. Of the 31 women, 25 had positive and 6 had negative PST result. Of the 31 women, 25 did not respond to therapy with one or more anticholinergic medications, and 24 (96%) of these 25 had had a positive PST. The remaining 6 women responded to treatment with oxybutynin, and only 1 (16.7%) had had a positive PST (P = 0.0002). The odds ratio of a positive PST for women in whom anticholinergic therapy failed compared with women in whom it did not was 120.0 (95% confidence interval 6.4 to 2257.5; P = 0.0002)., Conclusions: These preliminary findings suggest that there is a high prevalence of interstitial cystitis in women with detrusor overactivity that does not respond to anticholinergic medication.

Objective: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated., Methods: In a two-stage 6-month trial, subjects were randomized to use rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20) microg/day of EE. Subjects were to keep rings continuously in situ until menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to occur 96 h later. After the randomized stage, an open-label 6-month trial of rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with the same menstrually signaled regimen., Results: Two-hundred forty-six subjects participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3 to 3.9 per 100. For each ring dose combination, 6-month continuation rates were above 80 per 100. Bleeding and spotting (B+S) days in women with the 50 microg/day NES rings were similar in number to those experienced by cycling women not using contraception. Nevertheless, in the initial 90 days, fewer B+S days were reported by subjects with the 50/20 ring than by subjects with the 50/10 ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported significantly fewer B+S episodes than did subjects with either 50 microg/day NES ring., Conclusion: Combined contraceptive rings used with a bleeding-signaled regimen led to few terminations attributed to bleeding problems and to acceptable continuation rates. The 150/15 ring appeared to induce fewer bleeding problems than did the lower-dose NES combination rings, but no important difference in 6-month continuation rates among the three doses was noted.

Objectives: This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days., Methods: Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE., Results: One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study., Conclusion: Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Objectives: The safety and efficacy of a single-rod implantable contraceptive containing etonogestrel (Implanontrade mark) were investigated in a multicenter clinical trial., Study Design: Sexually active American women (N=330) with apparently normal menstrual cycles used the implant for up to 2 years. All subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed through adverse experiences (AEs), laboratory tests and physical and gynecologic examinations., Results: Total exposure was 474 woman-years (6186 cycles), and 68% of subjects had at least 1 year of exposure. No pregnancies occurred. The most common bleeding pattern observed throughout the study was infrequent bleeding, defined as less than three episodes of bleeding in a reference period (excluding amenorrhea). The least common pattern was frequent bleeding, defined as more than five episodes of bleeding in a reference period. Infrequent, prolonged and frequent bleeding patterns were most common early in the study and declined thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from the study because of bleeding pattern changes and 76 subjects (23%) discontinued because of other AEs. Other common AEs leading to discontinuation, besides bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%), depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index. The average length of time required for ENG implant insertion and that for removal were 0.5 and 3.5 min, respectively, and all the procedures were uncomplicated. The return to normal menstrual cycles and fertility was rapid after removal., Conclusions: Implanon is a safe, highly effective and rapidly reversible new method of contraception.

Female hormonal contraceptive methods have undergone slow change over the past four decades. Due to social, political and legal reasons, as well as medical complications, several new methods have been removed from the contraceptive armamentarium almost as quickly as they have been added. With worldwide unintended pregnancy rates approaching 50% of all pregnancies, there is an increased need for the development of new methods of effective, safe, acceptable hormonal contraception. Pharmacological methods of contraception are reversible and contraceptive steroids are now formulated in pills, patches, intravaginal rings, subdermal implants and injections. All currently marketed formulations are made from synthetic steroids and contain no natural oestrogens or progestins. This article reviews the current state of female contraception and explores future directions.