Drospirenone: a Latin American perspective for oestrogen-free oral contraception.

AIM: Combined hormonal contraceptives, despite their high efficacy, are associated with an increased relative risk of cardiovascular events. The contraceptive mechanism of action of combined pills depends fundamentally on their progestin component. METHODS: A narrative review was performed. RESULTS: The drospirenone-only pill, including this synthetic progestogen with antimineralocorticoid and antiandrogenic activity, has high contraceptive efficacy that has been demonstrated with a 24-day schedule of 4-day administration of hormone-free pills. Due to its safety profile, the drospirenone-only pill is suitable even in high-risk populations, such as women with high blood pressure, thromboembolism, smoking or dyslipidemia. CONCLUSION: Considering the increasing prevalence of these comorbidities in Latin America, the 4 mg drospirenone-only pill is suggested as one of the strategies of choice in the region for those women who choose oral contraceptives.

Low-dose mifepristone increased angiogenesis in a manner involving AQP1.

PURPOSE: To investigate the molecular mechanisms governing aquaporin-1 (AQP1)-mediated, mifepristone-induced angiogenesis and improve the understanding of low-dose mifepristone serving as an anti-implantation contraceptive drug. METHODS: Human umbilical vein endothelial cells (HUVECs) were used to explore the effects of different concentrations of mifepristone (0, 65, and 200 nmol/L) on the activity of angiogenesis. Forty-five pregnant mice during the "window of implantation" were treated with different concentrations of mifepristone. HUVECs' proliferation was examined using a methyl thiazolyl tetrazolium (MTT) assay. The microvessel density (MVD) and the expression of AQP1 in endometrium were determined with immunohistochemical methods. RESULTS: The MVD and the expression of AQP1 were significantly higher than controls. Mifepristone at 200 nmol/L significantly affected HUVECs' proliferation during culture over 12 h, and pretreatment with AQP1-specific siRNA significantly inhibited the mifepristone-enhanced cell proliferation. CONCLUSIONS: Low-dose mifepristone increased angiogenesis in a manner involving AQP1. This affords a new insight into the molecular mechanism underpinning the angiogenic effects of low-dose mifepristone.

Discontinuation rate of Implanon and its associated factors among women who ever used Implanon in Dale District, Southern Ethiopia.

BACKGROUND: Early discontinuation of the Implanon contraceptive method and reasons for such discontinuation remains a major concern for family planning programs. In less developed countries, contraceptive discontinuation due to health concerns is generally higher, these complaints are often related to service quality. Significant numbers of women become exposed to conception after discontinuation and accidental pregnancies that end up with abortion & stillbirth. The aim of this study was to assess the early discontinuation rate of Implanon and identify its associated factors among women who ever used Implanon in 2016 in Dale district, Southern Ethiopia. METHODS: Community based cross-sectional study design was conducted from January to February, 2017. A total number of 711 women who ever used Implanon in 2016 were selected using multistage sampling. The data were entered and cleaned in Epi Info and analyzed using SPSS. Multivariate logistic regression analysis was used to determine the effect of factors on the outcome variables. Finally, the results were presented using adjusted odds ratio (AOR) & confidence interval of 95%. RESULT: Early Implanon discontinuation rate in this study was 160 (23.4%) with a mean duration of Implanon use of 9.6 ± 2.5 months. The main reasons for discontinuation of Implanon were 55 (34.4%) the facing of side effects. Factors for discontinuation of Implanon were women age 20-24 years (AOR =. 44 (95% CI: 23-. 85), 25-29 years (AOR =. 52 (95% CI: 27-. 96), 35+ years, (AOR =. 08 (95% CI: 02-. 41), less likely to discontinue. Women who weren't counseled about the side effects during Implanon insertion were 1.93 times (AOR = 1.93 (95% CI: 1.27-2.93), women who didn't satisfied by the service (AOR = 2.55(CI: 95%: 1.63-3.97), women who didn't appointed for follow up (AOR = 3.13 (CI: 95%: 2.0-4.95), women who didn't choose the method by themselves (AOR = 1.83 (CI: 95%: 1.18-2.83) and women who didn't have information on family planning before Implanon insertion (AOR = 1.52 (CI: 95%: 1.1-2.28) were the predictors of Implanon discontinuation. CONCLUSIONS: Implanon discontinuation rate in this study area was high. Appropriate counseling prior to insertion and proper follow up, autonomous choice will improve the continuation rate of Implanon.

Ecological study on the use of hormonal contraception, abortions and births among teenagers in the Nordic countries.

OBJECTIVES: Compare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries. DESIGN: Ecological study using national registry data concerning births and abortions among all women aged 15-19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008-2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008-2015 were obtained from national databases in Denmark, Norway and Sweden. SETTING: Denmark, Finland, Iceland, Norway and Sweden. PARTICIPANTS: Women 15-19 years old in all Nordic countries (749 709) and 13-19 years old in Denmark, Norway and Sweden (815 044). RESULTS: Both annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15-19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18-19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden. CONCLUSIONS: Birth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers.

Pericoital contraception.

PURPOSE OF REVIEW: To evaluate the literature on repeat use of emergency contraception and pericoital approaches to contraception. RECENT FINDINGS: Women are very interested in an oral, on-demand contraceptive option, were one available. Ulipristal acetate and a combination of levonorgestrel (LNG) and meloxicam (a cyclo-oxygenase-2 inhibitor) both appear to be more effective at disrupting ovulation than LNG alone. Recent advisories from the United Kingdom regarding daily dosing of ulipristal for fibroids emphasize the need for more safety data. SUMMARY: Repeat pericoital dosing of 1.5-mg LNG is approximately as effective as other on-demand contraceptive methods and is overall very safe. The most common side effect is irregular bleeding. Repeat on-demand ulipristal acetate or meloxicam/other cyclo-oxygenase-2 inhibitors have potential as an on-demand option either alone or in combination but have not been evaluated for contraceptive efficacy in a large-scale study. Given the high unmet need for contraception, even among women with access to available options, there is a distinct need for options that address needs of women who are interested in an on-demand option. On-demand oral contraception has the potential to expand the convenience of contraceptive options and overall contraceptive use.

Norethindrone acetate versus extended-cycle oral contraceptive (Seasonique®) in the treatment of endometriosis symptoms: A prospective open-label comparative study.

INTRODUCTION: This patient preference prospective study was designed to compare patients' satisfaction in women with endometriosis treated either by an extended-cycle oral contraception (OC) or by norethindrone acetate (NETA). METHODS: This patient preference prospective study included women of reproductive age with endometriosis. Patients were submitted to one of the following 12 months' treatments: Group A, continuous oral treatment with NETA (2.5 mg/day) and Group B, a 91-day extended-cycle OC (LNG/EE 150/30 mcg for 84 days and EE 10 mcg for 7 days). Patient satisfaction was the primary endpoint. RESULTS: There was no statistically significant difference in the rate of satisfied patients at 12-month follow up between the two study groups, 82.2% and 68.4% in Group A and Group B respectively (p = 0.143). At 6 and 12-months, there was a significant amelioration in the intensity of all pain in both groups. The median number of days of unscheduled bleeding during the first cycle was significantly higher in Group B compared to Group A. CONCLUSION: Both NETA and extended-cycle OC are effective in treating pain symptoms related to endometriosis. Extended-cycle OC may cause more unscheduled bleeding, but the rate of satisfaction for those who completed the treatment was similar in the two groups.

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

The purpose of this study was to assess the proportion of patients satisfied with their treatment after a change from a low-dose oral contraceptive (OC) to norethisterone acetate (NETA) because of inefficacy of OC on pain symptoms. To this end, prospective, self-controlled study was conducted on 153 women using OC as a treatment for endometriosis and with persistence of one or more moderate or severe pain symptoms. At baseline and during 12 months after a shift from OC to oral NETA, 2.5 mg/d, pelvic pain was measured by means of a 0- to 10-point numerical rating scale and a multidimensional categorical rating scale. Variations in health-related quality of life, psychological status, and sexual function were also evaluated with validated scales. At the end of the study period, participants indicated the degree of satisfaction with their treatment according to a 5-degree scale from very satisfied to very dissatisfied. A total of 28 women dropped out of the study, the main reason was intolerable side effects (n = 15). At 12-month assessment, 70% of participants were very satisfied or satisfied with NETA treatment (intention-to-treat analysis). Statistically significant improvements were observed in health-related quality of life, psychological status, and sexual function. At per-protocol analysis, almost half of the patients (58/125) reported suboptimal drug tolerability. However, complaints were not severe enough to cause dissatisfaction, drug discontinuation, or request for surgery. These encouraging results could be used to counsel women with symptomatic endometriosis not responding to OC and to inform their decisions on modifications of disease management.

Effectiveness of the progestin-only pill for migraine treatment in women: A systematic review and meta-analysis.

Background Migraine is highly prevalent in women (18%). Peak morbidity affects their most productive years, coinciding with peak fertility. Hormonal contraception is often tailored for migraine prevention. Estrogen-containing contraceptives may be contraindicated in women experiencing migraine with aura due to the risk of vascular events. While improvements in migraine with a progestin-only pill (POP), which inhibits ovulation are documented, the strength and quality of evidence has not been formally evaluated. Objectives To determine the effectiveness of progestin-only contraceptives for migraine treatment by systematic review and meta-analysis. Data sources and selection MEDLINE, EMBASE and Cochrane Libraries were searched (1980 to September 2016) for studies on progestin-only treatments for migraine. Studies in English on >4 non-menopausal women aged 18-50 with migraine diagnosed by formal criteria were included. Data extraction and analysis Data were quality-assessed using the GRADE system. A random effects model was used for pooled analyses. Results Pooled analyses of four studies demonstrated that desogestrel 75 mcg/day, POP significantly but modestly reduced the number of migraine attacks and migraine days. Reduced intensity and duration, reduced analgesic and triptan use were observed, along with improved headache-related quality of life. GRADE analysis indicated evidence was low to very low for each outcome measure. Adverse effects resulted in treatment cessation for <10% of participants. Two studies compared desogestrel POP to a combined oral contraceptive, demonstrating similar migraine outcomes for both treatments. Conclusions The desogestrel POP shows promise in improving migraine in women. Current evidence is observational and based on small samples of women using only one oral progestin-only formulation. Further randomized trials on additional progestin-only contraceptives are required to confirm their role in migraine management.

Clinical efficacy of levonorgestrel and norethisterone for the treatment of chronic abnormal uterine bleeding.

OBJECTIVE: To compare the clinical efficacy of levonorgestrel intrauterine system with oral norethisterone for the treatment of idiopathic chronic abnormal uterine bleeding. METHODS: This cross-sectional study was conducted at Bahawal Victoria Hospital, Jubilee Female Hospital, Civil Hospital and private clinics of consultant gynaecologists in Bahawalpur, Pakistan, from March to August 2014, and comprised patients presenting with abnormal uterine bleeding. The patients were equally and randomly divided into two groups, i.e. intrauterine levonorgestrel administered (group A) and norethisterone administered (group B). Mean age, duration of the disease and parity were determined using a predesigned questionnaire. The primary outcomes of the treatments, i.e. reduction in menstrual blood loss assessed by the pictorial blood assessment chart score, were recorded before the initiation of therapy, at 3 months and at 6months of the study. SPSS 16 was used for data analysis. RESULTS: There were 76 subjects; 38(50%) in each group. In group A, the mean age and mean duration of the disease was 34.16±6.327 years and 6.18±2.415 years compared to 34.21±3.595 years and 6.21±2.418 years in group B. The reduction in menstrual blood loss did not differ significantly between the groups after 3 months (p= 0.321). However, levonorgestrel intrauterine system was found more effective in reducing menstrual blood loss in 36(94.73%) patients, compared to norethisterone-treated patients 28(73.68%) after 6 months of the treatment (p=0.041). The response of both the treatments was found independent of patient's age, parity and chronicity of the disease. CONCLUSIONS: The levonorgestrel intrauterine system was better than norethisterone with marked clinical benefit of profound reduction in menstrual blood loss.

Sometimes You Do Get a Second Chance: Emergency Contraception for Adolescents.

Unplanned or unintended pregnancy remains a significant challenge for adolescents; many teens who plan ahead but opt not to choose long-acting reversible contraceptive methods have high failure rates with condom usage, oral contraceptives, and other less long-acting methods. Emergency contraception (EC) remains a necessity for those adolescents seeking a second chance to prevent the unintended consequences of unplanned sexual activity. At present, 5 postcoital methods remain available as EC globally: intrauterine devices, ulipristal acetate, a selective progesterone modulator, mifepristone; levonorgestrel, and ethinyl estradiol plus levonorgestrel or norgestrel (rarely used now that progestin only methods are more readily available).

Contraceptive use in the Nordic countries.

INTRODUCTION: The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral contraception containing low-dose estrogen and levonorgestrel, norethisterone or norgestimate. MATERIAL AND METHODS: Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden in 2010-2013. RESULTS: Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). Combined oral contraception was the most used method in all countries, with the highest use in Denmark (26%). The second most used method was the levonorgestrel-releasing intrauterine system, with the highest use in Finland (15%) and ≈10% in the other countries. Copper intrauterine devices (7%) and the progestin-only pill (7%) were most often used in Sweden. Combined oral contraception use decreased with increasing age and levonorgestrel-releasing intrauterine system and progestin-only pills use increased. The use of long-acting reversible methods of contraception (=levonorgestrel-releasing intrauterine system, copper intrauterine devices, and implants) increased with time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended combined oral contraception was in Denmark, increasing from 13 to 50% between 2010 and 2013. In Finland, recommended combined oral contraception remained below 1%. CONCLUSIONS: Contraceptive use was highest in Denmark and Sweden, levonorgestrel-releasing intrauterine system use was highest in Finland and all long-acting methods were most common in Sweden. The use of combined oral contraception recommended by the European Medicines Agency was highest in Denmark.

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

AIM: Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. MATERIAL AND METHODS: A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. RESULTS: Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. CONCLUSIONS: Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

Efficacy of combined hormonal vaginal ring in comparison to combined hormonal pills in heavy menstrual bleeding.

OBJECTIVE: To compare the efficacy, acceptability and compliance of combined hormonal vaginal ring (CVR), with combined hormonal pills (CHP) in patients with heavy menstrual bleeding (HMB). STUDY DESIGN: This prospective study was conducted in 50 women with HMB in age group of 25-40 years. Patients were divided in two groups of 25 each and followed for six treatment cycles. In each group, cycle comprised of three weeks of CVR (releases 15µg of EE and 120µg of the etonogestrel per day) or CHP (containing 30µgm of EE and 150µgm of LNG) use, followed by one ring or pill free week. After each cycle, patients were evaluated about the amount of blood loss and duration of bleeding by the pictoral blood assessment chart (PBAC), early bleeding (EWB), continued bleeding (CWB), intermenstrual bleeding, intended bleeding, compliance, and user acceptability. The collected data were analyzed using the Chi square test, t-test and ANOVA test. RESULT: Reduction in PBAC score for CVR (70.73%) and CHP group (70.02%), duration of bleeding and incidence of EWB was comparable among the two groups. The incidence of intermenstrual bleeding was lower in CVR than in CHP group in cycle 3 and 4 with significant p value. The incidence of CWB was significantly lower and the incidence of intended bleeding pattern in CVR group was significantly higher in cycle 3, 4, 5 and 6, signifying better cycle control. Compliance was also higher in CVR (88%) than CHC (75.33% of all cycles). CONCLUSION: This trial suggests that both the CVR and CHP are very effective short-term treatments for HMB in reproductive age group. However, women had better cycle control and compliance with CVR. This may be an attractive option among the wide variety of medications used to treat HMB.

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.

STUDY QUESTION: Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER: Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY: LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION: This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE: There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION: This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS: A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTERESTS: This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE: 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT: 10 January 2012.

Role of Medical Management for Uterine Leiomyomas.

Uterine leiomyomas, or fibroids, are the most common benign tumor in reproductive aged women. Affected women may remain asymptomatic or may report symptoms related to abnormal uterine bleeding, infertility, or pelvic pain and pressure. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy). In those wishing to defer surgical management, non-hormonal therapies such as non-steroidal anti-inflammatory drugs and tranexamic acid have been shown to decrease menstrual blood loss. In patients with more symptomatic leiomyomas, hormonal therapies such as gonadotropin-releasing hormone agonists and selective progesterone receptor modulators are effective at reducing leiomyoma volume, uterine size, and menstrual blood loss. This manuscript will detail the available and emerging hormonal and non-hormonal treatments for symptomatic uterine leiomyomas.

A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.

STUDY QUESTION: Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day? SUMMARY ANSWER: In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG. WHAT IS KNOWN ALREADY: UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA. STUDY DESIGN, SIZE, DURATION: A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU). PARTICIPANTS/MATERIAL, SETTING, METHODS: A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL). MAIN RESULTS AND THE ROLE OF CHANCE: Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles. LIMITATIONS, REASONS FOR CAUTION: This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images. WIDER IMPLICATIONS OF THE FINDINGS: Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.

Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

STUDY OBJECTIVE: To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. DESIGN: Cohort study (Canadian Task Force II-2). SETTING: An academic institution in the upper Midwest. PATIENTS: All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. INTERVENTION: Radiofrequency EA, thermal balloon ablation, and LNG-IUS. MEASUREMENTS AND MAIN RESULTS: The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. CONCLUSION: LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB.